Clinical characteristics and outcomes of adult alveolar rhabdomyosarcoma patients on first-line systemic therapies: A single-institution cohort.

Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival.

Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group.

Background: The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy.

Event-free survival in relapsed and refractory rhabdomyosarcoma treated on cooperative group phase II trials: A report from the Children's Oncology Group.

Background: Novel therapies are needed for relapsed and refractory rhabdomyosarcoma (RRMS). Phase II clinical trials in RRMS have typically utilized radiologic response as the primary activity endpoint, an approach that poses several limitations in RRMS. In this analysis, we aimed to estimate an event-free survival (EFS) endpoint for RRMS that could be used as a benchmark for future studies.

Adolescents and young adults with rhabdomyosarcoma: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

Introduction: The impact of established prognostic factors on survival outcomes for childhood rhabdomyosarcoma (RMS) have not been well described in the adolescent and young adult (AYA) RMS patient population.

Methods: This is a retrospective analysis of patients with newly diagnosed RMS enrolled between 1997 and 2016 on seven previously reported Children's Oncology Group (COG) clinical trials. Demographics, clinical features, treatment details, and outcome data were collected.

Soft Tissue Sarcomas in Adolescents and Young Adults.

Soft tissue sarcomas (STS) represent a heterogeneous group of extraskeletal mesenchymal tumors that affect individuals throughout the entire age continuum. Despite this pervasive influence, key differences exist in the presentation of these sarcomas across varying age groups that have prevented a more uniform approach to management. Notably, rhabdomyosarcoma (RMS) is more common in children, while most nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) subtypes are more prevalent in adults.

Impact of Biomarker-Matched Therapies on Outcomes in Patients with Sarcoma Enrolled in Early-Phase Clinical Trials (SAMBA 101).

Purpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma.

Trastuzumab Deruxtecan, Antibody-Drug Conjugate Targeting HER2, Is Effective in Pediatric Malignancies: A Report by the Pediatric Preclinical Testing Consortium.

HER2 is expressed in many pediatric solid tumors and is a target for innovative immune therapies including CAR-T cells and antibody-drug conjugates (ADC). We evaluated the preclinical efficacy of trastuzumab deruxtecan (T-DXd, DS-8201a), a humanized monoclonal HER2-targeting antibody conjugated to a topoisomerase 1 inhibitor, DXd, in patient- and cell line-derived xenograft (PDX/CDX) models. HER2 mRNA expression was determined using RNA-seq and protein expression via IHC across multiple pediatric tumor PDX models.

Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma.

Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous and comprehensive surfaceome profiling approach to identify osteosarcoma-specific cell-surface antigens can similarly enable development of effective therapeutics in this disease. Herein, we describe an integrated proteomic and transcriptomic surfaceome profiling approach to identify cell-surface proteins that are highly expressed in osteosarcoma but minimally expressed on normal tissues.

Clinical group and modified TNM stage for rhabdomyosarcoma: A review from the Children's Oncology Group.

The Children's Oncology Group (COG) uses Clinical Group (CG) and modified Tumor Node Metastasis (TNM) stage to classify rhabdomyosarcoma (RMS). CG is based on surgicopathologic findings and is determined after the completion of initial surgical procedure(s) but prior to chemotherapy and/or radiation therapy. The modified TNM stage is based on clinical and radiographic findings and is assigned prior to any treatment.

Pain and Analgesia in Children with Cancer after Hemipelvectomy: A Retrospective Analysis.

A paucity of data exists centering on the pain experience of children following hemipelvectomy performed for primary bone and soft tissue sarcomas. In this study, we aimed to describe the incidence, severity, and evolution of perioperative pain and function in pediatric oncology patients undergoing hemipelvectomy, and, additionally, we sought to detail the analgesic regimens used for these patients perioperatively. A retrospective chart review was conducted, studying cancer patients, aged 21 years and under, who underwent hemipelvectomy at MD Anderson Cancer Center (MDACC) from 2018 to 2021.

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.

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.

Disease Control and Patterns of Failure After Proton Beam Therapy for Rhabdomyosarcoma.

Purpose: Pediatric patients with rhabdomyosarcoma (RMS) are treated with multimodal therapy, often with radiation therapy (RT) as part of local therapy. We report on the efficacy and patterns of failure after proton beam therapy (PBT) for RMS.

Methods And Materials: Between January 2006 and February 2017, patients with RMS were enrolled in a prospective institutional review board-approved registry protocol for pediatric patients undergoing PBT.

Metabolic response as assessed by F-fluorodeoxyglucose positron emission tomography-computed tomography does not predict outcome in patients with intermediate- or high-risk rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

Background: Strategies to optimize management in rhabdomyosarcoma (RMS) include risk stratification to assign therapy aiming to minimize treatment morbidity yet improve outcomes. This analysis evaluated the relationship between complete metabolic response (CMR) as assessed by F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET) imaging and event-free survival (EFS) in intermediate-risk (IR) and high-risk (HR) RMS patients.

Methods: FDG-PET imaging characteristics, including assessment of CMR and maximum standard uptake values (SUVmax) of the primary tumor, were evaluated by central review.

ABBV-085, Antibody-Drug Conjugate Targeting LRRC15, Is Effective in Osteosarcoma: A Report by the Pediatric Preclinical Testing Consortium.

Membrane protein leucine-rich repeat containing 15 (LRRC15) is known to be expressed in several solid tumors including osteosarcoma. ABBV-085, an antibody-drug conjugate against LRRC15, conjugated to monomethyl auristatin E (MMAE), was studied in osteosarcoma patient-derived xenografts (PDXs) by the Pediatric Preclinical Testing Consortium (PPTC). expression data were obtained from PPTC RNA-sequencing data for the PDX models.

Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium.

The pediatric preclinical testing program previously demonstrated activity of eribulin in osteosarcoma patient-derived xenograft (PDX) models. The phase 2 trial in patients with relapsed osteosarcoma failed to meet response endpoints. Eribulin was evaluated in the original and an expanded set of PDX models and tested at multiple dose levels and schedules to evaluate dose-response.

PET with F-Fluorodeoxyglucose/Computed Tomography in the Management of Pediatric Sarcoma.

The role for PET with fludeoxyglucose F 18 (F-FDG PET)/computed tomography (CT) in the management of pediatric sarcomas continues to be controversial. The literature supports a role for PET/CT in the staging and surveillance of certain specific pediatric sarcoma subtypes; however, the data are less clear regarding whether PET/CT can be used as a biomarker for prognostication. Despite the interest in using this imaging modality in the management of pediatric sarcomas, most studies are limited by retrospective design and small sample size.

Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing Consortium.

Background: Regorafenib is a small molecule multikinase inhibitor that inhibits multiple kinases including BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3.

Procedures: The in vivo anticancer effects of regorafenib were assessed in a panel of six osteosarcoma models, three rhabdomyosarcoma models, and one Ewing sarcoma model.

Results: Regorafenib induced modest inhibition of tumor growth in the models evaluated.

Patterns of failure and toxicity profile following proton beam therapy for pediatric bladder and prostate rhabdomyosarcoma.

Purpose/objective(s): Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy.

Materials/methods: Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT.

Patterns of failure following proton beam therapy for head and neck rhabdomyosarcoma.

Purpose: Pediatric patients with rhabdomyosarcoma (RMS) of the head and neck (H&N) are treated with multimodal therapy, often with radiotherapy (RT) as definitive local therapy. We report on the patterns of failure following proton beam therapy (PBT) for H&N RMS.

Methods: Forty-six H&N RMS patients were enrolled on a prospective registry protocol between 2006 and 2015.

Pediatric Musculoskeletal Imaging: The Indications for and Applications of PET/Computed Tomography.

The use of PET/computed tomography (CT) for the evaluation and management of children, adolescents, and young adults continues to expand. The principal tracer used is 18F-fluorodeoxyglucose and the principal indication is oncology, particularly musculoskeletal neoplasms. The purpose of this article is to review the common applications of PET/CT for imaging of musculoskeletal issues in pediatrics and to introduce the use of PET/CT for nononcologic issues, such as infectious/inflammatory disorders, and review the use of 18F-sodium fluoride in trauma and sports-related injuries.

Alveolar soft part sarcoma in children and young adults: A report of 69 cases.

Background: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by ASPL-TFE3 translocation. Apart from complete surgical resection, there is no standard management strategy.

Procedure: The clinical data of 69 children and young adults less than 30 years old with ASPS diagnosed from 1980-2014 were retrospectively collected from four major institutions.

Current and future therapeutic approaches for osteosarcoma.

Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%. Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma.

The Role of F-FDG-PET/CT in Pediatric Sarcoma.

Considerable debate remains regarding how best to incorporate F-FDG-PET/CT into clinical practice for pediatric sarcomas. Although there is a clear role for F-FDG-PET/CT in staging pediatric sarcoma, the value of F-FDG-PET/CT in prognostication for pediatric sarcomas remains unclear. In osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma, F-FDG-PET/CT may be most useful in the identification of skeletal metastases, where the literature consistently suggests that it has improved sensitivity and specificity as compared to bone scintigraphy.

Osteogenic Sarcoma: Systemic Chemotherapy Options for Localized Disease.

Treatment for osteosarcoma, the most common malignant tumor of bone in children and adolescents, has not changed in decades. Treatment is multimodal, employing neoadjuvant chemotherapy followed by aggressive and complete surgical resection to achieve negative margins and a prolonged course of adjuvant chemotherapy. The primary tumor is usually successfully managed via surgery, but micrometastases are likely present in most patients at diagnosis.