Measurement and Impact of Body Composition Using CT Imaging in Patients with Germ Cell Tumors Undergoing Chemotherapy on the NCTN Phase 3 Study AGCT1531
Abstract
Fiscal year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) Topic Area: Germ cell cancers FY22 PRCRP Military Heath Focus Areas: (1) Mission readiness: Gaps in prognosis and treatment that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public. (2) Mission readiness: Gaps in quality of life and survivorship that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public. FY22 PRCRP Overarching Challenges: (1) Transform cancer treatment through the identification of novel biomarkers and new targets, especially for advanced disease (metastatic), and eliminate the risks of therapy associated toxicity. (2) Develop strategies and biomarkers to predict cancer risk, treatment resistance, recurrence, and advanced disease to mitigate risk in target populations. Scientific Objective and Rationale: Malignant germ cell tumors are the most common solid tumor in adolescents and young adults. They are highly curable, yet current treatment regimens often come with unacceptable rates of toxicities. The current treatment regimens, which include a medication called cisplatin, are known to have significant short- and long-term toxicities, including permanent irreversible hearing loss and damage to the kidneys, which, in recent studies, have been shown to continue to worsen after treatment has been completed. The change in body composition (percentage of the body that is fat, skeletal muscle, and bone) over the course of treatment has not been previously studied in pediatric, adolescent, and young adult patients with germ cell tumors, and the potential role of body composition in predicting those who will develop adverse side effects from chemotherapy reactions remains a gap in knowledge. We hypothesize that body composition at diagnosis and changes in body composition during the course of chemotherapy, are predictive of the development of toxicity to chemotherapy. While it is known that different factors impact how our bodies break down chemotherapy drugs, one factor called body composition, which looks at the amount of muscle and fat an individual contains, has been overlooked. In two individuals with the same height and weight, but who differ in the components of muscle and fat tissue, there will likely be very significant differences in response to chemotherapy based on the impact of how different types of body tissue break down the drug. The importance of body composition and its role in chemotherapy toxicity has been demonstrated in adults with colon cancer treated with a drug called 5-Fluorouricil. To date, there has been no evaluation of how skeletal muscle characteristics affect outcome or toxicity in patients receiving chemotherapy for malignant germ cell tumors. The ongoing study AGCT1531, offers a diverse population with robust data collection including imaging scans, hearing exams, detailed toxicity, and outcome data to investigate this question. In this proposed imaging study, evaluation of skeletal muscle quality and quantity will be determined using baseline computed tomography (CT) scans collected for study purposes. Finally, we will use a new automated system to analyze body composition from CT and compare this to manual methods. Impact: This study will deliver in the near-term important and new research into the treatment of germ cell tumors. By embedding this research within a large and already rapidly recruiting clinical trial will allow this work to be completed within the next 4 years and will provide unique insights into side effects from chemotherapy and survivorship after treatment is complete. This study has the opportunity of completely change how chemotherapy is dosed in the future for germ cell tumors, and potentially for many other tumors in the future. This may lead to further refinement of prognostic/stratificati
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310837
Entities
People
- Christina M Dieli-Conwright
Organizations
- Dana–Farber Cancer Institute
- United States Army