Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)

Posted: October 23rd, 2023, 2:00am GMT

Conditions: Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma
Interventions: Biological: Peptide vaccine IPX
Sponsors: University Hospital Tuebingen; Deutsches Konsortium fürTranslationale Krebsforschung (DKTK); Cooperative Ewing Sarkom Studiengruppe; Cooperative Weichteilsarkom Study Group
Recruiting
PARP Inhibition, Stereotactic Body Radiotherapy and Immunotherapy for Metastatic or Advanced Sarcoma (PRIMA): a Prospective Phase 2 Trial

Posted: October 10th, 2023, 2:00am GMT

Conditions: Sarcoma; Sarcoma,Soft Tissue; Sarcoma of Bone
Interventions: Combination Product: Camrelizumab and fluzoparib with concurrent stereotactic body radiotherapy (SBRT)
Sponsors: Ruijin Hospital
Recruiting
Retrospective Study in FFPE Samples From Younger Patients With Rhabdomyosarcoma

Posted: September 15th, 2023, 2:00am GMT

Conditions: Alveolar Childhood Rhabdomyosarcoma; Embryonal Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma
Sponsors: Shandong First Medical University; Shandong Tumor Hospital
Completed
Analyzing Engagement Trends in Rhabdomyosarcoma Clinical Trials

Posted: September 8th, 2023, 2:00pm GMT

Conditions: Rhabdomyosarcoma
Sponsors: Power Life Sciences Inc.
Not yet recruiting
Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease

Posted: September 4th, 2023, 2:00pm GMT

Conditions: Rhabdomyosarcoma
Interventions: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Proton beam radiation or external beam radiation or brachytherapy; Drug: Liposomal irinotecan; Drug: Vinorelbine; Drug: Temozolomide; Drug: Filgrastim, peg-filgrastim
Sponsors: St. Jude Children's Research Hospital
Not yet recruiting
$Permalink for 'A Phase Ib Trial of Eribulin in Combination With Irinotecan and Temozolamide in Children With Relapsed or Refractory Solid Tumors'$
A Phase Ib Trial of Eribulin in Combination With Irinotecan and Temozolamide in Children With Relapsed or Refractory Solid Tumors

Posted: August 23rd, 2023, 2:00pm GMT

Condition: Refractory Solid Tumors
Interventions: Drug: Eribulin; Drug: Irinotecan; Drug: Temozolomide
Sponsor: M.D. Anderson Cancer Center
Recruiting
Ex Vivo Drug Sensitivity Testing and Multi-Omics Profiling

Posted: May 15th, 2023, 2:00pm GMT

Conditions: Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Large Cell Lymphoma; Refractory Childhood Acute Lymphoblastic Leukemia; Refractory Childhood Hodgkin Lymphoma; Refractory Childhood Malignant Germ Cell Neoplasm; Recurrent Childhood Brain Tumor; Recurrent Childhood Brainstem Glioma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Ependymoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Gliosarcoma; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Childhood Malignant Solid Neoplasm; Recurrent Childhood Malignant Solid Neoplasm; Recurrent Childhood Malignant Neoplasm; Refractory Childhood Malignant Neoplasm
Sponsors: Florida International University; Nicklaus Children's Hospital f/k/a Miami Children's Hospital; First Ascent Biomedical, Inc.; National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
PRospective rEgistry OF Advanced Stage cancER (PREFER) Patients to Assess Prevalence of Actionable Biomarkers and Driver Mutations to Address Disparities in Precision Medicine

Posted: January 25th, 2023, 3:00pm GMT

Conditions: Lung Cancer; Ovarian Cancer; Uterine Cancer; Colorectal Cancer; Stomach Cancer; Esophageal Cancer; Pancreatic Cancer; Melanoma; Breast Cancer; Head and Neck Cancer; Soft Tissue Sarcoma; Rhabdomyosarcoma; Prostate Cancer
Intervention: Diagnostic Test: OmniSeq Test
Sponsor: Labcorp Corporation of America Holdings, Inc
Recruiting
$Permalink for 'A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions as Adoptive Immunotherapy in Combination With Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Pediatric Bone and Soft Tissue'$
A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions as Adoptive Immunotherapy in Combination With Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Pediatric Bone and Soft Tissue

Posted: December 2nd, 2022, 3:00pm GMT

Conditions: Pediatric Sarcoma, Refractory; Pediatric Sarcoma, Relapsed
Interventions: Biological: GEM/DOX + TGFBi expanded NK cells
Sponsors: Nationwide Children's Hospital; National Pediatric Cancer Foundation
Recruiting
Doxorubicin Hydrochloride Liposome Combined With Irinotecan Versus VIT Regimen in the Treatment of Pediatric Rhabdomyosarcoma

Posted: July 14th, 2022, 2:00pm GMT

Conditions: Rhabdomyosarcoma, Child
Interventions: Drug: Doxorubicin Hydrochloride Liposome+Irinotecan; Drug: Temozolomide+Irinotecan+Vincristine
Sponsors: Sun Yat-sen University; CSPC Ouyi Pharmaceutical Co., Ltd.
Not yet recruiting
$Permalink for 'Study of Efficacy and Safety of Ribociclib (LEE011) in Combination With Topotecan and Temozolomide (TOTEM) in Pediatric Patients With Relapsed or Refractory Neuroblastoma and Other Solid Tumors'$
Study of Efficacy and Safety of Ribociclib (LEE011) in Combination With Topotecan and Temozolomide (TOTEM) in Pediatric Patients With Relapsed or Refractory Neuroblastoma and Other Solid Tumors

Posted: June 23rd, 2022, 2:00pm GMT

Conditions: Neuroblastoma
Interventions: Drug: Topotecan; Drug: Temozolomide; Drug: Ribociclib
Sponsors: Novartis Pharmaceuticals; Innovative Therapies For Children with Cancer Consortium
Recruiting
Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma

Posted: March 31st, 2022, 2:00pm GMT

Conditions: Embryonal Rhabdomyosarcoma; Fusion-Negative Alveolar Rhabdomyosarcoma; Spindle Cell/Sclerosing Rhabdomyosarcoma
Interventions: Procedure: Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dactinomycin; Procedure: Magnetic Resonance Elastography; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Drug: Vincristine
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Recruiting
$Permalink for 'Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors'$
Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors

Posted: March 31st, 2022, 2:00am GMT

Conditions: Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Relapsed Pediatric Solid Tumor; Refractory Pediatric Solid Tumor; Melanoma; Hepatoblastoma; Hepatocellular Carcinoma; Neuroblastoma; Wilms Tumor
Interventions: Procedure: Cryoablation Therapy; Drug: Nivolumab; Drug: Ipilimumab
Sponsors: Children's National Research Institute; Bristol-Myers Squibb
Active, not recruiting
A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

Posted: January 20th, 2022, 3:00pm GMT

Condition: Solid Tumors With PTCH1 Loss-of-function Mutations
Intervention: Drug: ENV-101 (taladegib)
Sponsor: Endeavor Biomedicines, Inc.
Recruiting
A Study of Cabozantinib as a Maintenance Agent to Prevent Progression or Recurrence in High-Risk Pediatric Solid Tumors

Posted: November 26th, 2021, 3:00pm GMT

Conditions: Neuroblastoma; Sarcoma
Intervention: Drug: Cabozantinib
Sponsors: Nationwide Children's Hospital; Exelixis
Recruiting
Multicohort Trial of Trabectedin and Low-dose Radiation Therapy in Advanced/Metastatic Sarcomas

Posted: November 23rd, 2021, 3:00pm GMT

Conditions: Soft Tissue Sarcoma; Bone Tumors; Small Round-cell Sarcomas
Intervention: Drug: Trabectedin
Sponsor: Grupo Espanol de Investigacion en Sarcomas
Recruiting
Improving Adolescent and Young Adult Self-Reported Data in ECOG-ACRIN Trials

Posted: November 4th, 2021, 2:00am GMT

Conditions: Breast Cancer, NOS; CNS Primary Tumor, NOS; Cervical Cancer, NOS; Colorectal Cancer, NOS; Leukemia, NOS; Lymphoma, NOS; Miscellaneous Neoplasm, NOS; Non-Rhabdomyosarcoma Soft Tissue Sarcoma, NOS; Testicular Nonseminomatous Germ Cell Tumor, NOS; Thyroid Cancer, NOS; Melanoma; Bone Cancer, NOS
Interventions: Other: Questionnaires
Sponsors: Eastern Cooperative Oncology Group
Recruiting
Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Hepatocellular Carcinoma

Posted: November 2nd, 2021, 2:00pm GMT

Conditions: Liver Cell Carcinoma; Solid Tumor; Wilms Tumor; Malignant Rhabdoid Tumor; Yolk Sac Tumor; Rhabdomyosarcoma; Liposarcoma; Embryonal Sarcoma of the Liver
Intervention: Genetic: CATCH T cells
Sponsors: Baylor College of Medicine; Center for Cell and Gene Therapy, Baylor College of Medicine; The Methodist Hospital Research Institute
Recruiting
Comparison Capsule Sparing Cystectomy and Radical Cystoprostatectomy in Men With Bladder Cancer

Posted: October 5th, 2021, 2:00am GMT

Conditions: Bladder Cancer
Interventions: Procedure: Capsule Sparing Cystectomy (CSC); Procedure: Conventional Radical Cystoprostatectomy (CRC)
Sponsors: Zhujiang Hospital
Not yet recruiting
Comparing Carbon Ion Therapy, Surgery, and Proton Therapy for Management of Pelvic Sarcomas Involving the Bone

Posted: September 2nd, 2021, 2:00pm GMT

Conditions: Bone Sarcoma; Chondrosarcoma; Chordoma; Ewing Sarcoma of Bone; Pelvic Rhabdomyosarcoma
Interventions: Other: Electronic Health Record Review; Other: Quality-of-Life Assessment
Sponsors: Mayo Clinic
Recruiting
HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma

Posted: August 6th, 2021, 2:00pm GMT

Conditions: Sarcoma; HER-2 Protein Overexpression; Osteosarcoma; Rhabdomyosarcoma; Ewing Sarcoma; Synovial Sarcoma; Soft Tissue Sarcoma; Undifferentiated Sarcoma
Interventions: Genetic: T cells or CAR T cells; Drug: Pembrolizumab Injectable Product; Drug: Nivolumab Injectable Product
Sponsors: Baylor College of Medicine; Center for Cell and Gene Therapy, Baylor College of Medicine; The Faris Foundation USA; Stand Up To Cancer; Triumph Over Kid Cancer Foundation; St. Baldrick's Foundation; National Cancer Institute (NCI)
Recruiting
B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma
Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells
Sponsor: St. Jude Children's Research Hospital
Recruiting
A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors

Posted: March 10th, 2021, 3:00pm GMT

Conditions: Solid Tumors; Soft Tissue Sarcoma; Ewing Sarcoma; Malignant Epithelial Neoplasm; Rhabdomyosarcoma; Wilms Tumor; Hepatic Tumor; Germ Cell Tumor; Bone Metastases
Interventions: Device: Magnetic Resonance-Guided High Intensity Focused Ultrasound; Drug: Lyso-thermosensitive Liposomal Doxorubicin
Sponsor: Children's National Research Institute
Recruiting
Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

Posted: January 20th, 2021, 3:00pm GMT

Conditions: Liver Cancer; Rhabdomyosarcoma; Malignant Rhabdoid Tumor; Liposarcoma; Wilms Tumor; Yolk Sac Tumor
Interventions: Genetic: CARE T cells; Drug: Cytoxan; Drug: Fludara
Sponsors: Baylor College of Medicine; Center for Cell and Gene Therapy, Baylor College of Medicine
Not yet recruiting
FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma

Posted: November 12th, 2020, 3:00pm GMT

Condition: Rhabdomyosarcoma
Interventions: Drug: Irinotecan; Drug: Actinomycin D; Drug: Doxorubicin; Drug: Ifosfamide; Drug: Vincristine; Drug: Vinorelbine; Drug: Cyclophosphamide; Drug: Temozolomide; Radiation: radiotherapy; Drug: Regorafenib
Sponsor: University of Birmingham
Recruiting
$Permalink for 'A Study of Lenvatinib (MK-7902) in Pediatric Participants With Relapsed or Refractory Solid Malignancies (MK-7902-013/E7080)'$
A Study of Lenvatinib (MK-7902) in Pediatric Participants With Relapsed or Refractory Solid Malignancies (MK-7902-013/E7080)

Posted: June 25th, 2020, 2:00am GMT

Conditions: Relapsed or Refractory Solid Tumors
Interventions: Drug: Lenvatinib
Sponsors: Merck Sharp & Dohme LLC; Eisai Inc.
Active, not recruiting
Personalized Risk-Adapted Therapy in Post-Pubertal Patients With Newly-Diagnosed Medulloblastoma

Posted: May 26th, 2020, 2:00pm GMT

Condition: Medulloblastoma
Interventions: Drug: Sonidegib; Drug: Cisplatin; Drug: Lomustine; Drug: Vincristine; Radiation: radiotherapy
Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Recruiting
Evolutionary Therapy for Rhabdomyosarcoma

Posted: May 14th, 2020, 2:00pm GMT

Conditions: Rhabdomyosarcoma
Interventions: Drug: Vincristine; Drug: Cyclophosphamide; Drug: Vinorelbine; Drug: Actinomycin D; Drug: Cyclophosphamide Pill
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; National Pediatric Cancer Foundation
Recruiting
Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors

Posted: April 7th, 2020, 2:00pm GMT

Conditions: Solid Tumors; Neuroblastoma; Rhabdomyosarcoma; Ewing Sarcoma; Hepatoblastoma; Medulloblastoma
Interventions: Drug: VAL-413; Drug: Temozolomide
Sponsor: Valent Technologies, LLC
Recruiting
$Permalink for 'Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies'$
Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies

Posted: March 16th, 2020, 2:00am GMT

Conditions: Ewing Sarcoma; Rhabdomyosarcoma; Wilms Tumor; Neuroblastoma; Hepatoblastoma; Germ Cell Tumor
Interventions: Drug: Vorinostat
Sponsors: New York Medical College
Recruiting
$Permalink for 'Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma'$
Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma

Posted: March 6th, 2020, 3:00pm GMT

Condition: Rhabdomyosarcoma
Interventions: Drug: Vinorelbine; Drug: Mocetinostat
Sponsors: Jonsson Comprehensive Cancer Center; Mirati Therapeutics Inc.; Phase One Foundation
Recruiting
$Permalink for 'Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for the Treatment of Resectable, Refractory, or Recurrent Abdominal or Pelvic Tumors in Pediatric Patients, T.O.A.S.T. I.T. Study'$
Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for the Treatment of Resectable, Refractory, or Recurrent Abdominal or Pelvic Tumors in Pediatric Patients, T.O.A.S.T. I.T. Study

Posted: December 30th, 2019, 3:00pm GMT

Conditions: Malignant Abdominal Neoplasm; Malignant Pelvic Neoplasm; Recurrent Colon Carcinoma; Recurrent Desmoplastic Small Round Cell Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Gastric Carcinoma; Recurrent Liposarcoma; Recurrent Malignant Mesothelioma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Rectal Carcinoma; Recurrent Rhabdomyosarcoma; Recurrent Sarcoma; Refractory Colon Carcinoma; Refractory Desmoplastic Small Round Cell Tumor; Refractory Fallopian Tube Carcinoma; Refractory Gastric Carcinoma; Refractory Liposarcoma; Refractory Malignant Mesothelioma; Refractory Ovarian Carcinoma; Refractory Primary Peritoneal Carcinoma; Refractory Rectal Carcinoma; Refractory Rhabdomyosarcoma; Refractory Sarcoma; Resectable Liposarcoma; Resectable Malignant Mesothelioma; Resectable Sarcoma
Interventions: Drug: Cisplatin; Procedure: Cytoreductive Surgery; Drug: Doxorubicin; Drug: Hyperthermic Intraperitoneal Chemotherapy; Drug: Sodium Thiosulfate
Sponsors: Mayo Clinic; National Cancer Institute (NCI)
Recruiting
A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

Posted: September 19th, 2019, 2:00am GMT

Conditions: Desmoplastic Small Round Cell Tumor; Rhabdomyosarcoma
Interventions: Drug: Prexasertib; Drug: Irinotecan
Sponsors: Memorial Sloan Kettering Cancer Center
Active, not recruiting
Indocyanine Green (ICG) Guided Tumor Resection

Posted: September 10th, 2019, 2:00pm GMT

Conditions: Neoplastic Disease; Solid Tumor
Interventions: Drug: Indocyanine Green
Sponsors: St. Jude Children's Research Hospital
Recruiting
$Permalink for 'Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors'$
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors

Posted: October 17th, 2018, 2:00pm GMT

Conditions: Ewing Sarcoma; Solid Tumors; Rhabdoid Tumor; Rhabdomyosarcoma; Neuroblastoma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma
Interventions: Drug: Palbociclib; Drug: Temozolomide; Drug: Irinotecan; Drug: Topotecan; Drug: Cyclophosphamide
Sponsors: Pfizer; Children's Oncology Group (COG)
Recruiting
Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

Posted: October 9th, 2018, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Ependymal Tumor; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Histiocytic and Dendritic Cell Neoplasm; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Primary Malignant Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Histiocytic and Dendritic Cell Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Primary Malignant Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Wilms Tumor
Interventions: Other: Pharmacokinetic Study; Drug: Ulixertinib
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
$Permalink for 'C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)'$
C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)

Posted: August 17th, 2018, 2:00pm GMT

Conditions: Relapsed Neuroblastoma; Refractory Neuroblastoma; Relapsed Osteosarcoma; Relapsed Ewing Sarcoma; Relapsed Rhabdomyosarcoma; Uveal Melanoma; Phyllodes Breast Tumor
Intervention: Genetic: C7R-GD2.CART cells
Sponsors: Baylor College of Medicine; Center for Cell and Gene Therapy, Baylor College of Medicine; The Methodist Hospital Research Institute; Cancer Prevention Research Institute of Texas
Recruiting
$Permalink for 'EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$
EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Posted: August 7th, 2018, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma
Interventions: Biological: second generation 4-1BBζ EGFR806-EGFRt; Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Sponsor: Seattle Children's Hospital
Recruiting
$Permalink for 'Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)'$
Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Posted: May 16th, 2018, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma
Interventions: Other: Laboratory Biomarker Analysis; Drug: Palbociclib; Other: Pharmacological Study
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
Biological Characterisation of High Risk CHildhood Cancer in Children, Adolescents and Young Adults (MICCHADO)

Posted: April 12th, 2018, 2:00pm GMT

Conditions: Neuroblastoma; Rhabdomyosarcoma; Ewing Sarcoma Family of Tumors; Osteosarcoma; Leukemia; Central Nervous System Tumor
Interventions: Other: Sampling on blood, bone marrow and cerebrospinal fluid
Sponsors: Institut Curie
Recruiting
Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients

Posted: March 8th, 2018, 3:00am GMT

Conditions: Relapsed or Refractory Solid Tumors or Lymphoma in Children; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Ewing Sarcoma
Interventions: Drug: Copanlisib (BAY806946)
Sponsors: Bayer
Terminated
$Permalink for 'Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors'$
Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors

Posted: August 10th, 2017, 2:00am GMT

Conditions: Recurrent and Refractory Solid Tumors
Interventions: Drug: Lenvatinib; Drug: Everolimus
Sponsors: Eisai Inc.; Merck Sharp & Dohme LLC
Completed
$Permalink for 'Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)'$
Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

Posted: July 28th, 2017, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Childhood Malignant Germ Cell Tumor; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; Wilms Tumor
Interventions: Drug: Olaparib
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
$Permalink for 'Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)'$
Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

Posted: July 18th, 2017, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ependymoma; Ewing Sarcoma; Hepatoblastoma; Langerhans Cell Histiocytosis; Malignant Germ Cell Tumor; Malignant Glioma; Osteosarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Central Nervous System Neoplasm; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma; Wilms Tumor
Interventions: Other: Laboratory Biomarker Analysis; Drug: Vemurafenib
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
$Permalink for 'Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)'$
Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

Posted: July 11th, 2017, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Hodgkin Lymphoma; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Low Grade Glioma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Primary Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor
Interventions: Drug: Tazemetostat
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
Active, not recruiting
$Permalink for 'Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)'$
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)

Posted: July 7th, 2017, 2:00am GMT

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Osteosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Primary Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Refractory Childhood Malignant Germ Cell Tumor; Refractory Childhood Osteosarcoma; Refractory Childhood Rhabdomyosarcoma; Refractory Childhood Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Wilms Tumor
Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Erdafitinib; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Other: Pharmacological Study; Procedure: Positron Emission Tomography; Procedure: Radionuclide Imaging; Procedure: X-Ray Imaging
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
Comparison of Safety and Efficacy of Detaenial Sigmoid Neobladder and Ileal Neobladder

Posted: April 11th, 2017, 2:00am GMT

Conditions: Bladder Cancer; Urinary Diversion
Interventions: Procedure: sigmoid; Procedure: ileal
Sponsors: Zhujiang Hospital; Sun Yat-sen University; The Third Affiliated Hospital of Southern Medical University; Fourth Affiliated Hospital of Guangxi Medical University; Ludwig-Maximilians - University of Munich
Recruiting
Familial Investigations of Childhood Cancer Predisposition

Posted: February 10th, 2017, 3:00pm GMT

Conditions: Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease
Intervention:
Sponsor: St. Jude Children's Research Hospital
Recruiting
$Permalink for 'Nab-Paclitaxel and Gemcitabine for Recurrent/Refractory Sarcoma'$
Nab-Paclitaxel and Gemcitabine for Recurrent/Refractory Sarcoma

Posted: October 26th, 2016, 2:00pm GMT

Conditions: Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Soft Tissue Sarcoma
Interventions: Drug: nab-Paclitaxel; Drug: Gemcitabine
Sponsors: H. Lee Moffitt Cancer Center and Research Institute; National Pediatric Cancer Foundation
Recruiting
$Permalink for 'Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors'$
Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

Posted: December 31st, 2015, 3:00am GMT

Conditions: Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory
Interventions: Drug: Abemaciclib
Sponsors: Emory University
Completed
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma

Posted: October 5th, 2015, 2:00am GMT

Conditions: Alveolar Rhabdomyosarcoma; Botryoid-Type Embryonal Rhabdomyosarcoma; Embryonal Rhabdomyosarcoma; Rhabdomyosarcoma; Sclerosing Rhabdomyosarcoma; Spindle Cell Rhabdomyosarcoma
Interventions: Drug: Cyclophosphamide; Biological: Dactinomycin; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Temsirolimus; Drug: Vincristine Sulfate; Drug: Vinorelbine
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
$Permalink for 'Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas'$
Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas

Posted: December 2nd, 2014, 3:00am GMT

Conditions: Metastatic Melanoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Rhabdomyosarcoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Hodgkin Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Rhabdomyosarcoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Unresectable Melanoma
Interventions: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study
Sponsors: National Cancer Institute (NCI)
Completed
Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

Posted: July 3rd, 2014, 2:00am GMT

Conditions: Alveolar Soft Part Sarcoma; Angiomatoid Fibrous Histiocytoma; Atypical Fibroxanthoma; Clear Cell Sarcoma of Soft Tissue; Epithelioid Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Osteosarcoma; Fibrohistiocytic Neoplasm; Fibrosarcoma; Inflammatory Myofibroblastic Tumor; Intimal Sarcoma; Leiomyosarcoma; Liposarcoma; Liver Embryonal Sarcoma; Low Grade Fibromyxoid Sarcoma; Low Grade Myofibroblastic Sarcoma; Malignant Cutaneous Granular Cell Tumor; Malignant Peripheral Nerve Sheath Tumor; Malignant Triton Tumor; Mesenchymal Chondrosarcoma; Myxofibrosarcoma; Myxoid Chondrosarcoma; Myxoinflammatory Fibroblastic Sarcoma; Nerve Sheath Neoplasm; PEComa; Pericytic Neoplasm; Plexiform Fibrohistiocytic Tumor; Sclerosing Epithelioid Fibrosarcoma; Skin Glomus Tumor; Stage IB Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Synovial Sarcoma; Undifferentiated High Grade Pleomorphic Sarcoma of Bone
Interventions: Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Ifosfamide; Drug: Pazopanib; Drug: Pazopanib Hydrochloride; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery
Sponsors: National Cancer Institute (NCI)
Active, not recruiting
Molecular-Guided Therapy for Childhood Cancer

Posted: June 13th, 2014, 2:00am GMT

Conditions: Neuroblastoma; Medulloblastoma; Glioma; Ependymoma; Choroid Plexus Neoplasms; Craniopharyngioma; Dysembryoplastic Neuroepithelial Tumor; Meningioma; Primitive Neuroectodermal Tumors (PNETs); Germ Cell Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma; Ewings Sarcoma; Osteosarcoma; Wilms Tumor; Renal Cell Carcinoma; Malignant Rhabdoid Tumor; Clear Cell Sarcoma; Liver Tumors
Interventions: Device: Guided Therapy
Sponsors: Giselle Sholler; Translational Genomics Research Institute; Dell, Inc.
Active, not recruiting
$Permalink for 'Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors'$
Adavosertib and Irinotecan Hydrochloride in Treating Younger Patients With Relapsed or Refractory Solid Tumors

Posted: March 24th, 2014, 2:00am GMT

Conditions: Central Nervous System Embryonal Tumor With Rhabdoid Features; Central Nervous System Embryonal Tumor, Not Otherwise Specified; Central Nervous System Ganglioneuroblastoma; Embryonal Tumor With Multilayered Rosettes, C19MC-Altered; Pineoblastoma; Primary Central Nervous System Neoplasm; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Rhabdomyosarcoma; Refractory Malignant Solid Neoplasm; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Rhabdomyosarcoma
Interventions: Drug: Adavosertib; Drug: Irinotecan Hydrochloride
Sponsors: National Cancer Institute (NCI)
Completed
$Permalink for 'A Phase I Dose Finding Study in Children With Solid Tumors Recurrent or Refractory to Standard Therapy'$
A Phase I Dose Finding Study in Children With Solid Tumors Recurrent or Refractory to Standard Therapy

Posted: March 12th, 2014, 2:00am GMT

Conditions: Pediatric Oncology
Interventions: Drug: Regorafenib (BAY73-4506); Drug: Vincristine (Cellcristin®); Drug: Irinotecan (Irinotecan Cell pharm®)
Sponsors: Bayer
Active, not recruiting
SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes

Posted: January 29th, 2014, 3:00am GMT

Conditions: Liposarcoma; Osteogenic Sarcoma; Ewing/Ewing-like Sarcoma; Rhabdomyosarcoma; Mesenchymal Chondrosarcoma
Interventions: Drug: Regorafenib; Drug: Placebo
Sponsors: Sarcoma Alliance for Research through Collaboration
Completed
Risk-Adapted Focal Proton Beam Radiation and/or Surgery in Patients With Low, Intermediate and High Risk Rhabdomyosarcoma Receiving Standard or Intensified Chemotherapy

Posted: June 7th, 2013, 2:00am GMT

Conditions: Rhabdomyosarcoma
Interventions: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Radiation; Drug: Bevacizumab; Drug: Sorafenib; Drug: Myeloid Growth Factor; Procedure: Lymph Node Sampling; Drug: Irinotecan; Drug: Ifosfamide; Drug: Etoposide; Drug: Etoposide Phosphate; Drug: Doxorubicin; Drug: Dexrazoxane; Drug: ^1^1C-methionine
Sponsors: St. Jude Children's Research Hospital
Active, not recruiting
Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

Posted: March 5th, 2013, 3:00pm GMT

Condition: Refractory and/or Relapsed Metastatic Solid Tumors
Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: low dose total body irradiation; Drug: Melphalan; Drug: Tacrolimus
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Recruiting
Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

Posted: January 6th, 2012, 3:00pm GMT

Conditions: Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors
Interventions: Drug: Ifosfamide; Drug: Etoposide; Drug: Mesna; Biological: G-CSF; Drug: Busulfan; Drug: Melphalan; Drug: Thiotepa; Biological: Autologous stem cell infusion; Radiation: Radiation; Drug: Carboplatin; Drug: Paclitaxel; Procedure: Leukapheresis; Drug: Anti-seizure prophylaxis; Drug: Ursodiol
Sponsor: Masonic Cancer Center, University of Minnesota
Recruiting
Molecular Analysis Of Solid Tumors

Posted: January 15th, 2010, 3:00pm GMT

Condition: Pediatric Solid Tumors
Intervention:
Sponsors: St. Jude Children's Research Hospital; Alex's Lemonade Stand Foundation
Recruiting
Collecting and Storing Tissue, Blood, and Bone Marrow Samples From Patients With Rhabdomyosarcoma or Other Soft Tissue Sarcoma

Posted: June 12th, 2009, 2:00am GMT

Conditions: Adult Rhabdomyosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Chordoma; Desmoid-Type Fibromatosis; Metastatic Childhood Soft Tissue Sarcoma; Non-Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Rhabdomyosarcoma; Stage I Adult Soft Tissue Sarcoma AJCC v7; Stage II Adult Soft Tissue Sarcoma AJCC v7; Stage III Adult Soft Tissue Sarcoma AJCC v7; Stage IV Adult Soft Tissue Sarcoma AJCC v7; Untreated Childhood Rhabdomyosarcoma
Interventions: Other: Cytology Specimen Collection Procedure; Other: Laboratory Biomarker Analysis
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Completed
Collecting and Storing Tissue From Young Patients With Cancer

Posted: May 12th, 2009, 2:00pm GMT

Conditions: Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Central Nervous System Neoplasm; Ewing Sarcoma; Germ Cell Tumor; Leukemia; Lymphoma; Malignant Neoplasm; Neuroblastoma; Osteosarcoma; Retinoblastoma; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma
Interventions: Other: Cytology Specimen Collection Procedure; Other: Laboratory Biomarker Analysis
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Recruiting
Methionine PET/CT Studies In Patients With Cancer

Posted: February 10th, 2009, 3:00pm GMT

Conditions: Brain Tumors and/or Solid Tumors Including; Brain Stem Glioma; High Grade CNS Tumors; Ependymoma; Medulloblastoma; Craniopharyngioma; Low Grade CNS Tumors; Hodgkin Lymphoma; Non Hodgkin Lymphoma; Ewing Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Other
Intervention: Drug: Methionine
Sponsor: St. Jude Children's Research Hospital
Recruiting
Long-Term Follow-Up of Patients Who Have Participated in Children's Oncology Group Studies

Posted: August 18th, 2008, 2:00pm GMT

Conditions: Acute Lymphoblastic Leukemia; Brain Neoplasm; Hematopoietic Cell Transplantation Recipient; Hodgkin Lymphoma; Osteosarcoma; Rhabdomyosarcoma
Interventions: Procedure: Assessment of Therapy Complications; Other: Questionnaire Administration
Sponsors: Children's Oncology Group; National Cancer Institute (NCI)
Recruiting
Irinotecan and Carboplatin as Upfront Window Therapy in Treating Patients With Newly Diagnosed Intermediate-Risk or High-Risk Rhabdomyosarcoma

Posted: February 11th, 2004, 3:00am GMT

Conditions: Sarcoma
Interventions: Biological: filgrastim; Drug: carboplatin; Drug: cyclophosphamide; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: irinotecan hydrochloride; Drug: vincristine sulfate; Procedure: conventional surgery; Radiation: radiation therapy
Sponsors: Memorial Sloan Kettering Cancer Center; National Cancer Institute (NCI)
Active, not recruiting

PubMed - Rhabdomyosarcoma

Embryonal rhabdomyosarcoma of the testis in a young male: A rare case report

Fetched: December 5th, 2023, 5:02am GMT by Jun Zou

Asian J Surg. 2023 Dec 3:S1015-9584(23)01864-X. doi: 10.1016/j.asjsur.2023.11.084. Online ahead of print.

NO ABSTRACT

PMID:38049349 | DOI:10.1016/j.asjsur.2023.11.084
Massive Primary Pulmonary Artery Rhabomyosarcoma: A Case Report

Fetched: December 4th, 2023, 5:02am GMT by Farid Rashidi

Rom J Intern Med. 2023 Dec 4. doi: 10.2478/rjim-2023-0032. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary artery sarcomas (PAS) are rare tumours causing an insidiously progressive obstruction of the pulmonary circulation. The clinical presentation is often indistinguishable from chronic thromboembolic pulmonary hypertension (CTEPH). However, the atypical appearance of a heterogeneous filling defect in CT pulmonary angiography (CTPA) should prompt further investigation.

CASE PRESENTATION: A previously healthy young man presented with massive haemoptysis, acute respiratory distress, and progressive exertional dyspnea since the year before. Echocardiography demonstrated severe right ventricular dysfunction and highly probable pulmonary hypertension. CTPA revealed an extensive filling defect with an appearance concerning PAS. Due to syncopal episodes at rest, the patient underwent urgent pulmonary artery endarterectomy (PEA). A massive tree-like tumour was excised as a result. Post-operatively, reperfusion injury and refractory pulmonary oedema mandated extracorporeal membrane oxygenation (ECMO). Unfortunately, ECMO was complicated with massive haemolysis and acute kidney injury. The patient succumbed to multi-organ failure. Through tissue analysis established a diagnosis of embryonal rhabdomyosarcoma.

DISCUSSION: Unfortunately, the patient had not reached out for his worsening dyspnea. PASs should not be mistaken for a thrombus and anticoagulation should be avoided. The urgent condition precluded biopsy and tissue diagnosis. Similarly, neoadjuvant chemotherapy was not feasible. Post-operatively, reperfusion injury and pulmonary oedema ensued, which mandated ECMO. This complication should be anticipated preoperatively. There is a need for more data on PASs to establish a consensus for management.

PMID:38044271 | DOI:10.2478/rjim-2023-0032
Critical elements of pediatric rhabdomyosarcoma surgery

Fetched: December 3rd, 2023, 5:02am GMT by Stephanie F Polites

Semin Pediatr Surg. 2023 Nov 21;32(5):151341. doi: 10.1016/j.sempedsurg.2023.151341. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, requires multimodal therapy which is determined by risk group stratification. Local control may be achieved by surgical resection, radiation, or both. Resection may occur upfront or following induction chemotherapy as a delayed primary excision. An R1 resection may allow a reduction in radiation exposure; however, debulking is not indicated nor is excision of residual masses at the end of therapy. Regional lymph node assessment is an important component of surgical care, as positive nodal basins require radiation. Depending on the tumor site and biology, sentinel lymph node biopsy vs biopsy of clinically or radiographically concerning nodes is indicated. Therapeutic lymph node dissection is never indicated. Familiarity with site-specific oncologic principles for RMS and participation in a multidisciplinary team including Pediatric Oncology and Radiation Oncology are necessary components of surgical care to ensure optimal outcomes.

PMID:38042091 | DOI:10.1016/j.sempedsurg.2023.151341
Nijmegen Breakage Syndrome

Fetched: December 2nd, 2023, 5:03am GMT by Raymonda Varon
1999 May 17 [updated 2023 Nov 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.

ABSTRACT

CLINICAL CHARACTERISTICS: Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, early growth deficiency that improves with age, recurrent respiratory infections, an increased risk for malignancy (primarily lymphoma), and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Other reported malignancies include solid tumors (e.g., medulloblastoma, glioma, rhabdomyosarcoma).

DIAGNOSIS/TESTING: The diagnosis of NBS is established in a proband with characteristic clinical features and biallelic pathogenic variants in NBN on molecular genetic testing and/or absent nibrin protein on immunoblotting assay.

MANAGEMENT: Treatment of manifestations: Standard antimicrobial therapies for infections; immunoglobulin replacement therapy in individuals with severe hypogammaglobulinemia and frequent infections; acellular vaccines; standard treatment of bronchiectasis and pulmonary infections; chemotherapy protocols for lymphoid malignancies adapted to individual tolerance; treatment of solid tumors adapted to individual tolerance; consideration of hematopoietic stem cell transplantation; hormone replacement therapy for females who have hypergonadotropic hypogonadism.

Surveillance:
1. For affected individuals. Periodic follow up to monitor physical growth, infection frequency, and developmental progress; lifelong monitoring of immune biomarkers; monitor for malignancy and particularly in those with weight loss, fever, weakness, enlargement of peripheral lymph nodes, dyspnea, cough, and hepatosplenomegaly (assessment should be considered using ultrasonography, MRI, biopsy); monitor pubertal progression in both sexes and for premature ovarian insufficiency in females; monthly breast self-examination when hormone replacement therapy is administered; assess cognitive developmental and intellectual abilities before starting school and follow up periodically.
2. For heterozygous adults. Monitor for malignancy, particularly breast cancer in women and prostate cancer in men.
Agents/circumstances to avoid: Because the cells from individuals with NBS are radiosensitive in vitro, doses of radiation used in radiotherapy need to be reduced. Unnecessary exposure to imaging studies that use ionizing radiation (plain radiograph, CT scan) should be avoided and use of MRI and/or ultrasound considered. Live vaccines (e.g., live vaccines for tuberculosis, measles, mumps, rubella, and varicella) should not be given.

Evaluation of relatives at risk: It is appropriate to offer molecular genetic testing for the familial NBN pathogenic variants to apparently asymptomatic adult relatives of an affected individual in order to identify family members who are heterozygous for an NBN pathogenic variant and would benefit from monitoring for malignancy.

GENETIC COUNSELING: NBS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of inheriting both pathogenic variants and being affected, a 50% chance of inheriting one pathogenic variant and being a heterozygote, and a 25% chance of inheriting neither of the familial NBN pathogenic variants. Heterozygotes are not at risk for NBS. However, heterozygous NBN pathogenic variants may be associated with an increased risk for breast cancer in women and prostate cancer in men. Carrier testing for at-risk family members and prenatal and preimplantation genetic testing are possible if the pathogenic variants in the family are known.

PMID:20301355 | Bookshelf:NBK1176
Latissimus Dorsi free flap reconstruction of a temporal defect following pediatric oncologic surgery: case report + literature review

Fetched: December 1st, 2023, 5:03am GMT by Estelle Piette

J Stomatol Oral Maxillofac Surg. 2023 Nov 27:101704. doi: 10.1016/j.jormas.2023.101704. Online ahead of print.

ABSTRACT

INTRODUCTION: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents. Around 35% of pediatric sarcomas occur in the head and neck region. Consequently, RMS is considered the most common type of childhood malignancy diagnosed in this region.

OBSERVATION: We report the clinical case of a 6 years old patient, who presented a large temporal hollowing following oncological excision surgery for temporal rhabdomyosarcoma. He underwent surgical reconstruction to fill the right temporalis fossa using a latissimus dorsi muscle free flap micro-anastomosed to the lingual vessels.

DISCUSSION: This clinical case highlights the value of plastic surgery in oncological reconstruction, which, combined with a multidisciplinary and collective approach, enables a holistic approach and facilitates socio-psychological integration after oncological surgery in the pediatric population.

PMID:38030124 | DOI:10.1016/j.jormas.2023.101704
Rapid liposomal formulation for nucleolin targeting to rhabdomyosarcoma cells

Fetched: December 1st, 2023, 5:03am GMT by Dzhangar Dzhumashev

Eur J Pharm Biopharm. 2023 Nov 27:S0939-6411(23)00309-0. doi: 10.1016/j.ejpb.2023.11.020. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. More effective and less toxic therapies are urgently needed for high-risk patients. Peptide-guided targeted drug delivery can increase the therapeutic index of encapsulated drugs and improve patients' well-being. To apply this strategy to RMS, we identified the peptide F3 in a screening for peptides binding to RMS cells surface. F3 binds to nucleolin, which is present on the surface of RMS cells and is abundantly expressed at the mRNA level in RMS patients' biopsies compared to healthy tissues. We developed a rapid microfluidic formulation of F3-decorated PEGylated liposomes and remote loading of the chemotherapeutic drug vincristine. Size, surface charge, drug loading and retention of targeted and control liposomes were studied. Enhanced cellular binding and uptake were observed in three different nucleolin-positive RMS cell lines. Importantly, F3-functionalized liposomes loaded with vincristine were up to 11 times more cytotoxic than non-targeted liposomes for RMS cell lines. These results demonstrate that F3-functionalized liposomes are promising for targeted drug delivery to RMS and warrant further in vivo investigations.

PMID:38029941 | DOI:10.1016/j.ejpb.2023.11.020
Primary paratesticular embryonal rhabdomyosarcoma - An unusual presentation

Fetched: December 1st, 2023, 5:03am GMT by Priyanka Singh

J Family Med Prim Care. 2023 Sep;12(9):2176-2180. doi: 10.4103/jfmpc.jfmpc_397_23. Epub 2023 Sep 30.

ABSTRACT

Paratesticular embryonal rhabdomyosarcoma (RMS) is a very rare and aggressive mesenchymal tumor. It is usually seen in children and adolescents presenting as a painless intrascrotal mass, localized in the paratesticular region. Hereby, we report two cases of paratesticular embryonal RMS in adults. One case was clinically suspected to be a testicular abscess, whereas the other presented with testicular swelling and lung metastasis. Localized forms have a good prognosis, whereas tumors presenting with metastases show a poor outcome. A treatment based on surgery and chemotherapy yields good results. Sperm cryopreservation and endocrine follow-up improve the overall survival and quality of life of these patients.

PMID:38024875 | PMC:PMC10657067 | DOI:10.4103/jfmpc.jfmpc_397_23
Differentiation-dependent chromosomal organization changes in normal myogenic cells are absent in rhabdomyosarcoma cells

Fetched: December 1st, 2023, 5:03am GMT by Joe Ibarra

Front Cell Dev Biol. 2023 Nov 7;11:1293891. doi: 10.3389/fcell.2023.1293891. eCollection 2023.

ABSTRACT

Myogenesis, the progression of proliferating skeletal myoblasts to terminally differentiated myotubes, regulates thousands of target genes. Uninterrupted linear arrays of such genes are differentially associated with specific chromosomes, suggesting chromosome specific regulatory roles in myogenesis. Rhabdomyosarcoma (RMS), a tumor of skeletal muscle, shares common features with normal muscle cells. We hypothesized that RMS and myogenic cells possess differences in chromosomal organization related to myogenic gene arrangement. We compared the organizational characteristics of chromosomes 2 and 18, chosen for their difference in myogenic gene arrangement, in cultured RMS cell lines and normal myoblasts and myotubes. We found chromosome-specific differences in organization during normal myogenesis, with increased area occupied and a shift in peripheral localization specifically for chromosome 2. Most strikingly, we found a differentiation-dependent difference in positioning of chromosome 2 relative to the nuclear axis, with preferential positioning along the major nuclear axis present only in myotubes. RMS cells demonstrated no preference for such axial positioning, but induced differentiation through transfection of the pro-myogenic miRNA miR-206 resulted in an increase of major axial positioning of chromosome 2. Our findings identify both a differentiation-dependent, chromosome-specific change in organization in normal myogenesis, and highlight the role of chromosomal spatial organization in myogenic differentiation.

PMID:38020905 | PMC:PMC10662331 | DOI:10.3389/fcell.2023.1293891
Current role of topoisomerase I inhibitors for the treatment of mesenchymal malignancies and their potential future use as payload of sarcoma-specific antibody-drug conjugates

Fetched: November 29th, 2023, 5:02am GMT by Patrick Schöffski

Oncol Res Treat. 2023 Nov 28. doi: 10.1159/000535491. Online ahead of print.

ABSTRACT

BACKGROUND: Topoisomerase I is an enzyme that plays a crucial part in DNA replication and transcription by the relaxation of supercoiled double-stranded DNA. Topoisomerase I inhibitors bind to the topoisomerase I cleavage complex, thereby stabilizing it and preventing the religation of the DNA strands, leading to DNA damage, cell cycle arrest and apoptosis. Various topoisomerase I inhibitors have been evaluated in solid tumors, and irinotecan and topotecan have been approved for the treatment of epithelial malignancies. None of them have been approved for sarcoma, a diverse group of rare solid tumors with an unmet need for effective treatments.

SUMMARY: Topoisomerase I inhibitors have been evaluated in preclinical studies as single agents or in combination in solid tumors, some of which have included sarcomas where activity was observed. Clinical trials evaluating topoisomerase I inhibitors for the treatment of sarcoma have shown limited efficacy as monotherapy. In combination with other cytotoxic agents, topoisomerase I inhibitors have become part of clinical routine in selected sarcoma subtypes. Regimen such as irinotecan/vincristine/temozolomide are used in relapsed rhabdomyosarcoma, irinotecan/temozolomide and vincristine/topotecan/cyclophosphamide are commonly given in refractory Ewing sarcoma, and topotecan/carboplatin showed some activity in advanced soft tissue sarcoma. This review provides an overview of key studies with topoisomerase I inhibitors for the treatment of sarcoma. Topoisomerase I inhibitors are currently also being assessed as "payloads" for antibody-drug conjugates (ADCs), allowing for the targeting of specific antigen expressing tumor cells and the delivery of the inhibitor directly to the tumor cells with the potential of enhancing therapeutic efficacy while minimizing systemic toxicity. Here, we also provide a brief overview on topoisomerase I-ADCs.

KEY MESSAGE: Topoisomerase I inhibitors are an important component of some systemic therapies for selected sarcomas, have potent cytotoxic properties and pharmacological characteristics that make them relevant candidates as payloads for the development of sarcoma-specific ADCs. ADCs are antibody-based targeted agents allowing for efficient and specific delivery of a given drug to the tumor cell. Topoisomerase I-ADCs are a novel targeted delivery approach which may have the potential to improve the therapeutic index of topoisomerase I inhibitors in the treatment of sarcoma and warrants investigation in a broad variety of mesenchymal malignancies.

PMID:38016427 | DOI:10.1159/000535491
Progress in preclinical models of pediatric rhabdomyosarcoma

Fetched: November 29th, 2023, 5:02am GMT by Yuxiang Hu

Minerva Surg. 2023 Nov 28. doi: 10.23736/S2724-5691.23.10017-7. Online ahead of print.

NO ABSTRACT

PMID:38015480 | DOI:10.23736/S2724-5691.23.10017-7
The elusive Nav1.7: From pain to cancer

Fetched: November 27th, 2023, 5:03am GMT by Umberto Banderali

Curr Top Membr. 2023;92:47-69. doi: 10.1016/bs.ctm.2023.09.003. Epub 2023 Sep 23.

ABSTRACT

Voltage-gated sodium channels (Nav) are protein complexes that play fundamental roles in the transmission of signals in the nervous system, at the neuromuscular junction and in the heart. They are mainly present in excitable cells where they are responsible for triggering action potentials. Dysfunctions in Nav ion conduction give rise to a wide range of conditions, including neurological disorders, hypertension, arrhythmia, pain and cancer. Nav family 1 is composed of nine members, named numerically from 1 to 9. A Nax family also exists and is involved in body-fluid homeostasis. Of particular interest is Nav1.7 which is highly expressed in the sensory neurons of the dorsal root ganglions, where it is involved in the propagation of pain sensation. Gain-of-function mutations in Nav1.7 cause pathologies associated with increased pain sensitivity, while loss-of-function mutations cause reduced sensitivity to pain. The last decade has seen considerable effort in developing highly specific Nav1.7 blockers as pain medications, nonetheless, sufficient efficacy has yet to be achieved. Evidence is now conclusively showing that Navs are also present in many types of cancer cells, where they are involved in cell migration and invasiveness. Nav1.7 is anomalously expressed in endometrial, ovarian and lung cancers. Nav1.7 is also involved in Chemotherapy Induced Peripheral Neuropathy (CIPN). We propose that the knowledge and tools developed to study the role of Nav1.7 in pain can be exploited to develop novel cancer therapies. In this chapter, we illustrate the various aspects of Nav1.7 function in pain, cancer and CIPN, and outline therapeutic approaches.

PMID:38007269 | DOI:10.1016/bs.ctm.2023.09.003
Insight into the design of FGFR4 selective inhibitors in cancer therapy: Prospects and challenges

Fetched: November 19th, 2023, 5:02am GMT by Xiaolu Chen

Eur J Med Chem. 2024 Jan 5;263:115947. doi: 10.1016/j.ejmech.2023.115947. Epub 2023 Nov 13.

ABSTRACT

Recently, FGFR4 has become a hot target for the treatment of cancer owing to its important role in cellular physiological processes. FGFR4 has been validated to be closely related to the occurrence of cancers, such as hepatocellular carcinoma, rhabdomyosarcoma, breast cancer and colorectal cancer. Hence, the development of FGFR4 small-molecule inhibitors is essential to further understanding the functions of FGFR4 in cancer and the treatment of FGFR4-dependent diseases. Given the particular structures of FGFR1-4, the development of FGFR4 selective inhibitors presents significant challenges. The non-conserved Cys552 in the hinge region of the FGFR4 complex becomes the key to the selectivity of FGFR4 and FGFR1/2/3 inhibitors. In this review, we systematically introduce the close relationship between FGFR4 and cancer, and conduct an in-depth analysis of the developing methodology, binding mechanism, kinase selectivity, pharmacokinetic characteristics of FGFR4 selectivity inhibitors, and their application in clinical research.

PMID:37976704 | DOI:10.1016/j.ejmech.2023.115947
GC-MS profiling and evaluation of acute oral toxicity, anti-tumour, antimicrobial and antioxidant activities of Croton socotranus Balf.f. aerial parts: in-vitro, in-vivo and in-silico studies

Fetched: November 19th, 2023, 5:02am GMT by Ibrahim Ali Al-Hakami

Nat Prod Res. 2023 Nov 16:1-10. doi: 10.1080/14786419.2023.2280820. Online ahead of print.

ABSTRACT

Croton socotranus Balf.f. shrub is widely used traditionally in Asia as an anti-infective. The study was conducted for metabolite profiling, oral acute toxicity and antioxidant studies, antimicrobial activity and anticancer effect against human hepatoma (HepG2), breast cancer (MCF-7) and rhabdomyosarcoma (RD) cells. Gas chromatography-mass spectrometry analysis revealed the presence of 39 compounds, predominantly comprising fatty acids (57.76%), sesquiterpenes (24.56%) and triterpenes (9.54%). The n-hexane fraction exhibited promising antimicrobial activity and displayed a potent anti-tumour effect against HepG2, MCF-7 and RD cells with IC50 values of 3.4, 6.5 and 7.1 μg/mL, respectively. Histological examination revealed significant morphological changes consistent with the changes observed in the apoptotic mechanism of action. The molecular docking study provided insights into the rational binding modes of the identified compounds with phosphoinositide 3-kinase and poly(ADP-ribose)polymerase-1 enzymes. Our findings suggest the potential of C. socotranus as a valuable source of antimicrobial and anticancer agents.

PMID:37971902 | DOI:10.1080/14786419.2023.2280820
Robotic retroperitoneal lymph node dissection for paratesticular rhabdomyosarcoma in adolescents: a case series

Fetched: November 19th, 2023, 5:02am GMT by Cody N Clark

J Robot Surg. 2023 Dec;17(6):3045-3048. doi: 10.1007/s11701-023-01735-3. Epub 2023 Nov 16.

ABSTRACT

Robotic assisted (RA) retroperitoneal lymph node dissection (RPLND) has grown in popularity as it offers decreased morbidity and faster recovery compared to the open technique. Proponents of open surgery raised concerns about the oncological fidelity of the RA approach for testicular tumors where complete resection is needed. In boys > 10 years with paratesticular rhabdomyosarcoma (RMS), RPLND is indicated for staging purposes only. In this population, the RA technique should provide its benefits without concerns for oncological compromise. We present an analysis of RA-RPLND for boys with paratesticular RMS. We queried our institution's prospectively collected database of pediatric robotic cases for patients undergoing RA-RPLND post-radical orchiectomy for paratesticular mass, confirmed by pathology as RMS. Demographic, surgical, follow-up, and oncological outcomes were evaluated between 2017 and 2023. Five patients underwent RA-RPLND for paratesticular RMS. The median age was 16.1 years (15-17), with median OR time of 456 min (357-508). No conversions to open occurred. Inpatient median total opioid use was 1.8 (0.4-2.7) morphine equivalent/kg. The median lymph node yield was 27 (8-44) and post-op length of stay was 3 days (2-5). The median time to initiating adjuvant chemotherapy was 10.5 days (7-13). One patient had complications: pneumothorax attributed to central line placement and chyle leak that resolved in 1 week with dietary restriction. Our series demonstrates the feasibility, safety, and efficacy of the RA approach for RPLND in pediatric patients with paratesticular RMS. This is the most extensive case series currently in the literature and the only one exclusively done for paratesticular RMS.

PMID:37971637 | DOI:10.1007/s11701-023-01735-3
PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors

Fetched: November 16th, 2023, 5:03am GMT by Madeline B Searcy

Nat Commun. 2023 Nov 15;14(1):7291. doi: 10.1038/s41467-023-43044-1.

ABSTRACT

Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers. Further, we describe a FP-RMS mouse model driven by P3F expression and Cdkn2a loss in endothelial cells. Additionally, we show that P3F expression in TP53-null human iPSCs blocks endothelial-directed differentiation and guides cells to become myogenic cells that form FP-RMS tumors in immunocompromised mice. Together these findings demonstrate that FP-RMS can originate from aberrant development of non-myogenic cells driven by P3F.

PMID:37968277 | PMC:PMC10651858 | DOI:10.1038/s41467-023-43044-1
Soft Tissue Sarcomas in Adolescents and Young Adults

Fetched: November 16th, 2023, 5:03am GMT by Aaron R Weiss

J Clin Oncol. 2023 Nov 15:JCO2301275. doi: 10.1200/JCO.23.01275. Online ahead of print.

ABSTRACT

Soft tissue sarcomas (STS) represent a heterogeneous group of extraskeletal mesenchymal tumors that affect individuals throughout the entire age continuum. Despite this pervasive influence, key differences exist in the presentation of these sarcomas across varying age groups that have prevented a more uniform approach to management. Notably, rhabdomyosarcoma (RMS) is more common in children, while most nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) subtypes are more prevalent in adults. Older patients with NRSTS appear to have more molecularly complex biology and often present with more advanced disease compared with children. Poorer outcome disparities are observed in older patients with RMS despite receiving similar treatment as younger patients. In this review, we highlight differences in epidemiology, biology, and management paradigms for pediatric and adult patients with STS and explore opportunities for a unified approach to enhance the care and outcomes within the AYA population.

PMID:37967293 | DOI:10.1200/JCO.23.01275
An unusual presentation of neonatal rhabdomyosarcoma: a case report

Fetched: November 16th, 2023, 5:03am GMT by Danielle Strah

Front Pediatr. 2023 Oct 27;11:1233334. doi: 10.3389/fped.2023.1233334. eCollection 2023.

ABSTRACT

A full-term infant with an unremarkable prenatal course presented at birth with a large midline facial mass and smaller masses in the head and neck. In addition, multiple diffuse flesh-colored nodules spread along all the upper and lower limbs. An extensive evaluation to cover a broad differential diagnosis of infectious, lymphatic/vascular, and oncologic etiology was undertaken. The initial suspicion was confirmed by biopsy of the skin lesion as congenital alveolar rhabdomyosarcoma (RMS). RMS is the most common soft tissue sarcoma that occurs in childhood. However, neonatal RMS is exceedingly rare. The infant's initial treatment included vincristine, dactinomycin, and cyclophosphamide in addition to salvage ifosfamide and etoposide, which were dose-adjusted for age. Herein, we present a case of an infant with RMS who showed initial improvement before relapsing and succumbing to her disease at 5 months of age. A review of the limited literature available on this rare condition and newer treatment regimens with improved mortality rates is performed.

PMID:37964815 | PMC:PMC10641497 | DOI:10.3389/fped.2023.1233334
Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies

Fetched: November 15th, 2023, 5:03am GMT by Ali Zarrabi

Cancers (Basel). 2023 Nov 2;15(21):5269. doi: 10.3390/cancers15215269.

ABSTRACT

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

PMID:37958442 | PMC:PMC10650215 | DOI:10.3390/cancers15215269
Inferring therapeutic vulnerability within tumors through integration of pan-cancer cell line and single-cell transcriptomic profiles

Fetched: November 15th, 2023, 5:03am GMT by Weijie Zhang

bioRxiv. 2023 Nov 1:2023.10.29.564598. doi: 10.1101/2023.10.29.564598. Preprint.

ABSTRACT

Single-cell RNA sequencing greatly advanced our understanding of intratumoral heterogeneity through identifying tumor subpopulations with distinct biologies. However, translating biological differences into treatment strategies is challenging, as we still lack tools to facilitate efficient drug discovery that tackles heterogeneous tumors. One key component of such approaches tackles accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations. Here, we present a transparent computational framework (nicknamed scIDUC) to predict therapeutic efficacies on an individual-cell basis by integrating single-cell transcriptomic profiles with large, data-rich pan-cancer cell line screening datasets. Our method achieves high accuracy, with predicted sensitivities easily able to separate cells into their true cellular drug resistance status as measured by effect size (Cohen's d > 1.0). More importantly, we examine our method's utility with three distinct prospective tests covering different diseases (rhabdomyosarcoma, pancreatic ductal adenocarcinoma, and castration-resistant prostate cancer), and in each our predicted results are accurate and mirrored biological expectations. In the first two, we identified drugs for cell subpopulations that are resistant to standard-of-care (SOC) therapies due to intrinsic resistance or effects of tumor microenvironments. Our results showed high consistency with experimental findings from the original studies. In the third test, we generated SOC therapy resistant cell lines, used scIDUC to identify efficacious drugs for the resistant line, and validated the predictions with in-vitro experiments. Together, scIDUC quickly translates scRNA-seq data into drug response for individual cells, displaying the potential as a first-line tool for nuanced and heterogeneity-aware drug discovery.

PMID:37961545 | PMC:PMC10634928 | DOI:10.1101/2023.10.29.564598
The Broad Spectrum of Paediatric Pancreatic Disease: A Single-center 26-years Retrospective Review

Fetched: November 14th, 2023, 5:02am GMT by Amr Alnagar

J Pediatr Surg. 2023 Oct 21:S0022-3468(23)00645-0. doi: 10.1016/j.jpedsurg.2023.10.035. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric pancreatic pathology and its management is rarely described. We present our experience.

METHODS: A retrospective case-note review of all patients with pancreatic disease from 1995 to 2021 was completed. Data are quoted as median (range).

RESULTS: Two hundred and twelve patients were identified with 75.9% presenting with pancreatitis. Referrals for pancreatitis increased during the study period and affected a wide age range (2 months-15.6 years). Acute pancreatitis (n = 118) (age 10.6 (0.18-16.3) years). The most common causes were idiopathic (n = 60, 50.8%) and biliary (n = 28, 23.8%). About 10% required treatment for complications or underlying biliary causes. Recurrent pancreatitis (n = 14) (11.6 (0.3-14.3) years). The most common cause was hereditary pancreatitis (n = 6, 42.9%). One patient required endoscopic drainage of pseudocyst. Chronic pancreatitis (n = 29) (16 (0.38-15.5) years). The underlying diagnosis was idiopathic (n = 14, 48.4%) or hereditary pancreatitis (n = 10, 34.5%). 13 patients required active management, including pancreaticojejunostomies (n = 5). Blunt Trauma (n = 34) was managed conservatively in 24 (70.5%). 6 patients required open surgery, but 4 were managed by either endoscopy or interventional radiology. Pancreatic tumours (n = 13) presented at 11.2 (2.3-16) years. Pathology included pancreaticoblastomas (n = 3), solid pseudopapillary tumours (n = 3), neuroendocrine tumours (n = 2), acinar cell cystadenoma (n = 1), intraductal papillary mucinous neoplasm (n = 1), pancreatic insulinoma (n = 1), pancreatic ductal adenocarcinoma (n = 1), and embryonal rhabdomyosarcoma (n = 1). OTHERS (N = 4): Pancreatic cyst (n = 3) and annular pancreas (n = 1).

CONCLUSION: Paediatric pancreatic disease spans a wide spectrum of both benign and malignant disease and benefits from access to specialist medical, surgical, endoscopic, and interventional radiology expertise. Referrals for paediatric pancreatitis are increasing, but aetiology is different to that seen in adults.

LEVEL OF EVIDENCE: IV.

PMID:37957099 | DOI:10.1016/j.jpedsurg.2023.10.035
Evaluation and mechanism study of Pien Tze Huang against EV-A71 infection

Fetched: November 14th, 2023, 5:02am GMT by Huiqiang Wang

Front Pharmacol. 2023 Oct 26;14:1251731. doi: 10.3389/fphar.2023.1251731. eCollection 2023.

ABSTRACT

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) infection, currently lacks specific preventive and therapeutic interventions. Here, we demonstrated that Pien Tze Huang (PZH) could dose-dependently inhibit EV-A71 replication at the cellular level, resulting in significant reductions in EV-A71 virus protein 1 (VP1) expression and viral yields in Vero and human rhabdomyosarcoma cells. More importantly, we confirmed that PZH could protect mice from EV-A71 infection for the first time, with Ribavirin serving as a positive control. PZH treatment reduced EV-A71 VP1 protein expression, viral yields in infected muscles, and improved muscle pathology. Additionally, we conducted a preliminary mechanism study using quantitative proteomics. The results suggested that the suppression of the PI3K/AKT/mTOR and NF-κB signaling pathways may contribute to the anti-EV-A71 activity of PZH. These findings provide strong evidence supporting the potential therapeutic application of PZH for EV-A71 infection management.

PMID:37954857 | PMC:PMC10637388 | DOI:10.3389/fphar.2023.1251731
The RRAS2 pathogenic variant (c.67G>T; p. Gly23Cys) produces Noonan syndrome with embryonal rhabdomyosarcoma

Fetched: November 10th, 2023, 5:02am GMT by Lan Zeng

Mol Genet Genomic Med. 2023 Nov 9:e2313. doi: 10.1002/mgg3.2313. Online ahead of print.

ABSTRACT

BACKGROUND: Noonan syndrome (NS) due to the RRAS2 gene, the pathogenic variant is an extremely rare RASopathies. Our objective was to identify the potential site of RRAS2, combined with the literature review, to find the correlation between clinical phenotype and genotype. De novo missense mutations affect different aspects of the RRAS2 function, leading to hyperactivation of the RAS-MAPK signaling cascade.

METHODS: Conventional G-banding was used to analyze the chromosome karyotype of the patient. Copy number variation sequencing (CNV-seq) was used to detect the chromosomal gene microstructure of the patient and her parents. The exomes of the patient and her parents were sequenced using trio-based whole exome sequencing (trio-WES) technology. The candidate variant was verified by Sanger sequencing. The pathogenicity of the variant was predicted with a variety of bioinformatics tools.

RESULTS: Chromosome analysis of the proband revealed 46, XX, and no abnormality was found by CNV-seq. After sequencing and bioinformatics filtering, the variant of RRAS2(c.67G>T; p. Gly23Cys) was found in the proband, while the mutation was absent in her parents. To the best of our knowledge, our patient was with the typical Noonan syndrome, such as short stature, facial dysmorphism, and developmental delay. Furthermore, our study is the first case of NS with embryonal rhabdomyosarcoma (ERMS) caused by the RRAS2 gene mutation reported in China.

CONCLUSIONS: Our investigations suggested that the heterozygous missense of RRAS2 may be a potential causal variant in a rare cause of Noonan syndrome, expanding our understanding of the causally relevant mutations for this disorder.

PMID:37942564 | DOI:10.1002/mgg3.2313
Synchronous Bilateral Ovarian Mesonephric-like Adenocarcinomas with Separate Origins from High-Grade Mullerian Adenosarcoma and Endometriosis: Report of a Rare Case

Fetched: November 7th, 2023, 5:02am GMT by Zitong Zhao

Int J Gynecol Pathol. 2023 Oct 4. doi: 10.1097/PGP.0000000000000997. Online ahead of print.

ABSTRACT

Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.

PMID:37922943 | DOI:10.1097/PGP.0000000000000997
Intractable Ventricular Tachycardia Prior to an Overt Cardiac Tumor Mass of Metastatic Cardiac Rhabdomyosarcoma (Spindle-cell Type)

Fetched: November 6th, 2023, 5:03am GMT by Yosuke Terui

Intern Med. 2023 Nov 6. doi: 10.2169/internalmedicine.2568-23. Online ahead of print.

ABSTRACT

We herein report a 37-year-old man who experienced recurrence of metastatic cardiac rhabdomyosarcoma along with intractable ventricular tachycardia (VT) 7 years after resection of rhabdomyosarcoma in his right elbow. At 36 years old, he developed VT unresponsive to radiofrequency catheter ablation (RFCA). Initially, the cardiac tumor was not detected, but it gradually grew in size at the RFCA site. A surgical biopsy confirmed the diagnosis of metastatic cardiac rhabdomyosarcoma. Despite radiation therapy, cardiac tumor progression and VT instability could not be prevented. Ultimately, the patient died 27 months after the initial documentation of VT.

PMID:37926544 | DOI:10.2169/internalmedicine.2568-23
CD276-CAR T cells and Dual-CAR T cells targeting CD276/FGFR4 promote rhabdomyosarcoma clearance in orthotopic mouse models

Fetched: November 5th, 2023, 5:02am GMT by Andrea Timpanaro

J Exp Clin Cancer Res. 2023 Nov 4;42(1):293. doi: 10.1186/s13046-023-02838-3.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood, whose prognosis is still poor especially for metastatic, high-grade, and relapsed RMS. New treatments are urgently needed, especially systemic therapies. Chimeric Antigen Receptor T cells (CAR Ts) are very effective against hematological malignancies, but their efficacy against solid tumors needs to be improved. CD276 (B7-H3) is a target upregulated in RMS and detected at low levels in normal tissues. FGFR4 is a very specific target for RMS. Here, we optimized CAR Ts for these two targets, alone or in combination, and tested their anti-tumor activity in vitro and in vivo.

METHODS: Four different single-domain antibodies were used to select the most specific FGFR4-CAR construct. RMS cell killing and cytokine production by CD276- and FGFR4-CAR Ts expressing CD8α or CD28 HD/TM domains in combination with 4-1BB and/or CD28 co-stimulatory domains were tested in vitro. The most effective CD276- and FGFR4-CAR Ts were used to generate Dual-CAR Ts. Tumor killing was evaluated in vivo in three orthotopic RMS mouse models.

RESULTS: CD276.V-CAR Ts (276.MG.CD28HD/TM.CD28CSD.3ζ) showed the strongest killing of RMS cells, and the highest release of IFN-γ and Granzyme B in vitro. FGFR4.V-CAR Ts (F8-FR4.CD28HD/TM.CD28CSD.3ζ) showed the most specific killing. CD276-CAR Ts successfully eradicated RD- and Rh4-derived RMS tumors in vivo, achieving complete remission in 3/5 and 5/5 mice, respectively. In CD276^low JR-tumors, however, they achieved complete remission in only 1/5 mice. FGFR4 CAR Ts instead delayed Rh4 tumor growth. Dual-CAR Ts promoted Rh4-tumors clearance in 5/5 mice.

CONCLUSIONS: CD276- and CD276/FGFR4-directed CAR Ts showed effective RMS cell killing in vitro and eradication of CD276^high RMS tumors in vivo. CD276^low tumors escaped the therapy highlighting a correlation between antigen density and effectiveness. FGFR4-CAR Ts showed specific killing in vitro but could only delay RMS growth in vivo. Our results demonstrate that combined expression of CD276-CAR with other CAR does not reduce its benefit. Introducing immunotherapy with CD276-CAR Ts in RMS seems to be feasible and promising, although CAR constructs design and target combinations have to be further improved to eradicate tumors with low target expression.

PMID:37924157 | PMC:PMC10625270 | DOI:10.1186/s13046-023-02838-3
Rhabdomyosarcoma or Fibrosarcoma? A Case of Large Ulcerated and Necrotic Lesion on the Forearm of a Newborn

Fetched: November 4th, 2023, 5:02am GMT by Jameel Soqia

J Investig Med High Impact Case Rep. 2023 Jan-Dec;11:23247096231209541. doi: 10.1177/23247096231209541.

ABSTRACT

Congenital infantile fibrosarcoma (CIFS) is a rare malignant soft tissue tumor. The incidence of fibrosarcoma is estimated to be 0.3 per 100 000 population per year, and it accounts for less than 1% of all soft tissue sarcomas. We present a case of a 7-day-old newborn with a large ulcerated and necrotic lesion on the left forearm, which was initially misdiagnosed as rhabdomyosarcoma. Magnetic resonance imaging (MRI) revealed a soft tissue mass with cystic components affecting the forearm and distal humerus muscles. Fine-needle biopsy was performed and initially diagnosed as rhabdomyosarcoma but later confirmed as low-grade fibrosarcoma with positive immunostaining for vimentin. The patient underwent a transhumeral amputation with follow-up chemotherapy at a specialized oncology center. This case underscores the importance of interdisciplinary collaboration and specialized care in managing complex medical conditions in infants. Early detection and appropriate management of these tumors are essential for improving outcomes and reducing morbidity and mortality. Despite the rarity of this case, it serves as a reminder of the importance of considering neoplastic lesions in the differential diagnosis of soft tissue masses in newborns.

PMID:37919979 | PMC:PMC10623988 | DOI:10.1177/23247096231209541
Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target

Fetched: November 3rd, 2023, 5:03am GMT by Sheetal Chauhan

Hum Cell. 2023 Nov 2. doi: 10.1007/s13577-023-00993-5. Online ahead of print.

ABSTRACT

Receptor tyrosine kinases (RTKs) serve as molecular targets for the development of novel personalized therapies in many malignancies. In the present study, expression pattern of receptor tyrosine kinases and its clinical significance in orbital RMS has been explored. Eighteen patients with histopathologically confirmed orbital RMS formed part of this study. Comprehensive q-PCR gene expression profiles of 19 RTKs were generated in the cases and controls. The patients were followed up for 59.53 ± 20.93 years. Clustering and statistical analysis tools were applied to identify the significant combination of RTKs associated with orbital rhabdomyosarcoma patients. mRNA overexpression of RTKs which included MET, AXL, EGFR was seen in 60-80% of cases; EGFR3, IGFR2, FGFR1, RET, PDGFR1, VEGFR2, PDGFR2 in 30-60% of cases; and EGFR4, FGFR3,VEGFR3 and ROS,IGFR1, EGFR1, FGFR2, VEGFR1 in 10-30% of cases. Immunoexpression of MET was seen in 89% of cases. A significant association was seen between MET mRNA and its protein expression. In all the cases MET gene expression was associated with worst overall survival (P = 0.03).There was a significant correlation of MET mRNA expression with RET, ROS, AXL, FGFR1, FGFR3, PDGFR1, IGFR1, VEGFR2, and EGFR3 genes. Association between MET gene and collective expression of RTKs was further evaluated by semi-supervised gene cluster analysis and Principal component analysis, which showed well-separated tumor clusters. MET gene overexpression could be a useful biomarker for identifying high risk orbital rhabdomyosarcoma patients. Well-separated tumor clusters confirmed the association between MET gene and collective expression of RTK genes. Therefore, the therapeutic potential of multi-kinase inhibitors targeting MET and the 9 other significant RTKs needs to be explored.

PMID:37914903 | DOI:10.1007/s13577-023-00993-5
Diversity of small round cell sarcoma in soft tissues around bone among Indian patients

Fetched: November 2nd, 2023, 5:02am GMT by Rani Singh Guddi

Bioinformation. 2023 Aug 31;19(8):871-875. doi: 10.6026/97320630019871. eCollection 2023.

ABSTRACT

Round cell tumors are a group of malignant tumors which shows overlapping microscopic features of small round monotonous cells with hyper-chromatic nucleus. It mostly occurs in children, adolescent, and young adults. The ancillary technique to confirm the differential diagnosis of round cells sarcoma is immuno-histo chemistry (IHC). Therefore, it is of interest to document the diversity of small round cell sarcoma in soft tissues around bones among Indian patients using IHC. A total of 334 cases among Indians were studied. Among them 160 cases were Non-Hodgkin's Lymphoma, 82 cases are poorly differentiated carcinoma and 92 cases of round cell sarcoma. Out of 92 cases, there were (40%) 27 cases of Wilms tumour, with the highest incidence. The highest incidence was observed in 0-14 years of age group with highest incidence in males. The distribution and diverse histology of different small round cell sarcoma offers challenge in the diagnosis by histopathology. Most frequent round cell tumour is Wilms tumour, followed by Rhabdomyosarcoma. Data shows the role of IHC in classifying soft tissue sarcoma but some time result of IHC remains inconclusive, where cytogenetic is important.

PMID:37908610 | PMC:PMC10613818 | DOI:10.6026/97320630019871
Climate Change and Force Majeure on Childhood Oncology Services in a Low Resource Setting: Experience from a Tertiary Institution in Nigeria

Fetched: November 1st, 2023, 5:02am GMT by T P West

West Afr J Med. 2023 Oct 31;40(10):1067-1071.

ABSTRACT

Childhood cancer patients are a vulnerable population who are adversely affected by any disaster that disrupts the healthcare ecosystem. The objective of this study was to describe the impact of flooding on access to care for childhood cancer patients in Bayelsa state, southern Nigeria. We review the effect of the 2022 flooding on childhood cancer care at the paediatric oncology unit of the Niger Delta University Teaching Hospital, southern Nigeria. The devastating floods caused closure of the health facility for four weeks. The challenges faced by the oncology patients included inability to access the facility due to destruction of roads and telecommunication networks, inaccessibility to chemotherapy drugs, postponement of surgeries, parental financial constraints due to income loss occasioned by the flood and worsened by inadequate health insurance. Two children, who were undergoing chemotherapy for rhabdomyosarcoma and retinoblastoma had their care transferred to an unaffected secondary care facility 24km away. Through teamwork and determination, the oncology team was able to overcome various obstacles to provide uninterrupted care for the patients and improve on future patient care during disasters. Care for childhood cancer patients should be prioritized by healthcare facilities especially in predictable flood prone areas like Bayelsa state. Emphasis should be on disaster preparedness training, development of outstations equipped with patient information, chemotherapy drugs and other requirements for continued care to prevent adverse childhood cancer care outcomes.

Les patients atteints de cancer pédiatrique constituent une population vulnérable fortement touchée par toute catastrophe perturbant l'écosystème de soins de santé. L'objectif de cette étude était de décrire l'impact des inondations sur l'accès aux soins des patients atteints de cancer pédiatrique dans l'État de Bayelsa, dans le sud du Nigeria. Nous examinons l'effet des inondations de 2022 sur les soins du cancer pédiatrique à l'unité d'oncologie pédiatrique de l'Hôpital universitaire de la Niger Delta, dans le sud du Nigeria. Les inondations dévastatrices ont entraîné la fermeture de l'établissement de santé pendant quatre semaines. Les défis auxquels sont confrontés les patients en oncologie comprennent l'incapacité d'accéder aux installations en raison de la destruction des routes et des réseaux de télécommunication, l'inaccessibilité aux médicaments de chimiothérapie, le report des interventions chirurgicales, des contraintes financières parentales en raison de la perte de revenus causée par les inondations et aggravées par une assurance maladieinsuffisante. par le manque d'assurance maladie. Deux enfants, qui suivaient une chimiothérapie pour un rhabdomyosarcome et un rétinoblastome, ont vu leurssoinstransférésversunétablissementdesoinssecondairesnonaffecté à 24 km de là. Grâce au travail d'équipe et à la détermination, l'équipe d'oncologie a réussi à surmonter les différents obstacles pour assurer des soins ininterrompus aux patients et améliorer les soins futurs aux patients en cas de catastrophes. Les soins aux patients atteints de cancer pédiatrique devraient être une priorité pour les établissements de santé, en particulier dans les zones sujettes aux inondations prévisibles comme l'État de Bayelsa. L'accent devrait être mis sur la formation à la préparation aux catastrophes, le développement de postes extérieurs équipés d'informations sur les patients, de médicaments de chimiothérapie et d'autres éléments nécessaires pour assurer des soins continus, afin de prévenir des résultats défavorables dans les soins del'enfance atteinte de cancer. Mots-clés : Enfance, Cancer, Inondation, Force majeure.

PMID:37906683
A case of spindle cell rhabdomyosarcoma with a ZFP64::NCOA3 fusion

Fetched: November 1st, 2023, 5:02am GMT by Ken-Ichi Yoshida

Genes Chromosomes Cancer. 2023 Oct 31. doi: 10.1002/gcc.23212. Online ahead of print.

NO ABSTRACT

PMID:37905771 | DOI:10.1002/gcc.23212
Chemical Carcinogen (Dimethyl-benzanthracene) Induced Transplantable Cancer in Fanconi Anemia (Fanca-/-) Mice

Fetched: November 1st, 2023, 5:02am GMT by Michael W Epperly

In Vivo. 2023 Nov-Dec;37(6):2421-2432. doi: 10.21873/invivo.13347.

ABSTRACT

BACKGROUND/AIM: Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations.

MATERIALS AND METHODS: Animal models for cancer in FA mice used orthotopic tumors from wild type mice. We derived a cancer cell line from Fanca-/- mice by topical application of the chemical carcinogen dimethyl benzanthracene (DMBA).

RESULTS: A Fanca-/- mouse rhabdomyosarcoma was derived from a Fanca-/- (129/Sv) mouse. The in vitro clonogenic survival of the Fanca-/- clone 6 cancer cell line was consistent with the FA genotype. Transplanted tumors demonstrated hypoxic centers surrounded by senescent cells.

CONCLUSION: This Fanca-/- mouse syngeneic cancer should provide a valuable resource for discovery and development of new normal tissue radioprotectors for patients with FA and cancer.

PMID:37905617 | PMC:PMC10621406 | DOI:10.21873/invivo.13347
Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan

Fetched: November 1st, 2023, 5:02am GMT by Kenji Tsuchihashi

BMC Cancer. 2023 Oct 31;23(1):1046. doi: 10.1186/s12885-023-11528-4.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy.

METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy.

RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions.

CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

PMID:37904096 | PMC:PMC10617040 | DOI:10.1186/s12885-023-11528-4
Navigating Complexities in Pediatric Rhabdomyosarcoma: A Case Report on Its Neurological Implications

Fetched: October 31st, 2023, 5:02am GMT by Anum Haider

Cureus. 2023 Sep 26;15(9):e45991. doi: 10.7759/cureus.45991. eCollection 2023 Sep.

ABSTRACT

This case report presents a 12-year-old male with a rare manifestation of rhabdomyosarcoma (RMS), emphasizing diagnostic and therapeutic challenges. The patient exhibited firm, tender facial swelling and underwent diagnostic procedures including imaging and biopsy, confirming RMS. Treatment involved a multi-agent chemotherapy regimen and radiotherapy, leading to a significant tumor reduction. However, neurological deficits emerged one month after treatment, suggesting neural invasion. The case highlights the need for vigilant monitoring and a multimodal treatment approach in managing RMS. It also raises questions about neural invasion risks post-treatment, contributing valuable insights to existing literature and advocating for further research in this rare pediatric cancer.

PMID:37900538 | PMC:PMC10601752 | DOI:10.7759/cureus.45991
Umbilical Cord Mesenchymal-Stem-Cell-Derived Exosomes Exhibit Anti-Oxidant and Antiviral Effects as Cell-Free Therapies

Fetched: October 29th, 2023, 5:02am GMT by Yi Meng

Viruses. 2023 Oct 15;15(10):2094. doi: 10.3390/v15102094.

ABSTRACT

The oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to cell aging and death. Equally, the skeletal muscle usually hosts enteroviral persistent infection in inflammatory muscle diseases. As excellent bioactive products, the exosomes derived from umbilical cord mesenchymal stem cells (ucMSCs) have been proven to be safe and have low immunogenicity with a potential cell-free therapeutic function. Here, exosomes derived from ucMSCs (ucMSC-EXO) were extracted and characterized. In a model of oxidative damage to skin fibroblasts (HSFs) under exposure to H2O2, ucMSC-EXO had an observable repairing effect for the HSFs suffering from oxidative damage. Furthermore, ucMSC-EXO inhibited mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) signaling pathways, thereby promoting p21 protein expression while decreasing lamin B1 protein expression, and finally alleviated oxidative stress-induced cell damage and aging. In a model of rhabdomyosarcoma (RD) cells being infected by enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the ucMSC-EXO enhanced the expression of interferon-stimulated gene 15 (ISG15) and ISG56 to inhibit enteroviral replication, whereafter reducing the virus-induced proinflammatory factor production. This study provides a promising therapeutic strategy for ucMSC-EXO in anti-oxidative stress and antiviral effects, which provides insight into extending the function of ucMSC-EXO in cell-free therapy.

PMID:37896871 | PMC:PMC10612094 | DOI:10.3390/v15102094
Bladder Neoplasia in Pediatric Patients-A Single-Center Experience Including a Case Series

Fetched: October 29th, 2023, 5:02am GMT by Frank-Martin Haecker

Children (Basel). 2023 Sep 25;10(10):1596. doi: 10.3390/children10101596.

ABSTRACT

Objective: Bladder lesions like urothelial carcinoma are rare in the first two decades of life. A biopsy of the bladder or urinary cytological examination is seldom required. Gross painless hematuria is the most relevant clinical syndrome. Methods: A retrospective analysis of surgical pathology records collected between 1984 and 2014 at our institution was performed in a search for cases of urothelial neoplasms originating within the urinary bladder in pediatric patients. Diagnoses were confirmed based on pathologic examination using the 2004 World Health Organization (WHO) classification system. We selected keywords such as bladder neoplasia, bladder lesion, urothelial neoplasia, rhabdomyosarcoma, and children. In addition, we describe clinical presentation and diagnostic procedures as well as treatment and follow-up of two patients. A review of the literature was performed to analyze recommendations concerning diagnostic staging, treatment, and follow-up examinations as well as surveillance of urothelial tumors in the pediatric population. Results: Screening the pathology database of the Institute of Medical Genetics and Pathology of the University Hospital Basel between 1988 and 2014 yielded 287 samples involving the urinary bladder, 110 autopsies, 135 biopsies, and 42 cytology specimens. Of these, most samples originated from malformations and inflammation. Only five were tumors: two were urothelial tumors and three were rhabdomyosarcomas. The majority of specimens comprised resections of the diverticula or distal ureter. Our case reports include two patients with a urothelial tumor. Among the urothelial tumors, one was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Painless hematuria was the directing clinical symptom. The tumor was investigated by FISH, and a 9p21 deletion was found. The second tumor-like lesion was a fibroepithelial polyp arising from the bladder neck. Conclusions: Bladder tumors in children are rare and mostly consist of urothelial and mesenchymal neoplasms. Rhabdomyosarcoma is the most common malignant bladder tumor in childhood. Similar to adult urothelial neoplasms, the loss of 9p21 is also implicated in urothelial neoplasms in childhood. Despite an increasing number of case reports and small series published within the last 2 decades, general treatment protocols including recommendations for staging, tumor markers, and follow-up examinations are still not yet available for this tumor entity in the pediatric population.

PMID:37892259 | PMC:PMC10605940 | DOI:10.3390/children10101596
Radiologic and Clinical Features of Infantile Hemangioma: Potential Pitfalls and Differential Diagnosis

Fetched: October 28th, 2023, 5:02am GMT by Emilio J Inarejos Clemente

Radiographics. 2023 Nov;43(11):e230064. doi: 10.1148/rg.230064.

ABSTRACT

Infantile hemangioma (IH) is the most common neoplasm in children, but it may mimic other types of vascular anomalies or nonvascular benign and malignant tumors. In most cases, the clinical appearance, time of onset, and pattern of involution facilitate its diagnosis. Imaging evaluation is not always needed since the IH features at clinical presentation are usually characteristic, but when needed, US and frequently MRI are the imaging modalities of choice. Clinical photography or photographic documentation plays a central role in monitoring these lesions over their clinical course. Photographic documentation can also add confidence and alert the radiologist when interpreting imaging studies. Some vascular anomalies, especially vascular malformations, are a frequent source of confusion, as these may resemble IHs clinically and at imaging. The lack of uniform terminology also hinders an accurate diagnosis. To unify the terminology and minimize confusion, the International Society for the Study of Vascular Anomalies created a helpful classification in 1994. In addition, radiologists need to be aware of and become familiar with other neoplasms in children that may resemble IH to avoid misdiagnosis and unnecessary procedures. Fibrous and lipomatous tumors are examples of benign tumors that can mimic IHs clinically and at imaging, whereas rhabdomyosarcoma, infantile fibrosarcoma, neuroblastoma, and lymphoproliferative disorders are examples of malignant neoplasms. The authors review the features of IH at clinical presentation and imaging evaluation, highlighting its different phases of evolution and stressing the importance of photographic documentation. The authors also review pitfalls of IH with helpful pearls for differentiation. ^©RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Khanna and Briones in this issue.

PMID:37883305 | DOI:10.1148/rg.230064
A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma

Fetched: October 28th, 2023, 5:02am GMT by Prethish Sreenivas

Mol Cell Biol. 2023;43(11):547-565. doi: 10.1080/10985549.2023.2256640. Epub 2023 Nov 17.

ABSTRACT

Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics of cells blocked in differentiation. NOTCH1 is an oncogene that promotes self-renewal and blocks differentiation in the fusion negative-RMS sub-type. However, how NOTCH1 expression is transcriptionally maintained in tumors is unknown. Analyses of SNAI2 and CTCF chromatin binding and HiC analyses revealed a conserved SNAI2/CTCF overlapping peak downstream of the NOTCH1 locus marking a sub-topologically associating domain (TAD) boundary. Deletion of the SNAI2-CTCF peak showed that it is essential for NOTCH1 expression and viability of FN-RMS cells. Reintroducing constitutively activated NOTCH1-ΔE in cells with the SNAI2-CTCF peak deleted restored cell-viability. Ablation of SNAI2 using CRISPR/Cas9 reagents resulted in the loss of majority of RD and SMS-CTR FN-RMS cells. However, the few surviving clones that repopulate cultures have recovered NOTCH1. Cells that re-establish NOTCH1 expression after SNAI2 ablation are unable to differentiate robustly as SNAI2 shRNA knockdown cells; yet, SNAI2-ablated cells continued to be exquisitely sensitive to ionizing radiation. Thus, we have uncovered a novel mechanism by which SNAI2 and CTCF maintenance of a sub-TAD boundary promotes rather than represses NOTCH1 expression. Further, we demonstrate that SNAI2 suppression of apoptosis post-radiation is independent of SNAI2/NOTCH1 effects on self-renewal and differentiation.

PMID:37882064 | DOI:10.1080/10985549.2023.2256640
Radiotherapy and long-term sequelae in pediatric patients with parameningeal rhabdomyosarcoma: Results of two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry

Fetched: October 28th, 2023, 5:02am GMT by Monika Sparber-Sauer

Pediatr Blood Cancer. 2024 Jan;71(1):e30742. doi: 10.1002/pbc.30742. Epub 2023 Oct 25.

ABSTRACT

BACKGROUND: Parameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome.

METHODS: Treatment and outcome of 395 children with PM RMS registered within two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1995-2021) were evaluated.

RESULTS: Patients were IRS group II (n = 15) and III (n = 380) and received systemic treatment according to the enrolled protocols: I2VA (n = 172), VAIA/CEVAIE (n = 223). Delayed resection was performed in 88/395 (22%) patients, and RT was additionally given in 79/88 (90%) resected patients. RT was the predominant local treatment in 355/395 (90%) patients: hyperfractionated accelerated photon (HART; n = 77), conventionally fractionated photon (n = 91) or proton beam (n = 126), brachytherapy (n = 4), heavy ions (n = 1), not available (n = 56). In the subgroup of RT as only local treatment (n = 278), no intracranial tumor extension and complete remission at end of treatment were significant positive prognostic factors. No significant difference on tumor outcome was seen between different radiotherapy concepts. Long-term toxicity with mostly endocrinological and visual deficiencies was reported in 161/279 (58%) surviving patients with a lower trend after proton beam RT (48%) when compared to HART or conventionally fractionated photon RT (71% and 72%, respectively). Ten-year event-free and overall survival in the overall group were 62% (±5, 95% confidence interval [CI]) and 67% (±5, 95% CI); in the RT-only group 67% (±6, 95% CI) and 71% (±6, 95% CI), respectively.

CONCLUSION: CWS data confirm the recent RT concept in PM RMS. Long-term sequelae as endocrinological and visual deficiencies need to be addressed.

PMID:37880926 | DOI:10.1002/pbc.30742
Melanoma with rhabdomyosarcomatous features: a potential diagnostic pitfall

Fetched: October 26th, 2023, 5:02am GMT by Henry Watter

BMJ Case Rep. 2023 Oct 24;16(10):e256427. doi: 10.1136/bcr-2023-256427.

ABSTRACT

Malignant melanoma is well-known for phenotypic plasticity, and rare cases of divergent differentiation have been described. This case report is of a tumour diagnosed as 'rhabdomyosarcoma' on the face of a man in his 80s. However, given the recent excision of an ulcerated melanoma (Breslow thickness 5.8 mm) from the same site, the more likely diagnosis would be recurrent melanoma with rhabdomyosarcomatous differentiation. This highlights a rare form of divergent differentiation and a potential diagnostic pitfall.

PMID:37879714 | PMC:PMC10603449 | DOI:10.1136/bcr-2023-256427
Conjunctival Spindle Cell/Sclerosing Rhabdomyosarcoma

Fetched: October 26th, 2023, 5:02am GMT by Yi-Wen Su

Ophthalmology. 2023 Oct 24:S0161-6420(23)00705-4. doi: 10.1016/j.ophtha.2023.09.027. Online ahead of print.

NO ABSTRACT

PMID:37877920 | DOI:10.1016/j.ophtha.2023.09.027
Inflammatory Rhabdomyoblastic Tumor: Clinicopathological and Molecular Analysis of 13 Cases

Fetched: October 24th, 2023, 5:02am GMT by Toru Odate

Mod Pathol. 2023 Oct 21;37(1):100359. doi: 10.1016/j.modpat.2023.100359. Online ahead of print.

ABSTRACT

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

PMID:37871654 | DOI:10.1016/j.modpat.2023.100359
A Simple Step-by-Step Guide to Permanent Punctal Occlusion with the Ophthalmic Burr and Suture Technique

Fetched: October 24th, 2023, 5:02am GMT by Driton Gjukaj

Klin Monbl Augenheilkd. 2023 Oct;240(10):1179-1184. doi: 10.1055/a-2179-4498. Epub 2023 Oct 23.

ABSTRACT

The medical treatment of dry eye disease usually follows a step-wise approach to achieve clinical improvement, ranging from non-surgical interventions with intensive lubrication to permanent surgical punctal occlusion. While frequent lubrication is essential, the intense regime is often too burdensome and difficult to maintain at the required frequency. Punctal plugs are an invaluable alternative approach, but also have limitations, especially in conscious children, in whom inserting and re-inserting punctum plugs in clinic can be challenging. If a patient has permanent and severe dry eye disease and responded well to a trial of temporary punctal plugging, a permanent surgical solution should be considered next. Liu et al showed that a more successful, yet simple technique to achieve permanent occlusion is to combine de-epithelialising the punctum and ampulla with the immediate firm apposition of the de-epithelialised surface using a self-absorbable suture - with a success rate of 92% in a prospective study. This article demonstrates this technique step-by-step in an 8-year-old child with severe chronic dry eye disease following proton beam therapy for orbital rhabdomyosarcoma. She underwent this procedure with excellent results.

PMID:37871593 | DOI:10.1055/a-2179-4498
Gorlin-Goltz Syndrome: A Case Series

Fetched: October 24th, 2023, 5:02am GMT by Ameera Salahudheen

Cureus. 2023 Sep 21;15(9):e45656. doi: 10.7759/cureus.45656. eCollection 2023 Sep.

ABSTRACT

Gorlin-Goltz syndrome (GGS) among Indians is rarely reported. Since 1960, only 38 cases having 48 patients of Gorlin-Goltz syndrome have been identified in the Indian population. It is crucial to diagnose this illness early because it can be connected to a malignant lesion like fibrosarcoma, leiomyosarcoma or rhabdomyosarcoma. The four patients in this case series were identified and treated in our department between 2019 and 2023. The average patient age was around 20 years old. Jaw swelling and tooth movement were the two most typical presenting concerns. Odontogenic keratocysts (100%), palmer pits (100%), plantar pits (50%), calcification of falx cerebri (50%), and rib abnormalities (50%), were the most prevalent characteristics. None of the patients had basal cell cancer, cleft lip, or medulloblastoma. Multiple odontogenic keratocysts were present in three cases, whereas a single odontogenic keratocyst (OKC) was seen in one patient. Patients were managed with either marsupialization or enucleation, depending on the size of the cyst. Two cases with a large cyst size were marsupialized by using a modified obturator. Two cases with small cysts were managed with enucleation of the cyst followed by chemical cauterization. Recurrence was seen in two cases. In one patient, we noticed the formation of a new cyst. A GGS diagnosis can be made by having a systemic evaluation of the patient. A thorough examination of the patient should be performed in every histopathology-diagnosed case of OKC. This will help to miss the syndromic cases. The treatment part should be conservative, like marsupialization with an obturator in a large cyst. The obturator helps maintain patient hygiene and prevents regular visits for changing dressings. Small-sized cysts can be managed with enucleation and chemical cauterization. Radical resection should be avoided.

PMID:37868392 | PMC:PMC10589734 | DOI:10.7759/cureus.45656
Residential proximity to vines and risk of childhood embryonal tumours in France - GEOCAP case-control study, 2006-2013

Fetched: October 22nd, 2023, 5:02am GMT by Danielle Awounou

Environ Res. 2024 Jan 1;240(Pt 2):117417. doi: 10.1016/j.envres.2023.117417. Epub 2023 Oct 20.

ABSTRACT

BACKGROUND: Exposure to pesticides has been suggested as a potential risk factor for childhood embryonal tumour. The existing literature has mainly focused on parental occupational exposure and domestic use of pesticides, and is very limited for residential exposures to agricultural pesticides. The study aimed to test the hypothesis of an increased risk of embryonal tumour in children living close to viticultural plots, likely to be subject to frequent pesticide applications.

METHODS: The study is part of the French national registry-based GEOCAP program. We included 2761 cases of neuroblastoma, retinoblastoma, Wilms tumour and rhabdomyosarcoma diagnosed before the age of 15 years in the 2006-2013 period, and 40,196 controls representative of the same age population during this period. Indicators of proximity to vines, the presence of vines and viticulture density within 1000 m of the geocoded addresses of residence, were evaluated combining three sources of data on agricultural land use in a geographic information system. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regressions and carried out several sensitivity analyses to test the stability of the results.

RESULTS: Approximately 10% of the controls lived within 1000 m of vines, with regional variations ranging from <1% to 38%. We observed a 5% increase in the risk of neuroblastoma for a 10% increase in viticulture density (OR = 1.05, 95% CI: 0.98-1.13), with a regional heterogeneity. The indicators of proximity to vines were not associated with the other non-CNS embryonal tumours.

CONCLUSION: The study showed a slight increase in the risk of neuroblastoma in children living close to vines, suggesting that residential exposure to agricultural pesticides may be involved in the occurrence of these tumours.

PMID:37865323 | DOI:10.1016/j.envres.2023.117417
A Practical Approach to Small Round Cell Tumors Involving the Gastrointestinal Tract and Abdomen

Fetched: October 22nd, 2023, 5:02am GMT by Khin Thway

Surg Pathol Clin. 2023 Dec;16(4):765-778. doi: 10.1016/j.path.2023.05.012. Epub 2023 Jul 11.

ABSTRACT

Small round cell neoplasms are diagnostically challenging owing to their clinical and pathologic overlap, necessitating use of large immunopanels and molecular analysis. Ewing sarcomas (ES) are the most common, but EWSR1 is translocated in several diverse neoplasms, some with round cell morphology. Molecular advances enable classification of many tumors previously termed 'atypical ES'. The current WHO Classification includes two new undifferentiated round cell sarcomas (with CIC or BCOR alterations), and a group of sarcomas in which EWSR1 partners with non-Ewing family transcription factor genes. This article reviews the spectrum of small round cell sarcomas within the gastrointestinal tract and abdomen.

PMID:37863565 | DOI:10.1016/j.path.2023.05.012
Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells

Fetched: October 22nd, 2023, 5:02am GMT by Eleanor O'Brien

Clin Epigenetics. 2023 Oct 19;15(1):167. doi: 10.1186/s13148-023-01583-w.

ABSTRACT

BACKGROUND: Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign. The histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2) suppresses normal skeletal muscle differentiation and is highly expressed in RMS tumours.

RESULTS: We demonstrate combining inhibition of the epigenetic modulator EZH2 with the differentiating agent retinoic acid (RA) is more effective at reducing cell proliferation in RMS cell lines than single agents alone. In PAX3-FOXO1 positive RMS cells this is due to an RA-driven induction of the interferon pathway resulting in apoptosis. In fusion negative RMS, combination therapy led to an EZH2i-driven upregulation of myogenic signalling resulting in differentiation. In both subtypes, EZH2 is significantly associated with enrichment of trimethylated lysine 27 on histone 3 (H3K27me3) in genes that are downregulated in untreated RMS cells and upregulated with EZH2 inhibitor treatment. These results provide insight into the mechanism that drives the anti-cancer effect of the EZH2/RA single agent and combination treatment and indicate that the reduction of EZH2 activity combined with the induction of RA signalling represents a potential novel therapeutic strategy to treat both subtypes of RMS.

CONCLUSIONS: The results of this study demonstrate the potential utility of combining EZH2 inhibitors with differentiation agents for the treatment of paediatric rhabdomyosarcomas. As EZH2 inhibitors are currently undergoing clinical trials for adult and paediatric solid tumours and retinoic acid differentiation agents are already in clinical use this presents a readily translatable potential therapeutic strategy. Moreover, as inhibition of EZH2 in the poor prognosis FPRMS subtype results in an inflammatory response, it is conceivable that this strategy may also synergise with immunotherapies for a more effective treatment in these patients.

PMID:37858275 | PMC:PMC10588044 | DOI:10.1186/s13148-023-01583-w
Inflammatory Myofibroblastic Tumor With ROS1 Gene Fusions in Children and Young Adolescents

Fetched: October 20th, 2023, 5:02am GMT by Reineke A Schoot

JCO Precis Oncol. 2023 Sep;7:e2300323. doi: 10.1200/PO.23.00323.

ABSTRACT

PURPOSE: Inflammatory myofibroblastic tumors (IMTs) are often driven by anaplastic lymphoma kinase fusions and less frequently by alternative fusions such as ROS1. We describe the clinical characteristics, treatment approach, and outcome for a series of young patients with IMTs and ROS1 alterations.

METHODS: This was a retrospective, international, multicenter study analyzing young patients (younger than 21 years) with ROS1-altered IMTs treated in 10 European referral centers between 2014 and 2022. Patients were included in the European pediatric Soft tissue sarcoma Study Group NRSTS-2005 protocol or registered in the Soft Tissue Sarcoma Registry. Primary surgery was recommended if a microscopic radical resection was feasible without mutilation. No standard systemic treatment protocol was available, but several medical options were recommended.

RESULTS: A total of 19 patients (median age 8.3 years) were included. Most patients had a biopsy at diagnosis (Intergroup Rhabdomyosarcoma Study [IRS] I; n = 2, IRS II; n = 1, IRS III biopsy; n = 11, IRS III resection; n = 3, IRS IV; n = 2). Twelve patients received neoadjuvant systemic therapy in first line (four received multiple treatments): high-dose steroids (n = 2), vinorelbine/vinblastine with methotrexate (n = 6), or ROS1 inhibitors (n = 8). After a median follow-up of 2.8 years (range, 0.2-13.4), seven patients developed an event. The 3-year event-free survival was 41% (95% CI, 11 to 71), and the 3-year overall survival was 100%.

CONCLUSION: Outcome for ROS1-altered IMTs appears excellent. A complete resection at diagnosis was often not feasible, and most patients needed neoadjuvant therapy. Patients who developed a tumor event could be cured with reinitiation of systemic therapy and/or surgery. This approach illustrates a switch in treatment philosophy moving from immediate, often mutilating, surgery to systemic (targeted) therapy as a bridge to more conservative surgery later in the treatment course.

PMID:37856763 | DOI:10.1200/PO.23.00323
"My Home Away From Home": Community Support for International Pediatric and Young Adult Patients and Their Families in End-of-Life Care and Bereavement

Fetched: October 20th, 2023, 5:02am GMT by Emily M Pang

J Palliat Med. 2023 Oct 19. doi: 10.1089/jpm.2023.0370. Online ahead of print.

ABSTRACT

Background: Foreign national patients and families can face life-limiting illness and end-of-life care far from home; this palliative need has not been well described. Case Description: We present a case of a 20-year-old Ugandan patient diagnosed with metastatic alveolar rhabdomyosarcoma who presented to a pediatric academic medical center in California. Despite treatment, her disease progressed and she was unable to return to Uganda due to symptom burden. The patient and her family met regularly with palliative care during their hospital stay; the palliative approach included cross-cultural sharing, connecting across differences, and fostering community. The family additionally cultivated a support system within the hospital and local African communities. This was illustrated in the memory album the patient created, and in her family's extensive bereavement support. Conclusions: This case explores opportunities for individualized psychosocial care and community-based support to enhance palliative care for foreign national patients and families.

PMID:37856163 | DOI:10.1089/jpm.2023.0370
Alveolar type of rhabdomyosarcoma of maxilla-A case report

Fetched: October 20th, 2023, 5:02am GMT by J Dinakar

J Oral Maxillofac Pathol. 2023 Apr-Jun;27(2):406-410. doi: 10.4103/jomfp.jomfp_534_22. Epub 2023 Jul 13.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common sarcoma among children and accounts for 20% of soft tissue sarcomas. In children, close to 50% of rhabdomyosarcomas arise in the head and neck. RMS of the oral cavity is rare and is seen in only 10-12% of all head and neck lesions and the involvement of the jaws is extremely rare. Histopathologically, the various types are pleomorphic type, botryoid type, spindle cell type, embryonal, and alveolar type of RMS. The alveolar variant accounts for almost 30% of all rhabdomyosarcomas and tends to arise in patients of the age group 10-25 years. We present a case of orofacial RMS in a young adult who was referred to our Institution for the management of an odontogenic lesion of the maxilla. The clinicopathological aspects and poor survival rate as a consequence of delayed diagnosis are discussed. We dentists may misdiagnose it as an odontogenic tumour due to its location in the oral and maxillofacial region. Careful clinical history and examination and investigations may help to narrow down the diagnosis. Expert opinion and referrals to oral pathologists and oncologists are essential to arrive at early diagnosis and to initiate the treatment.

PMID:37854913 | PMC:PMC10581309 | DOI:10.4103/jomfp.jomfp_534_22
Small bowel metastasis from embryonal rhabdomyosarcoma of the extremity- a case report

Fetched: October 19th, 2023, 5:03am GMT by P Joubert

S Afr J Surg. 2023 Oct 17;61(4). doi: 10.36303/SAJS.4120. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma is the most common soft tissue tumour in children and adolescents, but extremely rare in adults with comparatively worse outcomes. Metastatic disease is not uncommon, but intra-abdominal metastases are exceedingly rare. We report an unusual case of ileal metastases from an upper extremity rhabdomyosarcoma in a 17-year-old male who presented with abdominal pain during a routine follow-up visit. Laparotomy and ileocecectomy for a perforated ileal mass confirmed metastatic embryonal rhabdomyosarcoma with 1 out of 14 positive lymph node metastases. This case demonstrates that, although rare, intra-abdominal metastases should be considered when patients with a rhabdomyosarcoma present with abdominal complaints.

PMID:37849325 | DOI:10.36303/SAJS.4120
Epidemiology of Eye Cancer in Cali, Colombia: A 55-Year Study

Fetched: October 19th, 2023, 5:03am GMT by Katherine Vega-Escobar

Ophthalmic Epidemiol. 2023 Oct 17:1-11. doi: 10.1080/09286586.2023.2269253. Online ahead of print.

ABSTRACT

PURPOSE: To describe the epidemiology, incidence, mortality and survival of ocular cancer in Cali between 1962 and 2019.

METHODS: Ecological population-based study analyzing data of incidence, mortality, and 5-years survival of malignant ocular tumors from the Populational Cancer Registry of Cali between 1962 and 2019.

RESULTS: Between 1962 and 2019, 586 ocular tumors were found, 50.5% occurred in females, the mean age at diagnosis was 45 years (standard deviation = 25), 70.3% of ocular malignancies occurred in >14 years. The average annual incidence rate was 7.8 per million for male and 6.9 per million for females. Retinoblastoma (21%), squamous cell carcinoma (20%), melanoma (16%) and lymphoma (8%) were the most common neoplasm. In those <15 years, the most frequent malignant tumors were retinoblastomas (85.7%), followed by non-specified malignant neoplasm (NOS, 7.9%), and rhabdomyosarcoma (3.6%). In those >14 years, there were NOS (30%), followed by squamous cell carcinomas (28%), melanomas (23%), and lymphomas (9.7%). Conjunctiva (38.2%), retina (21%) and orbit (10%) constituted the majority of anatomical sites of ocular tumors. The survival rate was about 83.2% and mortality did not show a decreasing trend over time (p > .05).

CONCLUSIONS: The incidence of ocular cancer in Cali has a slightly increasing trend, with stable behavior in the last decades. Squamous cell carcinoma, retinoblastoma, melanoma and lymphoma are the most frequent ocular cancers, with being retinoblastoma more frequent than melanoma. In general, ocular cancer had good survival rates in Cali.

PMID:37849291 | DOI:10.1080/09286586.2023.2269253
Coxsackievirus A6 2C protein antagonizes IFN-β production through MDA5 and RIG-I depletion

Fetched: October 18th, 2023, 5:02am GMT by Shao-Hua Wang

J Virol. 2023 Oct 17:e0107523. doi: 10.1128/jvi.01075-23. Online ahead of print.

ABSTRACT

As a member of the enteroviruses, coxsackievirus A6 (CV-A6) has been a major cause of hand, foot, and mouth disease (HFMD) since 2008. It can infect both pediatric and adult populations, often leading to atypical HFMD. The host innate immune system plays a vital role in the development of enteroviral infections. However, the interplay between the host antiviral response and CV-A6 has not been well investigated. In the present study, we demonstrated that the 2C protein from CV-A6 (2CCV-A6) suppresses interferon beta (IFN-β) production in HEK293T cells. Further results indicated that 2CCV-A6 interacts with both melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) and induces the degradation of these RNA sensors through proteases in the lysosomal pathway. This function also applies to 2C proteins from enterovirus A71 (2CEV-A71) and coxsackievirus B3 (2CCV-B3) but not CV-A16 2C (2CCV-A16) for its incompetence in MDA5 and RIG-I recognition. Partial depletion and amino acid substitution analyses indicated that the F28A, V75A, and I96V mutations significantly compromised 2CCV-A6-induced MDA5/RIG-I depletion. Surprisingly, unlike V75A and I96V that interrupt the 2CCV-A6-MDA5/RIG-I interaction, 2CCV-A6 F28A remained competent in MDA5/RIG-I binding, suggesting that the interaction alone is not sufficient for 2C-mediated reduction. Additional tests indicated that CV-A6 viruses containing the 2C F28A mutation were less efficient in IFN-β suppression, which is associated with compromised viral replication and release in infected rhabdomyosarcoma (RD) cells, suggesting that 2C-mediated immune regulation plays a vital role in enteroviral replication. Taken together, our data reveal a novel mechanism by which enteroviral 2C proteins antagonize the host innate antiviral immune response. IMPORTANCE Coxsackievirus A6 (CV-A6) is a major emerging pathogen associated with atypical hand, foot, and mouth disease and can cause serious complications such as encephalitis, acute flaccid paralysis, and neurorespiratory syndrome. Therefore, revealing the associated pathogenic mechanisms could benefit the control of CV-A6 infections. In this study, we demonstrate that the nonstructural 2CCV-A6 suppresses IFN-β production, which supports CV-A6 infection. This is achieved by depleting RNA sensors such as melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I (RIG-I) through the lysosomal pathway. Such a function is shared by 2CEV-A71 and 2CCV-B3 but not 2CCV-A16, suggesting the latter might have an alternative way to promote viral replication. This study broadens our understanding of enterovirus 2C protein regulation of the RIG-I-like receptor signaling pathway and reveals a novel mechanism by which CV-A6 and other enteroviruses evade the host innate immune response. These findings on 2C may provide new therapeutic targets for the development of effective inhibitors against CV-A6 and other enterovirus infections.

PMID:37847581 | DOI:10.1128/jvi.01075-23
Staufen1 controls mitochondrial metabolism via HIF2α in embryonal rhabdomyosarcoma and promotes tumorigenesis

Fetched: October 18th, 2023, 5:02am GMT by Shekoufeh Almasi

Cell Mol Life Sci. 2023 Oct 17;80(11):328. doi: 10.1007/s00018-023-04969-4.

ABSTRACT

Elevated mitochondrial metabolism promotes tumorigenesis of Embryonal Rhabdomyosarcomas (ERMS). Accordingly, targeting oxidative phosphorylation (OXPHOS) could represent a therapeutic strategy for ERMS. We previously demonstrated that genetic reduction of Staufen1 (STAU1) levels results in the inhibition of ERMS tumorigenicity. Here, we examined STAU1-mediated mechanisms in ERMS and focused on its potential involvement in regulating OXPHOS. We report the novel and differential role of STAU1 in mitochondrial metabolism in cancerous versus non-malignant skeletal muscle cells (NMSkMCs). Specifically, our data show that STAU1 depletion reduces OXPHOS and inhibits proliferation of ERMS cells. Our findings further reveal the binding of STAU1 to several OXPHOS mRNAs which affects their stability. Indeed, STAU1 depletion reduced the stability of OXPHOS mRNAs, causing inhibition of mitochondrial metabolism. In parallel, STAU1 depletion impacted negatively the HIF2α pathway which further modulates mitochondrial metabolism. Exogenous expression of HIF2α in STAU1-depleted cells reversed the mitochondrial inhibition and induced cell proliferation. However, opposite effects were observed in NMSkMCs. Altogether, these findings revealed the impact of STAU1 in the regulation of mitochondrial OXPHOS in cancer cells as well as its differential role in NMSkMCs. Overall, our results highlight the therapeutic potential of targeting STAU1 as a novel approach for inhibiting mitochondrial metabolism in ERMS.

PMID:37847286 | DOI:10.1007/s00018-023-04969-4
Indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcoma: A study of the European paediatric Soft Tissue Sarcoma Study Group

Fetched: October 18th, 2023, 5:02am GMT by Chiara Giraudo

Cancer. 2023 Oct 17. doi: 10.1002/cncr.35061. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis.

METHODS: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared.

RESULTS: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086).

CONCLUSIONS: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules.

PLAIN LANGUAGE SUMMARY: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma.

PMID:37846799 | DOI:10.1002/cncr.35061
Ovarian Sarcoma a Diagnostic Dilemma- A Case Report

Fetched: October 17th, 2023, 5:02am GMT by Prashant K Zulpi

J Indian Assoc Pediatr Surg. 2023 Sep-Oct;28(5):436-438. doi: 10.4103/jiaps.jiaps_15_23. Epub 2023 Sep 5.

ABSTRACT

Primary sarcoma of the ovary is extremely rare. There are inadequate data in the literature regarding ovarian sarcoma in the pediatric age group. We report a case of an 8-year-old girl presenting with large abdominal mass and cachexia. Raised alpha-fetoprotein levels suggested germ cell tumor. Tru-cut biopsy histopathological report suggested a spindle cell tumor. The IHC staining suggested non rhabdomyosarcoma. As tumour was large and ovarian pediatric non rhabdomyosarcoma was not reported in the literature, we started on rhabdomyosarcoma neoadjuant regimen. Good response was noted for neoadjuvant chemotherapy, which was followed by complete surgical excision of the tumor and radiotherapy. At present, the overall outcome of the disease is dismal. Increased available data and gaining more evidence may help in improvising the treatment option.

PMID:37842220 | PMC:PMC10569281 | DOI:10.4103/jiaps.jiaps_15_23
Clinical Insight on Proton Therapy for Paediatric Rhabdomyosarcoma

Fetched: October 17th, 2023, 5:02am GMT by Sabina Vennarini

Cancer Manag Res. 2023 Oct 10;15:1125-1139. doi: 10.2147/CMAR.S362664. eCollection 2023.

ABSTRACT

This paper offers an insight into the use of Proton Beam Therapy (PBT) in paediatric patients with rhabdomyosarcoma (RMS). This paper provides a comprehensive analysis of the literature, investigating comparative photon-proton dosimetry, outcome, and toxicity. In the complex and multimodal scenario of the treatment of RMS, clear evidence of the therapeutic superiority of PBT compared to other modern photon techniques has not yet been demonstrated; however, PBT can be considered an excellent treatment option, in particular for young children and patients with specific primary sites, such as the head and neck area (and especially the parameningeal regions), genito-urinary, pelvic, and paravertebral regions. The unique depth-dose characteristics of protons can be exploited to achieve significant reductions in normal tissue doses and may allow an escalation of tumour doses and greater sparing of normal tissues, thus potentially improving local control while at the same time reducing toxicity and improving quality of life. However, access of children with RMS (and more in general with solid tumors) to PBT remains a challenge, due to the limited number of available proton therapy installations.

PMID:37842128 | PMC:PMC10576457 | DOI:10.2147/CMAR.S362664
Case Report: A 13-year-old adolescent diagnosed as malignant phyllodes tumor combined with rhabdomyosarcoma differentiation

Fetched: October 17th, 2023, 5:02am GMT by Jie Lian

Front Oncol. 2023 Sep 27;13:1233208. doi: 10.3389/fonc.2023.1233208. eCollection 2023.

ABSTRACT

Phyllodes tumor (PT) is an infrequent type of breast neoplasm, constituting a mere 0.5%-1.5% of the entirety of breast tumors. The malignant phyllodes tumor (MPT) comprises only 15% of all phyllodes tumors, and its transformation into rhabdomyosarcoma (RMS) is exceedingly rare in clinical practice. Given its insensitivity to chemotherapy and radiotherapy, treatment options for MPT patients are limited, leaving complete surgical resection as the only option. Therefore, it is imperative to investigate the effective utilization of the heterogeneous differentiation characteristics of MPT to expand treatment alternatives for these patients. In this case report, we represent a 13-year-old adolescent diagnosed with giant breast MPT with RMS differentiation and pulmonary metastasis. The initial step in the treatment process involved radical surgical resection, followed by the administration of four cycles of VDC/IC chemotherapy, which is widely recognized as the standard chemotherapy for RMS. Regrettably, the delay in initiating chemotherapy resulted in minimal observable changes in the size of the pulmonary metastatic nodule. Additionally, a comprehensive literature review on the characterization of MPT with heterogeneous differentiation was conducted to enhance comprehension of the diagnosis and treatment of this uncommon disease in clinical practice. Meanwhile, this case also reminds the doctors that when we diagnose a patient as MPT, it is crucial to consider its heterogenous nature and promptly initiate adjuvant treatment. By targeting the differentiation element of MPT, it becomes feasible to overcome the previously perceived limitation of surgical intervention as the sole treatment option.

PMID:37841438 | PMC:PMC10569689 | DOI:10.3389/fonc.2023.1233208
Patient-derived organoids facilitating individual therapy in an adolescent with embryonal rhabdomyosarcoma of the cervix: a case report and literature review

Fetched: October 17th, 2023, 5:02am GMT by Xinyu Qiao

Front Oncol. 2023 Sep 29;13:1241507. doi: 10.3389/fonc.2023.1241507. eCollection 2023.

ABSTRACT

Rhabdomyosarcoma (RMS) is a highly aggressive pediatric neoplasm that originates from striated muscle or undifferentiated mesenchymal cells. Based on its histopathological characteristics, the World Health Organization categorizes RMS into four distinct subtypes: embryonal RMS, alveolar RMS, pleomorphic RMS, and sclerosing/spindle cell RMS. Embryonal RMS represents the predominant subtype and primarily manifests in the head and neck region, with the genitourinary system being the subsequent most frequent site of occurrence. Embryonal rhabdomyosarcoma of the cervix (cERMS) is more insidious in the reproductive tract, and there is still a lack of consensus on its treatment. Patient-derived organoids (PDOs) are being prioritized for use in guiding personalized medicine. The application of PDOs to test the sensitivity of chemotherapy drugs in patients with cERMS has rarely been reported. In this case report, we delineate the presentation and diagnosis of a 16-year-old adolescent with cERMS, emphasizing the utilization of PDOs in the management of this infrequent neoplasm. We intend to elucidate the diagnostic and therapeutic processes associated with cERMS by referencing previously reported literature on this infrequent tumor, aiming to offer a foundation for clinical practice.

PMID:37841436 | PMC:PMC10570525 | DOI:10.3389/fonc.2023.1241507
Multifocal, biatrial, primary cardiac embryonal rhabdomyosarcoma

Fetched: October 14th, 2023, 5:02am GMT by Ioannis Panagiotopoulos

Prz Menopauzalny. 2023 Sep;22(3):173-176. doi: 10.5114/pm.2023.131459. Epub 2023 Sep 25.

ABSTRACT

Malignant primary cardiac tumors are rare, with atrial myxoma and rhabdomyosarcoma the common types in adult and pediatric populations respectively. Rhabdomyosarcomas are rare and are usually located in the atria; they present with symptomatology dependent on their location. A 63-year-old woman presented with the symptomatology of dyspnea, cough, and palpitations and was diagnosed with biatrial primary cardiac rhabdomyosarcoma, which required excision. The postoperative course was uneventful and the patient was discharged on the 5^th postoperative day. Postoperative cardiac functional tests revealed an ejection fraction of 60%, consistent with the preoperative value, and no mitral valve dysfunction. Biatrial rhabdomyosarcomas are extremely rare, with only 3 cases reported, including ours, reported in the literature, to the best of our knowledge. Transthoracic echocardiogram is useful in the diagnosis. They require surgical excision along with chemotherapy or radiotherapy. Their prognosis is poor, with a median survival of almost one year. Primary biatrial rhabdomyosarcoma is an extremely rare diagnosis that can present with symptomatology based on the location, size, and number of masses. There is no consensus on how to manage them due to the scarcity of cases, but they are managed as single rhabdomyosarcomas. The majority require surgical excision, with subsequent chemotherapy or radiotherapy. The prognosis is very poor, with the majority of the patients not surviving longer than one year.

PMID:37829268 | PMC:PMC10566335 | DOI:10.5114/pm.2023.131459
Phylogenetic characteristics and recombination analysis of echovirus 5 associated with severe acute respiratory infection in China

Fetched: October 12th, 2023, 5:02am GMT by Wenxia Li

Microbiol Spectr. 2023 Oct 11:e0171123. doi: 10.1128/spectrum.01711-23. Online ahead of print.

ABSTRACT

Echovirus 5 (E5) belongs to the enterovirus B (EV-B) species, which is one of the pathogens causing respiratory diseases. Only two whole genome sequences (WGSs) of E5 are available in GenBank, and few studies on E5 have been reported worldwide. In this study, human rhabdomyosarcoma (RD) cells were used to isolate E5 from respiratory samples associated with severe acute respiratory infection (SARI). The nucleotide sequence of the VP1 region and the WGSs of two E5 strains were sequenced using Sanger sequencing and high-throughput sequencing technology, respectively. Together with 31 E5 VP1 sequences and 2 WGSs downloaded from GenBank, a total of 33 complete VP1 sequences and 4 WGSs were used for genetic characterization and evolutionary analysis. Phylogenetic analysis revealed five genotypes (A-E) based on complete VP1 sequences. Evolutionary analysis showed that the time to the most recent common ancestor of E5 was approximately 1952 (95% highest posterior density [HPD] range, 1948-1953]), with a mean substitution rate of 7.74 × 10^-3 subs/site/year (95% HPD range, 6.44-9.11 × 10^-3). In addition, the WGS analyses showed that the nucleotide and amino acid similarities of the coding regions of the two strains obtained in this study with the prototype of the E5 strain Noyce were 80.2% and 97.2%, respectively. Recombination analysis showed that the two E5 strains may have intraspecific recombination with E6, EV-B85, and CVA9 serotypes in the nonstructural region. This study reports the isolation of E5 from SARI cases for the first time, and genetic characterization and evolutionary analysis provide valuable information on global E5 molecular epidemiology.IMPORTANCEThis study is the first report of echovirus 5 (E5) associated with severe acute respiratory infection and obtained the first E5 whole-genome sequence in China. Combined with the sequences available in the GenBank database, the first genotyping, phylogenetic characteristics, recombination, and genetic evolutionary analysis of E5 was performed in this study. Our findings providing valuable information on global E5 molecular epidemiology.

PMID:37819138 | DOI:10.1128/spectrum.01711-23
Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application

Fetched: October 11th, 2023, 5:03am GMT by Natalia Banaszek

J Cancer Res Clin Oncol. 2023 Dec;149(19):17635-17649. doi: 10.1007/s00432-023-05441-3. Epub 2023 Oct 10.

ABSTRACT

Sarcomas are a diverse group of malignant neoplasms of mesenchymal origin. They develop rarely, but due to poor prognosis, they are a challenging and significant clinical problem. Currently, available therapeutic options have very limited activity. A better understating of sarcomas' pathogenesis may help develop more effective therapies in the future. The Sonic hedgehog (Shh) signaling pathway is involved in both embryonic development and mature tissue repair and carcinogenesis. Shh pathway inhibitors are presently used in the treatment of basal cell carcinoma. Its increased activity has been demonstrated in many sarcomas, including osteosarcoma, Ewing sarcoma, chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma, and malignant rhabdoid tumor. In vitro studies have demonstrated the effectiveness of inhibitors of the Hedgehog pathway in inhibiting proliferation in those sarcomas in which the components of the pathway are overexpressed. These results were confirmed by in vivo studies, which additionally proved the influence of Shh pathway inhibitors on limiting the metastatic potential of sarcoma cells. However, until now, the efficacy of sarcomas treatment with Shh pathway inhibitors has not been established in clinical trials. The reason for that may be the non-canonical activation of the pathway or interactions with other signaling pathways, such as Wnt or Notch. In this review, we present the Shh signaling pathway's role in the pathogenesis of sarcomas, including both canonical and non-canonical signaling. We also propose how this knowledge could be potentially translated into clinics.

PMID:37815662 | PMC:PMC10657326 | DOI:10.1007/s00432-023-05441-3
Significance of fusion status, Oberlin risk factors, local and maintenance treatment in pediatric and adolescent patients with metastatic rhabdomyosarcoma: Data of the European Soft Tissue Sarcoma Registry SoTiSaR

Fetched: October 11th, 2023, 5:03am GMT by Amadeus T Heinz

Pediatr Blood Cancer. 2023 Oct 9:e30707. doi: 10.1002/pbc.30707. Online ahead of print.

ABSTRACT

BACKGROUND: Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis.

PROCEDURE: Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radiotherapy (RT) excluding total lung irradiation (TLI), complete resection of the primary tumor, and metastasectomy if possible. Kaplan-Meier estimators and Cox proportional hazard models were used to examine event-free survival (EFS) and overall survival (OS) involving also landmark analyses.

RESULTS: In the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018), 211 patients were analyzed. Many patients had fusion-positive alveolar RMS (n = 83; 39%). Median age was 9.4 years [0.1-19.7 years]. Treatment primarily consisted of CHT with CEVAIE (carboplatin, epirubicine, vincristine, actinomycin-D, ifosfamide, etoposide: 86%, other regimens: 14%), RT (71%), resection of primary tumor (37%), metastasectomy (19%), and lymph node sampling/dissection (21%). Maintenance treatment (MT) (oral trofosfamide, idarubicin, etoposide) was added in 74% of patients. Oberlin factors, fusion status, and MT were predictive for EFS and OS. MT with O-TIE was not improving outcome when adjusting for the immortal time bias. Local treatment of the primary tumor and radical irradiation (except TLI) improved EFS, not OS, when adjusting for the Oberlin score. Patients with fusion-negative alveolar RMS (n = 9) had an excellent outcome with a 5-year EFS and OS of 100%, compared to patients with embryonal RMS (49%/62%), PAX7- (22%/47%) and PAX3/FOXO1-positive ARMS (10/13%), respectively (p < .001).

CONCLUSIONS: Prognosis of metastatic RMS primarily depends on fusion status and Oberlin score. Fusion status needs to be considered in future trials to optimize treatment outcome. The role of radical irradiation needs further investigation.

PMID:37814424 | DOI:10.1002/pbc.30707
Surgical management of a laryngeal rhabdomyosarcoma in a cat

Fetched: October 10th, 2023, 5:04am GMT by Akash Alexander

JFMS Open Rep. 2023 Oct 6;9(2):20551169231194318. doi: 10.1177/20551169231194318. eCollection 2023 Jul-Dec.

ABSTRACT

CASE SUMMARY: An 11-year-old male castrated British Shorthair was referred for investigations into an upper respiratory tract mass. A partial laryngectomy was performed to excise the mass. Marginal resection of the mass involved excision of parts of the thyroid cartilage and left arytenoid cartilage. A tracheostomy tube was maintained for 48 h postoperatively. The cat recovered without complication and was discharged at 72 h postoperatively. Histopathology of the mass was deemed most consistent with a rhabdomyosarcoma (RMS).

RELEVANCE AND NOVEL INFORMATION: Telephone follow-up 12 months postoperatively confirmed resolution of the clinical signs. To our knowledge, this is the first report of a laryngeal RMS in a cat. RMS should be considered a differential diagnosis for a laryngeal mass in a cat. This case demonstrates that resection via a partial laryngectomy may be a viable therapeutic option.

PMID:37810575 | PMC:PMC10559712 | DOI:10.1177/20551169231194318
A Masquerading Hematoma Resulting in the Delayed Diagnosis of a Soft Tissue Sarcoma: A Case Report

Fetched: October 10th, 2023, 5:04am GMT by Matthew E Wells

Cureus. 2023 Sep 7;15(9):e44822. doi: 10.7759/cureus.44822. eCollection 2023 Sep.

ABSTRACT

A 27-year-old male with insidious right arm swelling was diagnosed with a hematoma secondary to a partial biceps tear, later identified as a rhabdomyosarcoma. Soft tissue sarcomas (STS) may present with misleading patient histories and nonspecific symptoms, resulting in misdiagnosis and delayed treatment. One of the classic masqueraders of soft tissue sarcomas is hematomas secondary to trauma. Obtaining a prudent history with careful scrutiny of appropriate imaging often helps establish the correct diagnosis. Ultimately, tissue biopsy can resolve any ambiguous cases and prevent delays in diagnosis and treatment.

PMID:37809226 | PMC:PMC10559263 | DOI:10.7759/cureus.44822
Financial costs of pediatric cancer management in Africa: systematic review

Fetched: October 10th, 2023, 5:04am GMT by Criss Koba Mjumbe

Front Public Health. 2023 Sep 22;11:1175560. doi: 10.3389/fpubh.2023.1175560. eCollection 2023.

ABSTRACT

The high costs of cancer treatment and the lack of investment in health care are significant barriers to public health on the African continent. The objective of this study was to investigate the financial cost of children cancer treating in sub-Saharan Africa. We systematically searched PubMed, Cochrane, and Google Scholar to identify relevant studies between March 2000 and December 2022. We selected articles that specifically addressed the US dollar financial costs of childhood cancer in African countries. Medians and interquartile ranges (IQR) were calculated. We also calculated the economic burden of childhood cancer at the individual level, by dividing the direct costs of cancer per patient by the GDP per capita, PPP of the country studied. The quality of economic studies was assessed using the CHEERS (2022) 28-point checklist. A total of 17 studies met our eligibility criteria. The median (IQR) of total childhood cancer costs by region was $909.5 ($455.3-$1,765) and ranged from $88803.10 for neuroblastoma to $163.80 for lymphoma. No significant differences (p < 0.05) were observed for comparisons of the direct cost of childhood cancer between the geopolitical zone of sub-Saharan Africa. Differences in the direct costs of childhood cancer were significant for different cancer types (p < 0.05). In the majority of 17 out of 54 countries on Africa the continent, the economic burden of childhood cancer exceeds 80% of GDP per capita, PPP, up to 345.38% of Nigeria's GDP for Rhabdomyosarcoma. The cost of treating childhood cancers is high in Africa is catastrophic, if not downright prohibitive for households in Sub-Saharan Africa. We believe that the data from our study will be able to help make different objective advocacy allowing it to be provided with funds based of the evidence that can strengthen this program in order to install cancerology structures in the countries and by following the system plan. Cost reduction in the treatment of childhood cancer in particular and in general all types of cancer.

SYSTEMATIC REVIEW REGISTRATION: Approval of the study was given by the ethics committee of the Faculty of Medicine of the University of Lubumbashi (UNILU/CEM/135/2018) and (UNILU/CEM/096/2019).

PMID:37808990 | PMC:PMC10556248 | DOI:10.3389/fpubh.2023.1175560
Trans-Orbital EUS (with videos)

Fetched: October 9th, 2023, 5:02am GMT by Joshua L Hudson

Gastrointest Endosc. 2023 Oct 6:S0016-5107(23)02956-5. doi: 10.1016/j.gie.2023.10.021. Online ahead of print.

ABSTRACT

A 31-year-old male presented with acute cholecystitis and history of metastatic alveolar rhabdomyosarcoma. He previously underwent left orbital exenteration and facial radiation. Given the patient's malnutrition, he was deemed a non-surgical candidate. The patient chose to pursue EUS-guided gallbladder drainage. Due to radiation-induced trismus, he was not able to open his mouth more than 5mm. Bougie dilation of an existing gastrostomy was considered, however there was concern for poor healing and gastrostomy leak. A discussion with his otolaryngologist revealed that because his left eye and surrounding bone were surgically removed, the left orbit gave direct access to the oropharynx. Therefore, transorbital intubation and endoscopy were pursued (A) (Video). Initially, neither the echoendoscope nor wire were able to intubate the esophagus antegrade due to radiation-associated scarring. A neonatal gastroscope was passed retrograde through the gastrostomy, up the esophagus, and into the orbit (B, C). A long 0.025-inch wire was passed and a forward-viewing echoendoscope was reinserted through the orbit over the wire. Esophageal intubation was successful by following a wire-guided balloon inflated to 13.5mm (D). An EUS-guided cholecystoduodenostomy was then performed. The patient tolerated the procedure well and discharged the day after without adverse events. The patient consented to publication.

PMID:37806402 | DOI:10.1016/j.gie.2023.10.021
Diagnosis of uterine sarcomas and rare uterine mesenchymal tumours with malignant potential. Guidelines of the French Sarcoma Group and Rare Gynaecological Tumours

Fetched: October 9th, 2023, 5:02am GMT by Sabrina Croce

Bull Cancer. 2023 Oct 6:S0007-4551(23)00348-X. doi: 10.1016/j.bulcan.2023.08.002. Online ahead of print.

ABSTRACT

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

PMID:37806863 | DOI:10.1016/j.bulcan.2023.08.002
Cytopathology of mesenchymal tumors of the thyroid gland: analysis of 12 cases from multinational institutions with review of the literature

Fetched: October 9th, 2023, 5:02am GMT by Carla Saoud

J Am Soc Cytopathol. 2023 Sep 13:S2213-2945(23)00225-9. doi: 10.1016/j.jasc.2023.09.004. Online ahead of print.

ABSTRACT

INTRODUCTION: Mesenchymal tumors of the thyroid gland are extremely rare. We report the cytomorphologic characteristics of 12 mesenchymal tumors occurring in the thyroid gland and highlight the diagnostic difficulties encountered in their cytologic evaluation.

MATERIALS AND METHODS: The cytopathology and surgical pathology archives from 5 large institutions were searched for thyroid mesenchymal tumors that had an FNA available for review. Clinicopathologic and cytomorphologic characteristics for each case were evaluated.

RESULTS: Twelve cases of mesenchymal tumors occurring in the thyroid were identified in our search. Patient age ranged from 28 to 84 years (median, 60 years). The cases occurred in 7 women and 5 men. The tumor size ranged from 1.4 to 14 cm (median, 3.3 cm). The tumors were as follows: hemangioma (n = 4; 33.3%), angiosarcoma (n = 2; 16.7%), schwannoma (n = 2; 16.7%), solitary fibrous tumor (n = 2, 16.7%), metastatic synovial sarcoma (n = 1, 8.3%) and metastatic pleomorphic rhabdomyosarcoma (n = 1, 8.3%). The cytomorphologic features of the tumors were similar to those of their counterparts occurring in different sites. An accurate diagnosis was achieved in six primary thyroid mesenchymal cases (60%). Five patients (41.7%) underwent total thyroidectomy, and 3 patients received partial thyroidectomy (25%). Three patients (25%) did not receive a thyroidectomy and subsequent surgical information was not available in 1 case (8.3%).

CONCLUSIONS: Mesenchymal tumors of the thyroid are extremely uncommon. Cytologic diagnosis of these tumors is often challenging due to the morphologic overlap with diverse epithelial and non-epithelial thyroid lesions. Ancillary studies such as immunohistochemistry and molecular studies are essential for accurate diagnosis.

PMID:37806808 | DOI:10.1016/j.jasc.2023.09.004
Successful Use of Acellular Small Intestinal Submucosa Graft in Vaginal Reconstruction

Fetched: October 7th, 2023, 5:02am GMT by Steven T Papastefan

J Pediatr Surg. 2023 Sep 12:S0022-3468(23)00521-3. doi: 10.1016/j.jpedsurg.2023.08.021. Online ahead of print.

ABSTRACT

PURPOSE: Various techniques for neovaginal construction have been employed in the pediatric and adult populations, including the use of intestinal segments, buccal mucosal grafts, and skin grafts. Small intestinal submucosa (SIS) extracellular matrix grafts have been described as a viable alternative, though prior experience is limited. Our purpose was to assess operative characteristics and patient outcomes with neovaginal construction using SIS grafts.

METHODS: Thirteen patients underwent vaginoplasty with acellular porcine SIS grafts at our institution between 2018 and 2022. Operative and clinical data, postoperative mold management, vaginal dilating length, and complications were reviewed.

RESULTS: Age at time of repair ranged from 13 to 30 years (median 19 years). Patient diagnosis included cloacal anomalies (n = 4), Mayer-Rokitansky-Küster-Hauser syndrome (n = 4), isolated vaginal atresia with or without a transverse vaginal septum (n = 4), and vaginal rhabdomyosarcoma requiring partial vaginectomy (n = 1). Following dissection of the neovaginal space, a silicon mold wrapped with SIS graft was placed with retention sutures and removed on postoperative day 7. Median (IQR) operative time was 171 (118-192) minutes, estimated blood loss was 10 (5-20) mL, and length of stay was 2 (1-3) days. The follow-up period ranged from 3 to 47 months (median 9 months). Two patients developed postoperative vaginal stenosis that resolved with dilation under anesthesia. Mean vaginal length on latest follow-up was 8.97 cm. All thirteen patients had successful engraftment and progressed to performing self-dilations or initiating intercourse to maintain patency. There were no cases of graft reaction or graft extrusion.

CONCLUSIONS: We conclude that acellular small intestinal submucosa grafts are effective and safe alternatives for mold coverage in neovaginal construction. Our experience demonstrates minimal perioperative morbidity, early mold removal, and progression to successful dilation with maintenance of a functional vaginal length. Future study on sexual outcomes, patient satisfaction, and comparison against alternative techniques has been initiated.

LEVEL OF EVIDENCE: IV.

TYPE OF STUDY: Retrospective Study.

PMID:37802758 | DOI:10.1016/j.jpedsurg.2023.08.021
Impact of Consolidative Radiation on Overall and Progression Free Survival in Pediatric, Adolescent and Young Adult Metastatic Bone and Soft Tissue Sarcoma

Fetched: October 6th, 2023, 5:03am GMT by Leslie Chang

Int J Radiat Oncol Biol Phys. 2023 Oct 3:S0360-3016(23)07920-8. doi: 10.1016/j.ijrobp.2023.09.007. Online ahead of print.

ABSTRACT

PURPOSE: To determine the association between consolidative radiation (RT) and survival in children, adolescents, and young adults with metastatic sarcoma.

METHODS AND MATERIALS: Eligibility criteria included patients aged ≤39 years with newly diagnosed metastatic bone or soft tissue sarcoma who completed local control of the primary tumor without disease progression. Consolidative RT was defined as RT to all known sites of metastatic disease. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The least absolute shrinkage and selection operator Cox provided adjusted estimates. To account for immortal time bias, consolidative RT was used as a time-varying covariate in a time dependent Cox model. Distant failure was estimated using the Fine-Gray model.

RESULTS: Patients (n = 85) had a median age at diagnosis of 14.8 years. Most common histology was Ewing Sarcoma (45.9%) followed by rhabdomyosarcoma (40.0%). Receipt of consolidative RT was associated with Ewing Sarcoma (P < .001) and local control modality as those who underwent local control with surgery and RT compared with surgery alone were more likely to be treated with consolidative RT (P = .034). Consolidative RT was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.17-0.98; P = .045) and improved PFS (HR, 0.37; 95% CI, 0.16-0.88; P = .024) after adjusting for confounding variables and immortal time bias. Patients treated with consolidative RT also experienced a lower risk of distant failure (HR, 0.33; 95% CI, 0.17-0.64; P = .001). In an independent data set of patients with metachronous progression (n = 36), consolidative RT remained independently associated with improved OS.

CONCLUSIONS: Consolidative RT was independently associated with improved OS and PFS and decreased risk of distant failure in child, adolescent, and young adult patients with metastatic sarcoma. Future work should evaluate biomarkers to optimize patient selection, timing, and dose for consolidative RT.

PMID:37797747 | DOI:10.1016/j.ijrobp.2023.09.007
Network pharmacology-based exploration identified the antiviral efficacy of Quercetin isolated from mulberry leaves against enterovirus 71 via the NF-κB signaling pathway

Fetched: October 6th, 2023, 5:03am GMT by Tianrun Liu

Front Pharmacol. 2023 Sep 19;14:1260288. doi: 10.3389/fphar.2023.1260288. eCollection 2023.

ABSTRACT

Introduction: Mulberry leaf (ML) is known for its antibacterial and anti-inflammatory properties, historically documented in "Shen Nong's Materia Medica". This study aimed to investigate the effects of ML on enterovirus 71 (EV71) using network pharmacology, molecular docking, and in vitro experiments. Methods: We successfully pinpointed shared targets between mulberry leaves (ML) and the EV71 virus by leveraging online databases. Our investigation delved into the interaction among these identified targets, leading to the identification of pivotal components within ML that possess potent anti-EV71 properties. The ability of these components to bind to the targets was verified by molecular docking. Moreover, bioinformatics predictions were used to identify the signaling pathways involved. Finally, the mechanism behind its anti-EV71 action was confirmed through in vitro experiments. Results: Our investigation uncovered 25 active components in ML that targeted 231 specific genes. Of these genes, 29 correlated with the targets of EV71. Quercetin, a major ingredient in ML, was associated with 25 of these genes. According to the molecular docking results, Quercetin has a high binding affinity to the targets of ML and EV71. According to the KEGG pathway analysis, the antiviral effect of Quercetin against EV71 was found to be closely related to the NF-κB signaling pathway. The results of immunofluorescence and Western blotting showed that Quercetin significantly reduced the expression levels of VP1, TNF-α, and IL-1β in EV71-infected human rhabdomyosarcoma cells. The phosphorylation level of NF-κB p65 was reduced, and the activation of NF-κB signaling pathway was suppressed by Quercetin. Furthermore, our results showed that Quercetin downregulated the expression of JNK, ERK, and p38 and their phosphorylation levels due to EV71 infection. Conclusion: With these findings in mind, we can conclude that inhibiting the NF-κB signaling pathway is a critical mechanism through which Quercetin exerts its anti-EV71 effectiveness.

PMID:37795035 | PMC:PMC10546324 | DOI:10.3389/fphar.2023.1260288
Multi-Institutional Experience of Proton Therapy for Rhabdomyosarcoma and Ewing Sarcoma in the Proton Collaborative Group (PCG) Prospective Registry

Fetched: October 4th, 2023, 5:03am GMT by K Von Werne

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e551-e552. doi: 10.1016/j.ijrobp.2023.06.1857.

ABSTRACT

PURPOSE/OBJECTIVE(S): To report on outcomes, acute toxicities, and the use of dose-escalation with proton therapy (PT) in patients with rhabdomyosarcoma and Ewing sarcoma in a prospective multi-institutional registry (PCG).

MATERIALS/METHODS: Data on patients with primary rhabdomyosarcoma and Ewing sarcoma treated with definitive PT (defined as ≥45 Gy) were queried from the PCG registry. A similar query was performed of our institutional database with IRB approval. Overall survival rates were calculated by Kaplan-Meier. Toxicities were scored using CTCAE v4.0.

RESULTS: A total of 354 patients across 10 institutions (203 rhabdomyosarcoma, 151 Ewing sarcoma) met the eligibility criteria. Median age was 9 years (Interquartile Range: 5-15). Median dose was 50.4 GyRBE for rhabdomyosarcoma patients (Range: 45-66 GyRBE) and 55.8 GyRBE for Ewing sarcoma patients (Range: 45-66 GyRBE). Median follow-up was 2.4 years (Range 0.3-12.3 years). Two-year overall survival rates were 81.1% (95% CI: 73.7%-88.5%) for rhabdomyosarcoma and 79.1% (95% CI: 71.7%-86.2%) for Ewing sarcoma. The Table lists the prescription doses delivered by tumor histology; 28.1% of rhabdomyosarcoma and 21.9% of Ewing sarcoma patients, respectively, received dose-escalated radiotherapy (defined as >50.4 Gy for rhabdomyosarcoma and >55.8 Gy for Ewing sarcoma). Excluding alopecia and skin desquamation, 153 patients (43.2%) developed any acute grade 2+ non-hematologic toxicity, while 49 patients (13.8%) developed one or more grade 3 toxicities. The most common grade 3 toxicities were anorexia/weight loss (7.3%), pain (7.3%) mucositis/esophagitis (4.8%), and nausea/vomiting (3.1%). One grade 4 toxicity (esophagitis) and no deaths were reported during treatment.

CONCLUSION: In this multi-institutional prospective registry, 28.1% of rhabdomyosarcoma and 21.9% of Ewing sarcoma patients received dose-escalated PT, with 13.8% of patients developing grade 3 toxicities. Long-term outcomes for disease control and late toxicity and anticipated cooperative group trial results are needed to fully assess the benefits and risks of dose-escalated radiotherapy for these tumors.

PMID:37785696 | DOI:10.1016/j.ijrobp.2023.06.1857
Treatment of Recurrent Orbital Rhabdomyosarcoma with Exenteration and HDR Brachytherapy in a Custom Mold

Fetched: October 4th, 2023, 5:03am GMT by C Jackson

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e520-e521. doi: 10.1016/j.ijrobp.2023.06.1789.

ABSTRACT

PURPOSE/OBJECTIVE(S): Rhabdomyosarcoma (RMS) is the most frequent cancer affecting the orbit in children. The orbit is classified as a favorable site for RMS as treatment with chemotherapy and radiation is effective. Local failure for patients with RMS of the orbit has ranged from 2-16% on IRS and COG protocols. In the event of local recurrence, survival is poor, and management is difficult. We report four patients with local recurrence of orbital RMS managed with orbital exenteration followed by high dose rate (HDR) brachytherapy.

MATERIALS/METHODS: Four patients were treated from 2016-2022. HDR brachytherapy with Ir-192 was delivered in a custom mold of the orbit made after the orbital exenteration procedure. Brachytherapy was given in 6-7 twice daily (BID) fractions starting 1 week after the orbital exenteration.

RESULTS: At the time of brachytherapy, patient ages were 3, 1, 7, and 7 years. Three patients had embryonal histology and underwent initial systemic therapy with ARST0331 regimen A. The fourth patient had alveolar, FOXO1 fusion positive RMS and was initially treated as per COG D9803 regimen A. All patients had received proton radiotherapy as part of initial treatment. Three received 50.40 Gy and one received 45 Gy. Patients developed biopsy-proven, recurrent disease an average of 56 weeks (range 38-77) after initial diagnosis. All patients received salvage chemotherapy before undergoing orbital exenteration at an average of 12 weeks after recurrence (range 5-16). Three patients received 30 Gy in 6 BID fractions, and one patient received 28 Gy in 7 fractions with HDR brachytherapy using an Ir-192 source. All four patients are alive without evidence of disease at an average of 27 months (range 6-70) from recurrence and 39 months (range 21-78) from initial diagnosis. All patients have acceptable orbit healing. Two patients have asymptomatic evidence of frontal lobe edema (and in one case possible necrosis) extending 1-2 cm above the orbit. This appears to be beyond the range of the brachytherapy dosimetry, but the combination of proton beam and brachytherapy are implicated. No other toxicities have occurred.

CONCLUSION: Orbital RMS has a favorable prognosis, but local failure after initial combined modality therapy can be fatal. Options for successful local salvage are limited. Orbital exenteration with HDR brachytherapy in a custom mold is an effective and safe procedure for local control in these difficult cases.

PMID:37785622 | DOI:10.1016/j.ijrobp.2023.06.1789
Patterns of Failure in Pediatric and Young Adult Rhabdomyosarcoma

Fetched: October 4th, 2023, 5:03am GMT by R Bhatia

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e504. doi: 10.1016/j.ijrobp.2023.06.1752.

ABSTRACT

PURPOSE/OBJECTIVE(S): To characterize patterns of failure in pediatric and young adult patients with rhabdomyosarcoma (RMS) from a single institution with over 20 years of experience.

MATERIALS/METHODS: Patients diagnosed with RMS from 2000 to 2022 were identified retrospectively. Time to failure was calculated from diagnosis. Local only failure was defined as first failure at the primary site without distant failure. Distant failure was defined as first failure outside of the primary site with or without local failure. Cumulative incidence (CI) of failure was calculated using death as a competing risk. Fine-Gray regression was used to evaluate impact of prognostic factors.

RESULTS: Ninety-five patients were eligible. Median age was 7.28 years (range 0 - 35 years), 41% of patients were >10 years old. Median follow up was 33.3 months. Approximately half (n = 47, 49.5%) of the tumors demonstrated alveolar histology. FOXO1 fusion status was available in 76 (80%) patients, of which 7 out of 37 alveolar tumors (18.9%) were FOXO1 fusion negative. The majority of tumors presented with unfavorable primary site (n = 72, 75.8%) and advanced stage (Stage III and IV, n = 72, 75.8%). The 5-yr CI of local only failure and distant failure for the entire cohort was 19.0% (95% CI 11.3, 28.3) and 34.6% (24.0, 45.5%), respectively. The predominant pattern of failure by Group was: Groups 1&2: Local only (5yr CI 14.8%), Group 3: Distant (5yr CI: 25.9%), Group 4: Distant (5yr CI: 67.6%). CI of distant failure by primary site was higher in perianal/gluteal (n = 2/5, 5yr CI 60.0%) and extremity (n = 8/19, 5yr CI 45.9%) sites. Of the 28 distant failures, 10 (36%) also had a local failure component. CI of local only failure by primary site was higher in parameningeal head and neck (n = 6/25, 5yr CI 30%) and bladder/prostate (n = 2/12, 5yr CI 23%) sites. The following were associated with an increased CI of distant failures: increasing age (HR 1.08, p<0.01), alveolar vs. embryonal histology (HR 3.01, p = 0.0095), FOXO1 fusion positive vs. negative (HR 2.8, p = 0.02) and Group IV vs. Groups I/II (HR 7.7, p = 0.0007). FOXO1 fusion and alveolar histology were associated with older age and Group IV, both of which were independently associated with increased distant failure on multivariate analysis.

CONCLUSION: Failures were predominantly distant in older patients and patients with Group IV RMS, both of which were associated with FOXO1 fusion and alveolar histology, highlighting the need to improve therapies in this population. Local only failures were highest in parameningeal head and neck and bladder/prostate primaries, highlighting the need to improve local control strategies at these sites.

PMID:37785583 | DOI:10.1016/j.ijrobp.2023.06.1752
Comparison of Survival Outcomes between Adults and Pediatrics with Non-Metastatic Head and Neck Rhabdomyosarcoma: A SEER Database Analysis of 550 Patients

Fetched: October 4th, 2023, 5:03am GMT by T Zou

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):e361. doi: 10.1016/j.ijrobp.2023.06.2449.

ABSTRACT

PURPOSE/OBJECTIVE(S): Despite the long-term survival rate for children with head and neck rhabdomyosarcoma (HNRMS) has improved to over 70-80% due to advancements in therapeutic approaches, the survival outcomes for adult HNRMS have not been thoroughly investigated. Our study aims to compare and analyze the survival outcomes of adult and pediatric patients with non-metastatic HNRMS, with a focus on the effect of different local treatment methods on disease outcomes.

MATERIALS/METHODS: We conducted a retrospective analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database covering the period from 2004 to 2018. Our study population consisted of patients with Head and Neck Rhabdomyosarcoma (HNRMS) who had not developed distant metastases and received at least one local treatment, either radiotherapy or surgery. The comparison of overall survival (OS) and cancer-specific survival (CSS) was performed between the adult and pediatric patient groups, and between patients who received surgery (with or without radiotherapy) and those who received radiotherapy only (non-surgery).

RESULTS: In the study of 550 patients diagnosed with Head and Neck Rhabdomyosarcoma (HNRMS), data was collected from 181 (32.9%) adult and 369 (67.1%) pediatric patients. The results showed that the adult patient group had a significantly worse outcome compared to the pediatric group in terms of 5-year overall survival (OS) rate (34.9% vs 81.6%, P<0.001) and 5-year cancer specific survival (CSS) rate (59.96% vs 87.48%, P<0.001). Of these patients, 308(56%) underwent radical surgery, with 228 (41.5%) receiving a combination of radiation and surgery and the remaining 242 (44%) receiving radiation therapy alone. No significant differences were found in 5-year OS and CSS rates between the surgery and non-surgery (radiation only) groups in adult patients (34.9% vs 35.0%, P = 0.900; 60.2% vs 59.6%, P = 0.988). However, there were slight differences observed in the pediatric patient group, with the 5-year OS and CSS rates being higher for the surgery group compared to the non-surgery group (86.9% vs 75.9%, P = 0.001 and 90.6% vs 84.2%, P = 0.054, respectively).

CONCLUSION: The results of this cohort study indicate that age plays a crucial role in predicting survival outcomes in patients diagnosed with Head and Neck Rhabdomyosarcoma (HNRMS). The findings highlight the need for age-specific treatment strategies for HNRMS patients. While the data suggests that radiotherapy may be a viable first-line option for non-metastatic adult HNRMS patients, additional research is required to validate these trends.

PMID:37785242 | DOI:10.1016/j.ijrobp.2023.06.2449
High-Dose-Rate Brachytherapy for Vaginal Rhabdomyosarcoma (RMS): Lessons Learned at a Single Institution

Fetched: October 4th, 2023, 5:03am GMT by K Lapen

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S77. doi: 10.1016/j.ijrobp.2023.06.392.

ABSTRACT

PURPOSE/OBJECTIVE(S): Botryoid RMS is a rare pediatric tumor most commonly arising within the vaginal wall of girls under age three. Most patients are successfully treated with low-risk chemotherapy protocols but local treatment is required to minimize risk of local relapse. Intravaginal brachytherapy is an effective local therapy that can minimize sequelae in these very young patients.

MATERIALS/METHODS: We reviewed records of all patients with RMS who received intravaginal high-dose-rate brachytherapy from 2010-2022 at a single institution. All were treated with multiagent chemotherapy with or without minor surgical procedures, and had no gross disease prior to intravaginal brachytherapy. All patients underwent CT simulation under anesthesia and optimal-sized cylindrical applicators were chosen based on patient anatomy.

RESULTS: Twelve girls, median age 23 months (range 3-33), were treated with daily anesthesia. All were Stage 1 and 92% had Group III disease. A single patient had Group IIA disease based on up-front resection. Early in the series, 5 patients received 21 Gy in 7 fractions according to COG protocol guidelines. Subsequent patients received higher doses of 28-30 Gy in 7-10 fractions. Custom sized cylinders were used with diameters ranging from 1.2-1.6 cm and dose was prescribed to a median depth of 3 mm. Median mean dose to the rectum, bladder, uterus, and bilateral ovaries was 8.7 Gy, 7.2 Gy, 6.9 Gy, and 5.0 Gy, respectively. Median follow-up was 4 years (range 1-10). No acute or late side effects have occurred. At follow-up, three girls were of pubescent age, all three exhibited signs of puberty and two had reached menarche. Three girls (25%) suffered local relapse at a median of 15 months (range 5-16 months) after brachytherapy. One-year and five-year local control rates were 92% (95% CI 54-99%) and 70% (95% CI 32-89%), respectively. All relapses were in patients receiving 21 Gy and two were beyond full dose coverage of brachytherapy at the introitus and in the uterus. Subsequent patients receiving higher doses and full coverage of the vagina have had no local failures. Two of three patients who failed were cured with salvage therapy resulting in one-year and five-year overall survival rates of 100% and 86% (95% CI 33-98%), respectively.

CONCLUSION: Intravaginal high-dose-rate brachytherapy is an excellent option for local control of vaginal RMS with fewer long-term risks than external beam proton therapy or radical surgery. A dose of 28 Gy in 7 fractions prescribed to the entire vagina is necessary for optimal prevention of relapse. Longer follow-up is needed to confirm preservation of ovarian, reproductive, and sexual function.

PMID:37784573 | DOI:10.1016/j.ijrobp.2023.06.392
Long Term Clinical Outcome and Quality of Life of Children, Adolescents and Young Adults Treated with Pencil Beam Scanning Proton Therapy for Rhabdomyosarcoma

Fetched: October 4th, 2023, 5:03am GMT by D Leiser

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S77. doi: 10.1016/j.ijrobp.2023.06.391.

ABSTRACT

PURPOSE/OBJECTIVE(S): To assess the long-term clinical outcomes of children, adolescents and young adults (CAYAs) with rhabdomyosarcoma (RMS) treated with pencil beam scanning proton therapy (pbsPT).

MATERIALS/METHODS: One hundred twenty-one RMS (embryonal, n = 102; 84.3%) patients treated between January 2000 and December 2020 were included in this analysis. The median age was 4.7 years (range, 0.1-35.3). All patients received systemic chemotherapy according to prospective protocols. The median total dose delivered was 54 Gy (RBE) (range, 41.4-74.0).

RESULTS: After a median follow-up time of 85.5 month (range,3.4-240.0), we observed 23 local/regional and 12 distant failures. The estimated 5-year local control (LC) and overall survival (OS) was 81.5% and 80%, respectively. For the subgroups of parameningeal (PM), orbital, urogenital and H&N non-PM the 5-year LC was 74.7%, 92%, 100% and 66.7%. The corresponding figures for OS were 68.8%, 100%, 100%, and 66.7, respectively. The 5-year non-ocular Grade 3 toxicity free survival was 78.9%. At the start of pbsPT children and their caregivers reported QoL significantly worse than the norm group. QoL improved however over the follow up period to normal values in nearly all domains. Median of PEDQOL PROXY reported QoL in Normgroup (children: 4- 18 yrs) and RMS patients (n = 27-42 answers per domain): CONCLUSION: Excellent clinical outcome was observed for CAYAs with RMS treated with pbsPT. Two thirds of treatment failures were local. High-grade late non-ocular toxicity was manageable. QoL improved towards normal scores in nearly all domains after therapy.

PMID:37784572 | DOI:10.1016/j.ijrobp.2023.06.391
State Mandatory Paid Family Leave and Survival among Children with Cancer

Fetched: October 4th, 2023, 5:03am GMT by J M Barnes

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S16-S17. doi: 10.1016/j.ijrobp.2023.06.235.

ABSTRACT

PURPOSE/OBJECTIVE(S): Childhood cancer treatment is often costly and time intensive and may require parents/caregivers to stop working. Since 2012, several states have introduced mandatory paid family leave policies. We hypothesized that such policies, whether by reducing financial toxicity or by providing parents greater flexibility to care for their sick children, would improve outcomes among children with cancer.

MATERIALS/METHODS: Children ages 0-18 years diagnosed with cancer between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results program (SEER) database. The primary outcome was overall survival (OS). The exposure of interest was state mandatory paid family leave. Difference-in-differences (DID) analyses with additive hazards regression models were utilized to compare changes in OS from pre- to post- mandatory paid sick leave policy implementation in states with vs. without paid sick leave policies. The models were adjusted for year fixed effects, state fixed effects, state Medicaid expansion status, age, race, sex, metropolitan residence status, county-level income and education, cancer site, cancer stage, and insurance status. Clustered standard errors by state were achieved via the cluster bootstrap. The plausibility of the common trends assumption was tested using event study analyses and was satisfied for all analyses.

RESULTS: A total of 38,053 children with cancer were identified. In adjusted difference-in-differences analyses, there was no significant change in OS in states with vs. without state mandatory paid family leave policies after policy enactment (hazard difference: 0.0001, 95% CI = -0.0002 to 0.0016, P = .47). However, among non-metropolitan residents, 1-year OS improved from 93.0% to 95.5% (2-year OS: 88.6% to 93.4%) in states with mandatory paid family leave policies compared to 92.7% to 92.5% (2-year OS: 88.0% to 87.7%) in states without such policies after policy enactment. This translates to a 2.7% improvement in 1-year OS (5.2%, 2-year OS) (hazard difference: -0.0021, 95% CI = -0.0034 to -0.0005, P = .037). There was no corresponding change for metropolitan residents (hazard DID = 0.0001, P = .47). By cancer site, the largest policy-associated improvements in survival were observed for rhabdomyosarcoma (hazard DID = -0.0037, P = .11), osteosarcoma (hazard DID = -0.0036, P<.001), and Intracranial and intraspinal embryonal tumors (hazard DID = -0.0026, P = .061).

CONCLUSION: State mandatory paid family leave policies were associated with improved survival for some children with cancer, most notably for those residing in non-metropolitan areas. The improvements for non-metropolitan residents may be related to alleviating otherwise increased travel burdens for cancer treatment if treatment occurs out-of-town, where working while taking care of a child is less feasible. These data also suggest a slight narrowing in rural-urban-metropolitan childhood cancer disparities associated with paid family leave policies.

PMID:37784400 | DOI:10.1016/j.ijrobp.2023.06.235
Dawn of Staging for Head and Neck Soft Tissue Sarcoma: Validation of the Novel 8th Edition AJCC T Classification and Proposed Stage Groupings

Fetched: October 4th, 2023, 5:03am GMT by R R Salunkhe

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S149. doi: 10.1016/j.ijrobp.2023.06.567.

ABSTRACT

PURPOSE/OBJECTIVE(S): After decades of stagnation, the 8^th edition TNM (TNM8) introduced a new T classification for head and neck (HN) soft tissue sarcomas (STS). New size cutoffs of 2 and 4 cm define T1-3, and a novel T4 category is defined by local invasion of adjoining structures. These size cutoffs had been chosen arbitrarily to advance data collection in this unique disease site since literature showed approximately 70% of HN STS did not reach the previous size threshold (5 cm) for the existing T1 category. The definition of the TNM8 T categories also align with mucosal HN cancers. No stage grouping for HN STS was defined since this new classification required more data collection to derive stage groups. This study aims to validate the TNM8 T classification and to propose stage groupings.

MATERIALS/METHODS: Clinical data of all adult (>16 years) HN STS patients treated from 1988 - 2019 with curative intent in our tertiary cancer center were retrieved from a prospective database, and supplemented with chart review. As per TNM8, cutaneous angiosarcoma, embryonal and alveolar rhabdomyosarcoma, Kaposi sarcoma, and dermatofibrosarcoma protuberans were excluded due to their different behavior. Multivariate analysis (MVA) identified prognostic factors for overall survival (OS). Adjusted hazard ratios (AHR) and recursive partitioning analysis (RPA) were used to derive stage groupings. Stage grouping performance for OS was assessed and also compared against the existing TNM8 groups for non-HN STS.

RESULTS: A total of 221 patients (N1: 2; M1: 2) were included. Of the 219 M0 patients, 63% were males; median tumor size was 3.0 cm (range: 0.3-14.0); the proportion of TNM8 T1-T4 were 35%, 34%, 26%, and 5%, respectively. Median follow up was 5.9 years. Five-year OS was 79%. MVA confirmed the prognostic value of T category (T4 HR 7.73, 95% CI 3.62-16.5) and grade (G2/3 vs G1 HR 3.7, 95% CI 1.82-7.53), in addition to age (HR 1.03, 95% CI 1.01-1.04) (all p<0.001) for OS. AHR model derived T1-3_Grade 1 as stage 1; T1-3_Grade 2/3 as stage II; and T4_any Grade or any T_N1 as stage III (Table 1); the corresponding 5-year OS was 93%, 73%, and 38%, respectively. Both patients with M1 died within 1.5 years after diagnosis and M1 disease was designated stage IV. The AHR-grouping outperformed the RPA and non-HN TNM8 stage grouping for hazard consistency, hazard discrimination, percent variance explained, hazard difference, and sample size balance.

CONCLUSION: The novel T4 category introduced in TNM8 is associated with a >7 fold increased risk of death. Grade continues to be a critical prognostic factor in HN STS. The TNM8 HN STS T classifications have been validated, and the proposed new stage groupings with TNM8 incorporating grade have excellent performance for OS.

PMID:37784378 | DOI:10.1016/j.ijrobp.2023.06.567
Outcomes for Patients with Head and Neck Sarcoma Treated Curatively with Radiation Therapy and Surgery

Fetched: October 4th, 2023, 5:03am GMT by A K Yoder

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S149-S150. doi: 10.1016/j.ijrobp.2023.06.568.

ABSTRACT

PURPOSE/OBJECTIVE(S): Soft tissue sarcomas (STS) of the head and neck are rare and diverse entities that are challenging to manage. Definitive treatment requires surgery, often with radiation therapy (RT). We sought to describe the outcomes of patients treated curatively with surgery and RT for head and neck STS.

MATERIALS/METHODS: We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic STS of the head and neck between 1968 and 2020; over half were treated in the modern era defined as 2005 or after. Patients with rhabdomyosarcomas or cutaneous angiosarcoma were excluded. The Kaplan-Meier method was used to estimate actuarial overall survival (OS), disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVA) were conducted using Cox proportional hazards model.

RESULTS: Median follow-up was 82 months. Of the 192 patients, the majority were male (n = 111, 58%), White (n = 158, 82%), and median age was 49.5 [IQR 32.5-64]. The highest proportion of tumors were in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). The most common histology was sarcoma, not otherwise specified (n = 44, 23%), followed by undifferentiated pleomorphic sarcoma (n = 32, 17%), and neurogenic sarcoma (n = 15, 8%). Most patients were treated with postoperative RT (n = 134, 70%). Patients treated with preoperative RT were older (median 56.5 yrs vs post-op 44 yrs, p = 0.009). Post-op RT doses were higher (median 60 Gy, pre-op 50 Gy, p<0.001), and margins were more likely to be negative in those treated with pre-op RT (n = 39, 67%, post-op 69, 51%, p = 0.02). 5-year LC, DSS, and OS for the entire cohort was 76% (95% CI 69-82), 74% (67-80), and 71% (64-77), respectively. LC was not affected by treatment sequence (pre-op RT 78% (63-88), post-op RT 75% (66-82), p = 0.48). Patients with negative margins had improved 5-yr LC (86% (77-92), positive/uncertain 65% (53-74), p = 0.003). On MVA, positive/uncertain margin was the only variable associated with LC (HR 2.54 (1.34-4.82), p = 0.004). Poorer 5-yr DSS was associated with higher grade (grade 3 75% (63-84), grade 1-2 89% (75-94), p = 0.02), and treatment era (pre-2005 68% (57-76), on/after 2005 80% (70-87), p = 0.04). These both remained significant on MVA (grade 3 HR 2.39 (1.07-5.36), p = 0.034; pre-2005 HR 2.31 (1.03-5.21), p = 0.043). Sixteen patients (8%) developed a late RT toxicity, including fibrosis (n = 4, 2%), necrosis (osteoradionecrosis n = 2, brain necrosis n = 1, soft tissue necrosis n = 1), and eye dryness (n = 2, 1%). Neither the timing of RT nor dose was found to be associated with developing a late RT toxicity.

CONCLUSION: Head and neck STS continues to have relatively poorer local control than STS of the trunk or extremities. Timing of RT did not impact oncologic or long-term RT-related toxicity outcomes. However, more data are needed to ascertain whether preoperative RT may impact acute surgical toxicities. These data contribute to multidisciplinary care planning for patients with STS in these challenging anatomic locations.

PMID:37784377 | DOI:10.1016/j.ijrobp.2023.06.568
Impact of Consolidative Radiation on Overall and Progression Free Survival in Pediatric, Adolescent and Young Adult Metastatic Sarcoma

Fetched: October 4th, 2023, 5:03am GMT by L Chang

Int J Radiat Oncol Biol Phys. 2023 Oct 1;117(2S):S132-S133. doi: 10.1016/j.ijrobp.2023.06.484.

ABSTRACT

PURPOSE/OBJECTIVE(S): To determine the association between consolidative radiation and survival in pediatric, adolescent, and young adult (AYA) metastatic sarcoma MATERIALS/METHODS: Eligible patients included those diagnosed with metastatic bone or soft tissue sarcoma at ≤39 years of age. Patients whose cancer progressed prior to the time of local control were excluded. Consolidative radiation (RT) was defined as RT to all sites of metastatic disease. Kaplan Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Cox proportional hazards was used to account for confounding variables. To adjust for immortal time bias (ITB), end of local control was chosen as a landmark time.

RESULTS: Patients (n = 77) had a median age at diagnosis of 14.5 years (range: 1.7-29.7 years). The most common histology was Ewing sarcoma (49%), followed by rhabdomyosarcoma (30%). Median follow up was 28.5 months, without significant difference between patients treated with and without consolidative RT (23.7 vs. 21.5 months, p = 0.270). Median time to completion of consolidative RT from diagnosis was 8.5 months. Ewing sarcoma was more likely to be treated with consolidative RT compared to other histologies (p<0.001). Consolidative RT was associated with improved OS (2yr OS: 81.9% vs. 57.9%, p = 0.009) and PFS (2yr PFS: 71.2% vs. 30%, p = 0.001). On multivariate analysis, after accounting for age, histology, number, and type of metastases (lung, bone or other), consolidative RT remained independently associated with improved OS (hazard ratio (HR):0.36, 95% confidence interval [CI]: 0.17, 0.78, p = 0.010) and improved PFS (HR = 0.34, 95% CI = 0.16, 0.73, p = 0.006). The OS benefit for consolidative RT persisted after adjusting for ITB (1yr OS post-local control: 80.9% vs. 89.7%, p = 0.016). The effect of consolidative RT was validated in a dataset consisting of patients who were diagnosed with localized disease but had metastatic progression (n = 30). In this metachronous population, consolidative RT remained independently associated with improved OS (HR = 0.11, 95% CI = 0.03, 0.51, p = 0.004) after accounting for age.

CONCLUSION: ConsolidativeRT was independently associated with improved OS and PFS in pediatric and AYA patients with metastatic sarcoma at diagnosis. The OS benefit extended to those who underwent consolidative RT for metastatic progression. Future work should evaluate biomarkers to optimize patient selection and timing and dose of consolidative RT.

PMID:37784340 | DOI:10.1016/j.ijrobp.2023.06.484
Prognosis of children and young adults with newly diagnosed rhabdomyosarcoma metastatic to bone marrow treated on Children's Oncology Group studies

Fetched: October 3rd, 2023, 5:02am GMT by Nathan J Schloemer

Pediatr Blood Cancer. 2023 Dec;70(12):e30701. doi: 10.1002/pbc.30701. Epub 2023 Oct 2.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Metastatic disease occurs in 16% of all RMS cases and has a poor prognosis. There are limited studies examining the outcomes specific to patients with RMS metastatic to bone marrow despite an incidence of 6% at diagnosis. Our study aims to document the outcomes, prognostic factors, and clinical courses of children presenting with RMS metastatic to bone marrow treated on Children's Oncology Group (COG) cooperative trials.

METHODS: We performed a retrospective analysis of the patients diagnosed with RMS metastatic to bone marrow between 1997 and 2013 enrolled on one of four COG RMS clinical trials of D9802, D9803, ARST0431, and ARST08P1.

RESULTS: We identified 179 cases with RMS metastatic to bone marrow. Patients had a median age of 14.8 years, 58% were male, predominantly alveolar histology (76%), extremity was the most common primary site (32%), and 87% had metastatic disease to additional sites; 83% (n = 149) received radiation as a treatment modality. The 3- and 5-year event-free survival was 9.4% and 8.2%, respectively. The 3- and 5-year overall survival was 26.1% and 12.6%, respectively. Age ≥10 years, alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation were identified as poor prognostic/predictive characteristics.

CONCLUSIONS: This study represents the largest analysis of RMS metastatic to bone marrow, defining the poor prognostic outcome for these patients. These patients may be eligible for therapy deintensification or early pursuit of novel treatments/approaches that are desperately needed.

PMID:37783659 | DOI:10.1002/pbc.30701
Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma

Fetched: October 1st, 2023, 5:03am GMT by Meijie Tian

Cell Rep Med. 2023 Oct 17;4(10):101212. doi: 10.1016/j.xcrm.2023.101212. Epub 2023 Sep 28.

ABSTRACT

Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS. The 3A11 CAR T cells induced robust cytokine production and cytotoxicity against RMS cell lines in vitro. In contrast, a panel of healthy human primary cells failed to activate 3A11 CAR T cells, confirming the selectivity of 3A11 CAR T cells against tumors with high FGFR4 expression. Finally, we demonstrate that 3A11 CAR T cells are persistent in vivo and can effectively eliminate RMS tumors in two metastatic and two orthotopic models. Therefore, our study credentials CAR T cell therapy targeting FGFR4 to treat patients with RMS.

PMID:37774704 | PMC:PMC10591056 | DOI:10.1016/j.xcrm.2023.101212
Corrigendum to "INternational Soft Tissue saRcoma ConsorTium (INSTRuCT) consensus statement: Imaging recommendations for the management of rhabdomyosarcoma" [Eur. J. Radiol. 166 (2023) 111012]

Fetched: October 1st, 2023, 5:03am GMT by Reineke A Schoot

Eur J Radiol. 2023 Nov;168:111108. doi: 10.1016/j.ejrad.2023.111108. Epub 2023 Sep 27.

NO ABSTRACT

PMID:37774530 | DOI:10.1016/j.ejrad.2023.111108
Clinicopathological Characteristics, Survival Outcomes, and Prognostic Factors in Adult Patients With Sinonasal Rhabdomyosarcoma: Insights from a Retrospective Cohort Study

Fetched: September 30th, 2023, 5:02am GMT by Monika Durzynska

Anticancer Res. 2023 Oct;43(10):4517-4524. doi: 10.21873/anticanres.16645.

ABSTRACT

BACKGROUND/AIM: Rhabdomyosarcoma (RMS) is a rare tumor with distinct morphological types and challenging diagnosis. This study aimed to investigate clinicopathological characteristics, survival outcomes, and factors influencing prognosis in adult patients with sinonasal RMS, addressing a critical gap in knowledge.

PATIENTS AND METHODS: This retrospective cohort study employed various statistical analyses to investigate patients with RMS. Descriptive statistics summarized demographic and clinical characteristics, while survival analysis using the Kaplan-Meier method and Cox proportional hazards model explored the relationship between covariates and survival outcomes.

RESULTS: We analyzed 13 cases (7 males, 6 females) of sinonasal RMS. The average age at onset was 42.5 years (standard deviation 18.9). Tumors were observed in multiple locations, predominantly in the maxillary sinus (n=7), followed by the ethmoid sinus (n=5), and the sphenoid sinus (n=1). The study revealed a low survival rate, with 12 patients succumbing to the disease and only one patient surviving. Over time, survival probabilities declined from 92.31% (at 0.5 months) to 7.69% (at 45 months). The analysis indicated a borderline statistically significant positive association between age at diagnosis below 40 years and survival (p=0.05). Sex was found to be significantly associated with survival (p=0.03), with male patients exhibiting a higher survival rate (hazard ratio=0.08, 95%CI=0.01-0.81).

CONCLUSION: This study highlights the complex nature of sinonasal RMS in adults. The low survival rate and distinct tumor locations emphasize the need for further research to improve diagnosis and treatment outcomes.

PMID:37772581 | DOI:10.21873/anticanres.16645
Correction to: Proteomic Profiling of Rhabdomyosarcoma-Derived Exosomes Yield Insights into Their Functional Role in Paracrine Signaling

Fetched: September 29th, 2023, 5:02am GMT by Ghina Rammal

J Proteome Res. 2023 Sep 28. doi: 10.1021/acs.jproteome.3c00567. Online ahead of print.

NO ABSTRACT

PMID:37769164 | DOI:10.1021/acs.jproteome.3c00567
Spindle Cell Rhabdomyosarcoma of the Inguinal Region Mimicking a Complicated Hernia in the Adult-An Unexpected Finding

Fetched: September 29th, 2023, 5:02am GMT by Valentin Titus Grigorean

Medicina (Kaunas). 2023 Aug 23;59(9):1515. doi: 10.3390/medicina59091515.

ABSTRACT

Rhabdomyosarcoma is a rare tumor that is diagnosed mostly in children and adolescents, rarely in adults, representing 2-5% of all soft tissue sarcomas. It has four subtypes that are recognized: embryonal (50%), alveolar (20%), pleomorphic (20%), and spindle cell/sclerosing (10%). The diagnosis of rhabdomyosarcoma is based on the histological detection of rhabdomyoblasts and the expression of muscle-related biomarkers. Spindle cell/sclerosing rhabdomyosarcoma consists morphologically of fusiform cells with vesicular chromatin arranged in a storiform pattern or long fascicles, with occasional rhabdomyoblasts. Also, dense, collagenous, sclerotic stroma may be seen more commonly in adults. We present a rare case of an adult who presented to the hospital with a tumor in the left inguinal area, was first diagnosed with a left strangulated inguinal hernia and was operated on as an emergency, although the diagnosis was ultimately a spindle cell rhabdomyosarcoma of the inguinal region.

PMID:37763635 | PMC:PMC10535666 | DOI:10.3390/medicina59091515
The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma

Fetched: September 29th, 2023, 5:02am GMT by Robert Cornelison

Int J Mol Sci. 2023 Sep 17;24(18):14196. doi: 10.3390/ijms241814196.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue cancer with a survival rate below 27% for high-risk children despite aggressive multi-modal therapeutic interventions. After decades of research, no targeted therapies are currently available. Therapeutically targeting actin-binding proteins, although promising, has historically been challenging. Recent advances have made this possibility more salient, including our lab's identification of advillin (AVIL), a novel oncogenic actin-binding protein that plays a role in many cytoskeletal functions. AVIL is overexpressed in many RMS cell lines, patient-derived xenograft models, and a cohort of 30 clinical samples of both the alveolar (ARMS) and embryonal (ERMS) subtypes. Overexpression of AVIL in mesenchymal stem cells induces neoplastic transformation both in vitro and in vivo, and reversing overexpression through genetic modulation reverses the transformation. This suggests a critical role of AVIL in RMS tumorigenesis and maintenance. As an actin-binding protein, AVIL would not traditionally be considered a druggable target. This perspective will address the feasibility of targeting differentially expressed actin-binding proteins such as AVIL therapeutically, and how critical cell infrastructure can be damaged in a cancer-specific manner.

PMID:37762498 | PMC:PMC10531751 | DOI:10.3390/ijms241814196
Simultaneous Occurrence of Multiple Neoplasms in Children with Cancer Predisposition Syndromes: Collaborating with Abnormal Genes

Fetched: September 29th, 2023, 5:02am GMT by Gabriela Telman

Genes (Basel). 2023 Aug 24;14(9):1670. doi: 10.3390/genes14091670.

ABSTRACT

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nephroblastoma, in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.

PMID:37761810 | PMC:PMC10530991 | DOI:10.3390/genes14091670
Comparison of 18F-FDG PET/CT and 68Ga-FAPI in Spindle Cell Rhabdomyosarcoma

Fetched: September 29th, 2023, 5:02am GMT by Zhihui Shen

Diagnostics (Basel). 2023 Sep 20;13(18):3006. doi: 10.3390/diagnostics13183006.

ABSTRACT

We report a rare case of spindle cell rhabdomyosarcoma. Sarcomas generally exhibit an abnormal increased FDG uptake on ¹⁸F-FDG PET/CT imaging, while spindle cell rhabdosarcomas exhibits a significantly increased lesion uptake on ⁶⁸Ga FAPI PET/CT imaging compared to ¹⁸F-FDG. This case suggests that ⁶⁸Ga-FAPI PET/CT has potential value in evaluating spindle cell rhabdomyosarcoma.

PMID:37761371 | PMC:PMC10530021 | DOI:10.3390/diagnostics13183006
Oclacitinib and Myxoma Virus Therapy in Dogs with High-Grade Soft Tissue Sarcoma

Fetched: September 29th, 2023, 5:02am GMT by Laura V Ashton

Biomedicines. 2023 Aug 23;11(9):2346. doi: 10.3390/biomedicines11092346.

ABSTRACT

Human rhabdomyosarcomas are rarely cured by surgical resection alone. This is also true for high-grade soft tissue sarcomas in dogs. Dogs with spontaneous sarcoma are good models for clinical responses to new cancer therapies. Strategic combinations of immunotherapy and oncolytic virotherapy (OV) could improve treatment responses in canine and human cancer patients. To develop an appropriate combination of immunotherapy and OV for dogs with soft tissue sarcoma (STS), canine cancer cells were inoculated with myxoma viruses (MYXVs) and gene transcripts were quantified. Next, the cytokine concentrations in the canine cancer cells were altered to evaluate their effect on MYXV replication. These studies indicated that, as in murine and human cells, type I interferons (IFN) play an important role in limiting MYXV replication in canine cancer cells. To reduce type I IFN production during OV, oclacitinib (a JAK1 inhibitor) was administered twice daily to dogs for 14 days starting ~7 days prior to surgery. STS tumors were excised, and MYXV deleted for serp2 (MYXV∆SERP2) was administered at the surgical site at two time points post-operatively to treat any remaining microscopic tumor cells. Tumor regrowth in dogs treated with OV was decreased relative to historical controls. However, regrowth was not further inhibited in patients given combination therapy.

PMID:37760788 | PMC:PMC10525839 | DOI:10.3390/biomedicines11092346
Pediatric presacral tumors with intraspinal extension: a rare entity with diagnostic challenges

Fetched: September 28th, 2023, 5:04am GMT by Ebinesh A

Acta Radiol. 2023 Sep 27:2841851231202688. doi: 10.1177/02841851231202688. Online ahead of print.

ABSTRACT

The presacral space is a potential space located between the rectum and the lumbosacral spine. It contains various primitive germ cell types that serve as the origin for a range of tumors. Imaging is crucial in characterizing, assessing the extent of and evaluating the treatment response to these tumors. We report a series of six cases of pediatric presacral tumors with intraspinal extension, including an immature sacrococcygeal teratoma (Altman type II), a malignant sacrococcygeal teratoma (Altman type IV), a neuroblastoma, a rhabdomyosarcoma, a clear cell sarcoma and an Ewing's sarcoma of the ilium. These tumors can be broadly categorized as tumors of germ cell, neuroblastic, mesenchymal and osteogenic origin. Despite overlapping imaging features, a review of the existing literature and careful retrospective observation revealed several distinctive features that aid in the optimal characterization of tumors. These include the tumor's epicenter, the pattern and degree of bone involvement, the status of sacral foramina and neural elements, and internal tumor characteristics such as the presence of fat, calcification, hemorrhage and necrosis.

PMID:37753549 | DOI:10.1177/02841851231202688
Unique manifestation of primary renal rhabdomyosarcoma in patient with autosomal polycystic kidneys: Case report and review of literature

Fetched: September 28th, 2023, 5:04am GMT by Abdulrahman Almutairi

Urol Case Rep. 2023 Sep 10;51:102557. doi: 10.1016/j.eucr.2023.102557. eCollection 2023 Nov.

ABSTRACT

Primary embryonal rhabdomyosarcomas of the kidney are extremely rare, especially in adults. The presented case, a 32-year-old female with a background of autosomal polycystic kidney disease, was initially referred with a left hemorrhagic renal cyst. Despite angioembolization, she eventually underwent radical nephrectomy which revealed the diagnosis of embryonal rhabdomyosarcoma. The diagnosis and presentation of this case is unique as she presented with hemorrhagic renal cyst. Adult renal rhabdomyosarcoma has a poor prognosis, as shown by other reported cases. Unfortunately, She passed away 88 days post operatively due to disease progression.

PMID:37753457 | PMC:PMC10518334 | DOI:10.1016/j.eucr.2023.102557
A retrospective study of conjunctival lesions in the Paediatric Eye Clinic over 12 years

Fetched: September 27th, 2023, 5:02am GMT by John Logan

Eye (Lond). 2023 Sep 26. doi: 10.1038/s41433-023-02727-1. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric conjunctival lesions are rare and diverse. Though often indolent and asymptomatic, they can in some cases be sight or life-threatening. Awareness of concerning features of conjunctival lesions is key to optimal management. We aim to provide insight into management of paediatric conjunctival lesions though a review of cases in our service in last 12 years.

METHODS: We present a retrospective analysis of our population-based cohort of children with conjunctival lesions presenting to our regional service in Belfast between 2011 and 2022 inclusive. We detail three rare cases of paediatric conjunctival lesions; a congenital intrascleral cyst leading to astigmatic amblyopia, a rapidly changing salmon-pink lesion confirmed as an embryonal rhabdomyosarcoma and an unusual presentation of a chronic granuloma arising from the caruncle.

RESULTS: 85 conjunctival lesions were identified in <16 year olds giving a cumulative incidence of 27 cases per 100,000 population over 12 years. Mean age at presentation was 7 years old. Most common lesions were naevi (40%), limbal dermoids (21%), conjunctival melanosis (14%), conjunctival cysts (7%) and phlycten (6%). When seen at presentation 8% of cases were immediately listed for surgery, 28% were discharged and 64% entered a phase of observation.

CONCLUSION: Paediatric conjunctival lesions have potential to cause visual manifestations, whilst some may undergo malignant transformation. Anterior segment photography is crucial in monitoring change and facilitating early discharge in the absence of sinister features. Malignant transformation must be considered in changing lesions which ought to have histological diagnosis obtained to prevent potentially sight and life-threatening conditions.

PMID:37752343 | DOI:10.1038/s41433-023-02727-1
Clinical characteristics of sarcoma patients: a population-based data analysis from a German clinical cancer registry

Fetched: September 27th, 2023, 5:02am GMT by Jörg Andreas Müller

J Cancer Res Clin Oncol. 2023 Sep 26. doi: 10.1007/s00432-023-05350-5. Online ahead of print.

ABSTRACT

PURPOSE: Sarcomas are a heterogeneous group of malignant neoplasms with a wide range of histological types and occur in almost any anatomic site and side. This study evaluated the prognostic factors in sarcoma patients based on German clinical cancer registry data.

METHODS: The German clinical cancer register of Saxony-Anhalt was used for all data analyses. Sarcoma cases of all clinical or pathological T-stages (T1a-T4c), all N-stages (N0-3) and M-stages (0-1b) corresponding to the Union for International Cancer Control (UICC) stages I to IVB were considered. In our analyses, 787 cases diagnosed between 2005 and 2022 were included. Further, we assessed the association of cancer-related parameters with mortality and hazard ratios (HR) from the Cox proportional hazard models. We included sex, age at diagnosis, histological grade, T-, N- and M-stages, tumor size, tumor localization and tumor side as parameters in our regression models.

RESULTS: The majority of sarcoma patients were diagnosed with leiomyosarcoma (12%), liposarcoma (11%), angiosarcoma (5.3%) and myxofibrosarcoma (2.7%). In our univariate regression models, tumors localized in more than one location, head, face and neck region as well as the pelvis and lower extremity were associated with increased mortality risk (more than one location: HR 7.10, 95% CI 2.20-22.9; head, face and neck: HR 1.35, 95% CI 0.89-2.06; pelvis: HR 1.27, 95% CI 0.86-1.89; lower extremity: HR 1.44, 95% CI 1.05-1.96). Higher histological grades, UICC-grades and TNM-stages were related to a higher mortality risk. Differing histological subtypes had significant influence on overall survival and progression-free survival. Patients diagnosed with fibromyxoid sarcoma, rhabdomyosarcoma and angiosarcoma were related to higher mortality risk compared to other histological subtypes (fibromyxoid sarcoma: HR 5.2, 95% CI 0.71-38.1; rhabdomyosarcoma: HR 2.93, 95% CI 1.44-6.00; angiosarcoma: HR 1.07, 95% CI 0.53-2.18).

CONCLUSIONS: Histological grade, tumor size, nodal and distant metastasis, tumor localization and histological subtype were determined as prognostic factors in terms of survival.

PMID:37750956 | DOI:10.1007/s00432-023-05350-5
Chorein sensitive microtubule organization in tumor cells

Fetched: September 26th, 2023, 5:03am GMT by Saad Alkahtani

PeerJ. 2023 Sep 20;11:e16074. doi: 10.7717/peerj.16074. eCollection 2023.

ABSTRACT

BACKGROUND: The purpose of this study is to analyzed the involvement of chorein in microtubules organization of three types of malignant; rhabdomyosarcoma tumor cells (ZF), rhabdomyosarcoma cells (RH30), and rhabdomyosarcoma cells (RD). ZF are expressing high chorein levels. Previous studies revealed that chorein protein silencing in ZF tumor cells persuaded apoptotic response followed by cell death. In addition, in numerous malignant and non-malignant cells this protein regulates actin cytoskeleton structure and cellular signaling. However, the function of chorein protein in microtubular organization is yet to be established.

METHODS: In a current research study, we analyzed the involvement of chorein in microtubules organization by using three types of malignant rhabdomyosarcoma cells. We have applied confocal laser-scanning microscopy to analyze microtubules structure and RT-PCR to examine cytoskeletal gene transcription.

RESULTS: We report here that in rhabdomyosarcoma cells (RH30), chorein silencing induced disarrangement of microtubular network. This was documented by laser scanning microscopy and further quantified by FACS analysis. Interestingly and in agreement with previous reports, tubulin gene transcription in RH cells was unchanged upon silencing of chorein protein. Equally, confocal analysis showed minor disordered microtubules organization with evidently weakened staining in rhabdomyosarcoma cells (RD and ZF) after silencing of chorein protein.

CONCLUSION: These results disclose that chorein silencing induces considerable structural disorganization of tubulin network in RH30 human rhabdomyosarcoma tumor cells. Additional studies are now needed to establish the role of chorein in regulating cytoskeleton architecture in tumor cells.

PMID:37744224 | PMC:PMC10517657 | DOI:10.7717/peerj.16074
EWSR1::POU2AF3(COLCA2) Sarcoma: An aggressive, polyphenotypic sarcoma with a head and neck predilection

Fetched: September 25th, 2023, 5:03am GMT by Olena Koshyk

Mod Pathol. 2023 Sep 22:100337. doi: 10.1016/j.modpat.2023.100337. Online ahead of print.

ABSTRACT

EWSR1::POU2AF3: (COLCA2) sarcomas are a recently identified group of undifferentiated round/spindle cell neoplasms with a predilection for the head and neck region. Herein we report our experience with 8 cases, occurring in 5 men and 3 women (age range: 37-74 years; median 60 years). Tumors involved the head/neck (4 cases), and one each the thigh, thoracic wall, fibula and lung. Seven patients received multimodal therapy, one patient was treated only with surgery. Clinical follow-up (8 patients; range 4-122 months; median: 32 months) showed 5 patients with metastases (often multifocal, with a latency ranging from 7-119 months), 3 of them along with local recurrence. The median local recurrence-free and metastasis-free survival rates were 24 months and 29 months, respectively. Of the 8 patients, 1 died of an unknown cause, 4 were alive with metastatic disease, 1 was alive with unresectable local disease and 2 were without disease. The tumors comprised of 2 morphologic subgroups: 1) relatively bland tumors consisting of spindled to stellate cells with varying cellularity and fibromyxoid stroma (2 cases) and 2) overtly malignant tumors comprised of nests of "neuroendocrine-appearing" round cells surrounded by spindled cells (6 cases). Individual cases in the 2^nd group showed glandular, osteogenic or rhabdomyoblastic differentiation. Immunohistochemical results included: CD56 (4/4 cases), GFAP (5/8) SATB2 (4/6), keratin (AE1/AE3) (5/8) and S100 protein (4/7). RNA sequencing identified EWSR1:: POU2AF3 gene fusion in all cases. EWSR1 gene rearrangement was confirmed by FISH in 5 cases. Our findings confirm the head/neck predilection and aggressive clinical behavior of EWSR1::POU2AF3 sarcomas, and widen the morphologic spectrum of these rare lesions to include relatively bland spindle cell tumors and tumors with divergent differentiation.

PMID:37742928 | DOI:10.1016/j.modpat.2023.100337
Extraocular Orbital and Peri-Orbital Masses

Fetched: September 24th, 2023, 5:02am GMT by Asthik Biswas

Neuroimaging Clin N Am. 2023 Nov;33(4):643-659. doi: 10.1016/j.nic.2023.05.012. Epub 2023 Jul 1.

ABSTRACT

In this article, we will describe relevant anatomy and imaging findings of extraocular and orbital rim pathologic conditions. We will highlight important clinical and imaging pearls that help in differentiating these lesions from one another, and provide a few practical tips for challenging cases.

PMID:37741663 | DOI:10.1016/j.nic.2023.05.012
Solid and Vascular Neck Masses in Children

Fetched: September 24th, 2023, 5:02am GMT by Mark D Mamlouk

Neuroimaging Clin N Am. 2023 Nov;33(4):607-621. doi: 10.1016/j.nic.2023.05.010. Epub 2023 Jun 28.

ABSTRACT

Neck masses are frequent in the pediatric population and are usually divided into congenital, inflammatory, and neoplastic. Many of these lesions are cystic and are often benign. Solid masses and vascular lesions are relatively less common, and the imaging appearances can be similar. This article reviews the clinical presentation and imaging patterns of pediatric solid and vascular neck masses.

PMID:37741661 | DOI:10.1016/j.nic.2023.05.010
Loss of Chromosome 3q Is a Prognostic Marker in Fusion-Negative Rhabdomyosarcoma

Fetched: September 23rd, 2023, 5:02am GMT by Carina A Dehner

JCO Precis Oncol. 2023 Sep;7:e2300037. doi: 10.1200/PO.23.00037.

ABSTRACT

PURPOSE: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures.

METHODS: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for prognostically significant CNV aberrations in FOXO1 fusion-negative (FN)- versus fusion-positive (FP)-RMS. FISH testing was performed on a cohort of FN-RMS to assess for chr3q loss and correlate with outcomes.

RESULTS: Chr8 gain is a highly prevalent CNV in embryonal RMS and shows slightly improved prognosis. Meanwhile, loss of chr3q was associated with worse outcome in FN-RMS compared with FP-RMS.

CONCLUSION: The pathogenesis of STS including FN-RMS remains poorly understood, emphasizing the need for new therapeutic advances and adequate risk stratification. Our data demonstrate that loss of chr3q is associated with poor OS in FN-RMS, supporting it as an important tool for risk stratification.

PMID:37738543 | DOI:10.1200/PO.23.00037

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