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Children's Oncology Group's 2023 blueprint for research: Germ cell tumors
Roma Bhuta1, Rachana Shah2, Joanna J Gell3,4,5
1Division of Pediatric Hematology-Oncology, Hasbro Children's Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Abstract:
Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment-related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard-risk disease, and intensify therapy for patients with poor-risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker-negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology-driven, biomarker-defined, histology-specific, risk-stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.
Insights
Extracranial germ cell tumors (GCTs) in young patients often have good outcomes, but treatment side effects and disease resistance remain challenges. Future research must focus on targeted therapies and improved risk stratification for better survivorship.
Area of Science:
- Pediatric Oncology
- Cancer Biology
- Tumorigenesis
Background:
- Extracranial germ cell tumors (GCTs) affect children, adolescents, and young adults.
- While many patients achieve excellent outcomes, treatment-related toxicities and disease resistance impact survivorship.
- A subset of patients succumb to GCTs, highlighting unmet clinical needs.
Purpose of the Study:
- To address current unmet needs in managing extracranial GCTs.
- To refine risk stratification, optimize treatment intensity, and improve relapse detection.
- To explore novel therapeutic targets by understanding GCT origins.
Main Methods:
- Review of current management strategies and outcomes for extracranial GCTs.
- Identification of critical areas for research, including molecular targets and treatment resistance.
- Emphasis on collaborative, multi-institutional clinical trials with harmonized data collection.
Main Results:
- Current management faces challenges in safely observing patients post-surgery and tailoring chemotherapy.
- Early detection of minimal residual disease and relapse, especially in marker-negative GCTs, is crucial.
- Understanding GCT biology may reveal novel therapeutic targets.
Conclusions:
- Future research should focus on biology-driven, biomarker-defined, and risk-stratified clinical trials.
- Collaborative efforts are essential for studying these rare tumors.
- Key priorities include understanding GCT biology, developing trials, managing late effects, and promoting equity.
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