Comparing Carbon Ion Therapy, Surgery, and Proton Therapy for the Management of Pelvic Sarcomas Involving the Bone, the PROSPER Study

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; National Cancer Institute (NCI)
Not yet recruiting
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma

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

Conditions: Alveolar Rhabdomyosarcoma; Botryoid-Type Embryonal Rhabdomyosarcoma; Embryonal Rhabdomyosarcoma; Rhabdomyosarcoma; Solid Alveolar Rhabdomyosarcoma; Spindle Cell Rhabdomyosarcoma; Spindle Cell/Sclerosing Rhabdomyosarcoma
Interventions: Drug: Cyclophosphamide; Biological: Dactinomycin; Radiation: Radiation Therapy; Drug: Vincristine Sulfate; Drug: Vinorelbine Tartrate
Sponsor: Children's Oncology Group
Not yet recruiting
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: March 25th, 2020, 2:00pm GMT

Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Histiocytic and Dendritic Cell Neoplasm; Recurrent Langerhans Cell Histiocytosis; Recurrent Lymphoma; 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 Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent WHO Grade II Glioma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Histiocytic and Dendritic Cell Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Lymphoma; 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 Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory WHO Grade II Glioma; Wilms Tumor
Intervention: Drug: Selpercatinib
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
Recruiting
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial

Posted: February 26th, 2020, 3:00pm GMT

Conditions: Recurrent Adrenal Gland Pheochromocytoma; Recurrent Ectomesenchymoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdoid Tumor of the Kidney; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Thyroid Gland Carcinoma; Recurrent WHO Grade II Glioma; Refractory Adrenal Gland Pheochromocytoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Melanoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdoid Tumor of the Kidney; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory Thyroid Gland Carcinoma; Refractory WHO Grade II Glioma
Intervention: Drug: Tipifarnib
Sponsor: National Cancer Institute (NCI)
Recruiting
A Study of Abemaciclib (LY2835219) in Combination With Temozolomide and Irinotecan and Abemaciclib in Combination With Temozolomide in Children and Young Adult Participants With Solid Tumors

Posted: January 23rd, 2020, 3:00pm GMT

Conditions: Relapsed Solid Tumor; Refractory Solid Tumor
Interventions: Drug: Abemaciclib; Drug: Irinotecan; Drug: Temozolomide
Sponsor: Eli Lilly and Company
Recruiting
Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)

Posted: December 12th, 2019, 3:00pm GMT

Conditions: Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; 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 Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent WHO Grade II Glioma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; 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 Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Refractory WHO Grade II Glioma; Wilms Tumor
Intervention: Drug: Ivosidenib
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
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, 2:00pm 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
Sponsor: National Cancer Institute (NCI)
Recruiting
Safety, Tolerability, Efficacy and Pharmacokinetics of Copanlisib in Pediatric Patients

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

Condition: Mixed Tumor, Malignant
Intervention: Drug: BAY806946
Sponsor: Bayer
Recruiting
$Permalink for 'Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)'$
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, 2:00pm 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
Intervention: Drug: Olaparib
Sponsor: National Cancer Institute (NCI)
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, 2:00pm 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
Sponsor: National Cancer Institute (NCI)
Recruiting
$Permalink for 'Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)'$
Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

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

Conditions: Advanced Malignant Solid Neoplasm; Recurrent Ependymoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; 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 Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Primary Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Wilms Tumor
Interventions: Drug: Larotrectinib; Drug: Larotrectinib Sulfate
Sponsor: National Cancer Institute (NCI)
Recruiting
$Permalink for 'Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)'$
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)

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

Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Recurrent Ependymoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent WHO Grade II Glioma; Refractory Ependymoma; Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; 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 Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma; Wilms Tumor
Interventions: Drug: Ensartinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Sponsors: National Cancer Institute (NCI); Children's Oncology Group
Recruiting
$Permalink for 'Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)'$
Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

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

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Malignant Glioma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; 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 Central Nervous System Neoplasm; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Central Nervous System Neoplasm; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor
Interventions: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Samotolisib
Sponsor: National Cancer Institute (NCI)
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, 2:00pm 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 Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Primary Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Central Nervous System Neoplasm; Rhabdoid Tumor; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor
Interventions: Drug: Erdafitinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study
Sponsor: National Cancer Institute (NCI)
Recruiting
$Permalink for 'Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)'$
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

Posted: May 16th, 2017, 2:00pm GMT

Conditions: Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Histiocytic Sarcoma; Juvenile Xanthogranuloma; Langerhans Cell Histiocytosis; Malignant Glioma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; 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 Central Nervous System Neoplasm; Recurrent Rhabdoid Tumor; Recurrent Soft Tissue Sarcoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; 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 Central Nervous System Neoplasm; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Ensartinib; Drug: Erdafitinib; Other: Laboratory Biomarker Analysis; Drug: Larotrectinib; Procedure: Mutation Carrier Screening; Drug: Olaparib; Drug: Palbociclib; Other: Pharmacological Study; Drug: Samotolisib; Drug: Selpercatinib; Drug: Selumetinib Sulfate; Drug: Tazemetostat; Drug: Tipifarnib; Drug: Ulixertinib; Drug: Vemurafenib
Sponsor: National Cancer Institute (NCI)
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
A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

Posted: December 22nd, 2015, 3:00pm GMT

Condition: Solid Tumors Harboring NTRK Fusion
Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
Sponsor: Bayer
Recruiting
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma

Posted: October 5th, 2015, 2:00pm 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
Sponsor: National Cancer Institute (NCI)
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

PubMed - Rhabdomyosarcoma

LncRNA RMST Regulates Neuronal Apoptosis and Inflammatory Response via Sponging miR-150-5p in Parkinson's Disease

Fetched: September 14th, 2021, 5:02am GMT by Chuanlei Chen

Neuroimmunomodulation. 2021 Sep 7:1-8. doi: 10.1159/000518212. Online ahead of print.

ABSTRACT

INTRODUCTION: LncRNA rhabdomyosarcoma 2-associated transcript (RMST) serves as a key regulator in neural stem cell fate and is involved in the progression of different neurological diseases. In this research, the serum level and clinical value of RMST in Parkinson's disease (PD) patients were detected, and the underlying mechanism was explored.

METHODS: Ninety-nine PD patients and 93 healthy individuals were collected for clinical experiments. SH-SY5Y cells were treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) to establish PD cell models. qRT-PCR was used for the detection of mRNA levels. CCK-8 and flow cytometry were used to detect neuronal viability and apoptosis. The target relationship of RMST with miR-15a-5p was confirmed applying luciferase reporter assay.

RESULTS: RMST was present at high levels in both serum of PD patients and PD cell models. Serum RMST had a certain clinical value for the diagnosis of PD with the AUC of 0.892 at a cutoff value of 1.225. Serum RMST was positively associated with the levels of TNF-α (r = 0.421, p < 0.001) and IL-1β (r = 0.567, p < 0.001) in PD patients. Knockdown of RMST alleviated the apoptosis and inflammatory response of SH-SY5Y cells induced by MPP+. miR-150-5p was the target gene of RMST and less expressed in the clinical serum samples and PD cell models.

CONCLUSION: Serum RMST serves as a promising biomarker for the diagnosis of PD. RMST downregulation may regulate the occurrence and development of PD through inhibiting neuron cell apoptosis and the release of inflammatory cytokines via targeting miR-150-5p.

PMID:34515176 | DOI:10.1159/000518212
What Would Next Generation Sequencing Bring to the Diagnosis and Treatment of Sarcomas? A Series of 20 Cases, a Single Institution's Experience

Fetched: September 14th, 2021, 5:02am GMT by Ibrahim Kulac

Turk Patoloji Derg. 2021 Jun 26. doi: 10.5146/tjpath.2021.01544. Online ahead of print.

ABSTRACT

OBJECTIVE: Soft tissue tumors comprise a small proportion of a pathologist's routine practice. Although morphology and immunohistochemistry are quite helpful for diagnosing these tumors, many require molecular tests. Fluorescence in-situ hybridization has been the most commonly used method for the detection of specific genomic alteration, but next generation sequencing (NGS) could be more informative in many ways. Here we present our targeted NGS experience on soft tissue tumors with a series of 20 cases.

MATERIAL AND METHOD: The Laboratory Information System (LIS) was screened for soft tissue tumors that had been sequenced by NGS (between January 2018 - February 2021). 20 consecutive cases were included in the study. All cases were sequenced using a commercial targeted sequencing panel designed for soft tissue tumors.

RESULTS: We were able to run a reliable sequencing study for 16 (80%) of the cases but 4 (20%) of them failed in quality tests. We have found pathogenic alterations in 12 (60%) of the cases. The most common alterations were EWSR1 fusions, FLI1 being the most common partner. NGS results drastically changed the initial diagnosis, and thus the treatment modalities, in 3 cases (15%): the case with ETV6-NTRK3 fusion, the case with FUS-TFCP2 fusion, and the case of rhabdomyosarcoma (RMS) that was favored to be of the alveolar subtype and turned out to lack FOXO1 fusions.

CONCLUSION: A targeted NGS panel is robust and very informative. It not only allows pathologists to further specify and/or confirm their diagnosis but it could also play an important role in predicting the outcome.

PMID:34514574 | DOI:10.5146/tjpath.2021.01544
Rhabdomyosarcoma in Adults: A Retrospective Analysis of Case Records Diagnosed between 1979 and 2018 in Western Denmark

Fetched: September 12th, 2021, 5:01am GMT by Vivi-Nelli Mäkinen

Sarcoma. 2021 Aug 30;2021:9948885. doi: 10.1155/2021/9948885. eCollection 2021.

ABSTRACT

INTRODUCTION: Adult rhabdomyosarcoma is a rare tumour that has an inferior survival compared to the paediatric patient population. The reason for this consistently worse outcome remains mostly unknown. It has been suggested that this disparity may be related to biological and/or treatment-related factors, which in the literature has been shown to be distributed differently among paediatric and adult patients. The aim of this study was to clarify treatment outcome and clinicopathological factors for adult patients with rhabdomyosarcoma that were treated in Aarhus, Denmark, since 1979.

METHODS: By searching the Aarhus Sarcoma Registers, data for all rhabdomyosarcoma patients, aged 18 years or more, between 1979 and 2018, were retrieved and analysed.

RESULTS: Data from 50 patients were collected. No patients were lost to follow-up. For the entire cohort, 5- and 10-year overall survival rates were 30% and 18%, respectively. The median age was 46.5 years, and the median overall survival was 2.3 years. Tumour histology was embryonal 18%, alveolar 22%, pleomorphic 44%, and not otherwise specified 16%. The tumour site was unfavourable in more than 80% of the patients. Significant factors associated with inferior overall survival were histology and disease stage, although histological subtype was not significant in the multivariate model. Five-year overall survival was 40% for localised disease versus 15% for metastatic disease.

CONCLUSION: Rhabdomyosarcoma in adults has a poorer prognosis than paediatric rhabdomyosarcoma and other high-grade sarcomas in adults. Adult rhabdomyosarcoma should continue to be treated aggressively, but new and tailored treatment strategies are needed to improve the long-term outcome. Previous predictors of poor survival in paediatric patients were valid in adults except for age, site (favourable versus unfavourable), and tumour size.

PMID:34504392 | PMC:PMC8423536 | DOI:10.1155/2021/9948885
Clinicopathological features of malignant mixed mesodermal tumor: analysis of 50 cases

Fetched: September 10th, 2021, 5:01am GMT by X H Ding

Zhonghua Bing Li Xue Za Zhi. 2021 Sep 8;50(9):1008-1013. doi: 10.3760/cma.j.cn112151-20210126-00083.

ABSTRACT

Objective: To investigate the clinicpathological, immunohistochemical and molecular genetic features of malignant mixed mesodermal tumor (MMMT) in the female reproductive system. Methods: To analyze its histopathological characteristics, we performed a retrospective review of the MMMT cases diagnosed at PLA General Hospital, Beijing, China during 2005-2019 using its surgical and pathological databases. EnVision immunohistochemical staining was used to detect the expression of ER, PR, p16, p53 and MMR proteins. Results: Fifty cases were conformed to the diagnosis, including 29 cases originated in the uterus, 16 cases in ovary, 4 cases of synchronous occurrence in uterus and ovary, 1 case in cervix. The tumor was histologically composed of two components, namely carcinoma and sarcoma ones, with clear borderline or blend mutually. The proportion of cancer component in the whole tumor ranged from 5%-90%. The proportion of carcinoma was more than 50% in 76% of the cases, and less than 50% in 24% of cases, including 2 cases with<10% of carcinoma. In the cases of primary uterine MMMT, the main carcinoma type was high grade endometrioid carcinoma (55%, 16/29). In ovarian MMMT, the main carcinoma type was serous carcinoma (12/16), while that of cervical MMMT was squamous cell carcinoma. The others were clear cell carcinoma or the undifferentiated carcinoma. There was one carcinoma type in most cases, only 7 cases had two carcinoma types. Homologous sarcomas, including stromal sarcoma, leiomyosarcoma and high-grade spindle cell sarcomas, were more commonly found in uterine MMMT (72.4%, 21/29). While heterogenic sarcomas, including chondrosarcoma, osteosarcoma and rhabdomyosarcoma, were more commonly noted in ovarian MMMT (12/16) than MMMT of other sites. There were 10 cases that consisted of two types of sarcomas. The synchronous MMMT of uterus and ovary had similar morphology and the types of carcinoma and sarcoma. The tumor cells that spread or metastasized to lymph node, omentum, intestinal wall or skin were all carcinoma cells, and were morphologically consistent with the original tumors. Immunohistochemically, ER and PR were both negative (23/25 in uterine, 8/10 in ovarian tumors). p16 was strongly positive (11/11 in uterine tumors, and 6/6 in ovarian tumors), with similar expression patterns in the carcinoma and sarcoma components. p53 showed mutant-type staining (64%, 21/33) and expressed synchronously in carcinoma and sarcoma components. p53 mutation was found in 35% cases of endometrial carcinoma and 46.7% cases of non-endometrial carcinoma. p53 mutation was also found in only 31.8% cases of heterogenic sarcomas, but in 50% of non-heterogenic sarcomas. Twenty-eight cases (28/33, 85%) presented intact mismatch repair proteins, while 5 cases (5/33, 15%) presented deficient mismatch repair proteins. Conclusions: MMMT in female reproductive system is a rare high-grade biphasic tumor with complex and diverse morphology. The immunohistochemical features are characterized by negative ER/PR and strongly positive p16, mostly mutant p53 and proficient mismatch repair proteins. The patients with a high FIGO stage have worse prognosis.

PMID:34496490 | DOI:10.3760/cma.j.cn112151-20210126-00083
Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease

Fetched: September 8th, 2021, 5:02am GMT by Hongbo Liu

Front Cell Infect Microbiol. 2021 Aug 16;11:700191. doi: 10.3389/fcimb.2021.700191. eCollection 2021.

ABSTRACT

Coxsackievirus A6 (CVA6) is a key pathogen causing hand, foot and mouth disease (HFMD). However, there are currently no specific antiviral drugs or vaccines for treating infections caused by CVA6. In this study, human rhabdomyosarcoma (RD), African green monkey kidney (Vero), and human embryonic lung diploid fibroblast (KMB17) cells were used to isolate CVA6 from 327 anal swab and fecal samples obtained during HFMD monitoring between 2009 and 2017. The VP1 genes of the isolates were sequenced and genotyped, and the biological characteristics of the representative CVA6 strains were analyzed. A total of 37 CVA6 strains of the D3 gene subtypes were isolated from RD cells, all of which belonged to the epidemic strains in mainland China. Using the adaptive culture method, 10 KMB17 cell-adapted strains were obtained; however, no Vero cell-adapted strains were acquired. Among the KMB17 cell-adapted strains, only KYN-A1205 caused disease or partial death in suckling mice, and its virulence was stronger than its RD cell-adapted strain. The pathogenic KYN-A1205 strain caused strong tropism to the muscle tissue and led to pathological changes, including muscle necrosis and nuclear fragmentation in the forelimb and hindlimb. Sequence analysis demonstrated that the KYN-A1205 strain exhibited multiple amino acid mutations after KMB17 cell adaptation. Moreover, it showed strong pathogenicity, good immunogenicity and genetic stability, and could be used as an experimental CVA6 vaccine candidate.

PMID:34490141 | PMC:PMC8418080 | DOI:10.3389/fcimb.2021.700191
Correction to: Magnetic resonance features and cranial nerve involvement in pediatric head and neck rhabdomyosarcomas

Fetched: September 8th, 2021, 5:02am GMT by Giacomo Talenti

Neuroradiology. 2021 Sep 6. doi: 10.1007/s00234-021-02797-6. Online ahead of print.

NO ABSTRACT

PMID:34487202 | DOI:10.1007/s00234-021-02797-6
Extremities Soft Tissue Sarcomas, more Common and as Dangerous as Bone Sarcomas

Fetched: September 8th, 2021, 5:02am GMT by Karen Voltan

Rev Bras Ortop (Sao Paulo). 2021 Aug;56(4):419-424. doi: 10.1055/s-0040-1712136. Epub 2020 Sep 25.

ABSTRACT

Musculoskeletal sarcomas are rare diseases that require attention. They often present high degree of malignancy at diagnosis and, if underestimated, they can evolve aggressively locally and systemically. They present as soft tissue sarcoma and bone sarcomas, with soft tissue being four to five times more common. Most soft tissue sarcomas occur in the extremities. The most common subtypes in children and adolescents are rhabdomyosarcoma and synovial sarcoma; in adults, undifferentiated pleomorphic sarcoma, liposarcoma, leiomyosarcoma, myxofibrosarcoma and synovial sarcoma; all with a high degree of histological malignancy. Many soft tissue sarcomas are confused with benign soft tissue tumors, 100 times more common, so they are resected without the necessary planning, resulting in amputation of a limb that could have been preserved. As in all cancers, the most important prognostic factor is metastatic disease. When it is present, the overall survival rate falls around 20 to 30%. Survival rates are generally similar between bone and soft tissue sarcomas. So soft tissue sarcomas, in addition to being more prevalent, are as aggressive as bone sarcomas, deserving a lot of attention from orthopedic surgeons, who are often the first line of care of carriers of these tumors.

PMID:34483383 | PMC:PMC8405272 | DOI:10.1055/s-0040-1712136
Patterns of Cancer Care and Association with Survival among Younger Adolescents and Young Adults: A Population-based Retrospective Cohort Study

Fetched: September 6th, 2021, 5:02am GMT by Chelsea L Collins

Cancer Epidemiol Biomarkers Prev. 2021 Sep 3:cebp.0530.2021. doi: 10.1158/1055-9965.EPI-21-0530. Online ahead of print.

ABSTRACT

BACKGROUND: Younger adolescents and young adults may receive care from either adult or pediatric oncologists. We explored patterns of care in this population and whether survival is associated with provider type.

METHODS: Utilizing the California Cancer Registry, we examined a cohort of 9,993 AYAs diagnosed with cancer aged 15-24 years from 1999-2008. Provider type (adult/pediatric) was determined by individual physician identifiers. For provider type, multivariable logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, diagnosis, and stage. For observed survival, Cox proportional hazard models were additionally adjusted for provider type. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (95%CI) were determined.

RESULTS: Most patients saw adult providers (87.3% overall; 72.7% aged 15-19 years). Patients with acute leukemia, sarcoma, and central nervous system (CNS) malignancies more often saw pediatric providers (OR [95%CI] adult versus pediatric 0.48 [0.39-0.59], 0.74 [0.60-0.92], 0.76 [0.60-0.96], respectively); those with germ cell tumors and other cancers, including carcinomas, more often saw adult providers (2.26 [1.72-2.98], 1.79 [1.41-2.27], respectively). In aggregate and for most cancers individually, there was no survival difference by provider type (overall HR [95%CI] 1.00 [0.86-1.18]). Higher survival was associated with pediatric providers for CNS malignancies (1.63 [1.12-2.37]) and rhabdomyosarcoma (2.22 [1.03-4.76]), and with adult providers for non-Hodgkin lymphoma (0.61 [0.39-0.96]).

CONCLUSIONS: Most AYAs 15-24 years old are treated by medical oncologists. In general, survival was not associated with provider type.

IMPACT: Current patterns of care for this population support increased collaboration between medical and pediatric oncology, including joint clinical trials.

PMID:34479948 | DOI:10.1158/1055-9965.EPI-21-0530
Primary alveolar rhabdomyosarcoma of bone

Fetched: September 6th, 2021, 5:02am GMT by Juan Tordecilla C

Andes Pediatr. 2021 Jun;92(3):440-445. doi: 10.32641/andespediatr.v92i3.2613.

ABSTRACT

INTRODUCTION: Rhabdomyosarcoma (RMS) is a malignant solid tumor of mesenchymal origin. It is the most com mon soft-tissue sarcoma in childhood and adolescence. 65% of cases are diagnosed before the age of 6. Histological subtypes include embryonal, alveolar, pleomorphic, and fused-cell RMS. The embryo nal subtype is more frequent in children, while the alveolar one is more frequent in adolescents and adults.

OBJECTIVE: To describe the clinical presentation of primary alveolar rhabdomyosarcoma in a schoolgirl.

CLINICAL CASE: 7-year-old schoolgirl with one-month history of progressive pain in her left thigh. X-ray shows a lytic lesion in the left femur diaphysis. A study was performed with 2 biopsies, immunohistochemistry, and PAX-FOXO1 studies which were compatible with alveolar RMS. Con clusion: Primary alveolar rhabdomyosarcoma of the bone is rare, but it should be considered within the differential diagnosis of primary small-round-blue cell bone tumors. Despite presenting a poor prognosis cytogenetic, this type of tumor seems to have better biological behavior, which for a successful treatment makes necessary to have a high index of suspicion in order to install a multimodal therapy in the context of a national protocol.

PMID:34479252 | DOI:10.32641/andespediatr.v92i3.2613
Inhibition of lipid metabolism exerts antitumor effects on rhabdomyosarcoma

Fetched: September 3rd, 2021, 5:01am GMT by Satoshi Miyagaki

Cancer Med. 2021 Sep 2. doi: 10.1002/cam4.4185. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma exhibits tumor-specific energy metabolic changes that include the Warburg effect. Since targeting cancer metabolism is a promising therapeutic approach, we examined the antitumor effects of suppressing lipid metabolism in rhabdomyosarcoma. We suppressed lipid metabolism in rhabdomyosarcoma cells in vitro by administering an inhibitor of malonyl-CoA decarboxylase, which increases malonyl-CoA and decreases fatty acid oxidation. Suppression of lipid metabolism in rhabdomyosarcoma cells decreased cell proliferation by inducing cell cycle arrest. Metabolomic analysis showed an increase in glycolysis and inactivation of the pentose phosphate pathway. Immunoblotting analysis revealed upregulated expression of the autophagy marker LC3A/B-II due to increased phosphorylation of AMP-activated protein kinase, a nutrient sensor. p21 protein expression level also increased. Inhibition of both lipid metabolism and autophagy suppressed tumor proliferation and increased apoptosis. In vivo studies involved injection of human Rh30 cells into the gastrocnemius muscle of 6-week-old female nude mice, which were divided into normal chow and low-fat diet groups. The mice fed a low-fat diet for 21 days showed reduced tumor growth compared to normal chow diet-fed mice. Suppression of lipid metabolism disrupted the equilibrium of the cancer-specific metabolism in rhabdomyosarcoma, resulting in a tumor growth-inhibition effect. Therefore, the development of treatments focusing on the lipid dependence of rhabdomyosarcoma is highly promising.

PMID:34472721 | DOI:10.1002/cam4.4185
SNAI2-mediated repression of BIM protects rhabdomyosarcoma from ionizing radiation

Fetched: September 1st, 2021, 5:01am GMT by Long Wang

Cancer Res. 2021 Aug 30:canres.4191.2020. doi: 10.1158/0008-5472.CAN-20-4191. Online ahead of print.

ABSTRACT

Ionizing radiation (IR) and chemotherapy are mainstays of treatment for patients with rhabdomyosarcoma (RMS), yet the molecular mechanisms that underlie the success or failure of radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator of IR sensitivity in normal and malignant stem cells through its repression of the proapoptotic BH3-only gene PUMA. Here, we demonstrate a clear correlation between SNAI2 expression levels and radiosensitivity across multiple RMS cell lines. Modulating SNAI2 levels in RMS cells through its overexpression or knockdown altered radiosensitivity in vitro and in vivo. SNAI2 expression reliably promoted overall cell growth and inhibited mitochondrial apoptosis following exposure to IR, with either variable or minimal effects on differentiation and senescence, respectively. Importantly, SNAI2 knockdown increased expression of the proapoptotic BH3-only gene BIM, and ChIP-seq experiments established that SNAI2 is a direct repressor of BIM. Since the p53 pathway is nonfunctional in the RMS cells used in this study, we have identified a new, p53-independent SNAI2/BIM signaling axis that could potentially predict clinical responses to IR treatment and be exploited to improve RMS therapy.

PMID:34462275 | DOI:10.1158/0008-5472.CAN-20-4191
Rare Adult Subtype of Rhabdomyosarcoma, a Common Childhood Soft Tissue Carcinoma

Fetched: August 31st, 2021, 5:01am GMT by Manasa Dondapati

J Investig Med High Impact Case Rep. 2021 Jan-Dec;9:23247096211042236. doi: 10.1177/23247096211042236.

ABSTRACT

Rhabdomyosarcoma is a malignant soft tissue sarcoma of primitive mesenchymal cells, showing varying degrees of striated skeletal muscle cell differentiation. It is a very common cancer of childhood and adolescence, but rarely seen in the adult population. Here, we present a case of a 33-year-old male presented with a poorly differentiated desmin positive alveolar rhabdomyosarcoma in the left arm. The prognosis of alveolar rhabdomyosarcoma in adults is very poor, frequently detected at advanced stages or with metastases. The alveolar subtype in particular has been found to have a more aggressive course with a high rate of metastasis. Recent studies have shown that using pediatric treatment guidelines resulted in better survival outcomes and local control, but the survival rates are still below that of the pediatric population. Newer studies are looking into using specific molecular markers for more targeted therapy in hopes of further improving survival rates in the adult population.

PMID:34459267 | PMC:PMC8408890 | DOI:10.1177/23247096211042236
Diagnostic and treatment intervals are not associated with survival in rhabdomyosarcoma: A Cancer in Young People in Canada study

Fetched: August 30th, 2021, 5:02am GMT by Sapna Oberoi

Pediatr Blood Cancer. 2021 Aug 29:e29306. doi: 10.1002/pbc.29306. Online ahead of print.

ABSTRACT

BACKGROUND: Delay in diagnosis and treatment initiation can be associated with adverse outcomes in children with cancer. Diagnostic interval (DI) is defined as the time between the date of first health care contact for symptoms related to cancer to the date of cancer diagnosis, and treatment interval (TI) is defined as interval between the definitive cancer diagnosis and cancer treatment initiation. We aimed to determine the predictors of DI and TI in children with rhabdomyosarcoma (RMS) and their association with event-free survival (EFS) and overall survival (OS).

METHODS: Using the Cancer in Young People in Canada (CYP-C) national population-based database, we conducted a retrospective cohort study of children (0-14.99 years) newly diagnosed with RMS between 2001 and 2015 in Canada. Quantile regression was used to assess the predictors of DI and TI, and Cox regression was used to determine if these intervals were associated with EFS and OS.

RESULTS: Median DI and TI were 16.5 days (interquartile range [IQR] 6.0-38.0) and 5 days (IQR 0-12), respectively. DI and TI were not significantly associated with age at diagnosis, sex, race, tumor site, stage or histology, treatment region, distance from treatment center, income quintile or diagnosis year (all p > .05). DI and TI were not associated with EFS (DI: hazard ratio [HR] 1.00, 95% CI 0.96-1.05, p = .871; TI: HR 1.03, 95% CI 1.00-1.05, p = .053) or OS (DI: HR 0.99, 95% CI 0.94-1.05, p = .797; TI: HR 1.02, 95% CI 0.99-1.05, p = .155).

CONCLUSIONS: In the publicly funded Canadian health care system, DI and TI did not affect the survival of children with RMS.

PMID:34455698 | DOI:10.1002/pbc.29306
In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC)

Fetched: August 29th, 2021, 5:01am GMT by Raushan T Kurmasheva

Pediatr Blood Cancer. 2021 Aug 28:e29304. doi: 10.1002/pbc.29304. Online ahead of print.

ABSTRACT

SP-2577(Seclidemstat), an inhibitor of lysine-specific demthylase KDM1A (LSD1) that is overexpressed in pediatric sarcomas, was evaluated against pediatric sarcoma xenografts. SP-2577 (100 mg/kg/day × 28 days) statistically significantly (p < .05) inhibited growth of three of eight Ewing sarcoma (EwS), four of five rhabdomyosarcoma (RMS), and four of six osteosarcoma (OS) xenografts. The increase in EFS T/C was modest (<1.5) for all models except RMS Rh10 (EFS T/C = 2.8). There were no tumor regressions or consistent changes in dimethyl histone H3(K4), HOXM1, DAX1, c-MYC and N-MYC, or tumor histology/differentiation. SP-2577 has limited activity against these pediatric sarcoma models at the dose and schedule evaluated.

PMID:34453478 | DOI:10.1002/pbc.29304
Vertebroplasty as a palliative treatment option for intractable pain in pediatric patients with spinal tumors

Fetched: August 29th, 2021, 5:01am GMT by Leandro Cardarelli-Leite

Pediatr Blood Cancer. 2021 Aug 27:e29307. doi: 10.1002/pbc.29307. Online ahead of print.

ABSTRACT

Primary and secondary malignant tumors of the spine are relatively uncommon in the pediatric population but are associated with high morbidity and significantly decreased quality of life due to pain. Local management of these tumors is often challenging due to the importance of maintaining vertebral mechanical integrity as well as the spinal growth potential. Typically, surgery and/or radiation therapy have been used in the primary management of these tumors. However, treatment options become more limited when there is relapse or refractory disease, with re-resection or additional radiotherapy often not being viable therapies. Vertebroplasty is a currently underutilized modality that might provide significant pain palliation in cases of relapsed cancer in the spine.

PMID:34453400 | DOI:10.1002/pbc.29307
What to Look Out for in a Newborn with Multiple Papulonodular Skin Lesions at Birth

Fetched: August 29th, 2021, 5:01am GMT by Sylvie Fraitag

Dermatopathology (Basel). 2021 Aug 17;8(3):390-417. doi: 10.3390/dermatopathology8030043.

ABSTRACT

Multiple papulonodular skin lesions at birth can indicate the presence of various benign and malignant disorders. Although the lesions' clinical aspect (color and consistency, in particular) may steer the clinician towards one disorder or another (infantile myofibromatosis, xanthogranuloma, or metastatic neuroblastoma), the diagnosis can only be confirmed by the histopathologic assessment of a biopsy. In neonates, a rapid but accurate diagnosis is critical because skin lesions may be the first manifestation of a malignant disorder like leukemia cutis or metastatic neuroblastoma. Here, we review the various disorders that may manifest themselves as multiple skin lesions at birth.

PMID:34449594 | PMC:PMC8395860 | DOI:10.3390/dermatopathology8030043
Primary sinonasal Ewing sarcoma: A case report

Fetched: August 29th, 2021, 5:01am GMT by M F Amri

Malays J Pathol. 2021 Aug;43(2):319-325.

ABSTRACT

BACKGROUND: Ewing sarcoma (ES) is an aggressive tumour which is typically skeletal in origin. ES involving the head and neck region is uncommon and can be easily confused with other small round blue cell tumours. We herein present a rare case of ES involving the sinonasal area.

CASE PRESENTATION: A 5-year-old Somalian boy with no known medical illness presented with progressive nasal blockage associated with clear nasal discharge and intermittent spontaneous epistaxis for three months. CT paranasal sinus and neck region revealed poorly enhancing expansile mass in the right maxillary sinus with areas of necrosis within. Initial radiological differential diagnoses were lymphoma and rhabdomyosarcoma. The mass was biopsied and histologically showed diffuse sheets of small round blue cells that was positive to CD99, NSE and vimentin. The muscle and lymphoid markers were negative. Fluorescence in-situ hybridisation (FISH) study revealed the presence of EWSR1 gene rearrangement thus diagnosis of ES was rendered.

CONCLUSIONS: ES of sinonasal tract is a rare entity and its pathological features significantly overlap with others small round blue cells tumour. Demonstration of EWSR1 gene translocation is recommended for the diagnosis of ES particularly at uncommon sites.

PMID:34448796
Uterine rhabdomyosarcoma complicated by cerebral venous thrombosis and uterine inversion in a young woman: case report and literature review

Fetched: August 29th, 2021, 5:01am GMT by Hongfa Peng

BMC Womens Health. 2021 Aug 26;21(1):314. doi: 10.1186/s12905-021-01459-2.

ABSTRACT

BACKGROUND: Uterine rhabdomyosarcoma is an extremely rare malignant tumor that usually affects young women and has a poor prognosis.

CASE PRESENTATION: A 19-year-old nulliparous woman presented to the emergency department under sedation due to seizures. Imaging examination revealed cerebral venous thrombosis. During thrombolytic therapy, she developed vaginal bleeding followed by uterine inversion secondary to uterine rhabdomyosarcoma. The inverted uterus was mistaken for a cervical tumour and was removed vaginally. The patient's disease progressed despite chemotherapy with vincristine, actinomycin D and cyclophosphamide and she died within 6 months. To our knowledge, this is the first case of uterine rhabdomyosarcoma complicated with cerebral venous thrombosis.

CONCLUSIONS: Malignancy is an important diagnostic in patients with cerebral venous thrombosis with no obvious cause. This case demonstrates the importance of considering uterine neoplasms in the differential diagnosis of adolescent girls with abnormal uterine bleeding. Further, careful anatomical evaluation of vaginal masses should be performed prior to surgical intervention.

PMID:34445980 | PMC:PMC8390075 | DOI:10.1186/s12905-021-01459-2
Semi-Automatic Volumetric and Standard Three-Dimensional Measurements for Primary Tumor Evaluation and Response to Treatment Assessment in Pediatric Rhabdomyosarcoma

Fetched: August 29th, 2021, 5:01am GMT by Ewelina Gowin

J Pers Med. 2021 Jul 26;11(8):717. doi: 10.3390/jpm11080717.

ABSTRACT

Current prognostic classification of rhabdomyosarcoma in children requires precise measurements of the tumor. The purpose of the study was to compare the standard three-dimensional (3D) measurements with semi-automatic tumor volume measurement method concerning assessment of the primary tumor size and the degree of response to treatment for rhabdomyosarcoma in children. Magnetic Resonance Imaging data on 31 children with treated rhabdomyosarcoma based on the Cooperative Weichteilsarkom Studiengruppe (CWS) guidance was evaluated. Tumor sizes were measured by two methods: 3D standard measurements and semi-automatic tumor volume measurement (VOI) at diagnosis, and after 9 and 17/18 weeks of the induction chemotherapy. Response to treatment and prediction values were assessed. The tumor volume medians calculated using VOI were significantly higher in comparison with those calculated using the 3D method both during the diagnosis as well as after 9 weeks of the chemotherapy and during the 17-18th week of the treatment. The volume measurements based on the generalized estimating equations on the VOI method were significantly better than the 3D method (p = 0.037). The volumetric measurements alone can hardly be considered an unequivocal marker used to make decisions on modification of the therapy in patients with rhabdomyosarcoma.

PMID:34442361 | PMC:PMC8399942 | DOI:10.3390/jpm11080717
Progression and Differentiation of Alveolar Rhabdomyosarcoma Is Regulated by PAX7 Transcription Factor-Significance of Tumor Subclones

Fetched: August 29th, 2021, 5:01am GMT by Klaudia Skrzypek

Cells. 2021 Jul 23;10(8):1870. doi: 10.3390/cells10081870.

ABSTRACT

Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the development of RMS are still poorly understood. Therefore, by analysis of two RMS RH30 cell line subclones, one subclone PAX7 negative, while the second one PAX7 positive, and comparison with other RMS cell lines we aimed at identifying new mechanisms crucial for RMS progression. RH30 subclones were characterized by the same STR profile, but different morphology, rate of proliferation, migration activity and chemotactic abilities in vitro, as well as differences in tumor morphology and growth in vivo. Our analysis indicated a different level of expression of adhesion molecules (e.g., from VLA and ICAM families), myogenic microRNAs, such as miR-206 and transcription factors, such as MYOD, MYOG, SIX1, and ID. Silencing of PAX7 transcription factor with siRNA confirmed the crucial role of PAX7 transcription factor in proliferation, differentiation and migration of RMS cells. To conclude, our results suggest that tumor cell lines with the same STR profile can produce subclones that differ in many features and indicate crucial roles of PAX7 and ID proteins in the development of RMS.

PMID:34440639 | PMC:PMC8391953 | DOI:10.3390/cells10081870
Proton beam therapy with concurrent chemotherapy is feasible in children with newly diagnosed rhabdomyosarcoma

Fetched: August 27th, 2021, 5:02am GMT by Ryoko Suzuki

Rep Pract Oncol Radiother. 2021 Aug 12;26(4):616-625. doi: 10.5603/RPOR.a2021.0082. eCollection 2021.

ABSTRACT

BACKGROUND: The optimal treatment for rhabdomyosarcoma (RMS) requires multidisciplinary treatment with chemotherapy, surgery, and radiotherapy. Surgery and radiotherapy are integral to the local control (LC) of RMS. However, postsurgical and radiotherapy-related complications could develop according to the local therapy and tumor location. In this study, we conducted a single-center analysis of the outcomes and toxicity of multidisciplinary treatment using proton beam therapy (PBT) for pediatric RMS.

MATERIALS AND METHODS: RMS patients aged younger than 20 years whose RMS was newly diagnosed and who underwent PBT at University of Tsukuba Hospital (UTH) during the period from 2009 to 2019 were enrolled in this study. The patients' clinical information was collected by retrospective medical record review.

RESULTS: Forty-eight patients were included. The 3-year progression-free survival (PFS) and overall survival (OS) rates of all the patients were 68.8% and 94.2%, respectively. The 3-year PFS rates achieved with radical resection, conservative resection, and biopsy only were 65.3%, 83.3%, and 67.6%, respectively (p = 0.721). The 3-year LC rates achieved with radical resection, conservative resection, and biopsy only were 90.9%, 83.3%, and 72.9%, respectively (p = 0.548). Grade 3 or higher mucositis/dermatitis occurred in 14 patients. Although the days of opioid use due to mucositis/dermatitis during the chemotherapy with PBT were longer than those during the chemotherapy without PBT [6.1 and 1.6 (mean), respectively, p = 0.001], the frequencies of fever and elevation of C-reactive protein were equivalent.

CONCLUSIONS: Multidisciplinary therapy containing PBT was feasible and provided a relatively fair 3-year PFS, even in children with newly diagnosed RMS without severe toxicity.

PMID:34434578 | PMC:PMC8382069 | DOI:10.5603/RPOR.a2021.0082
Local Lung Mass Masquerading a Very Aggressive Extraskeletal Ewing Sarcoma Presenting as Bilateral Paraparesis in a Young Adult

Fetched: August 27th, 2021, 5:02am GMT by Mytri Pokal

J Med Cases. 2020 Dec;11(12):388-393. doi: 10.14740/jmc3582. Epub 2020 Oct 21.

ABSTRACT

Ewing sarcoma is typically seen in children involving long bones. Although well described, its presentation in extraskeletal tissues is relatively rare and is classified as an Ewing sarcoma family of tumors. They are mostly curable when they occur in children. An extraskeletal Ewing sarcoma in adults is uncommon, limiting the experience in adult oncologists. The biopsy is essential for definitive diagnosis, which shows small round blue cells that must be differentiated from lymphoma, embryonal rhabdomyosarcoma, and small cell carcinoma. Management is multimodal, involving surgery, radiation for local treatment of primary tumor, and systemic chemotherapy. A multidisciplinary approach, coupled with risk-adapted intensive neoadjuvant and adjuvant multi-agent chemotherapies and other modalities such as radiation and surgery for control of the primary site and metastatic disease, is needed. The primary multidrug chemotherapy regimen consists of alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and ifosfamide/etoposide (IE) given every 2 weeks with growth factor support. Prognosis and the 5-year survival rate are better for localized than the metastatic disease, and in metastatic disease, it is better for patients with lung metastasis than other metastatic disease sites. We describe a rare extraskeletal tumor arising from a lung that tested positive for Ewing sarcoma, also known as Askin's tumor in a young adult. In our case, the tumor rapidly metastasized locally to involve the thoracic spine causing paraparesis. Timely diagnosis and early management are essential to improve outcomes. We also present how treatment can be delayed due to sepsis and emphasize the careful multispecialty approach's importance.

PMID:34434351 | PMC:PMC8383551 | DOI:10.14740/jmc3582
Clinicopathological and prognostic significance of H3K27 methylation status in malignant peripheral nerve sheath tumor: correlation with skeletal muscle differentiation

Fetched: August 27th, 2021, 5:02am GMT by Yoshihiro Ito

Virchows Arch. 2021 Aug 25. doi: 10.1007/s00428-021-03189-0. Online ahead of print.

ABSTRACT

Malignant peripheral nerve sheath tumor (MPNST) is a very aggressive peripheral nerve sheath-derived sarcoma, which is one of the most difficult tumors to diagnose due to its wide spectrum of histological findings and lack of specific immunohistochemical markers. Recently, it has been reported that losses of expression of H3K27me3 and H3K27me2 caused by PRC2 dysfunction may be useful diagnostic markers for MPNST, but there is no consensus on their clinicopathological significance. Here, we investigated the relationship between loss of H3K27 methylation and various parameters and clarified the clinicopathological significance of such loss. We analyzed the clinicopathological and immunohistochemical features in 84 MPNST cases. Complete losses of H3K27me3 and H3K27me2 were observed in 37 (44%) and 29 (35%) cases, respectively. Losses of H3K27me3 and H3K27me2 were significantly correlated with myogenic immunopositivity (H3K27me3 vs. desmin, P = 0.0051; H3K27me3 vs. myogenin, P = 0.0009; H3K27me2 vs. myogenin, P = 0.042). Meanwhile, there were significant correlations between preservation of immunohistochemical neurogenic markers and intact H3K27me3 and H3K27me2 (H3K27me3 vs. S-100 protein, P = 0.0019; H3K27me3 vs. SOX10, P = 0.014; H3K27me2 vs. S-100 protein, P = 0.0011; H3K27me2 vs. SOX10, P = 0.0087). In multivariate analysis, local recurrence, distant metastasis, high FNCLCC grade, and loss of SOX10 expression were independent prognostic factors for overall survival. H3K27me3 and H3K27me2 expression was retained in all 26 cases of rhabdomyosarcoma non-alveolar subtype. In conclusion, we suggest that H3K27me3 and H3K27me2 immunonegativity is useful but not definitive for diagnosing MPNST. Complete loss of H3K27 methylation may be involved in aggressive transdifferentiation from neural differentiation to skeletal muscle differentiation in MPNST.

PMID:34432163 | DOI:10.1007/s00428-021-03189-0
A bioengineering method for modeling alveolar Rhabdomyosarcoma and assessing chemotherapy responses

Fetched: August 27th, 2021, 5:02am GMT by Evan Stefanek

MethodsX. 2021 Jul 27;8:101473. doi: 10.1016/j.mex.2021.101473. eCollection 2021.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignant tumor. Treatment of RMS usually includes primary tumor resection along with systemic chemotherapy. Two-dimensional (2D) cell culture systems and animal models have been extensively used for investigating the potential efficacy of new RMS treatments. However, RMS cells behave differently in 2D culture than in vivo, which has recently inspired the adoption of three-dimensional (3D) culture environments. In the current paper, we will describe the detailed methodology we have developed for fabricating a 3D engineered model to study alveolar RMS (ARMS) in vitro. This model consists of a thermally cross-linked collagen disk laden with RMS cells that mimics the structural and bio-chemical aspects of the tumor extracellular matrix (ECM). This process is highly reproducible and produces a 3D engineered model that can be used to analyze the cytotoxicity and autophagy induction of drugs on ARMS cells. The most improtant bullet points are as following:•We fabricated 3D model of ARMS.•The current ARMS 3D model can be used for screening of chemotherapy drugs.•We developed methods to detect apoptosis and autophagy in ARMS 3D model to detect the mechansims of chemotherapy agents.

PMID:34430344 | PMC:PMC8374652 | DOI:10.1016/j.mex.2021.101473
Oral epithelioid rhabdomyosarcoma: Report of a rare case and literature review of a distinct variant of rhabdomyosarcoma

Fetched: August 25th, 2021, 5:02am GMT by Carla Isabelly Rodrigues-Fernandes

Oral Oncol. 2021 Aug 20:105498. doi: 10.1016/j.oraloncology.2021.105498. Online ahead of print.

ABSTRACT

Epithelioid rhabdomyosarcoma is a new and rare morphological variant of rhabdomyosarcoma, with only a few reports in the literature. We aimed to describe an atypical case of this variant involving the oral cavity. A 33-year-old male patient presented with an asymptomatic, gingival mass adjacent to the left maxillary canine with progressive growth over approximately 3 months. Microscopic and immunohistochemical assessment of the biopsy specimen were consistent with epithelioid rhabdomyosarcoma. After initial chemotherapy and radiotherapy, the patient had a partial response. Surgical resection was performed, followed by adjuvant chemotherapy. After local and distant recurrences, the patient died 22 months after the initial diagnosis. According to the literature, epithelioid rhabdomyosarcoma still lacks data regarding its aetiologic factors and therapeutic options. Whether this tumour is a true subtype or simply a variant of other subtypes of rhabdomyosarcoma also remains unconfirmed. Final diagnosis leads to a broad array of microscopic and immunohistochemical analyses.

PMID:34426069 | DOI:10.1016/j.oraloncology.2021.105498
PAX3-NCOA1 alveolar rhabdomyosarcoma of the tongue: A rare entity with challenging diagnosis and management

Fetched: August 24th, 2021, 5:04am GMT by Daniela Di Carlo

Pediatr Blood Cancer. 2021 Aug 23:e29288. doi: 10.1002/pbc.29288. Online ahead of print.

ABSTRACT

Alveolar rhabdomyosarcoma (ARMS) is associated with PAX3/PAX7-FOXO1 fusion, which confers specific clinic and biologic characteristics with inferior outcomes. A minority of tumors still histologically classified as "true" ARMS lack the canonical PAX-FOXO1 fusion but have new molecular alterations. We present the first case of PAX3-NCOA1 ARMS with clinical data and follow-up in a two-year-old girl with ARMS of the tongue and nodal extension, treated with chemotherapy, hemi glossectomy, lymph node dissection, and brachytherapy to conserve oral function and limit long-term sequelae. Given the rarity of such variant fusion in ARMS, international collaboration is required to evaluate its prognostic value.

PMID:34424607 | DOI:10.1002/pbc.29288
Paratesticular rhabdomyosarcoma: about a case and literature review

Fetched: August 24th, 2021, 5:04am GMT by Boris Amougou

Pan Afr Med J. 2021 May 26;39:71. doi: 10.11604/pamj.2021.39.71.29224. eCollection 2021.

ABSTRACT

We here report a case of embryonal paratesticular rhabdomyosarcoma in a young adult. The purpose of this study is to highlight this uncommon histological type of tumor in this age group, the rapid evolution of the lesion and the challenges of managing it in our context.

PMID:34422194 | PMC:PMC8363974 | DOI:10.11604/pamj.2021.39.71.29224
Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma

Fetched: August 24th, 2021, 5:04am GMT by Enrico Pozzo

Front Physiol. 2021 Aug 6;12:701354. doi: 10.3389/fphys.2021.701354. eCollection 2021.

ABSTRACT

Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells from uncertain origin. Currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and uncontrolled proliferation of FN-RMS. We and other groups recently found that microRNAs (miRNA) network contributes to myogenic epigenetic memory and can influence pluripotent stem cell commitments. Here, we used the previously identified promyogenic miRNAs and tailored it to the murine FN-RMS. Subsequently, we addressed the effects of miRNAs in vivo by performing syngeneic transplant of pre-treated FN-RMS cell line in C57Bl/6 mice. miRNA pre-treatment affects murine FN-RMS cell proliferation in vivo as showed by bioluminescence imaging analysis, resulting in better muscle performances as highlighted by treadmill exhaustion tests. In conclusion, in our study we identified a novel miRNA combination tackling the anti-myogenic features of FN-RMS by reducing proliferation and described novel antitumorigenic therapeutic targets that can be further explored for future pre-clinical applications.

PMID:34421639 | PMC:PMC8378536 | DOI:10.3389/fphys.2021.701354
Characterization of coxsackievirus A10 strains isolated from children with hand, foot, and mouth disease

Fetched: August 24th, 2021, 5:04am GMT by Jie Zhang

J Med Virol. 2021 Aug 13. doi: 10.1002/jmv.27268. Online ahead of print.

ABSTRACT

Hand, foot, and mouth disease (HFMD) is a contagious disease that threatens the health of children under 5 years of age. Coxsackievirus A10 (CV-A10) is one of the main pathogens of HFMD. Currently, preventive vaccines and specific therapeutic drugs are not available for CV-A10. In this study, a total of 327 stool specimens were collected from pediatric patients from 2009 to 2017 during HFMD surveillance, among which 14 CV-A10 strains could only be isolated from rhabdomyosarcoma cells, but not from KMB17 and Vero cells. Through adaptive culture, 2 and 11 CV-A10 strains were recovered from Vero and KMB17 cell cultures, respectively. The growth of CV-A10 strains in Vero cells was better than that in KMB17 cells. The 14 CV-A10 strains belonged to the F genotype, and the nucleotides and amino acids of their complete genomes shared 92.6%-96.3% and 98.4%-98.9% identities, respectively. The different CV-A10 strains exhibited varying virulence in vivo, but had similar effects on tissue injury, with the hind limb muscles, kidneys, and lungs being severely affected. Additionally, the hind limb muscles had the highest viral loads. CV-A10 was found to exhibit a strong tropism to muscle tissue. The results of this study are critical to developing vaccines against CV-A10 infections.

PMID:34387895 | DOI:10.1002/jmv.27268
Pleuropulmonary Blastoma

Fetched: August 22nd, 2021, 5:01am GMT by Mouna Mlika
2021 Aug 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.

ABSTRACT

Childhood tumors of the lung are rare malignant tumors accounting for 0.5% to 1% of all primary malignant lung tumors. These tumors are subdivided into 3 subtypes: pulmonary blastoma, fetal adenocarcinoma, and pleuropulmonary blastoma (PPB). An epithelial malignant and immature component characterizes fetal adenocarcinoma. A malignant immature mesenchymal proliferation characterizes the pleuropulmonary blastoma. Biphasic components define the blastoma; a mesenchymal and an epithelial malignant and immature component, that look like a 10- to 16-week gestational lung. In the 2015 World Health Organization Classification, fetal adenocarcinoma belongs to the group of adenocarcinomas, pulmonary blastoma belongs to the group of sarcomatoid carcinoma, and pleuropulmonary blastoma belongs to the group of mesenchymal tumors. Pleuropulmonary blastomas are rare tumors which present non-specific symptoms. Although the importance of the radiologic features to suspect the diagnosis, the positive diagnosis remains based on the microscopic features. Many synonyms of pleuropulmonary tumors exist in the literature including:
1. Cystic mesenchymal hamartoma
2. Mesenchymal cystic hamartoma
3. Pediatric pulmonary blastoma
4. Pneumoblastoma
5. Pulmonary rhabdomyosarcoma
6. Rhabdomyosarcoma in lung cyst
PMID:30480950 | Bookshelf:NBK534211
Amplification of ERBB2 (HER2) in embryonal rhabdomyosarcoma: a potential treatment target in rare cases?

Fetched: August 22nd, 2021, 5:01am GMT by Shamik Mitra

Genes Chromosomes Cancer. 2021 Aug 21. doi: 10.1002/gcc.22996. Online ahead of print.

ABSTRACT

The ERBB2 gene encodes a receptor tyrosine kinase also known as HER2. The gene is amplified and overexpressed in one-fifth of breast carcinomas; patients with such tumors benefit from targeted treatment with trastuzumab or other drugs blocking the receptor. In addition, ERBB2 has been shown to be amplified and/or overexpressed in a variety of other malignancies. Notably, both alveolar and embryonal rhabdomyosarcoma (RMS), especially in children, often show increased expression of ERBB2. Although high-level amplification of the gene has not been described in RMS, its frequent expression at the cell surface of RMS cells has been exploited for chimeric antigen receptor T-cell (CAR T)-based treatment strategies. We here describe two cases of pediatric, fusion-negative embryonal RMS with high-level amplification of the ERBB2 gene. One patient is currently treated with conventional chemotherapy for a recently detected standard risk RMS, whereas the other patient died from metastatic disease. Both tumors displayed focal amplicons (210 and 274 Kb, respectively) in chromosome band 17q12, with proximal and distal borders corresponding to those typically seen in breast cancer. In both tumors, the ERBB2 amplicon correlated with high expression at the RNA and protein levels. Thus, breast cancer-like ERBB2 amplification is a very rare, but recurrent feature of pediatric RMS, and should be exploited as an alternative treatment target.

PMID:34418214 | DOI:10.1002/gcc.22996
Single-cell imaging of T cell immunotherapy responses in vivo

Fetched: August 22nd, 2021, 5:01am GMT by Chuan Yan

J Exp Med. 2021 Oct 4;218(10):e20210314. doi: 10.1084/jem.20210314. Epub 2021 Aug 20.

ABSTRACT

T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell-based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease.

PMID:34415995 | PMC:PMC8383813 | DOI:10.1084/jem.20210314
Ileal rhabdomyosarcoma in a patient with a history of squamous cell lung cancer

Fetched: August 22nd, 2021, 5:01am GMT by B Yavuz

Ann R Coll Surg Engl. 2021 Aug 20. doi: 10.1308/rcsann.2021.0047. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma is an infrequent muscular cancer seen in adults. We present a case of ileal intussusception due to pleomorphic rhabdomyosarcoma in a patient diagnosed previously with squamous cell carcinoma of the lung (SCCL). The patient was a 68-year-old man with a history of SCCL. He was admitted to the emergency department for nausea, emesis and obstipation. Surgical investigation of the abdomen revealed an intussusception caused by a tumour located 160cm distal of the ligament of Treitz. Pathological examination showed that tumour was a primary rhabdomyosarcoma of the ileum. This case contributes to the literature by defining an infrequent presentation of rhabdomyosarcoma causing ileal intussusception in an adult patient.

PMID:34414778 | DOI:10.1308/rcsann.2021.0047
Establishment of an Academic Tissue Microarray Platform as a Tool for Soft Tissue Sarcoma Research

Fetched: August 22nd, 2021, 5:01am GMT by Che-Jui Lee

Sarcoma. 2021 Mar 15;2021:6675260. doi: 10.1155/2021/6675260. eCollection 2021.

ABSTRACT

Soft tissue sarcoma (STS) is a heterogeneous family of rare mesenchymal tumors, characterized by histopathological and molecular diversity. Tissue microarray (TMA) is a tool that allows performing research in orphan diseases in a more efficient and cost-effective way. TMAs are paraffin blocks consisting of multiple small representative tissue cores from biological samples, for example, from multiple donors, diverse sites of disease, or multiple different diseases. In 2015, we began constructing TMAs using archival tumor material from STS patients. Specimens were well annotated in terms of histopathological diagnosis, treatment, and clinical follow-up of the tissue donors. Each TMA block contains duplicate or triplicate 1.0-1.5 mm tissue cores from representative tumor areas selected by sarcoma pathologists. The construction of TMAs was performed with TMA Grand Master (3DHistech). So far, we have established disease-specific TMAs from 7 STS subtypes: gastrointestinal stromal tumor (72 cases included in the array), alveolar soft part sarcoma (n = 12 + 47), clear cell sarcoma (n = 22 + 32), leiomyosarcoma (n = 55), liposarcoma (n = 42), inflammatory myofibroblastic tumor (n = 12 + 21), and alveolar rhabdomyosarcoma (n = 24). We also constructed a multisarcoma TMA covering a representative number of important histopathological subtypes on arrays for screening purposes, namely, angiosarcoma, dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxoid liposarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma, with 7-11 individual cases per subtype. We are currently expanding the list of TMAs with additional sarcoma entities, considering the heterogeneity of this family of tumors. Our extensive STS TMA platform is suitable for rapid and cost-effective morphological, immunohistochemical, and molecular characterization of the tumor as well as for the identification of potential novel diagnostic markers and drug targets. It is readily available for collaborative projects with research partners.

PMID:34413700 | PMC:PMC8369337 | DOI:10.1155/2021/6675260
Tongue Spindle Cell Rhabdomyosarcoma: A Rare Case Report and Literature Review

Fetched: August 20th, 2021, 5:02am GMT by Ursula M Jariod-Ferrer

J Maxillofac Oral Surg. 2021 Sep;20(3):464-469. doi: 10.1007/s12663-020-01447-3. Epub 2020 Sep 26.

ABSTRACT

Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm with its origin in the skeletal muscle and is extremely rare in adults. By the World Health Organization (WHO), a new variant of RMS has been classified, i.e. the spindle cell (Sc) and sclerosing (S) RMS. While the Sc-RMS shows intersecting fascicles of nonpleomorphic spindle cells, the S-RMS is characterized by a marked hyalinization in a pseudovascular growth pattern associated with round-to-spindled tumour cells. According to the analysed data, the Sc/S-RMS variant has a worse outcome than other variants. The new classification of the Sc/S-RMS variant is valuable to the clinical practice. There are not many oral Sc/S-RMS cases reported. The aim of this paper is to demonstrate that an early diagnosis, an adequate treatment and a multidisciplinary approach have a positive effect on the prognosis of the patient. In this study, we analyse a new case of Sc-RMS variant in a young adult with an early diagnosis and a favourable outcome as a result of an appropriated multidisciplinary treatment: early surgery, radiotherapy and chemotherapy treatment.

PMID:34408375 | PMC:PMC8313614 | DOI:10.1007/s12663-020-01447-3
Treatment and management of orbital tumors

Fetched: August 19th, 2021, 5:02am GMT by Michael Zimbelmann

Ophthalmologe. 2021 Aug 18. doi: 10.1007/s00347-021-01471-9. Online ahead of print.

ABSTRACT

BACKGROUND: There are various options for the conservative treatment of the most frequent orbital tumors. These can delay, complement or be superior to the surgical approach, which is often prone to complications.

OBJECTIVE: This article gives a summary of the possible treatment options for the most common orbital tumors in childhood and adulthood.

METHODS: A literature search was carried out and the possible treatment pathways are presented.

RESULTS: 1. Frequent orbital tumors in childhood: a systemic treatment with noncardioselective beta blockers is the primary treatment for capillary orbital hemangiomas. In cases of no response, steroids, interferon alpha or cyclophosphamide are treatment options. Observation is a possible option for smaller dermoid cysts, in cases of progression excision can become necessary. Symptomatic optic nerve gliomas can also be observed and in cases of progression treated with chemotherapy, mTOR/MEK inhibitors or radiotherapy (children > 5 years). Rhabdomyosarcomas are biopsied and subsequently treated by radiotherapy and chemotherapy. 2. Frequent orbital tumors in adulthood: asymptomatic cases of cavernous hemangiomas of the orbit can just be observed. Symptomatic hemangiomas can be surgically excised or treated with radiotherapy. For meningiomas of the optic nerve sheath radiotherapy is a very effective treatment. Surgical excision should be reserved for cases with no prognosis of visual acuity. There is also the option to treat with antiprogesterone. Orbital lymphomas with purely orbital involvement can be treated with radiotherapy, chemotherapy or the application of rituximab.

CONCLUSION: There are now very effective conservative treatment options for many orbital tumors. In some cases a surgical procedure can be avoided and a good visual function can be retained.

PMID:34406460 | DOI:10.1007/s00347-021-01471-9
Expression of SS18-SSX fusion-specific antibody and SSX C-terminal antibody in synovial sarcoma and its diagnostic value

Fetched: August 19th, 2021, 5:02am GMT by X Wang

Zhonghua Bing Li Xue Za Zhi. 2021 Jul 8;50(7):740-744. doi: 10.3760/cma.j.cn112151-20201022-00802.

ABSTRACT

Objective: To investigate the expression and diagnostic value of SS18-SSX fusion-specific antibody and SSX C-terminal antibody in synovial sarcoma (SS). Methods: Immunohistochemical (IHC) EnVision method was used to detect the expression of SS18-SSX fusion-specific antibody and SSX C-terminal antibody in 51 genetically confirmed cases of SS and 94 non-SS tumors diagnosed at Nanjing Jinling Hospital from August 2013 to December 2020. Results: IHC staining for SS18-SSX fusion-specific antibody revealed strongly diffuse nuclear staining in 48 of 51 (48/51, 94.1%) SS cases, whereas none of the 94 non-SS tumors showed any staining. IHC staining for SSX C-terminal antibody showed strongly diffuse nuclear staining in all 51 (51/51, 100%) SS cases; six of the 94 (6/94, 6.4%) non-SS tumors showed variable staining, including two cases each of leiomyosarcoma and fibrosarcoma, and one case each of malignant peripheral nerve sheath tumor and embryonal rhabdomyosarcoma. The sensitivity and specificity of SS18-SSX fusion-specific antibody in diagnosing SS were 94.1% and 100% and these of SSX C-terminal antibody were 100% and 93.6%, respectively. Conclusions: SS18-SSX fusion-specific antibody and SSX C-terminal antibody are highly sensitive and specific markers for SS. Immunohistochemistry using these antibodies may replace FISH or molecular genetic testing in most cases.

PMID:34405607 | DOI:10.3760/cma.j.cn112151-20201022-00802
Germline ATM mutation and somatic PIK3CA and BCOR mutations found in an infant with aggressive orbital embryonal rhabdomyosarcoma

Fetched: August 18th, 2021, 5:02am GMT by Pimkwan Jaru-Ampornpan

Am J Ophthalmol Case Rep. 2021 Aug 4;23:101189. doi: 10.1016/j.ajoc.2021.101189. eCollection 2021 Sep.

ABSTRACT

PURPOSE: To report a case of aggressive infantile orbital embryonal rhabdomyosarcoma harboring germline ATM mutation and 2 somatic mutations as revealed by next-generation sequencing and the potential application for personalized therapy.

OBSERVATIONS: A 7-month-old male developed a rapidly progressive left proptosis over 6 weeks due to a large medial orbital mass. Biopsy revealed embryonal rhabdomyosarcoma. After the first cycle of chemotherapy, re-imaging showed interval tumor enlargement with intracranial extension. Craniotomy, combined with orbital exenteration, was performed. Tumor specimens and blood samples were sent for 596 gene DNA sequencing panels with RNA-sequencing focused on actionable mutations as well as gene fusion detection. Sequencing revealed 3 clinically relevant mutations: a germline ATM loss-of-function (LOF) mutation, a somatic PIK3CA gain-of-function mutation, and a somatic BCOR LOF mutation. No chromosomal translocation was detected. Workup for metastasis was positive for bone marrow involvement. Despite standard high-dose adjuvant chemotherapy in combination with radiation therapy, the patient died 10 months later with metastatic diseases.

CONCLUSIONS AND IMPORTANCE: This case highlights an aggressive form of embryonal rhabdomyosarcoma in an infantile orbit. The presence of germline mutation may explain the increased chemo-resistance and adverse prognosis, and may be used as the target for genomic-directed therapy.

PMID:34401606 | PMC:PMC8353380 | DOI:10.1016/j.ajoc.2021.101189
Intracardiac malignant nonchromaffin paraganglioma (chemodectoma) in a cat

Fetched: August 17th, 2021, 5:02am GMT by R Saunders

J Vet Cardiol. 2021 Jul 22;37:1-7. doi: 10.1016/j.jvc.2021.07.002. Online ahead of print.

ABSTRACT

A 5-year-old male castrated Domestic Shorthair cat was presented to a veterinary specialty hospital for evaluation of large-volume pleural effusion. Echocardiography revealed a large intracardiac mass at the level of the interatrial septum impairing right atrial inflow resulting in lymphocytic pleural effusion and ascites. Differential diagnoses included lymphoma, hemangiosarcoma, rhabdomyosarcoma, chemodectoma, neurofibrosarcoma, myxoma, metastatic carcinoma or intracardiac thrombus, abscess or granuloma. Due to poor long-term prognosis and recurrent, large-volume pleural effusion, the cat was humanely euthanized. The heart was submitted for histopathologic evaluation. The mass was subsequently determined to be a malignant extra-adrenal nonchromaffin paraganglioma (chemodectoma) arising from the pulmonary trunk near its bifurcation in the region of the glomus pulmonale. Chemodectomas are rare in cats and to the authors' knowledge, there are no reports of one originating from the glomus pulmonale.

PMID:34399378 | DOI:10.1016/j.jvc.2021.07.002
A case of primary CNS embryonal rhabdomyosarcoma with PAX3-NCOA2 fusion and systematic meta-review

Fetched: August 17th, 2021, 5:02am GMT by Ryuma Tanaka

J Neurooncol. 2021 Sep;154(2):247-256. doi: 10.1007/s11060-021-03823-6. Epub 2021 Aug 16.

ABSTRACT

PURPOSE: Primary central nervous system (CNS) rhabdomyosarcoma is a rare mesenchymal tumor predominantly seen in children and associated with a poor outcome. We report a case of primary CNS rhabdomyosarcoma with PAX3-NCOA2 fusion and present a systematic meta-review of primary CNS rhabdomyosarcoma to characterize this rare tumor.

METHODS: We present the case of a 6-year-old boy with primary CNS rhabdomyosarcoma in the posterior fossa. In a systematic meta-review, we compare the demographic data of primary CNS rhabdomyosarcoma with data of rhabdomyosarcoma at all sites from the SEER database and analyze clinical factors associated with survival outcome.

RESULTS: Our patient underwent gross total resection and received vincristine, actinomycin-D, cyclophosphamide with early introduction of concurrent focal radiation and remained alive with no evidence of disease for 2 years after the end of therapy. Histopathological review revealed embryonal-type rhabdomyosarcoma, and whole-transcriptome analysis revealed PAX3 (EX6)-NCOA2 (EX12) fusion. In all, 77 cases of primary CNS rhabdomyosarcoma were identified through the meta-review. The demographic data of primary CNS rhabdomyosarcoma were similar to data of rhabdomyosarcoma at all sites. Overall and event-free survival outcomes were available for 64 and 56 patients, respectively, with a 3-year OS of 29.0% and a 3-year EFS of 25.7%. The group that received trimodal treatment exhibited better survival outcomes, with a 3-year OS of 57.4% and a 3-year EFS of 46.3%.

CONCLUSIONS: Primary CNS rhabdomyosarcoma shares common histological, molecular, and demographic features with non-CNS rhabdomyosarcoma. A trimodal treatment approach with early introduction of radiation therapy may result in favorable survival outcomes.

PMID:34398431 | DOI:10.1007/s11060-021-03823-6
Single-cell transcriptional profiling reveals the heterogeneity in embryonal rhabdomyosarcoma

Fetched: August 17th, 2021, 5:02am GMT by Bo Hong

Medicine (Baltimore). 2021 Aug 6;100(31):e26775. doi: 10.1097/MD.0000000000026775.

ABSTRACT

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, and embryonal rhabdomyosarcoma is the most typical type of rhabdomyosarcoma. The heterogeneity, etiology, and origin of embryonal rhabdomyosarcoma remain unknown.After obtaining the gene expression data of every cell in the tumor tissue by single-cell RNA sequencing, we used the Seurat package in R studio for quality control, analysis, and exploration of the data. All cells are divided into tumor cells and non-tumor cells, and we chose tumor cells by marker genes. Then, we repeated the process to cluster the tumor cells and divided the subgroups by their differentially expressed genes and gene ontology/Kyoto Encyclopedia of Genes and Genomes analysis. Additionally, Monocle 2 was used for pseudo-time analysis to obtain the evolution trajectory of cells in tumor tissues.Tumor cells were divided into 5 subgroups according to their functions, which were characterized by high proliferation, sensing and adaptation to oxygen availability, enhanced epigenetic modification, enhanced nucleoside phosphonic acid metabolism, and ossification. Evolution trajectory of cells in tumor tissues is obtained.We used pseudo-time analysis to distinguish between mesenchymal stem cells and fibroblasts, proved that embryonal rhabdomyosarcoma in the pelvic originated from skeletal muscle progenitor cells, showed the evolutionary trajectory of embryonal rhabdomyosarcoma, and improved the method of evaluating the degree of malignancy of embryonal rhabdomyosarcoma.

PMID:34397824 | PMC:PMC8341243 | DOI:10.1097/MD.0000000000026775
Analysis of Extended Resection of Limb Soft Tissue Leiomyosarcoma

Fetched: August 17th, 2021, 5:02am GMT by Qiang Liu

Biomed Res Int. 2021 Aug 3;2021:2106972. doi: 10.1155/2021/2106972. eCollection 2021.

ABSTRACT

Leiomyosarcoma is an uncommon soft tissue sarcoma that composed of malignant mesenchymal cells with distinct features of the smooth muscle lineage. Typically affects the uterus and gastrointestinal tract, it can rarely be seen in large blood vessels, lymphatic and glandular duts, the mesentery, the omentum, retroperitoneum, and limbs. Occurrence is particularly rare in the limb region. Retrospective study based on patient records and postoperative pathological histological features. Four patients with limb leiomyosarcoma that were operated between 2016 and 2020 were included, three of them arising in the subcutis of the thigh region and one in cubitus. Extend resection with satisfactory outcomes is reported. Pathological examination showed that masses were composed of a fascicular arrangement of hyperchromatic spindle-shaped cells, characterized by the proliferation of epithelioid cells with eosinophilic cytoplasm for epithelioid leiomyosarcoma. Leiomyosarcomas that arise in the soft tissue, although rare, should be differentiated from other lesions, such as neurilemoma, neurofibroma, liomyoma,lipomyoma, synoviosarcoma, rhabdomyosarcoma, malignant fibrous histiotoma, and malignant neurinoma.

PMID:34395610 | PMC:PMC8357493 | DOI:10.1155/2021/2106972
DICER1 Mutation Detected in an Infant Guides Accurate Diagnosis of Auto-Amputated Embryonal Rhabdomyosarcoma

Fetched: August 15th, 2021, 5:02am GMT by Lydia M Nashed

J Pediatr Adolesc Gynecol. 2021 Aug 11:S1083-3188(21)00267-9. doi: 10.1016/j.jpag.2021.08.006. Online ahead of print.

ABSTRACT

BACKGROUND: The DICER1 mutation is a pathogenic, germline mutation that predisposes patients to uncommon malignancies at a young age.

CASE: A six-month-old female presented with vaginal bleeding and a protruding vaginal mass of unclear pathogenesis. Chemotherapy was initially targeted toward a germ cell tumor; following pathologic testing and auto-amputation of the tumor, the patient was diagnosed with a rare DICER1 associated embryonal rhabdomyosarcoma. Subsequently, her treatment course was restructured and family genetic surveillance instituted.

SUMMARY AND CONCLUSION: Consideration for DICER1 mutation in tumors with complex pathology and unique presentation is critical to aid in diagnosis, management, and direct future comprehensive surveillance.

PMID:34390861 | DOI:10.1016/j.jpag.2021.08.006
Expression of oncogenic HRAS in human Rh28 and RMS-YM rhabdomyosarcoma cells leads to oncogene-induced senescence

Fetched: August 15th, 2021, 5:02am GMT by Jenny J Li

Sci Rep. 2021 Aug 13;11(1):16505. doi: 10.1038/s41598-021-95355-2.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. The two predominant histologic variants of RMS, embryonal and alveolar rhabdomyosarcoma (eRMS and aRMS, respectively), carry very different prognoses. While eRMS is associated with an intermediate prognosis, the 5-year survival rate of aRMS is less than 30%. The RMS subtypes are also different at the molecular level-eRMS frequently has multiple genetic alterations, including mutations in RAS and TP53, whereas aRMS often has chromosomal translocations resulting in PAX3-FOXO1 or PAX7-FOXO1 fusions, but otherwise has a "quiet" genome. Interestingly, mutations in RAS are rarely found in aRMS. In this study, we explored the role of oncogenic RAS in aRMS. We found that while ectopic oncogenic HRAS expression was tolerated in the human RAS-driven eRMS cell line RD, it was detrimental to cell growth and proliferation in the human aRMS cell line Rh28. Growth inhibition was mediated by oncogene-induced senescence and associated with increased RB pathway activity and expression of the cyclin-dependent kinase inhibitors p16 and p21. Unexpectedly, the human eRMS cell line RMS-YM, a RAS wild-type eRMS cell line, also exhibited growth inhibition in response to oncogenic HRAS in a manner similar to aRMS Rh28 cells. This work suggests that oncogenic RAS is expressed in a context-dependent manner in RMS and may provide insight into the differential origins and therapeutic opportunities for RMS subtypes.

PMID:34389744 | PMC:PMC8363632 | DOI:10.1038/s41598-021-95355-2
Childhood head and neck cancer in France: Incidence, survival and trends from 2000 to 2015

Fetched: August 15th, 2021, 5:02am GMT by Luc Person

Int J Pediatr Otorhinolaryngol. 2021 Aug 3;150:110858. doi: 10.1016/j.ijporl.2021.110858. Online ahead of print.

ABSTRACT

INTRODUCTION: Childhood head and neck cancers (HNC) are rare and represent a complex group of anatomical topographies. The aim of this study is to describe the distribution, the incidence and survival rates of children with malignant HNC in France.

METHODS: A population-based study was conducted between 2000 and 2015 in children less than 15 years with a diagnosis of HNC using the French National Registry of Childhood Cancers database (RNCE). Age-standardized incidence rates (ASR) and survival analysis were performed.

RESULTS: The 1623 included HNC represented 5.6% of all cancers included in the RNCE. The thyroid was the leading tumor site category (26.6%), followed by head and neck soft tissue location (15.4%) and the nasopharynx (10.8%). The most common cancers were thyroid gland carcinomas (26.1%), rhabdomyosarcomas (23.9%) and Burkitt Lymphomas (8.6%). Nasopharynx cancers and soft-tissue sarcomas were statistically more frequent in boys, while thyroid carcinomas were significantly more frequent in girls. The annual ASR was 8.6 new cancer cases per million children. For all HNC combined, the 5-year overall survival (OS) was 87.7% [95%CI: 85.9-89.2]. There was no statistically significant variation in 5-year OS between 2000-2007 and 2008-2015.

CONCLUSIONS: Epidemiological data on HNC distribution, incidence and survival contributes to better understand these tumors by quantifying their impact on the French population and assessing their burden. Regarding the exclusion of topographies and some histological origins performed by some authors, this report proposes new recommendations to study HNC in a pediatric population.

PMID:34388659 | DOI:10.1016/j.ijporl.2021.110858
Evidence of pioneer factor activity of an oncogenic fusion transcription factor

Fetched: August 14th, 2021, 5:02am GMT by Benjamin D Sunkel

iScience. 2021 Jul 16;24(8):102867. doi: 10.1016/j.isci.2021.102867. eCollection 2021 Aug 20.

ABSTRACT

Recent characterizations of pioneer transcription factors provide insights into their structures and patterns of chromatin recognition associated with their roles in cell fate commitment and transformation. Intersecting with these basic science concepts, identification of pioneer factors (PFs) fused together as driver translocations in childhood cancers raises questions of whether these fusions retain the fundamental ability to invade repressed chromatin, consistent with their monomeric PF constituents. This study defines the cellular and chromatin localization of PAX3-FOXO1, an oncogenic driver of childhood rhabdomyosarcoma (RMS), derived from a fusion of PFs. To quantitatively define its chromatin-targeting functions and capacity to drive epigenetic reprogramming, we developed a ChIP-seq workflow with per-cell normalization (pc-ChIP-seq). Our quantitative localization studies address structural variation in RMS genomes and reveal insights into inactive chromatin localization of PAX3-FOXO1. Taken together, our studies are consistent with pioneer function for a driver oncoprotein in RMS, with repressed chromatin binding and nucleosome-motif targeting.

PMID:34386729 | PMC:PMC8346656 | DOI:10.1016/j.isci.2021.102867
Hemoperitoneum Due to Ruptured Botryoid Sarcoma of the Uterus in Young Girl

Fetched: August 14th, 2021, 5:02am GMT by Rajendran Ramaswamy

J Indian Assoc Pediatr Surg. 2021 Jul-Aug;26(4):262-264. doi: 10.4103/jiaps.JIAPS_131_20. Epub 2021 Jul 12.

ABSTRACT

Five-year-old girl presented with lower abdominal pain, pelvi-abdominal mass, and generalized abdominal tenderness. Ultrasound and computed tomography scans diagnosed heterogeneous pelvi-abdominal soft-tissue mass and a large amount of free peritoneal fluid. Laparotomy revealed hemoperitoneum and ruptured tumor at the posterior uterine wall. Histopathology report was botryoid rhabdomyosarcoma (BRMS). This case is unique due to ruptured BRMS of the uterus in early childhood, with no vaginal bleeding.

PMID:34385773 | PMC:PMC8323582 | DOI:10.4103/jiaps.JIAPS_131_20
Role of (18)F-FDG-PET/CT in the staging of metastatic rhabdomyosarcoma: a report from the European paediatric Soft tissue sarcoma Study Group

Fetched: August 14th, 2021, 5:02am GMT by Federico Mercolini

Eur J Cancer. 2021 Sep;155:155-162. doi: 10.1016/j.ejca.2021.07.006. Epub 2021 Aug 9.

ABSTRACT

BACKGROUND: Initial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes magnetic resonance imaging, chest computed tomography (CT) and bone scintigraphy, but 18 Fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (¹⁸F-FDG-PET/CT (PET-CT)) use is increasing. The aim of this study was to evaluate the impact of PET-CT in the initial staging of patients with metastatic rhabdomyosarcoma enrolled in the European protocol MTS2008.

METHODS: Two authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared.

RESULTS: Among 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118 of 121 patients, both PET-CT and radiological reports were available for review. PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% versus 78.5%, P value = 0.0013) and distant lymph node involvement (94.8% versus 79.3%, P value = 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% versus 100%, P value = 0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% versus 67.9%, P value = 0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively. The mean number of metastatic sites was 1.94 (range 0-5) with PET-CT and 1.72 (range 0-5) with SRW. In four patients (3.4%), PET-CT changed the staging from localised to metastatic disease.

CONCLUSION: PET can identify metastatic disease not evident on SRW in a small number of patients. This is because of its higher ability to recognise lymph node and bone involvement. Chest CT remains essential to detect lesions in intrathoracic sites, which can be performed in a one stop-shot routine examination or on a dedicated chest CT scan. PET-CT could replace bone scintigraphy to study bone involvement.

PMID:34385068 | DOI:10.1016/j.ejca.2021.07.006
Reasonable Attempt at a Randomized Trial in Relapsed Rhabdomyosarcoma

Fetched: August 13th, 2021, 5:02am GMT by Abha A Gupta

J Clin Oncol. 2021 Sep 20;39(27):2977-2978. doi: 10.1200/JCO.21.01631. Epub 2021 Aug 12.

NO ABSTRACT

PMID:34383578 | DOI:10.1200/JCO.21.01631
What is the likelihood of nonpulmonary metastasis occurring in the absence of lung metastasis in bone and soft tissue sarcoma? A nested case-control from a sarcoma referral centre

Fetched: August 13th, 2021, 5:02am GMT by Obada Hasan

J Surg Oncol. 2021 Aug 12. doi: 10.1002/jso.26645. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Nonpulmonary metastases (NPM) are rare, associated with a poorer prognosis, and maybe missed on conventional chest imaging for sarcoma surveillance. We determined (1) the proportion of NPM occurring in isolation or with synchronous or prior pulmonary metastases (PM), and (2) if initial NPM would have been recognized with a standard surveillance protocol.

METHODS: Investigators identified patients who developed initial NPM without prior evidence of or concurrent PM from an ongoing cohort of bone and soft tissue sarcoma (STS) patients. Logistic regression at univariate level was done.

RESULTS: There were 138/630 (22%) patients with metastasis and 66 (10%) had NPM: 50 (8%) patients had PM presenting first, while 16 (3%) had initial NPM. Malignant peripheral nerve sheath tumor, angiosarcoma, rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma were six times more likely to develop initial NPM than other subtypes of STS with odds ratio = 6 (95% confidence interval: 1.93-18.65, p value < 0.01). Chest imaging and physical examination were sufficient to identify NPM in all except three bone sarcoma patients.

CONCLUSIONS: Patients who develop initial NPM are rare and demonstrate a predilection towards some subtypes of extremity sarcoma. They develop oligometastatic disease, which may be amenable for surgical excision. All isolated or initial NPM in STS patients were discovered by physical examination and standard chest imaging.

PMID:34382687 | DOI:10.1002/jso.26645
An Unusual Enteric Yolk Sac Tumor: First Report of an Ovarian Germ Cell Tumor Associated With a Germline Pathogenic Variant in DICER1

Fetched: August 13th, 2021, 5:02am GMT by W Glenn McCluggage

Int J Gynecol Pathol. 2021 Aug 11. doi: 10.1097/PGP.0000000000000818. Online ahead of print.

ABSTRACT

A variety of unusual tumors are associated with both germline and somatic DICER1 pathogenic variants (PVs), including, in the female genital tract, embryonal rhabdomyosarcoma at various sites and ovarian Sertoli-Leydig cell tumor. There have been occasional reported cases of ovarian germ cell tumors [mainly yolk sac tumor (YST)] harboring DICER1 PVs but, as far as we are aware, none of these has been proven to have a germline provenance. We report an unusual enteric variant of ovarian YST in a 28-yr-old woman associated with a germline PV c.901C>T (p.Gln301Ter) in exon 7 of DICER1, accompanied by a somatic (YST-only) hotspot mutation: c.5437G>A, p.E1813K. To our knowledge, this is the first report of an ovarian germ cell tumor associated with a germline DICER1 PV. We review other reported cases of ovarian germ cell tumor with DICER1 PVs and discuss the differential diagnosis of this unusual variant of YST which was originally diagnosed as a mucinous adenocarcinoma.

PMID:34380971 | DOI:10.1097/PGP.0000000000000818
Genome research project detected TP53mutation in a girl with rhabdomyosarcoma

Fetched: August 12th, 2021, 5:02am GMT by Ida Behrendt-Møller

Ugeskr Laeger. 2021 Aug 9;183(32):V03210228.

ABSTRACT

In this case report, a germ line genome project identified a pathogenic variant in TP53 in a three-year-old girl diagnosed with rhabdomyosarcoma. The variant causes the cancer predisposition syndrome Li-Fraumeni syndrome (LFS). The girl's family was genetically counselled, and the same variant was identified in her mother and sister. The family was afterwards offered surveillance according to national guidelines. With this report, we want to focus on cancer predisposition syndromes and to discuss the benefits regarding surveillance of children with LFS.

PMID:34378529
Integrative analysis of lncRNA-miRNA-mRNA-associated competing endogenous RNA regulatory network involved in EV71 infection

Fetched: August 12th, 2021, 5:02am GMT by Yanzhi Lu

Am J Transl Res. 2021 Jul 15;13(7):7440-7457. eCollection 2021.

ABSTRACT

The competing endogenous RNA (ceRNA) axis has been shown to play a critical role in the pathogenesis of various viral infections. Generally, the ceRNA network involves long non-coding RNAs (lncRNAs) that act as sponges for miRNA to regulate mRNA expression. However, no information is available regarding the involvement of ceRNA networks in Enterovirus type 71 (EV71) infections. In the present study, data obtained from Gene Expression Omnibus (GEO) database was analyzed using various bioinformatics tools. EV71 infection in rhabdomyosarcoma (RD) cells was associated with differential expression of six lncRNAs, 28 miRNAs, and 349 mRNAs. Gene function enrichment analysis suggested induction of cytoplasmic vesicle process upon EV71 infection. The ceRNA networks were constructed, in which 20 hub genes were predicted by protein-protein interaction. To confirm the MALAT1/miR-194-5p/DUSP1 ceRNA regulatory axis in EV71 infection, real-time quantitative polymerase chain reaction (qRT-PCR) and luciferase reporter assay were performed. The results of the study also revealed the involvement of the MALAT1/miR-194-5p axis in apoptosis induced by EV71 infection, while no association with autophagy was observed. Thus, the present study provided novel insights into the pathogenic mechanism of EV71 infection.

PMID:34377228 | PMC:PMC8340214
PRC2: an epigenetic multiprotein complex with a key role in the development of rhabdomyosarcoma carcinogenesis

Fetched: August 11th, 2021, 5:01am GMT by Stefano Zoroddu

Clin Epigenetics. 2021 Aug 9;13(1):156. doi: 10.1186/s13148-021-01147-w.

ABSTRACT

Skeletal muscle formation represents a complex of highly organized and specialized systems that are still not fully understood. Epigenetic systems underline embryonic development, maintenance of stemness, and progression of differentiation. Polycomb group proteins play the role of gene silencing of stemness markers that regulate muscle differentiation. Enhancer of Zeste EZH2 is the catalytic subunit of the complex that is able to trimethylate lysine 27 of histone H3 and induce silencing of the involved genes. In embryonal Rhabdomyosarcoma and several other tumors, EZH2 is often deregulated and, in some cases, is associated with tumor malignancy. This review explores the molecular processes underlying the failure of muscle differentiation with a focus on the PRC2 complex. These considerations could open new studies aimed at the development of new cutting-edge therapeutic strategies in the onset of Rhabdomyosarcoma.

PMID:34372908 | PMC:PMC8351429 | DOI:10.1186/s13148-021-01147-w
Embryonic cervical rhabdomyosarcoma complicated with uterine inversion with cerebral venous sinus thrombosis as the first symptom: a case report and literature review

Fetched: August 10th, 2021, 5:01am GMT by Li Meng

J Int Med Res. 2021 Aug;49(8):3000605211031776. doi: 10.1177/03000605211031776.

ABSTRACT

The probability of rhabdomyosarcoma occurring in the cervix is less than 0.5% and may be associated with a pathogenic dicer 1, ribonuclease III (DICER1) gene variation. Tumour-induced hypercoagulability and high levels of cancer antigen (CA) 125 are risk factors for cerebral venous sinus thrombosis (CVST). In addition, although nonpuerperal uterine inversion is very rare and is usually caused by leiomyomas from the uterus, large cervical masses can also be the cause. This case report describes a 24-year-old woman with uterine inversion caused by an embryonic cervical rhabdomyosarcoma that presented with CVST as her first symptom. The patient underwent laparoscopic total uterus and bilateral salpingectomy, during which the uterus was found to be completely inverted. Postoperative pathology confirmed embryonic cervical rhabdomyosarcoma. The patient quickly developed lung and para-aortic lymph node metastases. Two months later, the patient died of complications. When coagulation indices in patients with tumours are abnormal, especially when the levels of D-dimer and CA125 increase, it is recommended that anticoagulant therapy is administered in a timely manner to prevent the occurrence of CVST. Furthermore, for large cervical tumours, physicians should also be alert to the occurrence of uterine inversion.

PMID:34369193 | PMC:PMC8358511 | DOI:10.1177/03000605211031776
Autoantibody profiling of alveolar rhabdomyosarcoma patients unveils tumor-associated antigens with diagnostic and prognostic significance

Fetched: August 10th, 2021, 5:01am GMT by Elena Poli

Oncoimmunology. 2021 Jul 25;10(1):1954765. doi: 10.1080/2162402X.2021.1954765. eCollection 2021.

ABSTRACT

Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive subtype of childhood cancer for which efficacious treatments are needed. Immunotherapy represents a new therapeutic opportunity to pursue, but it requires the identification of worthwhile tumor antigens. Herein, we exploited the capacity of ARMS autoantibodies to recognize tumor self-antigens, probing human protein microarrays with plasma from ARMS patients and healthy subjects. We assessed the autoantibody response in ARMS, validated data with independent techniques, and estimated autoantibodies diagnostic and prognostic significance by receiver-operator characteristic curves (ROC), uni- and multivariate analysis. Of the 48 tumor antigens identified, General Transcription Factor II-I (GTF2i) and Protocadherin Gamma Subfamily C5 (PCDHGC5) were selected as candidate targets to validate tumor-restricted antigen expression and autoantibody reactivity through an independent technique and wider cohort of cases. GTF2i and PCDHGC5 overexpression was observed in tumor tissues compared to normal counterparts, and anti-GTF2i and -PCDHGC5 autoantibodies were found able to distinguish ARMS patients from healthy subjects as well as cases with different histology. Moreover, low levels of PCDHGC5 autoantibodies characterized patients with worse event-free survival and proved to be an independent negative prognostic factor. This approach provided the first comprehensive autoantibody profile of ARMS, gave novel insights into the immune response of this malignancy and paved the way toward novel potential antibody-based therapeutic applications suitable to improve the survival of ARMS patients.

PMID:34367733 | PMC:PMC8312597 | DOI:10.1080/2162402X.2021.1954765
Protein Arginine Methyltransferase (PRMT) Inhibitors-AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures

Fetched: August 8th, 2021, 5:01am GMT by Joanna Janisiak

Int J Mol Sci. 2021 Jul 27;22(15):8023. doi: 10.3390/ijms22158023.

ABSTRACT

Rhabdomyosarcoma (RMS) is a malignant soft tissue cancer that develops mostly in children and young adults. With regard to histopathology, four rhabdomyosarcoma types are distinguishable: embryonal, alveolar, pleomorphic and spindle/sclerosing. Currently, increased amounts of evidence indicate that not only gene mutations, but also epigenetic modifications may be involved in the development of RMS. Epigenomic changes regulate the chromatin architecture and affect the interaction between DNA strands, histones and chromatin binding proteins, thus, are able to control gene expression. The main aim of the study was to assess the role of protein arginine methyltransferases (PRMT) in the cellular biology of rhabdomyosarcoma. In the study we used two pan-inhibitors of PRMT, called AMI-1 and SAH, and evaluated their effects on proliferation and apoptosis of RMS cells. We observed that AMI-1 and SAH reduce the invasive phenotype of rhabdomyosarcoma cells by decreasing their proliferation rate, cell viability and ability to form cell colonies. In addition, microarray analysis revealed that these inhibitors attenuate the activity of the PI3K-Akt signaling pathway and affect expression of genes related to it.

PMID:34360791 | PMC:PMC8348967 | DOI:10.3390/ijms22158023
Rhabdomyosarcoma of the Cervix in a Post-Menopausal Woman-An Unparalleled Phenomenon

Fetched: August 8th, 2021, 5:01am GMT by Jakub Pawlik

Int J Environ Res Public Health. 2021 Jul 24;18(15):7851. doi: 10.3390/ijerph18157851.

ABSTRACT

Rhabdomyosarcoma of the cervix is a soft tissue sarcoma that usually occurs in young women. It is very rare in adulthood. We discuss symptoms, the process of diagnosis of rhabdomyosarcoma embryonale of the cervix in a 61-year-old women and differences in treatment dependent on patient's age. A 61-year-old woman with symptoms such as palpable mass in the external cervical opening and post-menopausal hemorrhaging was admitted to the oncology ward where excision of the polyp was performed. Embryonal rhabdomyosarcoma (ERMS) was diagnosed by histopathological examination of obtained tissues. The diagnosis was complemented by chest computed tomography and pelvis magnetic resonance imaging to exclude metastases. A Wertheim-Meigs operation and excision of the ovaries, the fallopian tubes and the surrounding tissue was performed in the course of treatment. In the patient's follow-up of 25 months to date, there have been no signs of recurrence or symptoms connected to ERMS. Based on the therapeutic outcome, the decision to limit the treatment to a surgical resection was adequate for a post-menopausal patient. Because of the rarity of ERMS in the post-menopausal age, we think that the patient should be carefully followed up to further examine this issue and develop diagnostic and treatment guidelines.

PMID:34360144 | PMC:PMC8345433 | DOI:10.3390/ijerph18157851
HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy

Fetched: August 8th, 2021, 5:01am GMT by Carla De Giovanni

Cells. 2021 Jul 16;10(7):1808. doi: 10.3390/cells10071808.

ABSTRACT

Rhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features allow for distinction between subtypes: morphology and presence/absence of a translocation between the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy. HER family members could be exploited for therapeutic approaches in two ways: blocking the HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting expressed HER members to vehiculate toxins or immune effectors.

PMID:34359977 | PMC:PMC8305095 | DOI:10.3390/cells10071808
Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors

Fetched: August 8th, 2021, 5:01am GMT by Atsushi Makimoto

Cancers (Basel). 2021 Jul 23;13(15):3698. doi: 10.3390/cancers13153698.

ABSTRACT

Most pediatric cancers are highly chemo-sensitive, and cytotoxic chemotherapy has always been the mainstay of treatment. Anthracyclines are highly effective against most types of childhood cancer, such as neuroblastoma, hepatoblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, and so forth. However, acute and chronic cardiotoxicity, one of the major disadvantages of anthracycline use, limits their utility and effectiveness. Hydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), which targets tumor tissue highly selectively via the enhanced permeability and retention (EPR) effect, and secondarily releases active pirarubicin molecules quickly into the acidic environment surrounding the tumor. Although, the latter rarely occurs in the non-acidic environment surrounding normal tissue. This mechanism has the potential to minimize acute and chronic toxicities, including cardiotoxicity, as well as maximize the efficacy of chemotherapy through synergy with tumor-targeting accumulation of the active molecules and possible dose-escalation. Simply replacing doxorubicin with P-THP in a given regimen can improve outcomes in anthracycline-sensitive pediatric cancers with little risk of adverse effects, such as cardiotoxicity. As cancer is a dynamic disease showing intra-tumoral heterogeneity during its course, continued parallel development of cytotoxic agents and molecular targeting agents is necessary to find potentially more effective treatments.

PMID:34359599 | PMC:PMC8345214 | DOI:10.3390/cancers13153698
Rhabdomyosarcoma in the maxillary gingiva of a child patient

Fetched: August 5th, 2021, 5:02am GMT by Yuko Komatsu

J Surg Case Rep. 2021 Jul 31;2021(7):rjab322. doi: 10.1093/jscr/rjab322. eCollection 2021 Jul.

ABSTRACT

Rhabdomyosarcoma (RMS) is a rare, rapidly growing and aggressive malignant neoplasm mainly affecting children. However, mean age at the diagnosis of patients with gingival RMS is 26.9 years. A 12-year-old girl presented to our clinic with a chief complaint of trismus. The examination findings indicated a malignant tumor in the left maxillary gingiva. We performed a biopsy of the tumor, and the histopathological diagnosis was RMS. We report a rare case of primary RMS of the maxillary gingiva in a child patient.

PMID:34345404 | PMC:PMC8326001 | DOI:10.1093/jscr/rjab322
$Permalink for 'Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer'$
Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer

Fetched: August 4th, 2021, 5:02am GMT by Anne-Sophie Defachelles

J Clin Oncol. 2021 Aug 3:JCO2100124. doi: 10.1200/JCO.21.00124. Online ahead of print.

ABSTRACT

PURPOSE: The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS).

METHODS: In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m² once a day on day 1 and day 8) and irinotecan (50 mg/m² once a day from day 1 to day 5) with and without temozolomide (125 mg/m² once a day from day 1 to day 5 and 150 mg/m² once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445).

RESULTS: Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025).

CONCLUSION: The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.

PMID:34343032 | DOI:10.1200/JCO.21.00124
PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma in Schuurs-Hoeijmakers syndrome

Fetched: August 4th, 2021, 5:02am GMT by Teppei Ohkawa

J Hum Genet. 2021 Aug 2. doi: 10.1038/s10038-021-00965-3. Online ahead of print.

ABSTRACT

PAX3/7-FOXO1 fusion-negative alveolar rhabdomyosarcoma (ARMS) developed in a patient presenting with intellectual disability and dysmorphic facial features. Whole exome sequencing analysis of a germline sample identified a PACS1 c.607 C>T de novo variant and the patient was diagnosed with Schuurs-Hoeijmakers syndrome (SHS). SHS is a rare disease characterized by intellectual disability and dysmorphic facial features, among various physical abnormalities, due to PACS1 c.607 C>T de novo variant. Due to the rarity of the SHS, diagnosis based on phenotypic information is difficult. To date, there have been no previous reports describing malignancy associated with SHS. Comprehensive somatic mutation analysis revealed a unique pattern of genetic alterations in the PAX3/7-FOXO1 fusion-negative ARMS tumor, including mutations in the oncogene, HRAS; MYOD1, a molecule essential for muscle differentiation; and KMT2C and TET1, genes encoding factors involved in epigenetic regulation. Although the role of PACS1 in tumorigenesis is unclear, it is reported to function in apoptosis regulation. Our case suggests that PACS1 could have a novel role in oncogenesis.

PMID:34341476 | DOI:10.1038/s10038-021-00965-3
Rhabdomyosarcoma on the Forelimb of a Common Musk Turtle (Sternotherus odoratus)

Fetched: August 4th, 2021, 5:02am GMT by Sarah Schwarz

J Comp Pathol. 2021 Jul;186:73-76. doi: 10.1016/j.jcpa.2021.06.002. Epub 2021 Jul 16.

ABSTRACT

Malignant mesenchymal tumours are only rarely reported in turtles. In the present case, an 8-year-old female common musk turtle (Sternotherus odoratus) was presented with a solid, reddened, non-mobile mass on the right forelimb. The mass had a thin, membranous lining and a grey-white cut surface. Histological examination revealed a cell-rich, focally infiltrative neoplasm consisting of spindloid tumour cells arranged in bundles and streams. Rarely, indistinct cytoplasmic cross-striations were seen in the neoplastic cells. Transmission electron microscopy revealed cytoplasmic, disorganized muscle fibrils and haphazardly arranged, attenuated Z-lines in the neoplastic cells. The histological, histochemical and ultrastructural findings led to the diagnosis of a rhabdomyosarcoma. This is the first description of rhabdomyosarcoma in a freshwater turtle.

PMID:34340808 | DOI:10.1016/j.jcpa.2021.06.002
Somatic-type Malignancies in Testicular Germ Cell Tumors: A Clinicopathologic Study of 63 Cases

Fetched: August 3rd, 2021, 5:02am GMT by Michael J Hwang

Am J Surg Pathol. 2021 Aug 2. doi: 10.1097/PAS.0000000000001789. Online ahead of print.

ABSTRACT

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality.

PMID:34334690 | DOI:10.1097/PAS.0000000000001789
Loss of p16/Ink4a drives high frequency of rhabdomyosarcoma in a rat model of Duchenne muscular dystrophy

Fetched: August 3rd, 2021, 5:02am GMT by Naomi Teramoto

J Vet Med Sci. 2021 Jul 31. doi: 10.1292/jvms.21-0243. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma (RMS) is an aggressive type of soft tissue sarcoma, and pleomorphic RMS is a rare subtype of RMS found in adult. p16 is a tumor suppressor which inhibits cell cycle. In human RMS, p16 gene is frequently deleted, but p16-null mice do not develop RMS. We reported that genetic ablation of p16 by the crossbreeding of p16 knock-out rats (p16-KO rats) improved the dystrophic phenotype of a rat model of Duchenne muscular dystrophy (Dmd-KO rats). However, p16/Dmd double knock-out rats (dKO rats) unexpectedly developed sarcoma. In the present study, we raised p16-KO, Dmd-KO, and dKO rats until 11 months of age. Twelve out of 22 dKO rats developed pleomorphic RMS after 9 months of age, while none of p16-KO rats and Dmd-KO rats developed tumor. The neoplasms were connected to skeletal muscle tissue with indistinct borders and characterized by diffuse proliferation of pleomorphic cells which had eosinophilic cytoplasm and atypical nuclei with anisokaryosis. For almost all cases, the tumor cells immunohistochemically expressed myogenic markers including desmin, MyoD, and myogenin. The single cell cloning from tumor primary cells gained 20 individual Pax7-negative MyoD-positive RMS cell clones. Our results demonstrated that double knock-out of p16 and dystrophin in rats leads to the development of pleomorphic RMS, providing an animal model that may be useful to study the developmental mechanism of pleomorphic RMS.

PMID:34334511 | DOI:10.1292/jvms.21-0243
Recurrence and treatment of adult primary nonmetastatic bladder rhabdomyosarcoma: A systematic review

Fetched: August 2nd, 2021, 5:01am GMT by Andrew Nguyen

Urol Oncol. 2021 Jul 28:S1078-1439(21)00309-4. doi: 10.1016/j.urolonc.2021.07.008. Online ahead of print.

ABSTRACT

INTRODUCTION: While survival for pediatric bladder rhabdomyosarcoma (RMS) has recently improved with risk-based multimodality treatment protocols, survival for adult bladder RMS remains to be poor. Survival is poor likely because adult bladder RMS is rare, understudied, and consequently lacking in high-level evidence to inform standardization of treatment. In addition, adult bladder RMS exhibits high rates of recurrence. The purpose of this systematic review is to determine associations between patient clinicopathologic factors and recurrence for adult primary bladder RMS, as well as to provide an updated survey of the various treatments employed for this disease in adults.

MATERIAL AND METHODS: Studies involving adult primary bladder RMS were acquired from MEDLINE (OVID), Scopus, and Cochrane Central Register of Controlled Trials from 1947 to 2018. Cases with no metastatic disease at diagnosis and at least 6 months follow-up were included. Multivariable Cox-regression hazard analysis was utilized to determine associations of age, sex, histology, and TNM stage with recurrence. Kaplan-Meier analysis and log-rank testing was used to calculate overall survival (OS) for patients who underwent surgical treatment only, and to evaluate differences in survival between radical cystectomy and partial cystectomy.

RESULTS: 20 articles were selected for the review, and 22 cases were obtained. The mean age of the patients was 55.7 ± 18.4 (range = 28-83). With a mean follow-up time of 21.4 ± 18.6 months, 36.4% of the patients experienced disease recurrence. Recurrence was not associated with age, sex, histology, or stage (p = 0.366, p = 0.754, p = 0.889, and p = 0.590, respectively). Most patients underwent surgery only as their initial therapy (n = 12), while the remaining had chemotherapy, radiation, or some combination of these therapies (including surgery). The median OS of patients who underwent surgery only was 21.0 months (95% CI: 0.0-44.6 months). Among these patients, no difference in OS between radical cystectomy and partial cystectomy was found (p = 0.841).

CONCLUSION: Adult bladder RMS is a rare, lethal tumor with a high proclivity for recurrence. No association between age, sex, histology, or stage and recurrence was found. Radical cystectomy is not superior to partial cystectomy in terms of survival, suggesting a role for bladder preservation in select patients. Our study is the first to provide a comprehensive summary of the various treatments employed with clinical outcomes for adult primary bladder RMS.

PMID:34332845 | DOI:10.1016/j.urolonc.2021.07.008
Unusual phenotypes in patients with a pathogenic germline variant in DICER1

Fetched: August 1st, 2021, 5:01am GMT by Kateryna Venger

Fam Cancer. 2021 Jul 31. doi: 10.1007/s10689-021-00271-z. Online ahead of print.

ABSTRACT

Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms' tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.

PMID:34331184 | DOI:10.1007/s10689-021-00271-z
Repurposing proscillaridin A in combination with decitabine against embryonal rhabdomyosarcoma RD cells

Fetched: August 1st, 2021, 5:01am GMT by Marielle Huot

Cancer Chemother Pharmacol. 2021 Jul 31. doi: 10.1007/s00280-021-04339-6. Online ahead of print.

ABSTRACT

PURPOSE: Embryonal rhabdomyosarcoma (eRMS) is the most common type of rhabdomyosarcoma in children. eRMS is characterized by malignant skeletal muscle cells driven by hyperactivation of several oncogenic pathways including the MYC pathway. Targeting MYC in cancer has been extremely challenging. Recently, we have demonstrated that the heart failure drug, proscillaridin A, produced anticancer effects with specificity toward MYC expressing leukemia cells. We also reported that decitabine, a hypomethylating drug, synergizes with proscillaridin A in colon cancer cells. Here, we investigated whether proscillaridin A exhibits epigenetic and anticancer activity against eRMS RD cells, overexpressing MYC oncogene, and its combination with decitabine.

METHODS: We investigated the anticancer effects of proscillaridin A in eRMS RD cells in vitro. In response to drug treatment, we measured growth inhibition, cell cycle arrest, loss of clonogenicity and self-renewal capacity. We further evaluated the impact of proscillaridin A on MYC expression and its downstream transcriptomic effects by RNA sequencing. Then, we measured protein expression of epigenetic regulators and their associated chromatin post-translational modifications in response to drug treatment. Chromatin immunoprecipitation sequencing data sets were coupled with transcriptomic results to pinpoint the impact of proscillaridin A on gene pathways associated with specific chromatin modifications. Lastly, we evaluated the effect of the combination of proscillaridin A and the DNA demethylating drug decitabine on eRMS RD cell growth and clonogenic potential.

RESULTS: Clinically relevant concentration of proscillaridin A (5 nM) produced growth inhibition, cell cycle arrest and loss of clonogenicity in eRMS RD cells. Proscillaridin A produced a significant downregulation of MYC protein expression and inhibition of oncogenic transcriptional programs controlled by MYC, involved in cell replication. Interestingly, significant reduction in total histone 3 acetylation and on specific lysine residues (lysine 9, 14, 18, and 27 on histone 3) was associated with significant protein downregulation of a series of lysine acetyltransferases (KAT3A, KAT3B, KAT2A, KAT2B, and KAT5). In addition, proscillaridin A produced synergistic growth inhibition and loss of clonogenicity when combined with the approved DNA demethylating drug decitabine.

CONCLUSION: Proscillaridin A produces anticancer and epigenetic effects in the low nanomolar range and its combination with decitabine warrants further investigation for the treatment of eRMS.

PMID:34331108 | DOI:10.1007/s00280-021-04339-6
A combinatorial drug screen in PDX-derived primary rhabdomyosarcoma cells identifies the NOXA - BCL-XL/MCL-1 balance as target for re-sensitization to first-line therapy in recurrent tumors

Fetched: August 1st, 2021, 5:01am GMT by Gabriele Manzella

Neoplasia. 2021 Jul 27;23(9):929-938. doi: 10.1016/j.neo.2021.07.001. Online ahead of print.

ABSTRACT

First-line therapy for most pediatric sarcoma is based on chemotherapy in combination with radiotherapy and surgery. A significant number of patients experience drug resistance and development of relapsed tumors. Drugs that have the potential to re-sensitize relapsed tumor cells toward chemotherapy treatment are therefore of great clinical interest. Here, we used a drug profiling platform with PDX-derived primary rhabdomyosarcoma cells to screen a large drug library for compounds re-sensitizing relapse tumor cells toward standard chemotherapeutics used in rhabdomyosarcoma therapy. We identified ABT-263 (navitoclax) as most potent compound enhancing general chemosensitivity and used different pharmacologic and genetic approaches in vitro and in vivo to detect the NOXA-BCL-XL/MCL-1 balance to be involved in modulating drug response. Our data therefore suggests that players of the intrinsic mitochondrial apoptotic cascade are major targets for stimulation of response toward first-line therapies in rhabdomyosarcoma.

PMID:34329950 | PMC:PMC8329430 | DOI:10.1016/j.neo.2021.07.001

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