9-ING-41Combined With Chemotherapy in Adolescents and Adults

Posted: May 28th, 2021, 2:00pm GMT

Conditions: Sarcoma; Soft Tissue Sarcoma; Metastatic Sarcoma; Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Leiomyosarcoma; Liposarcoma; Angiosarcoma; Synovial Sarcoma; Rhabdomyosarcoma; Spindle Cell Sarcoma; High Grade Sarcoma; Bone Sarcoma
Interventions: Drug: Gemcitabine; Drug: Docetaxel; Drug: 9-ING-41
Sponsors: Brown University; Actuate Therapeutics Inc.
Not yet recruiting
Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma

Posted: May 25th, 2021, 2:00pm GMT

Conditions: Recurrent Solid Tumor; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Recurrent Wilms Tumor; Refractory Ewing Sarcoma; Refractory Hepatoblastoma; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma
Interventions: Drug: Onivyde; Drug: Talazoparib; Drug: Temozolomide
Sponsors: St. Jude Children's Research Hospital; Pfizer; Ipsen
Recruiting
B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

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

Conditions: Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma
Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells
Sponsor: St. Jude Children's Research Hospital
Not yet recruiting
$Permalink for 'Phase 1/2 Study of Vincristine and Temozolomide in Combination With PEN-866 for Adolescents and Young Adults With Relapsed or Refractory Solid Tumors'$
Phase 1/2 Study of Vincristine and Temozolomide in Combination With PEN-866 for Adolescents and Young Adults With Relapsed or Refractory Solid Tumors

Posted: May 18th, 2021, 2:00pm GMT

Conditions: Sarcoma, Ewing; Rhabdomyosarcoma
Interventions: Drug: PEN-866; Drug: Vincristine; Drug: Temozolomide
Sponsor: National Cancer Institute (NCI)
Not yet recruiting
Indo-cyanine Green (ICG) in Paediatric Oncology MIS

Posted: April 22nd, 2021, 2:00pm GMT

Conditions: Pediatric Renal Tumor; Metastatic Osteosarcoma; Metastatic Ewing Sarcoma; Pulmonary Metastasis; Rhabdomyosarcoma; Non-Rhabdo. Soft Tissue Sarcoma
Intervention: Drug: Indocyanine green
Sponsor: Birmingham Women's and Children's NHS Foundation Trust
Not yet recruiting
A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors

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

Conditions: Solid Tumors; Soft Tissue Sarcoma; Ewing Sarcoma; Malignant Epithelial Neoplasm; Rhabdomyosarcoma; Wilms Tumor; Hepatic Tumor; Germ Cell Tumor; Bone Metastases
Interventions: Device: Magnetic Resonance-Guided High Intensity Focused Ultrasound; Drug: Lyso-thermosensitive Liposomal Doxorubicin
Sponsor: Children's National Research Institute
Not yet recruiting
Molecular Characterization of Genetic Alterations in Pediatric Solid Tumors

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

Condition: Pediatric Solid Tumors
Intervention:
Sponsor: National Council of Scientific and Technical Research, Argentina
Recruiting
$Permalink for 'B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$
B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Posted: July 23rd, 2020, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma; Melanoma
Interventions: Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR; Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
Sponsor: Seattle Children's Hospital
Recruiting
Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

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

Conditions: Liver Cancer; Rhabdomyosarcoma; Malignant Rhabdoid Tumor; Liposarcoma; Wilms Tumor; Yolk Sac Tumor
Interventions: Genetic: AGAR T cells; Drug: Cytoxan; Drug: Fludara
Sponsors: Baylor College of Medicine; Center for Cell and Gene Therapy, Baylor College of Medicine
Not yet recruiting
$Permalink for 'Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma'$
Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma

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

Condition: Rhabdomyosarcoma
Interventions: Drug: Vinorelbine; Drug: Mocetinostat
Sponsors: Jonsson Comprehensive Cancer Center; Mirati Therapeutics Inc.; Phase One Foundation
Recruiting
A Study of the Drugs Prexasertib, Irinotecan, and Temozolomide in People With Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

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

Conditions: Desmoplastic Small Round Cell Tumor; Rhabdomyosarcoma
Interventions: Drug: Prexasertib; Drug: Irinotecan
Sponsor: Memorial Sloan Kettering Cancer Center
Recruiting
Indocyanine Green (ICG) Guided Tumor Resection

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

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

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

Conditions: Solid Tumors; Ewing Sarcoma; Rhabdoid Tumor; Rhabdomyosarcoma; Neuroblastoma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma
Interventions: Drug: Palbociclib; Drug: Temozolomide; Drug: Irinotecan; Drug: Topotecan; Drug: Cyclophosphamide
Sponsor: Pfizer
Recruiting
$Permalink for 'EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$
EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

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

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma
Interventions: Biological: second generation 4-1BBζ EGFR806-EGFRt; Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Sponsor: Seattle Children's Hospital
Recruiting
$Permalink for 'Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma'$
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma

Posted: March 27th, 2018, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Pediatric Lymphoma; Pediatric Brain Tumor; DIPG; Neuroblastoma; Ewing Sarcoma; Rhabdomyosarcoma; Osteosarcoma
Intervention: Drug: CLR 131
Sponsor: Cellectar Biosciences, Inc.
Recruiting
Clinical and Biological Activity of an Anti-PD-L1 (Atezolizumab) in Operable Localised Soft Tissue Sarcomas Patients to be Treated With Radiotherapy

Posted: March 22nd, 2018, 2:00pm GMT

Condition: Sarcoma,Soft Tissue
Interventions: Combination Product: Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery; Combination Product: 2 cycles of atezolizumab followed by surgery then post-operative radiotherapy; Combination Product: Pre-operative radiotherapy followed by surgery then 2 cycles of atezolizumab.
Sponsors: Centre Leon Berard; Roche Pharma AG
Recruiting
International PPB/DICER1 Registry

Posted: December 22nd, 2017, 3:00pm GMT

Conditions: Pleuropulmonary Blastoma; Sertoli-Leydig Cell Tumor; DICER1 Syndrome; Cystic Nephroma; Wilms Tumor; Pineoblastoma; Renal Sarcoma; Nodular Hyperplasia of Thyroid; Nasal Chondromesenchymal Hamartoma; Ciliary Body Medulloepithelioma; Neuroblastoma; Pituitary Cancer; Embryonal Rhabdomyosarcoma
Intervention:
Sponsors: Children's Hospitals and Clinics of Minnesota; Children's National Research Institute; Washington University School of Medicine; ResourcePath, LLC; Beijing Children's Hospital; University of Cambridge; Emory University; Dana-Farber Cancer Institute
Recruiting
Comparison of Safety and Efficacy of Detaenial Sigmoid Neobladder and Ileal Neobladder

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

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

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

Conditions: Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease
Intervention:
Sponsor: St. Jude Children's Research Hospital
Recruiting
Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in People With Embryonal and Alveolar Rhabdomyosarcoma

Posted: February 3rd, 2017, 3:00pm GMT

Conditions: Rhabdomyosarcoma; Rhabdomyosarcoma- Alveolar; Rhabdomyosarcoma-Embryonal
Interventions: Drug: Dasatinib; Drug: Ganitumab
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
Phase I Trial of Universal Donor NK Cell Therapy in Combination With ALT803

Posted: September 7th, 2016, 2:00pm GMT

Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Myeloproliferative Syndromes; Plasma Cell Myeloma; Colon Carcinoma; Adenocarcinoma of Rectum; Soft Tissue Sarcoma; Ewing's Sarcoma; Rhabdomyosarcoma
Interventions: Biological: Natural Killer (NK) Cells; Biological: ALT803
Sponsor: David Wald
Recruiting
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors

Posted: July 24th, 2015, 2:00pm GMT

Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Syndrome; Rhabdomyosarcoma; Ewing Sarcoma; Primitive Neuroectodermal Tumor; Osteosarcoma; Neuroblastoma
Interventions: Procedure: TCRαβ+/CD19+ depleted Haploidentical HSCT; Drug: Zoledronate
Sponsor: University of Wisconsin, Madison
Recruiting
Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

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

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

PubMed - Rhabdomyosarcoma

European guideline for imaging in paediatric and adolescent rhabdomyosarcoma - joint statement by the European Paediatric Soft Tissue Sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society o

Fetched: June 18th, 2021, 5:02am GMT by Roelof van Ewijk

Pediatr Radiol. 2021 Jun 17. doi: 10.1007/s00247-021-05081-0. Online ahead of print.

ABSTRACT

Appropriate imaging is essential in the treatment of children and adolescents with rhabdomyosarcoma. For adequate stratification and optimal individualised local treatment utilising surgery and radiotherapy, high-quality imaging is crucial. The paediatric radiologist, therefore, is an essential member of the multi-disciplinary team providing clinical care and research. This manuscript presents the European rhabdomyosarcoma imaging guideline, based on the recently developed guideline of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) Imaging Committee. This guideline was developed in collaboration between the EpSSG Imaging Committee, the Cooperative Weichteilsarkom Studiengruppe (CWS) Imaging Group, and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR). MRI is recommended, at diagnosis and follow-up, for the evaluation of the primary tumour and its relationship to surrounding tissues, including assessment of neurovascular structures and loco-regional lymphadenopathy. Chest CT along with [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT or PET/MRI are recommended for the detection and evaluation of loco-regional and distant metastatic disease. Guidance on the estimation of treatment response, optimal long-term follow-up, technical imaging settings and standardised reporting are described. This European imaging guideline outlines the recommendations for imaging in children and adolescents with rhabdomyosarcoma, with the aim to harmonise imaging and to advance patient care.

PMID:34137936 | DOI:10.1007/s00247-021-05081-0
Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas

Fetched: June 17th, 2021, 5:02am GMT by Daisuke Ichikawa

NPJ Genom Med. 2021 Jun 15;6(1):49. doi: 10.1038/s41525-021-00210-y.

ABSTRACT

Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies.

PMID:34131151 | DOI:10.1038/s41525-021-00210-y
Childhood Rhabdomyosarcoma Treatment (PDQ): Health Professional Version

Fetched: June 16th, 2021, 5:02am GMT by PDQ Pediatric Treatment Editorial Board

2021 Jun 9. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–.

ABSTRACT

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood rhabdomyosarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

PMID:26389243 | Bookshelf:NBK65802
Clinicopathological analysis and genomic profiling of a rare histiocyte-rich rhabdomyoblastic tumor: A case report

Fetched: June 16th, 2021, 5:02am GMT by Yan Xia

Medicine (Baltimore). 2021 Jun 18;100(24):e26105. doi: 10.1097/MD.0000000000026105.

ABSTRACT

RATIONALE: Skeletal muscle tumors are traditionally classified as rhabdomyomas or rhabdomyosarcomas. However, some soft tissue tumors cannot easily be identified as benign or malignant. We report a case of a histiocyte-rich rhabdomyoblastic tumor, with pathologic characteristics distinct from either rhabdomyoma or rhabdomyosarcoma. In contrast to rhabdomyosarcomas, the tumor cells exhibited low mitotic activity, lacking obvious morphologic atypia. Clinically, the tumor followed a very indolent course. Overall, the tumor did not fit classification criteria for either benign or malignant.

PATIENT CONCERNS: A 58-year-old Chinese man was admitted to Qilu Hospital on September 8, 2018, with a >20 year history of a mass in the middle of the left thigh. A few months prior to admission, he had experienced the pain from the mass extending to the distal left lower extremity. He had no prior history of significant disease or relevant family history.

DIAGNOSES: Microscopically, numerous histiocytes and foamy cells covered the actual tumor cells that were positive for desmin, MyoD1, and myogenin, suggesting striated skeletal muscle cell differentiation. However, cross-striations were not detected in the tumor cells. The tumor was characterized by a non-infiltrative growth pattern and a low level of Ki67. A diagnosis of histiocyte-rich rhabdomyoblastic tumor was suggested.

INTERVENTIONS: The thigh mass was surgically resected September 12, 2018.

OUTCOMES: The patient recovered well postoperatively, and was free of tumor recurrence or metastasis, followed to September 12, 2020 (23 months).

LESSONS: Histiocyte-rich rhabdomyoblastic tumor cells have minor atypia, indicating possible malignant potential. However, the tumor behavior was quit indolent. Due to the conflicting clinical and pathologic aspects of the tumor, to label it as rhabdomyosarcoma seemed inaccurate, potentially prompting over treatment. Interestingly, mutations were detected in NF1, AXIN2, CHEK2, DNMT3A, KMT2D, and RB1 through next-generation sequencing. These mutations suggest disruptions in Ras signaling, the Wnt pathway, methyltransferases, and the cell cyclepotentially influencing the development of this histiocyte-rich rhabdomyoblastic tumor. This unusual tumor should be incorporated into the WHO Classification of Soft Tissue Tumors owing to its unique characteristics.

PMID:34128847 | DOI:10.1097/MD.0000000000026105
$Permalink for 'Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults'$
Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults

Fetched: June 16th, 2021, 5:02am GMT by Hee Young Ju

Cancer Res Treat. 2021 Jun 14. doi: 10.4143/crt.2021.178. Online ahead of print.

ABSTRACT

PURPOSE: No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults.

MATERIALS AND METHODS: We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5mg/m2 intravenously on day 1, irinotecan, 50mg/m2/day intravenously on days 1-5, and temozolomide, 100mg/m2/day orally on days 1-5.

RESULTS: A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (CR + PR + SD) of 52%. PR was seen in one (50%) of the 2 evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at two years, respectively. There was no treatment-related mortality.

CONCLUSION: The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

PMID:34126703 | DOI:10.4143/crt.2021.178
Primary intratesticular rhabdomyosarcoma, a rare entity: A case report with review of literature

Fetched: June 15th, 2021, 5:02am GMT by Pavan Kumar Lachi

J Cancer Res Ther. 2021 Apr-Jun;17(2):590-592. doi: 10.4103/jcrt.JCRT_585_15.

ABSTRACT

Paratesticular rhabdomyosarcoma is a very rare mesenchymal tumor. It is an intrascrotal tumor that is localized in paratesticular structures such as the epididymis or spermatic cord. Rhabdomyosarcoma is most often observed in children and adolescents, presenting as a painless scrotal mass. An 18-year-old man presented with a painless left scrotal mass and lump abdomen that had evolved over four months. A histological examination of the lesion revealed rhabdomyosarcoma. Chemotherapy with alternative cycles of Vincristine, Adriamycin, Cyclophosphamide followed by Ifosphamide, Etoposide was given. Paratesticular rhabdomyosarcoma is a rare aggressive tumor manifesting in children and very young adults. Localized forms have a good prognosis whereas metastatic tumors show very poor results. A well-defined treatment based on surgery and chemotherapy yields good results.

PMID:34121716 | DOI:10.4103/jcrt.JCRT_585_15
Radiation cystitis: A late effect of radiotherapy in a patient with cervical rhabdomyosarcoma

Fetched: June 15th, 2021, 5:02am GMT by Rituraj Upadhyay

J Cancer Res Ther. 2021 Apr-Jun;17(2):580-583. doi: 10.4103/jcrt.JCRT_500_19.

ABSTRACT

We report the case of a 22-year old female presenting with an embryonal rhabdomyosarcoma of the cervix that was successfully treated by surgery followed by adjuvant radiation therapy and chemotherapy. She subsequently developed radiation cystitis after 10 years of follow-up. She was successfully treated with cystoscopic fulguration. In this report, we discuss a review of management strategies for cervical rhabdomyosarcoma and also throw some light on incidence and management of radiation cystitis after pelvic radiotherapy. We discuss the dose independence of radiation cystitis, which can be seen after as low as 4500 cGy of pelvic radiation.

PMID:34121713 | DOI:10.4103/jcrt.JCRT_500_19
The fetal outcomes after neoadjuvant platinum and paclitaxel chemotherapy during pregnancy: analysis of three cases and review of the literature

Fetched: June 12th, 2021, 5:01am GMT by Ming Wang

Arch Gynecol Obstet. 2021 Jun 11. doi: 10.1007/s00404-021-06113-8. Online ahead of print.

ABSTRACT

OBJECTIVE: Data on the outcomes of fetus who are exposed to neoadjuvant platinum and paclitaxel chemotherapy during pregnancy are lacking.

METHODS: Relevant data were abstracted from patients in our institution, PubMed, Embase and Cochrane Library databases. The primary assessment was the frequency of fetal death and congenital abnormalities. The secondary assessment was other negative fetal/infant outcomes including FGR, RDS, secondary malignant diseases and other recorded adverse events.

RESULTS: Of the three infants in our center who exposed to platinum and paclitaxel chemotherapy during pregnancy, the physical evaluation and qualified Denver Developmental Screening Test showed normal findings at the last follow-up (19-24 months). Hearing evaluation among three children also showed normal findings. Another 34 infants (including a twins) of 21 studies in previous studies who exposed to platinum and paclitaxel chemotherapy during pregnancy were included in the final analysis. Of the 37 infants identified, 24 were exposed to cisplatin plus paclitaxel, and 13 were exposed to carboplatin plus paclitaxel. None of the 37 fetuses was abortion or dead during the pregnancy. 97.3% (36/37) infants were delivered by cesareans and the median gestational ages of delivery were 34.76 weeks (95% CI, 34.08-35.44). 1 fetus showed intrauterine growth restriction and one was found with left-sided ventriculomegaly and hydramnios before chemotherapy. Adverse events occurred in 18.9% (7/37) infants at birth, including two RDS, one hearing loss, one pathological jaundice, one first-degree intraventricular hemorrhage, one erythema, one corresponding to -0.5 standard deviation from average body weight of the same gestational weeks. No reports of neonatal cardiologic abnormalities are reported in these infants after the initiating of chemotherapy. The infant with congenital anomaly died 5 days after birth. During the follow-up, 5.4% (2/37) of the infants were diagnosed with malignant diseases. One retroperitoneal embryonal rhabdomyosarcoma at 5 years old and one acute myeloid leukemia at 22 months of age. 32/37 (86.5%) children were healthy at the end of follow-ups (median 33 months, IQR 15.75-54.25 months).

CONCLUSIONS: Our results showed that neoadjuvant platinum and paclitaxel combined chemotherapy was a feasible and safe choice for the management of patients with cervical and ovarian cancer during the second and third trimesters of gestation.

PMID:34115181 | DOI:10.1007/s00404-021-06113-8
ASO Visual Abstract: The Value of the Sentinel Node Procedure in Pediatric Extremity Rhabdomyosarcoma-A Systematic Review and Retrospective Cohort Study

Fetched: June 11th, 2021, 5:02am GMT by Bernadette Jeremiasse

Ann Surg Oncol. 2021 Jun 10. doi: 10.1245/s10434-021-10076-0. Online ahead of print.

NO ABSTRACT

PMID:34110525 | DOI:10.1245/s10434-021-10076-0
Expanding mutational spectrum of HRAS by a patient with Schimmelpenning-Feuerstein-Mims syndrome

Fetched: June 11th, 2021, 5:02am GMT by Qi Luo

J Dermatol. 2021 Jun 9. doi: 10.1111/1346-8138.15922. Online ahead of print.

ABSTRACT

As one of the epidermal nevus syndromes, Schimmelpenning-Feuerstein-Mims (SFM) is characterized by craniofacial nevus sebaceous (NS) and extracutaneous abnormalities (e.g., brain, eyes, and bone). Here, we report a case of a 4-year-old boy who presented with significant skin abnormalities (NS in the scalp, extensive epidermal nevus along Blaschko's lines), ocular abnormalities (strabismus), central nervous system abnormalities (seizure and mental retardation), lymphatic dysplasia (chylous pleural and pericardial effusion), cardiac abnormalities (patent foramen ovale), urogenital system abnormalities (cryptorchidism, hypospadias), and a tumor predisposition (embryonal rhabdomyosarcoma). DNA samples from NS, rhabdomyosarcoma, and peripheral blood leukocytes were analyzed by next-generation sequencing. A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a mosaic state in NS, rhabdomyosarcoma, and peripheral blood leukocytes, with different ratio of heterozygous mutation (HRAS c.38G>T) of 39.90% (9412/23 588 reads), 73.03% (205 562/281 468 reads), and 14.16% (15 837/111 842 reads), respectively. By predicting the impact of the mutation on the biological function of protein, we found that the novel HRAS mutation (c.38G>T; p.Gly13Val) had the highest damaging scores among other HRAS mutations reported so far. This is the first reported SFM syndrome patient with novel mosaic HRAS mutation, which may help to expand the mutational spectrum of HRAS and better understand the role of HRAS in the disease.

PMID:34109654 | DOI:10.1111/1346-8138.15922
PAX7 Is a Sensitive Marker of Skeletal Muscle Differentiation in Rhabdomyosarcoma and Tumors With Rhabdomyosarcomatous Differentiation in the Female Genital Tract

Fetched: June 11th, 2021, 5:02am GMT by Julianna J Weiel

Int J Gynecol Pathol. 2021 Jun 9. doi: 10.1097/PGP.0000000000000799. Online ahead of print.

ABSTRACT

In the female genital tract, rhabdomyosarcoma may occur in "pure" form or as a heterologous constituent of a biphasic neoplasm such as carcinosarcoma or adenosarcoma. Discriminating rhabdomyosarcoma from its histologic mimics relies on confirmation of skeletal muscle differentiation by morphology or immunohistochemistry (IHC), which can be challenging to interpret in some cases owing to limited expression. PAX7, a transcription factor expressed in mammalian muscle progenitor cells, has been reported in up to 86% of soft tissue rhabdomyosarcomas by IHC. To determine whether PAX7 IHC could augment current approaches to identify rhabdomyosarcoma in gynecologic malignancies, we assessed PAX7, myogenin, and MyoD1 IHC on whole tissue sections from 100 gynecologic tumors: 50 with rhabdomyosarcomatous differentiation and 50 with features mimicking rhabdomyosarcoma. PAX7 expression was present in 96% (48/50) of gynecologic tumors with rhabdomyosarcomatous differentiation and was absent in all rhabdomyosarcoma mimics; it was more diffusely expressed than myogenin in 16 cases and was positive in a greater percentage of tumor cells in 28 cases. PAX7 and myogenin were typically coexpressed, and no rhabdomyosarcoma exhibited complete absence of both markers; however, 2 myogenin-negative tumors were PAX7-postive. Morphologically, PAX7 localized to the nuclei of primitive-appearing cells, whereas myogenin was observed in maturing rhabdomyoblasts including strap cells. Our findings highlight the utility of PAX7 as a complementary diagnostic marker of rhabdomyosarcomatous differentiation in gynecologic tumors. PAX7 should be used in combination with other markers of skeletal muscle differentiation, namely myogenin, and may be particularly helpful in cases where myogenin and/or MyoD1 expression is limited.

PMID:34108399 | DOI:10.1097/PGP.0000000000000799
Rhabdomyosarcoma: How Advanced Molecular Methods Are Shaping the Diagnostic and Therapeutic Paradigm

Fetched: June 11th, 2021, 5:02am GMT by Petros Giannikopoulos

Pediatr Dev Pathol. 2021 Jun 9:10935266211013621. doi: 10.1177/10935266211013621. Online ahead of print.

ABSTRACT

For the past 40 years, progress in rhabdomyosarcoma (RMS) has been focused on understanding its molecular basis and characterizing the mutations that drive its tumorigenesis and progression. Genetic predisposition to RMS has allowed discovery of key genetic pathways and driver mutations. Subclassification of RMS into embryonal (ERMS) and alveolar (ARMS) subtypes has shifted from histology to PAX-FOXO1 fusion status, and new driver mutations have been found in spindle cell RMS. Comprehensive molecular profiling leveraging genome-scale next-generation sequencing (NGS) indicates that the RAS/RAF/PI3K axis is mutated in the majority of ERMS and modulated by downstream effects of PAX-FOXO1 fusions in ARMS. Because of the continued poor outcome of high-risk RMS, a variety of molecular targets have been or are now being tested in current or recent therapy trials. New techniques such as single cell sequencing, spatial multi-omics, and CRISPR/Cas9 genome editing offer potential for further discovery, but a need for clinically annotated specimens persists.

PMID:34107813 | DOI:10.1177/10935266211013621
Insights into how H19 works in glioma cells. A review article

Fetched: June 10th, 2021, 5:02am GMT by Mohammed A Azab

Cancer Treat Res Commun. 2021 Jun 2;28:100411. doi: 10.1016/j.ctarc.2021.100411. Online ahead of print.

ABSTRACT

Glioblastoma is a highly aggressive brain tumor and considered to be the most common primary one. Recurrence after treatment is a significant problem, with a survival rate after one year of about 39.7%. The recurrence of GBM is linked to different cellular pathways and molecular signaling. Long non-coding RNA (LncRNA) comprises more than 200 nucleotides and is suggested to play a role in controlling genes that regulate the cell cycle, apoptosis and cellular growth in various tissues. Little is known about LncRNA compared to microRNAs, which are extensively studied in the literature. H19 is one of the most plentiful and conserved transcripts suggested to be involved in mammalian development and tumorigenesis. H19 is one of the LncRNA members transcribed by RNA polymerase II, spliced and polyadenylated, and the product is transferred to the cytoplasm without translation. HI9 maps to 1lp15, a region thought to be relevant to some childhood tumors as embryonal rhabdomyosarcoma and Wilm's Tumor. In these tumors, the analysis of the 11p15 locus showed loss of heterozygosity which is a feature associated with the tumor-suppressing activity. However, the role played by H19 in GBM is still enigmatic and needs further extensive evaluation. Uncovering the hidden role of such molecules in the pathogenesis in glioma will help tailor new targeted therapies that may affect the prognosis and survival of GBM.

PMID:34107413 | DOI:10.1016/j.ctarc.2021.100411
Regional air transportation of ovarian tissue for cryopreservation in a prepubertal female with cancer

Fetched: June 10th, 2021, 5:02am GMT by Sophia M V Schermerhorn

Pediatr Blood Cancer. 2021 Jun 8:e29107. doi: 10.1002/pbc.29107. Online ahead of print.

ABSTRACT

Ovarian tissue cryopreservation is the only fertility preservation (FP) option available to prepubescent females receiving gonadotoxic therapy, but it has limited availability. A 6-year-old female was diagnosed with high-risk rhabdomyosarcoma, and the planned treatment carried an 80% risk of ovarian failure. Her parents desired FP, but the nearest center was 500 miles away. The patient underwent oophorectomy at the cancer center with air transport of the tissue to the oncofertility center, where it was successfully cryopreserved. Formation of networks between full-service and limited oncofertility centers in a hub-and-spoke model would increase access to FP services, particularly in children.

PMID:34105898 | DOI:10.1002/pbc.29107
Rare Variant of Adult Rhabdomyosarcoma Presenting as a Palatal Swelling

Fetched: June 10th, 2021, 5:02am GMT by Hafiz Aamer Iqbal

Pak J Med Sci. 2021 May-Jun;37(3):922-925. doi: 10.12669/pjms.37.3.3305.

ABSTRACT

A 26-year-old male was referred to the Department of Oral and Maxillofacial Surgery of a tertiary care hospital in Lahore with chief complaint of painless swelling on the right palate of 40 days duration. Clinical differential diagnosis included squamous cell carcinoma, Ewing sarcoma, fibrosarcoma, neuroblastoma and rhabdomyosarcoma. Computed tomography scan revealed hypodense mass with necrotic changes. Histological examination of the excised tumor revealed malignant neoplasm arranged in fascicles and bundles comprising of spindle cells with pleomorphic, hyperchromatic nuclei and increased atypical mitosis. Immunohistochemical analysis showed negative staining with Cytokeratin, S100, CD34, Stat6, h-Caldesmon and EMA while the tumour cells were positive for desmin, myogenin, smooth muscle actin, CD-99 and MyoD1 thus confirming the diagnosis of spindle cell rhabdomyosarcoma.

PMID:34104191 | PMC:PMC8155427 | DOI:10.12669/pjms.37.3.3305
Bone and soft tissue tumours in children : Proposal for a rational diagnostic approach

Fetched: June 9th, 2021, 5:01am GMT by M Uhl

Radiologe. 2021 Jun 7. doi: 10.1007/s00117-021-00859-7. Online ahead of print.

ABSTRACT

CLINICAL/METHODOLOGICAL ISSUE: Bone and soft tissue tumours are often incidental findings in children. Because they are usually benign tumours, nonspecialised radiologists generally have little experience in the diagnosis and differentiation from malignant tumours. Various imaging techniques are used in the diagnosis of skeletal tumours.

STANDARD RADIOLOGICAL METHODS: Imaging techniques used to evaluate bone and soft tissue tumours include sonography, computed tomography (CT) and magnetic resonance imaging (MRI).

METHODOLOGICAL INNOVATIONS: An algorithm to determine malignancy of bone and soft tissue tumours in children is proposed.

PERFORMANCE: By using the presented algorithms, further diagnostic procedures such as biopsies can be avoided in the majority of children with bone and soft tissue tumours. Aggressive bone lesions and unclear soft tissue tumours are guided to biopsy to confirm diagnosis.

ACHIEVEMENTS: The algorithms presented are based on the proposals of European professional societies and have been adapted by the authors for use in children and adolescents.

PRACTICAL RECOMMENDATIONS: In the clarification of soft tissue tumours, sonography is the first diagnostic tool; depending on the sonographic findings, MRI is the technique for further clarification. Biopsy confirmation of the diagnosis in unclear cases or in cases of probable malignancy should be carried out in a paediatric oncology centre.

PMID:34100121 | DOI:10.1007/s00117-021-00859-7
A Case report: Co-occurrence of IMAGe syndrome and Rhabdomyosarcoma

Fetched: June 9th, 2021, 5:01am GMT by Maria Bolomiti

Cancer Genet. 2021 May 26;256-257:100-105. doi: 10.1016/j.cancergen.2021.05.006. Online ahead of print.

ABSTRACT

IMAGe syndrome is a rare congenital disorder, presenting with intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies (in males). So far only 17 individuals have been diagnosed molecularly with IMAGe syndrome, this patient is the first case of an individual diagnosed with IMAGe and concurrent rhabdomyosarcoma. The patient was born at 30 weeks' gestation and received treatment for hyponatremia and hyperkalemia. At 4 9/12 years of age the patient showed a painless, non-mobile mass on the left thigh. In the biopsy performed a sarcoma weave with solid, nest-like growth, with characteristics of rhabdomyosarcoma was identified. The family history and physical examination indicated IMAGe syndrome so genetic testing was requested. A whole exome sequencing procedure with use of SureSelectXT Human ALL Exon V7, confirmed a single nucleotide variant NM_000076.2(CDKN1C):c.820G>A (p.Asp274Asn); identifying a missense mutation in the imprinted gene CDKN1C associated with IMAGe syndrome. Although tumours associated with CDKN1C are rare, deregulation of imprinted genes is increasingly being recognised as a mechanism of tumorigenesis in cancer; chromosomal region 11p15.5 contains a cluster of imprinted genes. This same region is the most consistent site of allele loss in rhabdomyosarcoma and is the same region altered in both IMAGe and Beckwith-Wiedemann syndrome. Molecular studies have found genetic changes in the 11p15 region in a variety of embryonal tumours like Wilms tumours which are commonly developed in Beckwith-Wiedemann syndrome and embryonal rhabdomyosarcoma. Through this case we aim to present the possibility of oncogenesis in patients with IMAGe syndrome, specifically rhabdomyosarcoma.

PMID:34098225 | DOI:10.1016/j.cancergen.2021.05.006
Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma

Fetched: June 8th, 2021, 5:02am GMT by Jung Kim

JCO Precis Oncol. 2021 Jan 11;5:PO.20.00218. doi: 10.1200/PO.20.00218. eCollection 2021.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts.

MATERIALS AND METHODS: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort.

RESULTS: We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants (ATM, CDKN1C) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with FOXO1 fusion-negative RMS patients versus the patients with FOXO1 fusion-positive RMS. We identified pathogenic germline variants in CSGs previously (TP53, NF1, DICER1, mismatch repair genes), rarely (BRCA2, CBL, CHEK2, SMARCA4), or never (FGFR4) reported in RMS. Numerous genes (TP53, BRCA2, mismatch repair) were on the ACMG Secondary Findings 2.0 list.

CONCLUSION: In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.

PMID:34095712 | PMC:PMC8169077 | DOI:10.1200/PO.20.00218
Enhancement of myogenic differentiation and inhibition of rhabdomyosarcoma progression by miR-28-3p and miR-193a-5p regulated by SNAIL

Fetched: June 8th, 2021, 5:02am GMT by Klaudia Skrzypek

Mol Ther Nucleic Acids. 2021 Apr 20;24:888-904. doi: 10.1016/j.omtn.2021.04.013. eCollection 2021 Jun 4.

ABSTRACT

Rhabdomyosarcoma (RMS) is a soft tissue mesenchymal tumor that affects mostly children and adolescents. It originates from the impaired myogenic differentiation of stem cells or early progenitors. SNAIL, a transcription factor that regulates epithelial-to-mesenchymal transition in tumors of epithelial origin, is also a key regulator of RMS growth, progression, and myogenic differentiation. Here, we demonstrate that the SNAIL-dependent microRNAs (miRNAs) miR-28-3p and miR-193a-5p are crucial regulators of RMS growth, differentiation, and progression. miR-28-3p and miR-193a-5p diminished proliferation and arrested RMS cells in G0/G1 phase in vitro. They induced the myogenic differentiation of both RMS cells and human myoblasts by upregulating myogenic factors. Furthermore, miR-28-3p and miR-193a-5p inhibited migration in a scratch assay, adhesion to endothelial cells, chemotaxis, and invasion toward SDF-1 and HGF and regulated angiogenic capabilities of the cells. Overexpression of miR-28-3p and miR-193a-5p induced formation of fibrotic structures and abnormal blood vessels in RMS xenografts in immunodeficient mice in vivo. Simultaneous overexpression of both miRNAs diminished tumor growth after subcutaneous implantation and inhibited the engraftment of RMS cells into bone marrow after intravenous injection in vivo. To conclude, we discovered novel SNAIL-dependent miRNAs that may become new therapeutic targets in RMS in the future.

PMID:34094709 | PMC:PMC8141673 | DOI:10.1016/j.omtn.2021.04.013
Durability of oncological outcomes of combination chemotherapy as a monotherapy for a select patient subset with non-metastatic non-alveolar bladder/prostate rhabdomyosarcoma

Fetched: June 8th, 2021, 5:02am GMT by Ahmed Abdelhalim

J Pediatr Urol. 2021 May 17:S1477-5131(21)00281-3. doi: 10.1016/j.jpurol.2021.05.013. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: We aim to assess the long-term oncological outcomes of children with bladder/prostate rhabdomyosarcoma (B/P RMS) treated with multiagent chemotherapy as a monotherapy. We hypothesize that a highly select patient subset can be treated with multiagent chemotherapy as a monotherapy and spared the morbidity of local treatment with similar oncological outcomes.

METHODS: Patients (≤21-year-old) treated for non-metastatic non-alveolar B/P RMS at a tertiary center and followed for>one year, were retrospectively reviewed. After pathological confirmation, patients received 12 weeks of induction VAC chemotherapy (IC) followed by second-look biopsies. Between 1996 and 2006 (group A), patients with>50% tumor size reduction and negative second-look biopsies following IC were spared local treatment and followed-up closely. Between 2007 and 2020 (group B), local treatment was routinely given at 12 weeks according to the COG protocols, irrespective of IC response. For all patients, consolidation chemotherapy was administered for additional 12-18 months.

RESULTS: Between 1996 and 2020, 27 patients (10 stage II, 17 stage III) with a median age of 3(1-21) years were included. Median follow-up was 87.5(15.3-247.1) months. Among 15 patients in group A, 3 were ineligible for the monotherapy protocol and received local treatment. The remaining 12 patients [9 complete (CR) and 3 incomplete response (IR) to IC] were treated exclusively with chemotherapy, of whom 9 were alive free of relapse at last follow-up. Two patients with IR to IC had disease relapse: one had pulmonary relapse at 8.2 months and one had local relapse at 35 months. The 5-year OS and EFS of group A were 86.7% and 80%, respectively. Analyzing survival according to IC response, CR to IC was achieved in 10 patients (9 group A and one group B) and was associated with significantly better OS and EFS than IR(p = 0.026 and 0.004, respectively) (Summary figure). All patients with CR to IC were alive free of relapse at last follow-up.

DISCUSSION: Treatment of RMS is traditionally multimodal. Local treatment of B/P RMS is associated with significant patient morbidity. In this study, CR to IC predicted better OS and EFS. Patients who achieved CR (radiological and pathological) to IC remained alive free of relapse irrespective of local treatment.

CONCLUSIONS: Our results suggest that patients with non-metastatic non-alveolar B/P RMS who achieve CR to IC can be treated with combination chemotherapy as a monotherapy and spared the morbidity of local treatment with durable survival outcomes. Prospective validation in a larger patient cohort is needed to support our hypothesis.

PMID:34092511 | DOI:10.1016/j.jpurol.2021.05.013
Genomic analysis and preclinical xenograft model development identify potential therapeutic targets for MYOD1-mutant soft-tissue sarcoma of childhood

Fetched: June 5th, 2021, 5:02am GMT by Michelle A Ting

J Pathol. 2021 Jun 4. doi: 10.1002/path.5736. Online ahead of print.

ABSTRACT

The MYOD1 p.L122R somatic mutation was first discovered in a subset of clinically aggressive embryonal rhabdomyosarcomas and has since been described in both pediatric and adult spindle cell/sclerosing rhabdomyosarcomas. Relatively little is known about the clinical, molecular, and histopathological feature of these tumors in children. In order to further characterize the genomic and clinical features of pediatric MYOD1-mutant sarcomas, we evaluated a cohort of soft-tissue sarcoma patients treated at Texas Children's Hospital. Tumor DNA was subjected to next-generation panel sequencing and/or Sanger sequencing of the MYOD1 hotspot mutation. The MYOD1 p.L122R mutation was identified in six tumors, with a variant allele fraction greater than 0.8 in three cases, suggestive of loss of heterozygosity (LOH). One sclerosing rhabdomyosarcoma lacking the MYOD1 hotspot mutation was observed to have a MYOD1 copy number gain, also with evidence of LOH. Cancer gene panel sequencing revealed potentially targetable alterations in 6/7 (86%) patients with MYOD1 alterations, including four patients with an alteration in the PI3K-AKT pathway: two hotspot PIK3CA mutations and deletions in PTEN and TSC2. On histopathologic review, MYOD1-altered tumors exhibited spindle and/or round cells and varying degrees of hyaline sclerosis. At last follow-up, six patients had died of disease and the seventh progressed early and was subsequently lost to follow-up. Both pre- and post-therapy patient-derived xenograft (PDX) models were generated from one patient's tumor. These models were confirmed to harbor the MYOD1 and PIK3CA mutations seen in the primary tumor and were shown to be sensitive to PI3K/mTOR inhibition in vitro and in vivo. In conclusion, this study adds to recent reports describing the clinicopathologic and genomic features of MYOD1-altered soft-tissue sarcomas in children, including dismal prognosis and potential molecular targets for therapy. The novel pre-clinical models developed will facilitate further biological and pre-clinical study of this rare and aggressive tumor. This article is protected by copyright. All rights reserved.

PMID:34086347 | DOI:10.1002/path.5736
Rare Paratesticular Masses in Children

Fetched: June 5th, 2021, 5:02am GMT by Mehak Sehgal

J Indian Assoc Pediatr Surg. 2021 Mar-Apr;26(2):117-119. doi: 10.4103/jiaps.JIAPS_182_19. Epub 2021 Mar 4.

ABSTRACT

Pediatric paratesticular mass is common in pediatric surgical practice, and they could be because of an underlying encysted hydrocele, a teratoma, or an epididymal cyst. Furthermore, a malignant lesion such as rhabdomyosarcoma should be ruled out. Rare entities, such as fibrous hamartoma of infancy and cellular angiofibroma, are rarely encountered. We report two such cases of paratesticular masses with these rare pathologies.

PMID:34083896 | PMC:PMC8152395 | DOI:10.4103/jiaps.JIAPS_182_19
Living donor liver transplantation for hepatic malignancies in children

Fetched: June 3rd, 2021, 5:02am GMT by Aurore Pire

Pediatr Transplant. 2021 Jun 2:e14047. doi: 10.1111/petr.14047. Online ahead of print.

ABSTRACT

BACKGROUND: Living donor liver transplantation is a treatment option for unresectable hepatic tumors in children.

METHODS: We enrolled 45 living donor transplantations performed between 1993 and 2018 for liver malignacies, which included hepatoblastoma (n = 33), hepatocellular carcinoma (n = 10), hepatic angiosarcoma (n = 1), and rhabdomyosarcoma (n = 1).

RESULTS: No mortality or major morbidities were encountered in any donor, and the complication rate was 9%. In the hepatoblastoma group, 5-year overall and event-free survival rate in recipients was 87.4% and 75.8%, respectively, and mortality was significantly higher in patients after rescue transplantation (p = .001). Inferior vena cava replacement in these recipients appeared to be associated with reduced mortality (p = .034), but this was not confirmed when rescue patients were excluded (p = .629). In hepatocellular carcinoma group, both 5-year overall and event-free survival rates were 75.4% each, and invasion of hepatic veins was significantly associated with increased risk of recurrence and death (p = .028). The patient with rhabdomyosarcoma died from EBV-induced lymphoma 2 months after transplantation. The patient with angiosarcoma was in complete remission at the last follow-up. Overall, 5-year graft survival rate was 81.3%, and one patient underwent re-transplantation due to chronic rejection.

CONCLUSIONS: Pediatric oncological liver transplantation has become a key player in the management of malignancies with cancer cure in 84% of patients in this series. Living donor liver transplantation for pediatric recipients with unresectable tumors might be a beneficial surgical option, which is technically safe for donors and recipients, thus, allowing timely planning according to chemotherapy protocols.

PMID:34076944 | DOI:10.1111/petr.14047
Correlation between oncological family history and clinical outcome in a large monocentric cohort of pediatric patients with rhabdomyosarcoma

Fetched: June 3rd, 2021, 5:02am GMT by Valentina Sottili

Int J Clin Oncol. 2021 Jun 1. doi: 10.1007/s10147-021-01934-8. Online ahead of print.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS), an aggressive soft tissue sarcoma of the skeletal muscle generally affecting children and adolescents, shows extensive heterogeneity in histology, site and age of onset, clinical course, and prognosis. Tumorigenesis of RMS is multifactorial and genetic predisposition together with the family history of cancer may provide critical information to enhance the current knowledge and foster genetic counseling and testing.

METHODS: In our study, we evaluated the possible correlation of oncological family history with clinical outcomes in a cohort of RMS 512 patients and treated at the Pediatric Oncology Unit of our Institute. Family history was retrospectively collected from the specific ad hoc form available in medical records and filled in through an interview with the patients' parents at the time of RMS diagnosis.

RESULTS: While our series did not show a specific association between oncological family history and clinical variables, we observed an association with survival probabilities: among patients with a history of cancer-affected first-degree relatives at the time of the diagnosis, all children with alveolar RMS (ARMS) died of disease.

CONCLUSION: Our study not only reports an interesting and not previously described association between a poor clinical outcome and ARMS in patients with young cancer-affected relatives, but also stimulates the discussion on oncological family history in RMS, to improve the clinical management of these young patients and their families.

PMID:34075482 | DOI:10.1007/s10147-021-01934-8
Establishment and Characterization of a Cell Line (S-RMS1) Derived from an Infantile Spindle Cell Rhabdomyosarcoma with SRF-NCOA2 Fusion Transcript

Fetched: June 3rd, 2021, 5:02am GMT by Marta Colletti

Int J Mol Sci. 2021 May 22;22(11):5484. doi: 10.3390/ijms22115484.

ABSTRACT

Background: Spindle cell rhabdomyosarcoma (S-RMS) is a rare tumor that was previously considered as an uncommon variant of embryonal RMS (ERMS) and recently reclassified as a distinct RMS subtype with NCOA2, NCOA1, and VGLL2 fusion genes. In this study, we established a cell line (S-RMS1) derived from a four-month-old boy with infantile spindle cell RMS harboring SRF-NCOA2 gene fusion. Methods: Morphological and molecular characteristics of S-RMS1 were analyzed and compared with two RMS cell lines, RH30 and RD18. Whole genome sequencing of S-RMS1 and clinical exome sequencing of genomic DNA were performed. Results: S-RMS1 showed cells small in size, with a fibroblast-like morphology and positivity for MyoD-1, myogenin, desmin, and smooth muscle actin. The population doubling time was 3.7 days. Whole genome sequencing demonstrated that S-RMS1 retained the same genetic profile of the tumor at diagnosis. A Western blot analysis showed downregulation of AKT-p and YAP-p while RT-qPCR showed upregulation of endoglin and GATA6 as well as downregulation of TGFßR1 and Mef2C transcripts. Conclusion: This is the first report of the establishment of a cell line from an infantile spindle cell RMS with SRF-NCOA2 gene fusion. S-RMS1 should represent a useful tool for the molecular characterization of this rare and almost unknown tumor.

PMID:34067464 | PMC:PMC8196948 | DOI:10.3390/ijms22115484
Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility

Fetched: June 3rd, 2021, 5:02am GMT by Bailey A Martin-Giacalone

J Clin Med. 2021 May 9;10(9):2028. doi: 10.3390/jcm10092028.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet little is known about its etiology. Studies that examine either environmental exposures or germline genetic predisposition in RMS have begun to identify factors that contribute to this malignancy. Here, we summarize epidemiological reports of RMS incidence in terms of several factors, including age at diagnosis, biological sex, and geographic location. We then describe findings from association studies, which explore the role of parental exposures, birth and perinatal characteristics, and childhood exposures in RMS. Further, we discuss RMS predisposition syndromes and large-scale sequencing studies that have further identified RMS-associated genes. Finally, we propose future directions of study, which aim to advance our understanding of the origin of RMS and can provide knowledge for novel RMS therapies.

PMID:34065162 | PMC:PMC8125975 | DOI:10.3390/jcm10092028
Value of the Sentinel Node Procedure in Pediatric Extremity Rhabdomyosarcoma: A Systematic Review and Retrospective Cohort Study

Fetched: June 1st, 2021, 5:02am GMT by Bernadette Jeremiasse

Ann Surg Oncol. 2021 May 31. doi: 10.1245/s10434-021-10035-9. Online ahead of print.

ABSTRACT

BACKGROUND: Our aim is to show whether the sentinel node procedure (SNP) is recommendable for pediatric patients with extremity rhabdomyosarcoma (RMS). Lymph node metastases are an important prognostic factor in pediatric patients with extremity RMS. Accurate nodal staging is necessary to treat the patient accordingly. An alternative to the current recommended lymph node sampling is the sentinel node procedure (SNP).

METHODS: A systematic review was performed summarizing all published cases of SNP in addition to 13 cases from our hospital and 8 cases from two other hospitals that have not been published before.

RESULTS: For all patients (n = 55), at least one SLN was identified, but the SNP technique used was not uniform. The SNP changed the nodal classification of eight patients (17.0%) and had a false-negative rate of 10.5%.

CONCLUSIONS: The SNP is recommendable for pediatric patients with extremity RMS. It can change lymph node status and can be used to sample patients in a more targeted way than nodal sampling alone. Therefore, we recommend use of the SNP in addition to clinical and radiological nodal assessment for pediatric patients with extremity RMS.

PMID:34057567 | DOI:10.1245/s10434-021-10035-9
Novel findings and expansion of phenotype in a mosaic RASopathy caused by somatic KRAS variants

Fetched: June 1st, 2021, 5:02am GMT by Caitlin A Chang

Am J Med Genet A. 2021 May 30. doi: 10.1002/ajmg.a.62356. Online ahead of print.

ABSTRACT

Mosaic KRAS variants and other RASopathy genes cause oculoectodermal, encephalo-cranio-cutaneous lipomatosis, and Schimmelpenning-Feuerstein-Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic KRAS variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic KRAS variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T-cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic KRAS variant. The purposes of this report are to expand the phenotypic spectrum of mosaic KRAS-related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.

PMID:34056834 | DOI:10.1002/ajmg.a.62356
Potential alternative treatment approach for pediatric patient with diffusely infiltrative primary rhabdomyosarcoma of the liver

Fetched: May 29th, 2021, 5:02am GMT by Rushil Patel

Rep Pract Oncol Radiother. 2021 Feb 25;26(1):143-148. doi: 10.5603/RPOR.a2021.0008. eCollection 2021.

ABSTRACT

Primary hepatic rhabdomyosarcoma is rare, making decisions regarding locoregional management with resection and/or conventional radiation difficult. We present a novel treatment approach for a pediatric patient diagnosed with rhabdomyosarcoma diffusely involving the liver. This patient underwent treatment with yttrium-90 (Y-90) microspheres followed by external beam radiation therapy (EBRT ) to residual disease, interdigitated with systemic chemotherapy. Initial post-radiation imaging showed significant response to treatment, and she experienced minimal acute toxicities and no long-term toxicities. She developed recurrent PET-avid disease 23 months after Y-90 treatment, necessitating further local and continued systemic therapies. We report on the tumor control following Y-90 and EBRT treatment.

PMID:34046225 | PMC:PMC8149128 | DOI:10.5603/RPOR.a2021.0008
Diagnosis and treatment of pleomorphic rhabdomyosarcoma of the uterus: a rare case report and review of the literature

Fetched: May 27th, 2021, 5:02am GMT by Zi-Jun Li

J Int Med Res. 2021 May;49(5):3000605211014360. doi: 10.1177/03000605211014360.

ABSTRACT

Pleomorphic rhabdomyosarcomas of the uterus (PRMSu) is a rare malignant tumor of the female genital tract. Accurate diagnosis and effective treatment of PRMSu are important. We report an 81-year-old woman who was diagnosed with PRMSu. She had an extremely unusual presentation of secondary dyspnea because of an extremely large uterus (26.0 cm). Pelvic magnetic resonance imaging showed rare severe enlargement and intrauterine filling with tumor tissue, and she was initially diagnosed with uterine leiomyosarcoma. The patient underwent hysterectomy, as well as bilateral salpingo-oophorectomy and omentectomy, and was finally confirmed as having PRMSu by histopathology combined with immunohistochemistry. We performed a systematic review of the literature between 1982 and 2020 and focused on different treatment strategies and prognosis of PRMSu. A retrospective review of 28 cases was conducted and survival analysis was estimated by using the Kaplan-Meier method. We found that the accuracy of diagnosis of PRMSu completely depends on histopathology and immunohistochemistry because of no special clinical symptoms, no sensitive tumor markers, and no special imaging findings. Although there is no standardized approach for treating this rare disease, the treatment strategy of a surgical operation combined with adjuvant chemotherapy appears to be the best choice.

PMID:34034549 | PMC:PMC8161909 | DOI:10.1177/03000605211014360
Increased 68Ga-FAPI Uptake in Neurofibromatosis in a Patient With Pleomorphic Rhabdomyosarcoma

Fetched: May 27th, 2021, 5:02am GMT by Junhao Wu

Clin Nucl Med. 2021 May 26. doi: 10.1097/RLU.0000000000003716. Online ahead of print.

ABSTRACT

A 48-year-old man presented with a painless enlarging mass on his right thigh for 2 months. He had a history of neurofibromatosis. MRI showed a mass in his right thigh. Malignant tumor was suspected. He was enrolled in the clinical trial of 68Ga-FAPI in solid tumors. Multiple increased FAPI uptake was observed in the right thigh mass, lung, and mediastinal lymph nodes, which were confirmed being pleomorphic rhabdomyosarcoma by biopsy. In addition, widespread metabolic activity was also observed in his cutaneous fibroma nodules. This case showed that benign neurofibromatosis can cause FAPI uptake.

PMID:34034317 | DOI:10.1097/RLU.0000000000003716
Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?

Fetched: May 25th, 2021, 5:02am GMT by Gian Luca Vita

J Neuromuscul Dis. 2021 May 19. doi: 10.3233/JND-210676. Online ahead of print.

ABSTRACT

BACKGROUND: Increasing evidence suggests that Duchenne muscular dystrophy (DMD) gene is involved in the occurrence of different types of cancer. Moreover, development of sarcomas was reported in mdx mice, the murine model of DMD, in older age. So far, nine isolated DMD patients were reported with concomitant cancer, four of whom with rhabdomyosarcoma (RMS), but no systematic investigation was performed about the true incidence of cancer in DMD.

METHODS: All members of the Italian Association of Myology were asked about the occurrence of cancer in their DMD patients in the last 30 years.

RESULTS: Four DMD patients with cancer were reported after checking 2455 medical records. One developed brain tumour at the age of 35 years. Two patients had alveolar RMS at 14 and 17 years of age. The fourth patient had a benign enchondroma when 11-year-old.

CONCLUSION: Prevalence of cancer in general in the Italian DMD patients does not seem to be different from that in the general population with the same age range. Although the small numbers herein presented do not allow definitive conclusion, the frequent occurrence of RMS in DMD patients raises an alert for basic researchers and clinicians. The role of DMD gene in cancer merits further investigations.

PMID:34024777 | DOI:10.3233/JND-210676
Proton radiotherapy for infant rhabdomyosarcoma: Rethinking young age as an adverse prognostic factor

Fetched: May 25th, 2021, 5:02am GMT by Akash D Parekh

Radiother Oncol. 2021 May 20:S0167-8140(21)06255-1. doi: 10.1016/j.radonc.2021.05.017. Online ahead of print.

ABSTRACT

BACKGROUND & PURPOSE: In infants with rhabdomyosarcoma, young age is considered an adverse prognostic factor and treatment is often attenuated to reduce side effects. Proton therapy may improve the therapeutic ratio in these patients. We report outcomes in infants with rhabdomyosarcoma treated with proton therapy.

MATERIALS & METHODS: Between 2009 and 2019, 37 infants <24 months old with non-metastatic rhabdomyosarcoma received proton therapy. Local control (LC), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier product limit. The log-rank test assessed significance between selected prognostic factors. Toxicity was graded per CTCAEv5.0.

RESULTS: Median follow-up was 5.1 years. Overall, 76% of patients had an unfavorable primary site. Median dose was 50.4GyRBE. At 5 years, LC, PFS, and OS rates were 83%, 78%, and 83%. On univariate analysis, 5-year LC and OS were inferior for favorable versus unfavorable disease sites (67% vs 89%, 67% vs 89%, respectively; p<.05) and 5-year OS was superior in stage 3 versus stage 1-2 disease (91% vs 69%; p=.05), owing to inclusion of nasal ala patients among stage 1. Of 9 recurrences, 7 were in-field, 4 occurring in infants with nasal ala primaries. Recategorizing nasal ala as an unfavorable site resulted in 100% 5-year LC and OS for favorable sites. Six infants experienced late grade 3 toxicity. None developed grade 4 or 5 late toxicity.

CONCLUSIONS: Young age alone may not be an adverse prognostic factor provided infants receive local therapy similar to older children. Consideration should be given to classifying nasal ala primaries as an unfavorable site.

PMID:34023329 | DOI:10.1016/j.radonc.2021.05.017
TP53 mutations increase radioresistance in rhabdomyosarcoma and Ewing sarcoma

Fetched: May 22nd, 2021, 5:01am GMT by Dana L Casey

Br J Cancer. 2021 May 20. doi: 10.1038/s41416-021-01438-2. Online ahead of print.

ABSTRACT

BACKGROUND: p53 plays a key role in the DNA repair process and response to ionising radiation. We sought to determine the clinical phenotype of TP53 mutations and p53 pathway alterations in patients with rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) treated with radiation.

METHODS: Of patients with available genomic sequencing, we identified 109 patients with RMS and ES treated to a total of 286 radiation sites. We compared irradiated tumour control among tumours with TP53 mutations (n = 40) to those that were TP53 wild-type (n = 246). We additionally compared irradiated tumour control among tumours with any p53 pathway alteration (defined as tumours with TP53 mutations or TP53 wild-type tumours identified to have MDM2/4 amplification and/or CDKN2A/B deletion, n = 78) to those without such alterations (n = 208).

RESULTS: The median follow-up was 26 months from radiation. TP53 mutations were associated with worse irradiated tumour control among the entire cohort (hazard ratio, HR = 2.8, P < 0.0001). Tumours with any p53 pathway alteration also had inferior irradiated tumour control (HR = 2.0, P = 0.003). On multivariable analysis, after controlling for tumour histology, intent of radiation, presence of gross disease, and biologically effective dose, TP53 mutations continued to be associated with a radioresistant phenotype (HR = 7.1, P < 0.0001).

CONCLUSIONS: Our results show that TP53 mutations are associated with increased radioresistance in RMS and ES. Novel strategies to overcome this radioresistance are important for improved outcomes in p53 disruptive RMS and ES.

PMID:34017087 | DOI:10.1038/s41416-021-01438-2
Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations

Fetched: May 22nd, 2021, 5:01am GMT by Jennifer A Bennett

Mod Pathol. 2021 May 20. doi: 10.1038/s41379-021-00821-x. Online ahead of print.

ABSTRACT

Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (≤20%) of classic morphology, with anaplasia noted in four and tumor cell necrosis in three. The most frequent mutations detected were in DICER1 (14/21), TP53 (7/20), PI3K/AKT/mTOR pathway (7/20), and KRAS/NRAS (5/20). Copy-number alterations were present in 10/19 tumors. Overall, 8/14 DICER1-associated ucERMS showed concurrent loss of function and hotspot mutations in DICER1, which is a feature more likely to be seen in tumors associated with DICER1 syndrome. Germline data were available for two patients, both DICER1 wild type (one with concurrent loss of function and hotspot alterations). DICER1-associated ucERMS were more likely to show a classic histological appearance including heterologous elements than DICER1-independent tumors. No differences in survival were noted between the two groups, but both patients with extrauterine disease at diagnosis and two with recurrences died from disease. As no patients had a known personal or family history of DICER1 syndrome, we favor most DICER1-associated ucERMS to be sporadic.

PMID:34017064 | DOI:10.1038/s41379-021-00821-x
Uterine alveolar rhabdomyosarcoma in an elderly patient manifesting extremely poor prognosis; a rare subtype of rhabdomyosarcoma

Fetched: May 22nd, 2021, 5:01am GMT by Haewon Choi

Obstet Gynecol Sci. 2021 May;64(3):336. doi: 10.5468/ogs.20127.e1. Epub 2021 May 13.

NO ABSTRACT

PMID:34015887 | PMC:PMC8138071 | DOI:10.5468/ogs.20127.e1
Melanoma and Li-Fraumeni syndrome - family history not essential for screening recommendation

Fetched: May 20th, 2021, 5:02am GMT by H Regan

Clin Exp Dermatol. 2021 May 19. doi: 10.1111/ced.14748. Online ahead of print.

ABSTRACT

Li-Fraumeni Syndrome (LFS) is a recognised cancer predisposition syndrome associated with early onset of multiple cancer types. It was first described in 1969 following the identification of two soft tissue sarcomas in five families with the index case presenting with rhabdomyosarcoma in childhood.¹ The tumour spectrum classically includes a range of soft tissue sarcomas, bone tumours, haematological malignancies, breast cancer and adrenal cortical cancer.

PMID:34008262 | DOI:10.1111/ced.14748
Rhabdomyosarcoma with epithelioid morphology: A challenging cytologic diagnosis in a pleural effusion

Fetched: May 19th, 2021, 5:01am GMT by Shannon Rodgers

Diagn Cytopathol. 2021 May 18. doi: 10.1002/dc.24803. Online ahead of print.

ABSTRACT

Rhabdomyosarcomas (RMS) are rare malignant skeletal muscle tumors that present more commonly in pediatric populations. The WHO currently classifies RMS into four types, embryonal, alveolar, pleomorphic, and spindle cell/sclerosing variants. Epithelioid rhabdomyosarcoma (EpiRMS) is another rare, recently described subtype of RMS presenting in older patients with a male predominance and has a rapidly progressive clinical course with frequent metastases. EpiRMS closely mimics poorly differentiated carcinoma or melanoma, demonstrating discohesive large epithelioid cells with abundant eosinophilic cytoplasm, frequent glassy cytoplasmic inclusions, large vesicular nuclei, and prominent nucleoli. We present a case of metastatic rhabdomyosarcoma with features reminiscent of EpiRMS presenting as a pleural effusion, closely followed by an inguinal lymph node biopsy. The malignant cells in the pleural fluid were diffusely positive for desmin, negative for MyoD1, myogenin, S100 and SOX10, and retained INI-1 expression. Subsequent lymph node biopsy demonstrated identical malignant epithelioid cells that were positive for desmin, myoD1 and myogenin, and a cytological diagnosis of "metastatic rhabdomyosarcoma, favor epithelioid rhabdomyosarcoma" was given considering the concurrent lymph node biopsy morphology and immunoprofile. A diagnosis of rhabdomyosarcoma, though rare and challenging, should not be overlooked when considering malignant cells with an epithelioid morphology in cytology specimens.

PMID:34004052 | DOI:10.1002/dc.24803
MicroRNAs miR-18a and miR-452 regulate the replication of enterovirus 71 by targeting the gene encoding VP3

Fetched: May 19th, 2021, 5:01am GMT by Zhuo Yang

Virus Genes. 2021 May 17. doi: 10.1007/s11262-021-01842-z. Online ahead of print.

ABSTRACT

MicroRNAs (miRNAs) are crucial in the process of host-pathogen interaction. In this study, we established a screening system for miRNAs of target genes to detect the effect of miRNAs on Enterovirus 71 (EV71) replication in rhabdomyosarcoma (RD) cells. A 3'-untranslated region (UTR) dual-luciferase assay was performed to confirm putative miRNA targets in EV71 genome. Firstly, 13 fragments of EV71 genome were inserted into the vector pMIR, and luciferase activities were analyzed to identify the putative miRNAs of target genes. The expression of the reporter protein was significantly downregulated in cells transfected with the vector containing gene VP3. Then we screened for miRNAs that might target to VP3 through online analysis software. In addition, Western blot, real-time PCR, virus titration, and morphological changes were considered to examine the effects of miRNAs on virus replication. The results suggested that miR-18a and miR-452 repress the reproduction of EV71 virus by binding to VP3. Moreover, EV71 infection also affected the expression of endogenous miR-18a and miR-452. In addition, no significant cytotoxic effects were observed. The results from this study suggest that the intracellular miRNAs may play vital roles in the host-virus interaction.

PMID:34002325 | DOI:10.1007/s11262-021-01842-z
Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck: Highlighting a Novel Fusion and Potential Diagnostic Pitfall

Fetched: May 19th, 2021, 5:01am GMT by Darcy A Kerr

Am J Surg Pathol. 2021 May 18. doi: 10.1097/PAS.0000000000001735. Online ahead of print.

ABSTRACT

Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites. Therefore, we analyzed a cohort of head and neck IMTs through a multi-institutional approach. Fourteen cases were included in the provisional cohort, but 1 was excluded after molecular analysis prompted reclassification. Patients in the final cohort included 7 males and 6 females, with a mean age of 26.5 years. Tumors were located in the larynx (n=7), oral cavity (n=3), pharynx (n=2), and mastoid (n=1). Histologically, all tumors showed neoplastic spindle cells in storiform to fascicular patterns with associated chronic inflammation, but the morphologic spectrum was wide, as is characteristic of IMT in other sites. An underlying fusion gene event was identified in 92% (n=11/12) of cases and an additional case was ALK-positive by IHC but could not be evaluated molecularly. ALK represented the driver in all but 1 case. Rearrangement of ALK, fused with the TIMP3 gene (n=6) was most commonly detected, followed by 1 case each of the following fusion gene partnerships: TPM3-ALK, KIF5B-ALK, CARS-ALK, THBS1-ALK, and a novel alteration, SLC12A2-ROS1. The excluded case was reclassified as spindle cell rhabdomyosarcoma after detection of a FUS-TFCP2 rearrangement and retrospective immunohistochemical confirmation of rhabdomyoblastic differentiation, illustrating an important diagnostic pitfall. Two IMT patients received targeted therapy with crizotinib, with a demonstrated radiographic response. One tumor recurred but none metastasized. These results add to the growing body of evidence that kinase fusions can be identified in the majority of IMTs and that molecular analysis can lead to increased diagnostic accuracy and broadened therapeutic options for patients.

PMID:34001695 | DOI:10.1097/PAS.0000000000001735
Spindle cell/sclerosing rhabdomyosarcoma with a novel YAP1-MAML2 fusion in a 1-year-old: not all strongly TRK-expressing spindle cell sarcomas in infants are infantile fibrosarcomas!

Fetched: May 18th, 2021, 5:02am GMT by Fleur Cordier

Pathology. 2021 May 13:S0031-3025(21)00105-7. doi: 10.1016/j.pathol.2021.02.009. Online ahead of print.

NO ABSTRACT

PMID:33994171 | DOI:10.1016/j.pathol.2021.02.009
Coexistence of orbital rhabdomyosarcoma and adrenal neuroblastic tumor in a child

Fetched: May 13th, 2021, 5:02am GMT by Jia-Jian Hu

Pediatr Int. 2021 May 12. doi: 10.1111/ped.14504. Online ahead of print.

NO ABSTRACT

PMID:33979458 | DOI:10.1111/ped.14504
Romidepsin (FK228) fails in counteracting the transformed phenotype of rhabdomyosarcoma cells but efficiently radiosensitizes, in vitro and in vivo, the alveolar phenotype subtype

Fetched: May 13th, 2021, 5:02am GMT by Alessandra Rossetti

Int J Radiat Biol. 2021 Jun 4:1-15. doi: 10.1080/09553002.2021.1928786. Online ahead of print.

ABSTRACT

PURPOSE: Herein we describe the in vitro and in vivo activity of FK228 (Romidepsin), an inhibitor of class I HDACs, in counteracting and radiosensitizing embryonal (ERMS, fusion-negative) and alveolar (ARMS, fusion-positive) rhabdomyosarcoma (RMS).

METHODS: RH30 (ARMS, fusion-positive) and RD (ERMS, fusion-negative) cell lines and human multipotent mesenchymal stromal cells (HMSC) were used. Flow cytometry analysis, RT-qPCR, western blotting and enzymatic assays were performed. Irradiation was delivered by using an x-6 MV photon linear accelerator. FK228 (1.2 mg/kg) in vivo activity, combined or not with radiation therapy (2 Gy), was assessed in murine xenografts.

RESULTS: Compared to HMSC, RMS expressed low levels of class I HDACs. In vitro, FK228, as single agents, reversibly downregulated class I HDACs expression and activity and induced oxidative stress, DNA damage and a concomitant growth arrest associated with PARP-1-mediated transient non-apoptotic cell death. Surviving cells upregulated the expression of cyclin A, B, D1, p27, Myc and activated PI3K/Akt/mTOR and MAPK signaling, known to be differently involved in cancer chemoresistance. Interestingly, while no radiosensitizing effects were detected, in vitro or in vivo, on RD cells, FK228 markedly radiosensitized RH30 cells by impairing antioxidant and DSBs repair pathways in vitro. Further, FK228 when combined with RT in vivo significantly reduced tumor mass in mouse RH30 xenografts.

CONCLUSION: FK228 did not show antitumor activity as a single agent whilst its combination with RT resulted in radiosensitization of fusion-positive RMS cells, thus representing a possible strategy for the treatment of the most aggressive RMS subtype.

PMID:33979259 | DOI:10.1080/09553002.2021.1928786
Contemporary analysis of epididymal tumors using a national database

Fetched: May 13th, 2021, 5:02am GMT by Rohit Bhatt

Cent European J Urol. 2021;74(1):39-43. doi: 10.5173/ceju.2021.0249.R1. Epub 2021 Feb 19.

ABSTRACT

INTRODUCTION: Epididymal tumors are rare malignancies with sparse research available to guide recommendations. We sought to characterize malignant epididymal tumors in the United States using population level data.

MATERIAL AND METHODS: The Surveillance, Epidemiology, and End-Results database was queried for patients diagnosed with malignant epididymal tumors between 1975-2016. International classification of disease for oncology code C63.0 was used to identify population with disease of interest. Primary objective was to characterize patient demographics, disease characteristics, and management. Secondary objectives included overall and cancer-specific survival (CSS) utilizing Kaplan-Meier (KM) analysis.

RESULTS: A total of 66 cases of malignant epididymal tumors were identified during the study period. The cohort was largely white (84.8%), with a mean age of diagnosis of 46.9 years old. The predominant histology consisted of rhabdomyosarcoma 26%, leiomyosarcoma 23%, liposarcoma 17%, adenocarcinoma 9%, and malignant fibrous histiocytoma 5%. During histopathological assessment, 21.1% of tumors were classified as high-grade while 71.2% exhibited sarcomatoid elements. Majority of patients presented with localized disease (68.2%), whereas regional (18.2%) and distant (13.2%) disease was less frequently discovered. All patients were diagnosed by surgical therapy consisting of radical epididymectomy (39.4%), partial epididymectomy (27.3%) or 'unknown surgery' (33.3%). Meanwhile, 15.2% and 34.8% received radiation and chemotherapy, respectively. KM analysis revealed an 84.9% CSS at 5-years. Over 60% of documented cases have arisen since 2000, with 3.0% of the cohort diagnosed in 2016, increased from 1.5% of the diagnoses in 1975.

CONCLUSIONS: Malignant epididymal tumors are exceedingly rare and typically present with localized disease. Surgical excision is associated with an estimated 85% CSS at 5-years.

PMID:33976913 | PMC:PMC8097649 | DOI:10.5173/ceju.2021.0249.R1
Orbital malignant schwannoma and embryonal rhabdomyosarcoma in rats caused by leakage of locally injected nickel subsulfide to the orbit

Fetched: May 13th, 2021, 5:02am GMT by Yoshinori Yamagiwa

J Toxicol Pathol. 2021 Apr;34(2):151-156. doi: 10.1293/tox.2020-0079. Epub 2021 Feb 27.

ABSTRACT

Nickel subsulfide (Ni3S2) is known to induce intraocular neoplasms when injected intravitreally into the eyes of rats. Here, we found two extraocular orbital neoplasms in two different rat strains, presumably due to the leakage of locally injected Ni3S2 to the extraocular orbital tissues. In the F344/DuCrlCrlj rat, an orbital mass arose at 30 weeks after injection, and invaded into the cranium. Histologically, the orbital mass was composed of areas arranged in parallel bundles formed by densely packed elongated or spindle-shaped cells with indistinct cytoplasmic borders, and of areas of hypocellular arrangement consisting of round cells in eosinophilic myxoid-like substances. Metastases were observed in the right submandibular and cervical lymph nodes. The neoplastic cells were immunopositive for S-100 protein and vimentin. Transmission electron microscopy revealed that the neoplastic cells had cellular processes and pericytoplasmic basal laminae. In the RccHan^TM:WIST rat, an orbital mass arose at 36 weeks after injection. Histologically, the mass consisted of rhabdoid-like large round cells with proliferation of small round-to-polygonal cells, and these neoplastic cells infiltrated into the extraocular muscles. Immunohistochemically, the neoplastic cells were positive for desmin and vimentin. Transmission electron microscopy detected immature myofibrils with Z-band structures in the cytoplasm of these neoplastic cells. Consequently, the tumors were diagnosed as an orbital malignant schwannoma in an F344/DuCrlCrlj rat and an orbital embryonal rhabdomyosarcoma in a RccHan^TM:WIST rat. The results of this case report suggest that leakage of Ni3S2 to the orbit caused the induction of orbital malignant schwannoma or rhabdomyosarcoma in rats.

PMID:33976471 | PMC:PMC8100253 | DOI:10.1293/tox.2020-0079
Childhood Thoracic Rhabdomyosarcoma

Fetched: May 12th, 2021, 5:01am GMT by Lei Tang

Radiology. 2021 May 11:204254. doi: 10.1148/radiol.2021204254. Online ahead of print.

ABSTRACT

Online supplemental material is available for this article.

PMID:33973834 | DOI:10.1148/radiol.2021204254
Pediatric Head and Neck Tumors Associated with Li-Fraumeni Syndrome

Fetched: May 12th, 2021, 5:01am GMT by Kenny D Rodriguez

Ann Otol Rhinol Laryngol. 2021 May 10:34894211014786. doi: 10.1177/00034894211014786. Online ahead of print.

ABSTRACT

INTRODUCTION: Cancer predisposition syndromes are germline pathogenic variants in genes that greatly raise the risk of developing neoplastic diseases. One of the most well-known is Li-Fraumeni syndrome (LFS), which is due to pathogenic variants in the TP53 gene. Children with LFS have higher risks for multiple malignancies before adulthood, often with rare and aggressive subtypes.

OBJECTIVE: To examine head and neck manifestations of LFS in children treated at a tertiary children's hospital over a 20-year period.

METHODS: A retrospective review of LFS children with neoplastic disease presenting in traditional Otolaryngologic head and neck subsites from 2000 to 2019, with patient charts reviewed for relevant clinical, imaging, and operative data.

RESULTS: Of the 40 LFS patients initially identified, 27 neoplastic tumors were identified in 20 children within this cohort (20 primary, 7 second primary). Head and neck subsites aside from the brain or orbit were involved in 22% (6/27) of these tumors, representing 20% (4/20) of primary tumors and 29% (2/7) of second primary tumors. Both second primaries within the head and neck were within the radiation fields of the first primary tumor. The mean ages at primary and second primary diagnosis were 4.6 years (SD 3.5) and 12 years (SD 1.4), respectively. The male/female ratio was 1:6 among all patients with head and neck tumors. All 6 head and neck tumors were sarcomas. Rhabdomyosarcoma (N = 3, 50%) was the most common pathology, and the other 3 demonstrated rare tumor pathological subtypes (synovial cell sarcoma, pleomorphic myxoid liposarcoma, mandibular osteosarcoma). The neck was the most common subsite (75%) within this group for primary tumor presentation.

CONCLUSION: This study identifies a high potential for head and neck involvement in children with LFS, which has not been previously described in the literature. Otolaryngological care should be included in a multidisciplinary care team surveilling these patients.

PMID:33971750 | DOI:10.1177/00034894211014786
Non-parameningeal head and neck rhabdomyosarcoma in children, adolescents, and young adults: Experience of the European paediatric Soft tissue sarcoma Study Group (EpSSG) - RMS2005 study

Fetched: May 12th, 2021, 5:01am GMT by Heidi Glosli

Eur J Cancer. 2021 Jul;151:84-93. doi: 10.1016/j.ejca.2021.04.007. Epub 2021 May 7.

ABSTRACT

BACKGROUND/OBJECTIVES: The primary aim of this study was to analyse and evaluate the impact of different local treatments on the pattern of relapse in children with primary head and neck non-parameningeal (HNnPM) rhabdomyosarcoma (RMS), treated in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 study. The secondary aim was to assess whether current risk stratification is valid for this specific site.

DESIGN/METHODS: This study includes all patients with localised HNnPM RMS enrolled in the RMS2005 study between 2005 and 2016. Treatment comprised chemotherapy adapted to risk group, with local surgery and/or radiation therapy. The main outcome measures were event-free survival (EFS) and overall survival (OS).

RESULTS: A total of 165 patients were identified; the median age was 6.4 years (range, 0.1-25). The most common tumour sites were cheek/chin (22%) and nasal ala/nasolabial fold (20%). Histology was unfavourable for 40%, and regional nodal involvement present in 26%. Local therapy included surgery (58%) and/or radiotherapy (72%) to primary tumour and/or regional lymph nodes. After a median follow-up of 66 months (range, 6-158), 42 patients experienced an event, and 17 are still alive. Tumour events were frequent in oral primary (36%), parotid site (26%), cheek/chin (24%), and nasal ala/nasolabial fold (24%) and included locoregional failure in 84% of cases. The 5-year EFS and OS were 75% (95% confidence interval [CI]: 67.3-81.2) and 84.9% (95% CI: 77.5-89.7), respectively. Favourable histology was associated with a better EFS (82.3% versus 64.6%; p = 0.02) and nodal spread with a worse OS (88.6% versus 76.1%; p = 0.04). Different sublocations within the HNnPM primary did not have significant impact on outcome.

CONCLUSION: Locoregional relapse/progression is the main tumour failure event in this site. Despite frequent unfavourable risk factors, HNnPM RMS remains a favourable location in the context of a risk-adapted strategy.

PMID:33971448 | DOI:10.1016/j.ejca.2021.04.007
Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor

Fetched: May 8th, 2021, 5:02am GMT by Tatiana Tiago

Cell Death Dis. 2021 May 6;12(5):452. doi: 10.1038/s41419-021-03737-1.

ABSTRACT

One of the critical events that regulates muscle cell differentiation is the replacement of the lamin B receptor (LBR)-tether with the lamin A/C (LMNA)-tether to remodel transcription and induce differentiation-specific genes. Here, we report that localization and activity of the LBR-tether are crucially dependent on the muscle-specific chaperone HSPB3 and that depletion of HSPB3 prevents muscle cell differentiation. We further show that HSPB3 binds to LBR in the nucleoplasm and maintains it in a dynamic state, thus promoting the transcription of myogenic genes, including the genes to remodel the extracellular matrix. Remarkably, HSPB3 overexpression alone is sufficient to induce the differentiation of two human muscle cell lines, LHCNM2 cells, and rhabdomyosarcoma cells. We also show that mutant R116P-HSPB3 from a myopathy patient with chromatin alterations and muscle fiber disorganization, forms nuclear aggregates that immobilize LBR. We find that R116P-HSPB3 is unable to induce myoblast differentiation and instead activates the unfolded protein response. We propose that HSPB3 is a specialized chaperone engaged in muscle cell differentiation and that dysfunctional HSPB3 causes neuromuscular disease by deregulating LBR.

PMID:33958580 | PMC:PMC8102500 | DOI:10.1038/s41419-021-03737-1
Chronic Lymphocytic Leukemia in Neurofibromatosis Type 1 Patients: Case Report and Literature Review of a Rare Occurrence

Fetched: May 7th, 2021, 5:02am GMT by Philip R Cohen

Cureus. 2021 Apr 2;13(4):e14258. doi: 10.7759/cureus.14258.

ABSTRACT

Neurofibromatosis type 1 (NF1) is an autosomal dominant genodermatosis that may also occur as the result of a spontaneous mutation. The diagnosis can be established by the presence of two of the seven National Institutes of Health (NIH) diagnostic criteria; several dermatologic manifestations are NIH criteria used to establish the diagnosis: axillary and inguinal freckling, café-au-lait macules, and neurofibromas. Mucosal evaluation of the eyes may detect a fourth criteria: pigmented iris hamartomas (Lisch nodules). The remaining NIH criteria include optic path glioma, distinctive osseus lesions, and a positive family history of the condition. A breast cancer 2 (BRCA2) positive woman with NF1 and chronic lymphocytic leukemia is described. Patients with NF1 have an increased lifetime risk to develop breast cancer, gastrointestinal stromal tumor, malignant glioma, malignant peripheral nerve sheath tumor, and rhabdomyosarcoma. Chronic lymphocytic leukemia occurring in NF1 patients is rare; including my female patient reported in this paper, chronic lymphocytic leukemia has only been reported in three individuals with NF1--two women and one man. The man and the other woman presented with advanced chronic lymphocytic leukemia and treatment with antineoplastic therapy at diagnosis; the man achieved clinical remission and the woman passed away from complications associated with therapy-refractory progression of her leukemia. My female patient required treatment 41 months after diagnosis and had a good clinical response; she has been without significant disease progression for 34 months. Similar to NF1, breast cancer 1 (BRCA1) and BRCA2 mutations are associated with an increased lifetime risk of developing cancer--particularly breast and ovarian carcinoma. An increased risk of chronic lymphocytic leukemia has also been demonstrated in patients with mutations of either BRCA1 or BRCA2. Also, albeit uncommon, either BRCA1 or BRCA2 mutation has been detected in women with NF1 who develop breast cancer. In conclusion, the development of chronic lymphocytic leukemia in NF1 patients may be coincidental and not associated with the underlying genodermatosis; however, the occurrence of chronic lymphocytic leukemia in my patient with NF1, in part, may be related to her BRCA2 positivity.

PMID:33954070 | PMC:PMC8088774 | DOI:10.7759/cureus.14258
Bladder Mass Masquerading as Eosinophilic Cystitis in a Child: When to Think Beyond Malignancy?

Fetched: May 7th, 2021, 5:02am GMT by Lesa Dawman

J Indian Assoc Pediatr Surg. 2021 Jan-Feb;26(1):51-53. doi: 10.4103/jiaps.JIAPS_36_20. Epub 2021 Jan 11.

ABSTRACT

Eosinophilic cystitis is a rare inflammatory disease in the pediatric population with varied presentations. Diagnosis requires a high index of suspicion and cystoscopy with biopsy of the bladder mass. There are no standard treatment guidelines, however, these patients usually respond with medical management, but recurrence is a possibility. We present a case of eosinophilic cystitis in a 6-year-old boy who presented with lower urinary tract symptoms, gross hematuria, and bladder mass.

PMID:33953514 | PMC:PMC8074822 | DOI:10.4103/jiaps.JIAPS_36_20
Olfactory neuroblastoma associated with extensive "in situ" lesion and aberrant glandular and rhabdomyosarcomatous differentiation

Fetched: May 6th, 2021, 5:02am GMT by Masayuki Shintaku

Neuropathology. 2021 May 5. doi: 10.1111/neup.12730. Online ahead of print.

ABSTRACT

A case of olfactory neuroblastoma (ONB) associated with extensive intraepithelial neoplastic proliferation, evidenced by an "in situ" lesion, in the overlying olfactory epithelium and aberrant glandular and rhabdomyosarcomatous differentiation is reported. The tumor was a polypoid lesion that involved the upper nasal cavity and ethmoid sinus of a 63-year-old woman and consisted of an ONB surrounded by and mixed with a proliferative lesion of rhabdomyoblastic cells, consistent with an embryonal rhabdomyosarcoma. A few small foci of tubular glands with mucus-producing cells were also observed. In the olfactory epithelium covering the polypoid lesion, a nested or band-like arrangement of primitive-appearing small cells was found, and the tumor cells were immunoreactive for epithelial cell adhesion molecule (detected with Ber-EP4) and low-molecular weight cytokeratin (detected with CAM5.2) but not for synaptophysin or calretinin. The intraepithelial lesion was contiguous with the subepithelial cell nests of ONB and appeared to invade the subjacent stroma and show transition to ONB, and some tumor cell nests of ONB also contained small aggregates of similar primitive-appearing cells. The intraepithelial growth was considered to represent a preinvasive precursor lesion of ONB. Previous descriptions of an "in situ" lesion in ONB are limited. The aberrant glandular and rhabdomyosarcomatous differentiation noted in this case is also an exceptionally rare phenomenon of ONB.

PMID:33951746 | DOI:10.1111/neup.12730
The Upregulation of a Novel Long Noncoding RNA AK097647 Promotes Enterovirus 71 Replication and Decreases IFN-λ1 Secretion

Fetched: May 6th, 2021, 5:02am GMT by Min Chu

Intervirology. 2021 May 5:1-9. doi: 10.1159/000515903. Online ahead of print.

ABSTRACT

BACKGROUND: Enterovirus 71 (EV71) infects millions of children every year in China and has become a challenge to public health. However, there is no effective treatment for EV71 infection. Long noncoding RNAs (lncRNAs) have been found to play various roles in virus replication and infection.

OBJECTIVE: We aimed to explore the role of a novel long noncoding RNA AK097647 (lncRNA-AK097647) during EV71 infection.

METHODS: To assess the role of lncRNA-AK097647 during EV71 infection, siRNAs were used to silence lncRNA-K097647 expression. RT-qPCR assay and Western blotting were applied to measure the mRNA and protein levels of EV71 VP1 and the phosphorylation of NF-κB. ELISA was used to detect the level of IFN-λ1 expression.

RESULTS: The novel lncRNA-AK097647 was upregulated in human rhabdomyosarcoma cells and the blood of hand, foot, and mouth disease patients infected with EV71, as demonstrated by RT-qPCR. Interestingly, RNAi-mediated knockdown of lncRNA-AK097647 dramatically increased the level of IFN-λ1 expression, resulting in the suppression of EV71 replication. In contrast, overexpression of lncRNA-AK097647 decreased the level of IFN-λ1 expression and resulted in increased EV71 replication. In addition, we found that lncRNA-AK097647 could inhibit the phosphorylation of NF-κB.

CONCLUSION: These results suggest a novel mechanism by which EV71 evades the IFN-mediated host antiviral response by increasing lncRNA-AK097647 expression.

PMID:33951637 | DOI:10.1159/000515903
Cytotoxicity and Target Modulation in Pediatric Solid Tumors by the Proteasome Inhibitor Carfilzomib

Fetched: May 6th, 2021, 5:02am GMT by Satbir Thakur

Curr Cancer Drug Targets. 2021 May 3. doi: 10.2174/1568009621666210504085527. Online ahead of print.

ABSTRACT

BACKGROUND: Most children with recurrent metastatic solid tumors have high mortality rates. Recent studies have shown that proteasome inhibition leads to effective tumor killing in cells that have acquired treatment resistance and metastatic properties.

OBJECTIVE: The purpose of this study was to test the potential of Carfilzomib (CFZ), a proteasome inhibitor, in refractory pediatric solid tumors, which is currently unknown.

METHODS: A panel of pediatric solid tumor cell lines, including neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and atypical teratoid rhabdoid tumor (ATRT), was used to evaluate the cytotoxic and proteasomal inhibitory effects of CFZ. A drug scheduling experiment was performed to determine the optimal dose and time to obtain effective cell killing. Combination studies of CFZ with chemotherapeutic drugs of different classes were performed to determine the extent of synergy.

RESULTS: CFZ showed effective cytotoxicity against all cell lines tested (mean IC50 = 7nM, range = 1-20nM) and activity in a fluorophore-tagged cell-based proteasome assay. Drug scheduling experiments showed that the minimum exposure of 4-8 hours/day is needed for effective cumulative killing. CFZ, when combined with chemotherapeutic drugs of different classes, synergistically enhanced the extent of cell death.

CONCLUSIONS: CFZ showed cytotoxic activity against all the solid pediatric cancer cell lines tested. This study provides initial in vitro data on the potential of CFZ to treat pediatric solid tumors and supports further investigations into the components of drug scheduling, biological correlates, and drug combinations for future early phase clinical trials in children.

PMID:33949932 | DOI:10.2174/1568009621666210504085527
Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease: A Study of 4 Aggressive Cases With Clinical, Pathologic, Molecular, and Radiologic Findings

Fetched: May 6th, 2021, 5:02am GMT by Joanna Cyrta

Am J Surg Pathol. 2021 Jun 1;45(6):854-867. doi: 10.1097/PAS.0000000000001702.

ABSTRACT

VGLL2-rearranged rhabdomyosarcomas (RMS) are rare low-grade tumors with only favorable outcomes reported to date. We describe 4 patients with VGLL2-rearranged RMS confirmed by molecular studies, who experienced local progression and distant metastases, including 2 with fatal outcomes. Tumors were diagnosed at birth (n=3) or at 12 months of age (n=1), and were all localized at initial diagnosis, but unresectable and therefore managed with chemotherapy and surveillance. Metastatic progression occurred from 1 to 8 years from diagnosis (median, 3.5 y). Three patients experienced multimetastatic spread and one showed an isolated adrenal metastasis. At initial diagnosis, 3 tumors displaying bland morphology were misdiagnosed as fibromatosis or infantile fibrosarcoma and initially managed as such, while 1 was a high-grade sarcoma. At relapse, 3 tumors showed high-grade morphology, while 1 retained a low-grade phenotype. Low-grade primary tumors showed only very focal positivity for desmin, myogenin, and/or MyoD1, while high-grade tumors were heterogenously or diffusely positive. Whole-exome sequencing, performed on primary and relapse samples for 3 patients, showed increased genomic instability and additional genomic alterations (eg, TP53, CDKN2A/B, FGFR4) at relapse, but no recurrent events. RNA sequencing confirmed that high-grade tumors retained VGLL2 fusion transcripts and transcriptomic profiles consistent with VGLL2-rearranged RMS. High-grade samples showed a high expression of genes encoding cell cycle proteins, desmin, and some developmental factors. These 4 cases with distinct medical history imply the importance of complete surgical resection, and suggest that RMS-type chemotherapy should be considered in unresectable cases, given the risk of high-grade transformation. They also emphasize the importance of correct initial diagnosis.

PMID:33949344 | DOI:10.1097/PAS.0000000000001702
Multiple pediatric dermatomyofibromas in a patient with a history of embryonal rhabdomyosarcoma

Fetched: May 6th, 2021, 5:02am GMT by Blake Elizabeth Brooks

JAAD Case Rep. 2021 Mar 29;11:96-98. doi: 10.1016/j.jdcr.2021.03.004. eCollection 2021 May.

NO ABSTRACT

PMID:33948467 | PMC:PMC8079820 | DOI:10.1016/j.jdcr.2021.03.004
Aural polyp with facial asymmetry in an unfortunate infant

Fetched: May 6th, 2021, 5:02am GMT by Farah Syahida Zubir

Malays Fam Physician. 2021 Feb 8;16(1):133-135. doi: 10.51866/cr1070. eCollection 2021 Mar 25.

ABSTRACT

Temporal bone rhabdomyosarcoma is an aggressive entity that simulates chronic otitis ear infection. It is the most common soft tissue sarcoma amongst pediatric patients. Herein, we would like to report a case of temporal bone rhabdomyosarcoma involving a 2-year-old boy who presented with a one-month history of otorrhea with facial asymmetry. Early treatment led to remission of this severe neoplasm.

PMID:33948154 | PMC:PMC8088741 | DOI:10.51866/cr1070
Vincetoxicum arnottianum modulates motility features and metastatic marker expression in pediatric rhabdomyosarcoma by stabilizing the actin cytoskeleton

Fetched: May 6th, 2021, 5:02am GMT by Anna Adamus

BMC Complement Med Ther. 2021 May 4;21(1):136. doi: 10.1186/s12906-021-03299-x.

ABSTRACT

BACKGROUND: Prevention of metastatic invasion is one of the main challenges in the treatment of alveolar rhabdomyosarcoma. Still the therapeutic options are limited. Therefore, an anti-tumor screening was initiated focusing on the anti-metastatic and anti-invasion properties of selected medicinal plant extracts and phytoestrogens, already known to be effective in the prevention and treatment of different cancer entities.

METHODS: Treatment effects were first evaluated by cell viability, migration, invasion, and colony forming assays on the alveolar rhabdomyosarcoma cell line RH-30 in comparison with healthy primary cells.

RESULTS: Initial anti-tumor screenings of all substances analyzed in this study, identified the plant extract of Vincetoxicum arnottianum (VSM) as the most promising candidate, harboring the highest anti-metastatic potential. Those significant anti-motility properties were proven by a reduced ability for migration (60%), invasion (99%) and colony formation (61%) under 48 h exposure to 25 μg/ml VSM. The restricted motility features were due to an induction of the stabilization of the cytoskeleton - actin fibers were 2.5-fold longer and were spanning the entire cell. Decreased proliferation (PCNA, AMT, GCSH) and altered metastasis (e. g. SGPL1, CXCR4, stathmin) marker expression on transcript and protein level confirmed the significant lowered tumorigenicity under VSM treatment. Finally, significant alterations in the cell metabolism were detected for 25 metabolites, with levels of uracil, N-acetyl serine and propanoyl phosphate harboring the greatest alterations. Compared to the conventional therapy with cisplatin, VSM treated cells demonstrated a similar metabolic shutdown of the primary cell metabolism. Primary control cells were not affected by the VSM treatment.

CONCLUSIONS: This study revealed the VSM root extract as a potential, new migrastatic drug candidate for the putative treatment of pediatric alveolar rhabdomyosarcoma with actin filament stabilizing properties and accompanied by a marginal effect on the vitality of primary cells.

PMID:33947373 | PMC:PMC8097906 | DOI:10.1186/s12906-021-03299-x
A Nomogram Model to Predict Prognosis of Patients With Genitourinary Sarcoma

Fetched: May 4th, 2021, 5:02am GMT by Linde Li

Front Oncol. 2021 Apr 16;11:656325. doi: 10.3389/fonc.2021.656325. eCollection 2021.

ABSTRACT

OBJECTIVES: The aim of this study is to evaluate the significant factors influencing the overall survival (OS) and recurrence free survival (RFS) and make an attempt to develop a nomogram for predicting the prognosis of patients with genitourinary sarcoma (GS).

METHODS: Data on adult GS from 1985 to 2010 were collected. The impact of clinical factors on OS and RFS were estimated by Kaplan-Meier (KM) analysis, and differences between groups were analyzed by the log-rank test. To establish a nomogram, all patients were randomly divided into a training set (n = 125) and a testing set (n = 63). Cox proportion hazard model was utilized to assess the prognostic effect of variables. Then, a nomogram was established to estimate 1-, 3-, and 5-year OS based on Cox regression model. Subsequently, the nomogram was validated by a training set and a validation set.

RESULTS: A total of 188 patients were enrolled into our study. Male patients with bladder sarcoma had better OS rather than RFS when stratified by gender (P = 0.022). According to histological subtypes, patients with leiomyosarcoma (LMS) undergoing chemotherapy were associated with favorable OS (P = 0.024) and RFS (P = 0.001). Furthermore, LMS in kidney sarcoma were associated with lower recurrence rate in comparison to rhabdomyosarcoma (RMS) (P = 0.043). Margin status after surgical excision markedly influenced the OS and RFS of GS patients and negative margins presented optimal prognosis. Chemotherapy was associated with improved OS for patients without surgery (P = 0.029) and patients with positive margins (P = 0.026). Based on the multivariate analysis of the training cohort, age, gender, surgery status, histological subtype, and chemotherapy were included in our nomogram for prediction of OS. The nomogram had sufficient power with concordance index (C-index) of OS: 0.770, 95%CI: 0.760-0.772 and area under curve (AUC) of OS: 0.759, 95%CI: 0.658-0.859 in the training set and with C-index of OS: 0.741, 95%CI: 0.740-0.765, and AUC of OS: 0.744, 95%CI: 0.576-0.913 in the validation set.

CONCLUSIONS: Adults GS is a group of extremely rare tumors with poor prognosis. Of all histological types, LMS is sensitive to chemotherapy. We highlighted the cardinal role of surgical resection and the importance of achieving negative margins. We identified the efficacy of chemotherapy for patients with positive margins and those without surgery as well. A nomogram is validated as an effective tool predicting short-term outcomes.

PMID:33937065 | PMC:PMC8085422 | DOI:10.3389/fonc.2021.656325
Down-regulated long non-coding RNA RMST ameliorates dopaminergic neuron damage in Parkinson's disease rats via regulation of TLR/NF-κB signaling pathway

Fetched: May 4th, 2021, 5:02am GMT by Xuelian Ma

Brain Res Bull. 2021 Apr 30;174:22-30. doi: 10.1016/j.brainresbull.2021.04.026. Online ahead of print.

ABSTRACT

OBJECTIVE: Current treatment and prognosis of Parkinson's disease (PD) are not ideal. This study explored the mechanism of long non-coding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (RMST) in dopaminergic (DA) neuron damage in PD rats.

METHODS: PD rats were modeled and injected with RMST silence or overexpression vectors to figure out its roles in oxidative stress, the apoptosis of DA neurons in brain substantia nigra (SN), and neurobehavioral activities of PD rats. Tyrosine hydroxylase (TH), synaptophysin (SYN), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba-1) in SN were detected. RMST and Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) pathway-related factors were detected.

RESULTS: RMST expression in brain SN of rats, TLR2, TLR4 expression in neurons and NF-κB expression in cell nucleus were increased. Silenced RMST improved the neurobehavioral activities, depressed oxidative stress and neuronal apoptosis, increased TH and SYN expression, and reduced the activation degree of glial cells in SN and the inflammatory response via reducing GFAP and Iba-1. Moreover, reduced RMST reduced TLR2 and TLR4 expression in neurons and NF-κB expression in cell nucleus in PD rats.

CONCLUSION: Inhibited RMST attenuates DA neuron damage in PD rats, which may be implicated with TLR/NF-κB signaling pathway.

PMID:33933526 | DOI:10.1016/j.brainresbull.2021.04.026
A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Fetched: May 1st, 2021, 5:02am GMT by Raffaella Messina

Neurol Int. 2021 Apr 22;13(2):175-183. doi: 10.3390/neurolint13020017.

ABSTRACT

Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms "Li-Fraumeni" AND "pediatric high-grade glioma (HGG)", identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

PMID:33921960 | PMC:PMC8167566 | DOI:10.3390/neurolint13020017
Eosinophilic Cystitis Presenting as Possible Pediatric Rhabdomyosarcoma in Conventional Imaging Including (18)F-FDG-PET/CT/MRI-A Rare Case

Fetched: May 1st, 2021, 5:02am GMT by Naja Enevold Olsen

Diagnostics (Basel). 2021 Apr 8;11(4):672. doi: 10.3390/diagnostics11040672.

ABSTRACT

Eosinophilic cystitis (EC) is a relatively rare, but benign inflammatory bladder disease compared to that of the malignant pediatric rhabdomyosarcoma (RMS), in which it can be mimicking on initial suspicion. The origin, symptoms and findings of both EC and RMS are still discussed and hence, lead to the challenge in distinguishing them by cystoscopy and several image modalities. We present a case in which cross-sectional imaging modalities including fluorine-18-fluro-2-deoxy-D-glucose (¹⁸F-FDG)-positron emission tomography (PET) / computed tomography (CT) / magnetic resonance imaging (MRI) (¹⁸F-FDG-PET/CT/MRI (The imaging modality ¹⁸F-FDG-PET/CT/MRI referring to two continuous scans scanned on the same ¹⁸F-FDG-tracer dose for both the whole-body ¹⁸F-FDG-PET/CT and the regional ¹⁸F-FDG-PET/MRI of the pelvis.)) raised suspicion of RMS. Hence, the final diagnosis of EC was established by repeated histopathology. It is important to have EC in mind when seeking differential diagnosis of malignant diseases like RMS in order to provide the correct treatment for the patient and highly homogenously increased ¹⁸F-FDG-uptake should raise the suspicion of EC as a differential diagnosis. Furthermore, ¹⁸F-FDG-uptake rate is suggested as a future potential biomarker for monitoring of therapeutic response in eosinophilic inflammatory diseases, thus more research on this topic is needed.

PMID:33917971 | PMC:PMC8068401 | DOI:10.3390/diagnostics11040672
Role for the Histone Demethylase KDM4B in Rhabdomyosarcoma via CDK6 and CCNA2: Compensation by KDM4A and Apoptotic Response of Targeting Both KDM4B and KDM4A

Fetched: May 1st, 2021, 5:02am GMT by Zoë S Walters

Cancers (Basel). 2021 Apr 6;13(7):1734. doi: 10.3390/cancers13071734.

ABSTRACT

Histone demethylases are epigenetic modulators that play key roles in regulating gene expression related to many critical cellular functions and are emerging as promising therapeutic targets in a number of tumor types. We previously identified histone demethylase family members as overexpressed in the pediatric sarcoma, rhabdomyosarcoma. Here we show high sensitivity of rhabdomyosarcoma cells to a pan-histone demethylase inhibitor, JIB-04 and identify a key role for the histone demethylase KDM4B in rhabdomyosarcoma cell growth through an RNAi-screening approach. Decreasing KDM4B levels affected cell cycle progression and transcription of G1/S and G2/M checkpoint genes including CDK6 and CCNA2, which are bound by KDM4B in their promoter regions. However, after sustained knockdown of KDM4B, rhabdomyosarcoma cell growth recovered. We show that this can be attributed to acquired molecular compensation via recruitment of KDM4A to the promoter regions of CDK6 and CCNA2 that are otherwise bound by KDM4B. Furthermore, upfront silencing of both KDM4B and KDM4A led to RMS cell apoptosis, not seen by reducing either alone. To circumvent compensation and elicit stronger therapeutic responses, our study supports targeting histone demethylase sub-family proteins through selective poly-pharmacology as a therapeutic approach.

PMID:33917420 | PMC:PMC8038694 | DOI:10.3390/cancers13071734
Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

Fetched: May 1st, 2021, 5:02am GMT by Holly L Pacenta

J Clin Med. 2021 Apr 1;10(7):1416. doi: 10.3390/jcm10071416.

ABSTRACT

Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children's Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.

PMID:33915882 | PMC:PMC8037615 | DOI:10.3390/jcm10071416
Pattern of relapse in pediatric localized extremity rhabdomyosarcomas correlated with locoregional therapies administered

Fetched: April 30th, 2021, 5:02am GMT by Julien Welmant

Strahlenther Onkol. 2021 Apr 29. doi: 10.1007/s00066-021-01780-7. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered.

METHODS: All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging.

RESULTS: We identified 59 patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32 patients (54%) and modified the lymph node stage in 8 of the 59 patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26 patients underwent complete tumor resection, 17 had R1 margins, and 5 were not operated due to early tumor progression. With a median follow-up of 82 months (range: 5-287), 18 relapses had occurred, at least locoregional in 12 cases. The 5‑year local and nodal control rates were 73% (63-86%) and 86% (77-95%), respectively. Five-year progression-free and overall survival were 57% (95%CI [45-72%]) and 70% (95%CI [58-84%]), respectively.

CONCLUSION: The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity.

PMID:33914102 | DOI:10.1007/s00066-021-01780-7
MYOD1 as a prognostic indicator in rhabdomyosarcoma

Fetched: April 30th, 2021, 5:02am GMT by Atif A Ahmed

Pediatr Blood Cancer. 2021 Apr 29:e29085. doi: 10.1002/pbc.29085. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Rhabdomyosarcoma (RMS) is characterized by the expression of the myogenic regulatory protein MYOD1. Histologic types include alveolar, embryonal (ERMS), and spindle cell sclerosing RMS (SRMS). SRMS harbors MYOD1 mutations in a subset of adult cases in association with poor prognosis.

DESIGN/METHODS: To study the level of MYOD1 protein expression and its clinical significance, we have analyzed variable numbers of pediatric (<18 years of age) and adult (age range ≥18 to 35 years) ERMS and SRMS cases for presence or absence of MYOD1 immunoreactivity in correlation with clinical outcome and MYOD1 L122R mutations.

RESULTS: Lack of MYOD1 immunoreactivity, identified in 23.8% of nonalveolar RMS (non-ARMS) cases, was more prevalent in SRMS (44%) than ERMS (17.2%) and was significantly associated with low overall survival and unfavorable tumor sites (p < .05). Lack of MYOD1 immunoreactivity was not associated with MYOD1 L122R mutations, which were identified in 3/37 (8%) cases including only two of 31 (6.5%) pediatric cases, one of 11 or 9% pediatric SRMS, and one case of infant ERMS.

CONCLUSION: These studies highlight the prognostic role of MYOD1 in non-ARMS. Lack of MYOD1 immunoreactivity is associated with poor prognosis in ERMS and SRMS. MYOD1 gene mutations are generally infrequent in pediatric RMS. Although mutations are predominant in SRMS, they may exceptionally occur in infantile ERMS.

PMID:33913590 | DOI:10.1002/pbc.29085
A Case of Pseudomyogenic Hemangioendothelioma of the Lower Extremity

Fetched: April 30th, 2021, 5:02am GMT by Myoung Eun Choi

Ann Dermatol. 2020 Oct;32(5):426-429. doi: 10.5021/ad.2020.32.5.426. Epub 2020 Sep 29.

ABSTRACT

Pseudomyogenic hemangioendothelioma (PMH) is a rare vascular tumor and was recently recognized as a distinct entity. It has a predilection for young male adults and it frequently occurs in distal extremities. Although it is known to follow an indolent course, multi-focal presentation and local recurrence are common. PMH should be differentiated from epithelioid sarcoma, epithelioid hemangioendothelioma, dermatofibrosarcoma protuberans, and rhabdomyosarcoma. Its characteristic immunohistochemical staining pattern and recurrent translocation t(7:19)(q22:q13) are the basis for its diagnosis. Surgical excision is the mainstay treatment, although chemotherapy can be considered in non-operable patients. We present a rare case of a 40-year-old Korean male patient diagnosed with PMH through an excisional biopsy to facilitate the recognition PMH in the clinical practice.

PMID:33911779 | PMC:PMC7992577 | DOI:10.5021/ad.2020.32.5.426
An update on immunohistochemical and molecular genetic markers of selected soft tissue tumors

Fetched: April 30th, 2021, 5:02am GMT by Michael Michal

Cesk Patol. 2021 Spring;57(1):19-29.

ABSTRACT

Recent years have brought an immense increase of knowledge regarding the molecular genetic background of mesenchymal tumors which in turn has significantly expanded the repertoire of molecular markers available for the routine diagnostic practice. This progress has also been followed by a rising number of available immunohistochemical markers useful for the diagnosis of soft tissue neoplasia. Both lineage specific and tumor-specific immunohistochemical antibodies have been discovered and subsequently tested in the surgical pathology practice. This article will review some of the immunohistochemical and molecular genetic markers useful in the diagnosis of vascular tumors, malignant peripheral nerve sheath tumors, low-grade fibromyxoid sarcomas/sclerosing epithelioid fibrosarcomas, solitary fibrous tumors, epithelioid sarcomas, rhabdomyosarcomas and other lesions showing skeletal muscle differentiation. The immunohistochemical and molecular genetic features of some recently characterized and clinically particularly important entities will be discussed as well.

PMID:33910345
BCOR-CCNB3 Sarcoma with Prominent Rhabdoid Cells Mimicking Rhabdomyoblasts: Expanding the Morphologic spectrum of BCOR-CCNB3 Sarcoma

Fetched: April 29th, 2021, 5:02am GMT by Zhenjian Cai

Int J Surg Pathol. 2021 Apr 28:10668969211013891. doi: 10.1177/10668969211013891. Online ahead of print.

ABSTRACT

BCOR-CCNB3 sarcoma (BCS) is a rare recently defined undifferentiated sarcoma that predominantly affects children and young adults. The diagnosis of this tumor is difficult due to the highly variable morphology and nonspecific immunophenotype. Emerging data suggest that patients with BCS show response to Ewing sarcoma-based treatment regimen, thus correct diagnosis is of clinical relevance. In this study, we report a case of BCS arising from the big toe of a 15-year-old male patient. The tumor had a prominent population of rhabdoid cells with bright eosinophilic cytoplasm mimicking rhabdomyosarcoma. The tumor cells were focally positive for desmin and myogenin, and negative for CD99. Next-generation sequencing showed the presence of BCOR-CCNB3 gene fusion. BCS with prominent rhabdoid cells has not been described before. This study further expands the morphologic spectrum of BCS.

PMID:33909519 | DOI:10.1177/10668969211013891
Rhabdomyosarcoma and pleomorphic sarcoma in the same location : Recurrence or new entity?

Fetched: April 28th, 2021, 5:02am GMT by Daniel Steiner

Wien Klin Wochenschr. 2021 Apr 27. doi: 10.1007/s00508-021-01872-5. Online ahead of print.

ABSTRACT

Soft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk factors such as environmental factors, genetic predisposition, and prior radiotherapy. In STS patients with a novel swelling, differential diagnoses include recurrence, second primary cancer, metastasis from unknown primary cancer, and radiation-associated STS, the latter usually occurring approximately 10 years after radiotherapy. We present the case of a 64-year-old male patient with pleomorphic rhabdomyosarcoma, who underwent resection and radiotherapy. The patient presented again 5 years later with painful swelling in the area of the prior sarcoma, raising suspicion of recurrence. Resection was performed and a diagnosis of pleomorphic sarcoma (not otherwise specified [NOS]) was made. The patient was treated with radiotherapy and remained sarcoma-free for the following 7 years. A molecular analysis of both neoplasms, using RNA next-generation sequencing, did not detect any specific fusions. Due to the lack of rhabdomyoblastic differentiation in the second sarcoma and the low likelihood of a second primary in the same previously irradiated location, the diagnosis of a radiation-associated STS was suggested. This short report illustrates the difficult diagnostic work-up of a presumably radiation-associated STS, as these neoplasms lack characteristic morphological and immunohistochemical features. In our case, the suggested diagnosis may have pointed against another course of radiotherapy in an already irradiation-harmed region. Therefore, a relatively low latency period between surgery, radiotherapy, and diagnosis of another STS should not automatically point towards recurrence and may prompt further in-depth investigation.

PMID:33905030 | DOI:10.1007/s00508-021-01872-5
INI1-negative colorectal undifferentiated carcinoma with rhabdoid features and postoperative rapidly growing liver metastases: a case report and review of the literature

Fetched: April 28th, 2021, 5:02am GMT by Masatsugu Kojima

Surg Case Rep. 2021 Apr 27;7(1):104. doi: 10.1186/s40792-021-01189-5.

ABSTRACT

BACKGROUND: Malignant tumors with rhabdoid features are extremely rare. They can occur in various organs, including the gastrointestinal tract, with common clinical features of high malignancy and poor prognosis.

CASE PRESENTATION: A 41-year-old man visited our hospital complaining of lower abdominal pain and fever. Computed tomography (CT) revealed two wall-thickening lesions in the rectum and sigmoid colon, with the latter invading the small intestine and abdominal wall. Lymph nodes were swollen in the sigmoid mesocolon and at the roots of the inferior mesenteric artery. Colonoscopy revealed a circular type 3 lesion in the sigmoid colon and a semicircular type 2 lesion in the rectum. Biopsies of the sigmoid colon and rectum lesions revealed poorly and moderately differentiated adenocarcinoma cells, respectively. The sigmoid colon, rectum, invaded small intestine, and abdominal wall were resected; lymph node dissection was also performed. Histopathological finding of the sigmoid colon lesion revealed that the tumor cells had poor connectivity with each other, and each cell had eosinophilic cytoplasm and a polymorphic nucleus. These characteristics are termed rhabdoid features, because the morphology of these cells is similar to that of rhabdomyosarcoma tumor cells. Immunohistochemical examination showed that the tumor cells were positive for both epithelial (cytokeratin AE1/AE3) and mesenchymal cell markers (vimentin); however, they were negative for integrase interactor 1 (INI1). Therefore, the sigmoid colorectal cancer was diagnosed as an INI1-negative undifferentiated carcinoma with rhabdoid features. The patient continued to experience high fever after surgery; thus, we performed an abdominal CT scan that revealed cystic lesions in the liver 4 days after surgery. These were absent in the positron emission tomography (PET)-CT scan performed 14 days before surgery. These tumors grew rapidly, and fine needle aspiration cytology revealed that they were undifferentiated carcinomas compatible with metastatic lesions from the undifferentiated carcinoma with rhabdoid features from the sigmoid colon. Chemotherapy was administered but was not effective. The patient died 60 days after surgery.

CONCLUSIONS: INI1-negative colorectal undifferentiated carcinomas with rhabdoid features are extremely rare, have high histological malignancy, and a poor prognosis. Chemotherapy is not effective. Effective systemic therapy is desired.

PMID:33903966 | PMC:PMC8076409 | DOI:10.1186/s40792-021-01189-5
Improved patient-specific hyperthermia planning based on parametrized electromagnetic and thermal models for the SIGMA-30 applicator

Fetched: April 27th, 2021, 5:02am GMT by Jacek Nadobny

Int J Hyperthermia. 2021;38(1):663-678. doi: 10.1080/02656736.2021.1909757.

ABSTRACT

OBJECTIVE: To create an improved planning method for pediatric regional hyperthermia (RHT) using the SIGMA-30 applicator (SIGMA-30).

MATERIALS AND METHODS: An electromagnetic model of SIGMA-30 was generated for use with the finite-difference time-domain (FDTD) method. Applying special MATLAB-based algorithms, voxel models of a pediatric patient with pelvic rhabdomyosarcoma were created from Computed-Tomography (CT) contours for use with the FDTD method and the finite-difference (FD) method capable of using either temperature-independent or temperature-dependent perfusion models for solving the Bioheat Transfer Equation (BHTE). Patient models were parametrized regarding, first, the positioning in the applicator, second, the absorbed power range and, third, different perfusion models, resulting in the so-called Parametrized Treatment Models (PTMs). A novel dedicated optimization procedure was developed based on quantitative comparison of numerical calculations against temperature and power measurements from two RHT therapies.

RESULTS: Using measured data, a realistic absorbed power range in the patient model was estimated. Within this range, several FDTD and BHTE runs were performed and, applying the aforementioned optimization scheme, the best PTMs and perfusion models were identified for each therapy via a retrospective comparison with measurements in 14 temperature sensor positions: 5 in the tumor, 8 in rectum and one in bladder.

CONCLUSION: A novel dedicated optimization procedure for identification of suitable patient-specific electromagnetic and thermal models, which can be used for improved patient planning, was developed and evaluated by comparison with treatment-derived measurements using SIGMA-30. The optimization procedure can be extended to other hyperthermia applicators and to other patient types, including adults.

PMID:33899658 | DOI:10.1080/02656736.2021.1909757
Differential regulation of autophagy by STAU1 in alveolar rhabdomyosarcoma and non-transformed skeletal muscle cells

Fetched: April 27th, 2021, 5:02am GMT by Shekoufeh Almasi

Cell Oncol (Dordr). 2021 Apr 26. doi: 10.1007/s13402-021-00607-y. Online ahead of print.

ABSTRACT

PURPOSE: Recent work has highlighted the therapeutic potential of targeting autophagy to modulate cell survival in a variety of diseases including cancer. Recently, we found that the RNA-binding protein Staufen1 (STAU1) is highly expressed in alveolar rhabdomyosarcoma (ARMS) and that this abnormal expression promotes tumorigenesis. Here, we asked whether STAU1 is involved in the regulation of autophagy in ARMS cells.

METHODS: We assessed the impact of STAU1 expression modulation in ARMS cell lines (RH30 and RH41), non-transformed skeletal muscle cells (C2C12) and STAU1-transgenic mice using complementary techniques.

RESULTS: We found that STAU1 silencing reduces autophagy in the ARMS cell lines RH30 and RH41, while increasing their apoptosis. Mechanistically, this inhibitory effect was found to be caused by a direct negative impact of STAU1 depletion on the stability of Beclin-1 (BECN1) and ATG16L1 mRNAs, as well as by an indirect inhibition of JNK signaling via increased expression of Dual specificity phosphatase 8 (DUSP8). Pharmacological activation of JNK or expression silencing of DUSP8 was sufficient to restore autophagy in STAU1-depleted cells. By contrast, we found that STAU1 downregulation in non-transformed skeletal muscle cells activates autophagy in a mTOR-dependent manner, without promoting apoptosis. A similar effect was observed in skeletal muscles obtained from STAU1-overexpressing transgenic mice.

CONCLUSIONS: Together, our data indicate an effect of STAU1 on autophagy regulation in ARMS cells and its differential role in non-transformed skeletal muscle cells. Our findings suggest a cancer-specific potential of targeting STAU1 for the treatment of ARMS.

PMID:33899158 | DOI:10.1007/s13402-021-00607-y
Testis-sparing surgery in children with testicular tumors: A systematic review and meta-analysis

Fetched: April 25th, 2021, 5:02am GMT by Xuefeng Miao

Asian J Surg. 2021 Apr 21:S1015-9584(21)00151-2. doi: 10.1016/j.asjsur.2021.03.016. Online ahead of print.

ABSTRACT

Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility associated with TSS remain uncertain. This study aimed to present the clinical outcomes of TSS in children with TTs. The PubMed, Cochrane Library, and Embase databases were reviewed for relevant articles on the clinical outcomes of TSS in children. Recurrence rate, benign rate, rate of TSS and its 95% confidence interval (CI) were calculated. A total of nine relevant studies with 320 patients were included in this study. The recurrence rate was 5.8% (95% CI: 2.3%-14.1%), benign rate was 70.9% (95% CI: 56.3%-82.1%), the rate of TSS (RTSS) was 36.2% (95% CI: 26.1%-47.8%), RTSS in benign tumor was 48.4% (95% CI: 34.3%-62.9%) and rate of elevated AFP was 29.3% (95% CI: 19.7%-41.3%) in children with TTs. Regarding the distribution of TTs, 159 (49.6%) were teratomas, 74 (23.1%) were yolk sac tumors, 36 (11.3%) were epidermoid cysts, 3 (0.9%) were rhabdomyosarcomas, 7 (2.2%) were leydig cell tumor, 6 (1.8%) were sex-cord stromal tumor, 8(2.5%) were mixed malignant germ cell tumors, 3(0.9%) were hemangioma, and 4(1.3%) were adrenal rest tumors. The findings of this meta-analysis suggested that most of the TTs in children were benign, and the most common histologic subtype was teratoma. TSS should be provided to children with benign lesions. This study confirmed that very low rates of tumor recurrence were observed in children with TTs.

PMID:33893031 | DOI:10.1016/j.asjsur.2021.03.016
Nasal Embryonal Rhabdomyosarcoma in the Pediatric Population: Literature Review and Report of Midline Presentation

Fetched: April 24th, 2021, 5:02am GMT by Jordan H Larson

Plast Reconstr Surg Glob Open. 2021 Apr 20;9(4):e3534. doi: 10.1097/GOX.0000000000003534. eCollection 2021 Apr.

ABSTRACT

BACKGROUND: Congenital midline nasal masses are rare anomalies and are typically benign nasal dermoid sinus cysts (NDSCs). Rhabdomyosarcomas (RMSs) are even less common, and only a fraction affect sites like the external nose, nasal cavity, nasopharynx, and paranasal sinuses. We review the clinical presentation and treatment of nasal, nasopharyngeal, and paranasal RMSs and report the first documented midline presentation.

METHODS: We queried PubMed for articles with titles containing the terms rhabdomyosarcoma or sarcoma botryoides and nose, nasal, paranasal, sinonasal, nasopharynx, or nasopharyngeal. We then searched the references of each included article using the same parameters and continued this process iteratively until no new articles were found.

RESULTS: The paranasal sinuses were the most commonly affected site, followed by the nasopharynx, nasal cavity, and external nose. Two patients presented with involvement of the external nose, but each presented with involvement of the right ala rather than a midline mass. The rates of intracranial extension and/or skull base involvement were comparable to those of NDSCs. The alveolar subtype was most common, followed by the embryonal subtype.

CONCLUSIONS: Most midline nasal masses are benign; however, we report the first documented presentation of an RMS as a midline nasal mass. Accordingly, RMS should be included in the differential diagnosis of midline nasal masses in the pediatric population. Surgery for midline nasal masses is sometimes delayed due to the risks of interfering with developing structures and early anesthesia. However, early surgical treatment should be considered given this new differential and its predilection for early metastasis.

PMID:33889472 | PMC:PMC8057758 | DOI:10.1097/GOX.0000000000003534
Excision and Reconstruction of Alveolar Rhabdomyosarcoma Involving the Achilles Tendon in a Pediatric Patient: A Case Report

Fetched: April 23rd, 2021, 5:01am GMT by Joseph Koressel

JBJS Case Connect. 2021 Apr 22;11(2). doi: 10.2106/JBJS.CC.20.00263.

ABSTRACT

CASE: We describe a case of a 9-year-old boy who presented with a left calf mass consistent with alveolar rhabdomyosarcoma involving the Achilles tendon. The patient underwent radical resection of the Achilles tendon and Achilles tendon allograft reconstruction. At 2.5-year follow-up, the child had full ankle range of motion and strength and no signs of disease.

CONCLUSIONS: Radical resection of Achilles tendon in the setting of malignancy and reconstruction with allograft is a rare procedure that has not been previously described in the pediatric population. Orthopaedic oncologists can consider this option for the rare malignancies involving the Achilles tendon.

PMID:33886517 | DOI:10.2106/JBJS.CC.20.00263
Characterizing the relationship between the chemical structures of drugs and their activities on primary cultures of pediatric solid tumors

Fetched: April 21st, 2021, 5:04am GMT by Saw Simeon

Curr Med Chem. 2021 Apr 19. doi: 10.2174/0929867328666210419134708. Online ahead of print.

ABSTRACT

BACKGROUND: Despite continued efforts to develop new treatments, there is an urgent need to discover new drug leads to treat tumours exhibiting primary or secondary resistance to exiting drugs. Cell cultures derived from patient-derived orthotopic xenografts are promising pre-clinical models to better predict drug response in cancer recurrence.

OBJECTIVE: The aim of the study was to investigate the relationship between the physiochemical properties of drugs and their in vitro potency as well as identifying chemical scaffolds biased towards selectivity or promiscuity of such drugs.

METHODS: The bioactivities of 158 drugs screened against cell cultures derived from 30 cancer orthotopic patient-derived xenograft (O-PDX) models were considered. Drugs were represented by physicochemical descriptors and chemical structure fingerprints. Supervised learning was employed to model the relationship between features and in vitro potency.

RESULTS: Drugs with in vitro potency for alveolar rhabdomyosarcoma and osteosarcoma tend to have a higher number of rings, two carbon-hetero bonds and halogens. Selective and promiscuous scaffolds for these phenotypic targets were identified. Highly-predictive models of in vitro potency were obtained across these 30 targets, which can be applied to unseen molecules via a webserver [https:]

CONCLUSION: It is possible to identify privileged chemical scaffolds and predict the in vitro potency of unseen molecules across these 30 targets This information and models should be helpful to select which molecules to screen against these primary cultures of pediatric solid tumors.

PMID:33874867 | DOI:10.2174/0929867328666210419134708
Multimodal Treatment With Orbital Organ Preservation in Adult Patients With Locally Advanced Small-Round-Cell Malignancy of the Nasal Cavity and Paranasal Sinus

Fetched: April 20th, 2021, 5:02am GMT by Nanxiang Chen

Front Oncol. 2021 Apr 1;11:650385. doi: 10.3389/fonc.2021.650385. eCollection 2021.

ABSTRACT

BACKGROUND: To investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in adult patients with locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life.

METHODS: The clinical data of 49 patients with orbital involvement of locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between December 2009 and January 2019 were retrospectively analyzed. Treatment efficacy and side effects were assessed. The study included three different pathological types. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 3. The overall survival (OS) rate, progression-free survival (PFS) rate, and orbital preservation rate were calculated using the Kaplan-Meier method.

RESULTS: After multimodal treatment, the 3- and 5-year OS rates of the 49 patients were 63.8% and 54.5%, respectively, and the 3- and 5-year total PFS rates were 66.8% and 63.1%, respectively.

CONCLUSIONS: Multimodal treatment can preserve the orbital organs of adult patients with small-round-cell malignancy of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates, and improve quality of life, thus providing a new treatment option for these patients.

PMID:33869053 | PMC:PMC8047626 | DOI:10.3389/fonc.2021.650385
Deep-learning and MR images to target hypoxic habitats with evofosfamide in preclinical models of sarcoma

Fetched: April 17th, 2021, 5:02am GMT by Bruna V Jardim-Perassi

Theranostics. 2021 Mar 11;11(11):5313-5329. doi: 10.7150/thno.56595. eCollection 2021.

ABSTRACT

Rationale: Hypoxic regions (habitats) within tumors are heterogeneously distributed and can be widely variant. Hypoxic habitats are generally pan-therapy resistant. For this reason, hypoxia-activated prodrugs (HAPs) have been developed to target these resistant volumes. The HAP evofosfamide (TH-302) has shown promise in preclinical and early clinical trials of sarcoma. However, in a phase III clinical trial of non-resectable soft tissue sarcomas, TH-302 did not improve survival in combination with doxorubicin (Dox), possibly due to a lack of patient stratification based on hypoxic status. Therefore, we used magnetic resonance imaging (MRI) to identify hypoxic habitats and non-invasively follow therapies response in sarcoma mouse models. Methods: We developed deep-learning (DL) models to identify hypoxia, using multiparametric MRI and co-registered histology, and monitored response to TH-302 in a patient-derived xenograft (PDX) of rhabdomyosarcoma and a syngeneic model of fibrosarcoma (radiation-induced fibrosarcoma, RIF-1). Results: A DL convolutional neural network showed strong correlations (>0.76) between the true hypoxia fraction in histology and the predicted hypoxia fraction in multiparametric MRI. TH-302 monotherapy or in combination with Dox delayed tumor growth and increased survival in the hypoxic PDX model (p<0.05), but not in the RIF-1 model, which had a lower volume of hypoxic habitats. Control studies showed that RIF-1 resistance was due to hypoxia and not other causes. Notably, PDX tumors developed resistance to TH-302 under prolonged treatment that was not due to a reduction in hypoxic volumes. Conclusion: Artificial intelligence analysis of pre-therapy MR images can predict hypoxia and subsequent response to HAPs. This approach can be used to monitor therapy response and adapt schedules to forestall the emergence of resistance.

PMID:33859749 | PMC:PMC8039958 | DOI:10.7150/thno.56595
Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

Fetched: April 17th, 2021, 5:02am GMT by Mary Jo Rademacher

Sci Rep. 2021 Apr 15;11(1):8321. doi: 10.1038/s41598-021-87700-2.

ABSTRACT

Interleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

PMID:33859303 | PMC:PMC8050085 | DOI:10.1038/s41598-021-87700-2
Interleukin-4 Receptor Inhibition Targeting Metastasis Independent of Macrophages

Fetched: April 16th, 2021, 5:02am GMT by Megan M Cleary

Mol Cancer Ther. 2021 May;20(5):906-914. doi: 10.1158/1535-7163.MCT-20-0199. Epub 2021 Apr 14.

ABSTRACT

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children and carries a dismal prognosis when metastatic disease is detected. Our previous work has suggested the cytokine receptor IL4Rα may play a role in contributing to metastasis in the alveolar subtype of rhabdomyosarcoma (aRMS), and thus could present a therapeutic target. The IL4 signaling axis has been characterized in various adult cancers as well; however, pediatric trials often follow similar adult trials and the role of the IL4Rα receptor has not been explored in the context of a mediator of metastasis in adult disease. Here, we demonstrate that the impact of IL4Rα blockade in an orthotopic allograft model of aRMS is not mediated by a macrophage response. We further examine the effect of IL4 blockade in adult colon, breast, and prostate cancers and find that inhibition of IL4Rα signaling modulates in vitro cell viability of HCT-116 colon carcinoma cells; however, this finding did not translate to an autocrine-related in vivo difference in tumor burden or lung metastasis. Our results suggest that if humanized IL4 mouse host strains are not available (or not ideal due to the need for immunosuppressing the host innate immune response for xenograft systems), then genetically-engineered mice and mouse allograft studies may be the best indicator of therapeutic targeting efficacy.

PMID:33853867 | DOI:10.1158/1535-7163.MCT-20-0199
The fate of paratesticular masses: 13 years' experience in a tertiary referral centre

Fetched: April 16th, 2021, 5:02am GMT by Huseyin Cihan Demirel

Aktuelle Urol. 2021 Apr 14. doi: 10.1055/a-1345-6808. Online ahead of print.

ABSTRACT

OBJECTIVE: Paratesticular neoplasms exhibit different behaviours, depending on the embryological tissue of origin. Treatment modalities can depend on the differential diagnosis. The aim of this study is to present the clinical, morphological and histopathological features of patients with paratesticular masses and their follow-ups and is intended to increase awareness of the issues.

METHODOLOGY: We included 31 excisions of paratesticular masses, after radiological diagnosis as paratesticular mass in our hospital between 2007-2020. Information on treatment modalities, tumour recurrence, metastasis, and survival rates were obtained from hospital archives. All patients were evaluated by taking patients' history, physical examination, scrotal ultrasound, chest radiography, and serum tumour markers. Treatment modality was selected according to intraoperative findings. Haematoxylin-eosin sections were examined, and immunohistochemical analyses were performed for smooth muscle actin, desmin, Ki67, CD34, S100, and myogenin. Ten high-power fields were counted to document Ki67 and p53 nuclear positivity rates.

RESULTS: A total of 31 operations were performed with recurrence in three patients. Histomorphological and immunohistochemical examination revealed eleven malignant masses; eight rhabdomyosarcomas, a leiomyosarcoma, a liposarcoma and a large B cell lymphoma. Other excised masses were benign and infective lesions.

CONCLUSION: Paratesticular masses are heterogeneous tumours that follow different clinical courses. Clinicians must be aware of this histological diversity in order to plan a treatment pathway. This study is one of the largest published series, with a long follow-up period. It shows that the most critical features in determining prognosis are histopathological subtype and tumour grade.

PMID:33853159 | DOI:10.1055/a-1345-6808
Two rare presentations of embryonal rhabdomyosarcoma of the cervix in teenagers at a low-resource teaching hospital in Ghana: A case series

Fetched: April 15th, 2021, 5:02am GMT by Sarah G Bell

Gynecol Oncol Rep. 2021 Mar 19;36:100750. doi: 10.1016/j.gore.2021.100750. eCollection 2021 May.

ABSTRACT

We report two cases of embryonal rhabdomyosarcoma (ERMS) of the cervix in teenagers presenting to Komfo Anokye Teaching Hospital in Kumasi, Ghana within one month of each other. Between October and November 2019, two patients presented with ERMS of the cervix. They both underwent fertility-sparing surgery followed by chemotherapy with vincristine, actinomycin-D, and cyclophosphamide. Preoperative workup for the two patients was minimal due to limited availability and high cost of imaging in a low-resource setting. Both patients were discussed at a multidisciplinary tumor board meeting to guide best management practices. Both patients had local surgical resection with histological confirmation of ERMS and negative margins, followed by six cycles of vincristine, actinomycin-D, and cyclophosphamide. Neither of the patients had perioperative complications or received radiation therapy. At the time of publication, both patients are currently alive and without evidence of recurrence. Fertility-sparing surgery followed by chemotherapy for patients with ERMS of the cervix is accessible in low-income countries.

PMID:33850996 | PMC:PMC8022137 | DOI:10.1016/j.gore.2021.100750
Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup

Fetched: April 14th, 2021, 5:02am GMT by Felix K F Kommoss

Mod Pathol. 2021 Apr 12. doi: 10.1038/s41379-021-00804-y. Online ahead of print.

ABSTRACT

Embryonal rhabdomyosarcoma (ERMS) of the uterus has recently been shown to frequently harbor DICER1 mutations. Interestingly, only rare cases of extrauterine DICER1-associated ERMS, mostly located in the genitourinary tract, have been reported to date. Our goal was to study clinicopathologic and molecular profiles of DICER1-mutant (DICER1-mut) and DICER1-wild type (DICER1-wt) ERMS in a cohort of genitourinary tumors. We collected a cohort of 17 ERMS including nine uterine (four uterine corpus and five cervix), one vaginal, and seven urinary tract tumors. DNA sequencing revealed mutations of DICER1 in 9/9 uterine ERMS. All other ERMS of our cohort were DICER1-wt. The median age at diagnosis of patients with DICER1-mut and DICER1-wt ERMS was 36 years and 5 years, respectively. Limited follow-up data (available for 15/17 patients) suggested that DICER1-mut ERMS might show a less aggressive clinical course than DICER1-wt ERMS. Histological features only observed in DICER1-mut ERMS were cartilaginous nodules (6/9 DICER1-mut ERMS), in one case accompanied by foci of ossification. Recurrent mutations identified in both DICER1-mut and DICER1-wt ERMS affected KRAS, NRAS, and TP53. Copy number analysis revealed similar structural variations with frequent gains on chromosomes 2, 3, and 8, independent of DICER1 mutation status. Unsupervised hierarchical clustering of array-based whole-genome DNA methylation data of our study cohort together with an extended methylation data set including different RMS subtypes from genitourinary and extra-genitourinary locations (n = 102), revealed a distinct cluster for DICER1-mut ERMS. Such tumors clearly segregated from the clusters of DICER1-wt ERMS, alveolar RMS, and MYOD1-mutant spindle cell and sclerosing RMS. Only one tumor, previously diagnosed as ERMS arising in the maxilla of a 6-year-old boy clustered with DICER1-mut ERMS of the uterus. Subsequent sequencing analysis identified two DICER1 mutations in the latter case. Our results suggest that DICER1-mut ERMS might qualify as a distinct subtype in future classifications of RMS.

PMID:33846547 | DOI:10.1038/s41379-021-00804-y
Prognostic value of patient-derived xenograft engraftment in pediatric sarcomas

Fetched: April 11th, 2021, 5:02am GMT by Helena Castillo-Ecija

J Pathol Clin Res. 2021 Apr 9. doi: 10.1002/cjp2.210. Online ahead of print.

ABSTRACT

The goals of this work were to identify factors favoring patient-derived xenograft (PDX) engraftment and study the association between PDX engraftment and prognosis in pediatric patients with Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma. We used immunodeficient mice to establish 30 subcutaneous PDX from patient tumor biopsies, with a successful engraftment rate of 44%. Age greater than 12 years and relapsed disease were patient factors associated with higher engraftment rate. Tumor type and biopsy location did not associate with engraftment. PDX models retained histology markers and most chromosomal aberrations of patient samples during successive passages in mice. Model treatment with irinotecan resulted in significant activity in 20 of the PDXs and replicated the response of rhabdomyosarcoma patients. Successive generations of PDXs responded similarly to irinotecan, demonstrating functional stability of these models. Importantly, out of 68 tumor samples from 51 patients with a median follow-up of 21.2 months, PDX engraftment from newly diagnosed patients was a prognostic factor significantly associated with poor outcome (p = 0.040). This association was not significant for relapsed patients. In the subgroup of patients with newly diagnosed Ewing sarcoma classified as standard risk, we found higher risk of relapse or refractory disease associated with those samples that produced stable PDX models (p = 0.0357). Overall, our study shows that PDX engraftment predicts worse outcome in newly diagnosed pediatric sarcoma patients.

PMID:33837665 | DOI:10.1002/cjp2.210
MRI features of different types of sinonasan rhabdomyosarcomas: a series of eleven cases

Fetched: April 10th, 2021, 5:02am GMT by Junjie Zeng

Dentomaxillofac Radiol. 2021 Apr 9:20210030. doi: 10.1259/dmfr.20210030. Online ahead of print.

ABSTRACT

OBJECTIVE: To retrospectively analyze magnetic resonance imaging (MRI) features of various pathological subtypes of sinonasal rhabdomyosarcoma (RMS) and explore correlations between imaging features and pathological subtypes.

METHODS: In total, 11 cases with embryonal, alveolar or pleomorphic sinonasal RMSs, confirmed by surgical pathology, were selected. Their characteristics and distinctive imaging features were analysed, and the correlation between pathology and imaging features was explored.

RESULTS: Bone destruction was observed in all 11 cases with RMS. Expansive growth was predominant in three alveolar and three embryonal RMS cases, and creeping growth was predominant in two alveolar, two embryonal and one pleomorphic RMS cases. Signs of residual mucosa were observed in all 11 cases, and 10 cases showed involvement of multiple sinus cavities and orbital cavities. All cases exhibited mild-to-intermediate enhancement.

CONCLUSION: Sinonasal RMSs have the following characteristic MRI features: ethmoid sinuses and middle nasal conchae are the prevalent sites; lesions are mainly of mild enhancement; tumours exhibit signs of residual mucosa, mild-to-intermediate enhancement and frequent orbital involvement; bone invasion and bone destruction are frequently observed; and haematogenous metastasis is not as common as lymphatic metastasis. RMSs of various pathological subtypes were not significantly distinct by imaging.

PMID:33835837 | DOI:10.1259/dmfr.20210030
Bloom syndrome in a Mexican American family with rhabdomyosarcoma: evidence of a Mexican founder mutation

Fetched: April 10th, 2021, 5:02am GMT by Erin H Sybouts

Cold Spring Harb Mol Case Stud. 2021 Apr 8;7(2):a005751. doi: 10.1101/mcs.a005751. Print 2021 Apr.

ABSTRACT

Bloom syndrome is a rare autosomal recessive disorder with less than 300 cases reported in the literature. Bloom syndrome is characterized by chromosome instability, physical stigmata, growth deficiency, immunodeficiency, and a predisposition to cancer, most commonly leukemias, although solid tumors are reported as well. Bloom syndrome occurs in multiple ethnic groups with a higher incidence in persons of Ashkenazi Jewish origin. Few patients of Hispanic ethnicity have been reported. We report here a Mexican American family with a BLM pathogenic variant, c.2506_2507delAG, previously reported in a single patient from Mexico. In this family of four siblings, three have phenotypic features of Bloom syndrome, and BLM gene mutation was homozygous in these affected individuals. Our proband developed a rhabdomyosarcoma. Analysis of surrounding markers in the germline DNA revealed a common haplotype, suggesting a previously unrecognized founder mutation in the Hispanic population of Mexican origin.

PMID:33832920 | PMC:PMC8040734 | DOI:10.1101/mcs.a005751
Levels of Zinc Transporters mRNA Depending on Zinc Status and HIV-1 Tat Induced Inflammation in Muscle (Rhabdomyosarcoma) and Monocyte (THP-1) Cell Lines

Fetched: April 10th, 2021, 5:02am GMT by Kiran Alluri

Biochemistry (Mosc). 2021 Feb;86(2):168-178. doi: 10.1134/S000629792102005X.

ABSTRACT

Monocytes and muscles demonstrate functionally contrasting behavior under conditions of zinc deficiency with relation to zinc storage system (muscle retain zinc in contrast to monocytes). We aimed to understand the effects of zinc status and HIV-1 Tat mediated inflammation on expression of zinc transporters in these types of cells. Expression of zinc transporters [ZnTs, ZIPs, and metallothionein (MT)] was quantified by qRT-PCR in RD, THP-1 cells separately and in co-cultured THP-1-RD cells. ZnT1 protein expression levels were confirmed by Western blot. Significant increase of MT and ZnT1 mRNA in response to zinc supplementation and decrease during zinc deficiency indicates significance of the genes encoding transporters in maintaining zinc homeostasis in these tissues. In the RD cells ZIP10 exhibited inverse relation to zinc status whereas no correlation was found in the THP-1 cells. Tat-induced inflammation resulted in the significant elevation of MT, IL6, ZIP7, ZIP8, ZIP9 transcripts in the co-cultured RD cells, whereas THP-1 cells demonstrated increased IL-1β levels and reduced levels of ZIP7 and ZIP14. Zinc status and HIV-1Tat induced inflammation appear to influence differential expression of MT, ZnTs, and ZIPs in the muscle and monocyte cells.

PMID:33832415 | DOI:10.1134/S000629792102005X
Photodynamic therapy for radiation maculopathy: A case report

Fetched: April 10th, 2021, 5:02am GMT by Taro Baba

Medicine (Baltimore). 2021 Apr 9;100(14):e24888. doi: 10.1097/MD.0000000000024888.

ABSTRACT

RATIONALE: The best treatment protocol for radiation maculopathy in children has not been determined. The purpose of this study was to determine the effect of photodynamic therapy (PDT) on radiation maculopathy.

PATIENT CONCERNS: An 11-year-old boy who was originally diagnosed with orbital rhabdomyosarcoma when he was 1 year old, in October 2008. The lesion improved after peripheral blood stem cell transplantation, chemotherapy and radiation therapy. A cataract was detected in his right eye in May 2011, and he underwent cataract surgery in July 2011. Continuous amblyopia training maintained his visual acuity in his right eye. In January 2017, his visual acuity was reduced and macular edema was detected with optical coherence tomography.

DIAGNOSES: We diagnosed radiation maculopathy, from the history of radiation therapy, macular edema by optical coherence tomography, and hyperfluorescent site by fluorescein angiography.

INTERVENTIONS: We performed PDT in June 2017.

OUTCOMES: Treatment with PDT improved macular edema and his visual acuity.

LESSONS: Radiation retinopathy is progressive disorder with poor prognosis. PDT could be considered to treat radiation maculopathy.

PMID:33832069 | PMC:PMC8036116 | DOI:10.1097/MD.0000000000024888
A RETROSPECTIVE SURVEY OF NEOPLASIA IN MANAGED GIRAFFES (GIRAFFA CAMELOPARDALIS)

Fetched: April 9th, 2021, 5:02am GMT by Greta Doden

J Zoo Wildl Med. 2021 Apr;52(1):332-336. doi: 10.1638/2020-0100.

ABSTRACT

Giraffes (Giraffa camelopardalis) are commonly managed in zoos and conservation programs worldwide, but the current understanding of the occurrence and progression of neoplastic disease in this species is limited by the scarcity of published reports. This study collated documented cases of neoplasia on the basis of gross and histologic evaluation of ante- and postmortem samples. In total, 30 giraffes from 22 institutions across the United States were included. Subspecies was not reported in all cases, but those identified included Masai (Giraffa camelopardalis tippelskirchi), Rothschild (Giraffa camelopardalis rothschildi), and reticulated subspecies (Giraffe camelopardalis reticulata). Thirteen animals died natural deaths, 15 were euthanized, and 2 were alive at the time of this article. A total of 38 tumors were reported and classified as 18 different diagnoses, including leiomyoma (7), adenoma (4), luteoma (4), lymphoma (4), pheochromocytoma (3), squamous cell carcinoma (3), adenocarcinoma (2), ameloblastic fibroma (1), carcinomatosis of undetermined cell lineage (1), cavernous hemangioma (1), cystic granulosa cell tumor (1), dysgerminoma (1), fibrosarcoma (1), leukemia (1), lipoma (1), pituitary nerve sheath tumor (1), rhabdomyosarcoma (1), and teratoma (1). Multiple concurrent neoplastic lesions were documented in six cases. Mesenchymal tumors (18) were the majority of neoplasms. The most prevalent location, regardless of tumor type, was the female reproductive tract (14). Twenty-four neoplastic lesions were incidental findings at necropsy, whereas eight neoplasms were considered to be the primary cause of death. The findings reported here identify multiple neoplastic lesions in giraffes and could provide insight to the future management of this species.

PMID:33827195 | DOI:10.1638/2020-0100
Mismatch repair deficiency is rare in bone and soft tissue tumors

Fetched: April 8th, 2021, 5:02am GMT by Suk Wai Lam

Histopathology. 2021 Apr 7. doi: 10.1111/his.14377. Online ahead of print.

ABSTRACT

INTRODUCTION: There has been an increased demand for mismatch repair (MMR) status testing in sarcoma patients after the success of immune checkpoint inhibition (ICI) in MMR deficient tumors. However, data on MMR deficiency in bone and soft tissue tumors is sparse, rendering it unclear if routine screening should be applied. Hence, we aimed to study the frequency of MMR deficiency in bone and soft tissue tumors after we were prompted by two (potential) Lynch syndrome patients developing sarcomas.

METHODS: Immunohistochemical expression of MLH1, PMS2, MSH2 and MSH6 was assessed on tissue micro arrays (TMAs), and included 353 bone and 539 soft tissue tumors. Molecular data was either retrieved from reports or microsatellite instability (MSI) analysis was performed. In MLH1 negative cases, additional MLH1 promoter hypermethylation analysis followed. Furthermore, a systematic literature review on MMR deficiency in bone and soft tissue tumors was conducted.

RESULTS: Eight MMR deficient tumors were identified (1%), which included four leiomyosarcoma, two rhabdomyosarcoma, one malignant peripheral nerve sheath tumor and one radiation-associated sarcoma. Three patients were suspected for Lynch syndrome. Literature review revealed 30 MMR deficient sarcomas, of which 33% were undifferentiated/unclassifiable sarcomas. 57% of the patients were genetically predisposed.

CONCLUSION: MMR deficiency is rare in bone and soft tissue tumors. Screening focusing on tumors with myogenic differentiation, undifferentiated/unclassifiable sarcomas and in patients with a genetic predisposition / co-occurrence of other malignancies can be helpful in identifying patients potentially eligible for ICI.

PMID:33825202 | DOI:10.1111/his.14377
New in the current WHO classification (2020) for soft tissue sarcomas

Fetched: April 7th, 2021, 5:02am GMT by Eva Wardelmann

Pathologe. 2021 May;42(3):281-293. doi: 10.1007/s00292-021-00935-8. Epub 2021 Apr 6.

ABSTRACT

The current WHO classification for tumors of soft tissue and bone includes numerous new entities, most often defined by novel molecular findings. In this article, we present translocation-positive tumors to broaden the spectrum of monomorphic mesenchymal neoplasias. The undifferentiated small round cell sarcomas are now assembled in their own separate chapter to underline their occurrence in both soft tissue and bone, emphasizing their morphologic, molecular, and biologic differences. Another interesting new group are tumors with GLI1 activation, which, however, have not yet been included into the WHO classification. NTRK-driven tumors present with a potential therapeutic target for several established inhibitors. Finally, there have been novel findings in rhabdomyosarcomas allowing more precise subtyping associated with different biological behavior.

PMID:33822252 | DOI:10.1007/s00292-021-00935-8
Bioactive levan type exopolysaccharide produced by Pantoea agglomerans ZMR7: characterization and optimization for enhanced production

Fetched: April 7th, 2021, 5:02am GMT by Safaa A S Al-Qaysi

J Microbiol Biotechnol. 2021 Apr 5. doi: 10.4014/jmb.2101.01025. Online ahead of print.

ABSTRACT

Levan is an industrially important functional biopolymer with considerable applications in food and pharmaceutical fields owing to its safety and biocompatibility. Herein, levan type exopolysaccharide (EPS) produced by Pantoea agglomerans ZMR7 was purified by cold ethanol precipitation and characterized using TLC, FTIR, ¹H, and ¹³C NMR spectroscopy. The maximum production of levan (28.4 g/L) was achieved when sucrose and ammonium chloride were used as carbon and nitrogen sources, respectively, at 35 °C and an initial pH value of 8.0. Some biomedical applications of levan like antitumor, antiparasitic, and antioxidant activities were investigated in vitro. The results revealed the ability of levan at different concentrations to decrease the viability of rhabdomyosarcoma (RD) and breast cancer (MDA) cells compared with untreated cancer cells. Besides, levan appeared to have high antiparasitic activity against the promastigote of Leishmania tropica. Furthermore, levan had strong DPPH radical scavenging (antioxidant) activity. These findings suggest that levan produced by P. agglomerans ZMR7 can serve as a natural biopolymer candidate in pharmaceutical and medical fields.

PMID:33820887 | DOI:10.4014/jmb.2101.01025
Skin Toxicity Profile of Photon Radiotherapy versus Proton Beam Therapy in Paediatric and Young Adult Patients with Sarcomas

Fetched: April 7th, 2021, 5:02am GMT by S Gaito

Clin Oncol (R Coll Radiol). 2021 Apr 2:S0936-6555(21)00100-X. doi: 10.1016/j.clon.2021.03.009. Online ahead of print.

ABSTRACT

AIMS: Radiotherapy is key in the management of patients with both Ewing sarcoma and rhabdomyosarcoma. However, there is little evidence in the literature with regards to radiation-induced skin toxicities (RISTs) for patients treated with conventional radiotherapy with X-rays (XRT) or proton beam therapy (PBT) for these two conditions. In the present study we evaluated acute and late RIST in patients treated within European protocols with either PBT or XRT, taking both clinical and dosimetric variables into consideration.

MATERIALS AND METHODS: This was a retrospective analysis of 79 paediatric/young adult patients treated with radical radiotherapy (with XRT or PBT) and concurrent chemotherapy. In all cases, radiotherapy was given in conventional fractionation (1.8 Gy/fraction). Acute and late RISTs were registered according to the Radiation Therapy Oncology Group (RTOG) scoring system.

RESULTS: With regards to acute RIST, 47.9% (23/48) of XRT patients and 48.4% (15/31) of PBT patients had acute grade 2/3 toxicity. When it comes to late RIST, 17.5% (7/40 with known toxicity profile) of XRT patients and 29.0% (9/31) of PBT patients had grade 1/2 toxicity. This difference of -11.5% (95% confidence interval -31.2 to 7.9%) in grade 1/2 toxicity between XRT and PBT was not statistically significant (P = 0.25). Regardless of the radiotherapy technique, V30Gy seems a good predictor of acute RIST. Moreover, for the same value of V30Gy, patients who receive PBT may have a higher risk of moderate-severe acute RIST. Perhaps due to the small sample, definitive conclusions on the predictive factors of late RIST could not be drawn.

CONCLUSIONS: No clinically meaningful differences in acute and late RIST were observed between PBT and XRT subgroups. Systematic differences in the modelling of the build-up region may exist between XRT and PBT algorithms, which could make the comparison of dose metrics between techniques potentially biased. A more comprehensive analysis of dosimetric data on larger patient cohorts is needed to elucidate the most relevant skin dose metrics. Dose-effect models of RIST for this unique patient population would be an invaluable tool in radiotherapy plan optimisation.

PMID:33820695 | DOI:10.1016/j.clon.2021.03.009
Case Report: Paratesticular Rhabdomyosarcoma

Fetched: April 6th, 2021, 5:02am GMT by Yiyi Zhu

Front Oncol. 2021 Mar 17;11:629878. doi: 10.3389/fonc.2021.629878. eCollection 2021.

ABSTRACT

Paratesticular rhabdomyosarcoma (RMS) accounts for only 7% of all the RMS cases. Due to the limited available data, there is no consensus on the diagnosis and management of the paratesticular tumors. Here, we interrogated two paratesticular RMS cases in 25 and 27-year-old men presenting with painless and rapidly growing mass in the scrotum. Whereas the data showed no upregulation of tumor markers such as β-human chorionic gonadotropin (β-HCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH), scrotal ultrasonography and magnetic resonance imaging indicated the existence of paratesticular and inguinal lesions respectively. There was local recurrence in one patient who underwent radical orchiectomy for the sarcoma one year ago. In addition, the CT scans showed no occurrence of distant metastasis. The two patients underwent radical inguinal orchiectomy or resection of the recurrent tumors with nerve-sparing retroperitoneal lymph node dissection. Histologic examination revealed embryonal RMS (eRMS) without lymph node metastasis. We highlight the importance of multi-disciplinary participation for paratesticular RMS detection and preoperative ultrasound-guided needle biopsy (UNB) for rapid confirmatory diagnosis. Complete surgical resection coupled with chemotherapy and radiotherapy is the main treatment option for the paratesticular RMS. In addition, sperm cryopreservation treatment and endocrine follow-up could increase the overall survival and quality of life of the patients.

PMID:33816267 | PMC:PMC8010692 | DOI:10.3389/fonc.2021.629878
Adult Pleomorphic Rhabdomyosarcomas: Assessing Outcomes Associated with Radiotherapy and Chemotherapy Use in the National Cancer Database

Fetched: April 6th, 2021, 5:02am GMT by Vishruth K Reddy

Sarcoma. 2021 Mar 13;2021:9712070. doi: 10.1155/2021/9712070. eCollection 2021.

ABSTRACT

PURPOSE: Practice patterns for treatment of localized adult pleomorphic rhabdomyosarcoma (PRMS) remain quite variable given its rarity. Current national guidelines recommend management similar to that of other high-grade soft tissue sarcomas (STS), which include surgery with perioperative radiation (RT) with or without chemotherapy. Using the National Cancer Database (NCDB), we assessed practice patterns and overall outcomes of patients with localized PRMS. Patients and Methods. Patients with stage II/III PRMS treated with surgical resection from 2004 to 2015 were identified from the NCDB. Predictors of RT and chemotherapy use were assessed using multivariable logistic regression analysis. The association of radiation and chemotherapy status on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses.

RESULTS: Of 243 total patients, RT and chemotherapy were not uniformly utilized, with 44% receiving chemotherapy and in those who did not undergo amputation 62% receiving RT. In those who did not undergo amputation, RT was associated with improved survival on both univariate (HR: 0.49, 95% CI 0.32-0.73, P < 0.001) and multivariate analysis (HR: 0.40, 95% CI 0.26-0.62, P < 0.001), corresponding to greater 5-year overall survival (59% vs. 38%, P < 0.001). Chemotherapy was associated with a higher rate of 5-year overall survival (63% vs. 39%, P < 0.001). However, the survival benefit of chemotherapy did not reach statistical significance on multivariate analysis (HR: 0.65, 95% CI 0.41-1.03, P=0.064). Notable predictors of omission of RT included female gender (OR: 0.40, 95% CI 0.22-0.74, P < 0.01) and age ≥ 70 (OR: 0.55, 95% CI 0.30-1.00, P=0.05). Correspondingly, factors associated with omission of chemotherapy included age ≥70 (OR: 0.17, 95% CI 0.08-0.39, P < 0.001).

CONCLUSIONS: A significant proportion of patients with localized adult PRMS are not receiving RT. Likewise, use of chemotherapy was heterogeneous. Our findings note potential benefits and underutilization of RT, for which further investigation is warranted.

PMID:33814964 | PMC:PMC7987456 | DOI:10.1155/2021/9712070
Radiation therapy for infants with cancer

Fetched: April 6th, 2021, 5:02am GMT by Colette J Shen

Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28700. doi: 10.1002/pbc.28700.

ABSTRACT

The clinical outcomes for infants with malignant tumors are often worse than older children due to a combination of more biologically aggressive disease in some cases, and increased toxicity-or deintensification of therapies due to concern for toxicity-in others. Especially in infants and very young children, finding the appropriate balance between maximizing treatment efficacy while minimizing toxicity-in particular late side effects-is crucial. We review here the management of malignant tumors in infants and very young children, focusing on central nervous system (CNS) malignancies and rhabdomyosarcoma.

PMID:33818894 | DOI:10.1002/pbc.28700
Non-rhabdomyosarcoma soft-tissue sarcoma

Fetched: April 6th, 2021, 5:02am GMT by Sarah A Milgrom

Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28279. doi: 10.1002/pbc.28279.

ABSTRACT

Non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS) comprise 4% of childhood cancers and consist of numerous histologic subtypes. Prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability. Complete surgical resection is critical for the best oncologic outcomes and is prioritized in treatment algorithms. The use of radiation therapy (RT) and chemotherapy is based upon factors such as resectability, histologic grade, tumor size, and stage. North American and European trials are defining a risk-based approach to NRSTS to limit treatment-related toxicity and to maximize therapeutic efficacy. In this paper, we summarize the current roles of surgery, RT, and chemotherapy in NRSTS and describe ongoing research that is advancing the care of NRSTS patients.

PMID:33818885 | DOI:10.1002/pbc.28279
Rhabdomyosarcoma

Fetched: April 6th, 2021, 5:02am GMT by Raphael L Yechieli

Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28254. doi: 10.1002/pbc.28254.

ABSTRACT

Rhabdomyosarcoma is a heterogeneous disease both in presentation and histology. Improvements in a multimodality therapy resulted in the improved overall survival for patients with a low-risk and intermediate-risk disease but not for patients with a metastatic disease. We reviewed and contrasted the North American and European practice patterns, though ultimately the principles of staging, surgery, radiation therapy, and chemotherapy are similar in both Children's Oncology Group and International Society of Paediatric Oncology treatment approaches. Efforts are underway to investigate improved local control rates in higher risk patients using radiation dose escalation strategies, and delayed primary excision in select cases. The prognostic significance of imaging-based chemotherapy response, proton therapy, novel biomarkers, and targeted drugs will be determined in upcoming clinical trials.

PMID:33818882 | DOI:10.1002/pbc.28254
Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma

Fetched: April 6th, 2021, 5:02am GMT by Hiroshi Kubo

Mol Ther Oncolytics. 2021 Mar 5;20:646-658. doi: 10.1016/j.omto.2021.03.001. eCollection 2021 Mar 26.

ABSTRACT

Ephrin type-B receptor 4 (EPHB4), expressed in tumors including rhabdomyosarcoma, is a suitable target for chimeric antigen receptor (CAR)-T cells. Ligand-independent activation of EPHB4 causes cell proliferation and malignant transformation in rhabdomyosarcoma, whereas ligand-dependent stimulation of EPHB4 induces apoptosis in rhabdomyosarcoma. Therefore, we hypothesized that ligand-based, EPHB4-specific CAR-T cells may kill rhabdomyosarcoma cells without stimulating downstream cell proliferation mechanisms. We developed novel CAR-T cells by targeting EPHB4 via EPHRIN B2, a natural ligand of EPHB4. The generation of EPHB4-CAR-T cells via piggyBac (PB) transposon-based gene transfer resulted in sufficient T cell expansion and CAR positivity (78.5% ± 5.9%). PB-EPHB4-CAR-T cells displayed a dominant stem cell memory fraction (59.4% ± 7.2%) as well as low PD-1 expression (0.60% ± 0.21%) after 14 days of expansion. The PB-EPHB4-CAR-T cells inhibited EPHB4-positive tumor cells without activating cell proliferation downstream of EPHB4, even after multiple tumor re-challenges and suppressed tumor growth in xenograft-bearing mice. Therefore, PB-EPHB4-CAR-T cells possess a memory-rich fraction without early T cell exhaustion and show potential as promising therapeutic agents for treating rhabdomyosarcoma and other EPHB4-positive tumors.

PMID:33816783 | PMC:PMC7985479 | DOI:10.1016/j.omto.2021.03.001

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