SUN-341 A Natural History Study for Rare Tumors: An Avenue for Discovering and Understanding Endocrine Cancers

Introduction: Endocrine malignancies, as well as all pediatric cancers, are considered rare tumors, defined as <200,000 affected at any given time in US or <40,000 new cases per year. Rare tumors may present as part of a hereditary cancer syndrome, (e.g multipe endocrine neoplasia type 1) or isolated. These tumors have been traditionally understudied and lack descriptive epidemiology, comprehensive genomic profiles, and phenotypic characterization. In an effort to understand the natural history of these rare cancers, the Pediatric Oncology Branch (POB) of the National Cancer Institute (NCI) has undertaken a rare tumor initiative. Methods: A prospective study has been developed at the NCI to comprehensively and longitudinally evaluate the natural history of patients with rare solid tumors or tumor predisposition syndromes. The goals of this study are to 1) estimate and define the clinical spectrum of rare cancers, 2) evaluate and follow biological relatives of patients with rare tumors or carriers of germline genetic variants that predispose to development of rare tumors, and 3) develop a better understanding of these diseases in an effort to a) develop novel therapeutic interventions, b) preventive/screening guidelines, c) endpoints for future clinical trials, and d) identify relevant patient reported outcomes that can improve our understanding of patients’ psychosocial and functional needs. Results: The NCI Natural History Study of Rare Solid Tumor (NCT03739827) has recently opened. This expands on previous work within the NCI in rare tumors including a neurofibromatosis natural history study (NCT00924196) and a multiple endocrine neoplasia type 2 study (NCT01660984). The MEN2 natural history study has enrolled 59 total subjects including 46 patients with MEN2B and 13 with MEN2A. This work has led to a better understanding of the MEN2B phenotype and contributed to the development of vandetanib (NCT00514046) in pediatric patients. We have explored the psychosocial impact of living with MTC in both pediatric and adult patients. We are developing a sub-protocol on tumors with Krebs cycle abnormalities including succinate dehydrogenase deficient pheochromocytoma/paraganglioma and gastrointestinal stromal tumor. Discussion: Natural history studies track the course of the disease over time. They can identify demographic, genetic, environmental, and other variables that correlate with disease and outcomes, either in the absence or presence of experimental therapy or standard care. Comprehensive studies are a pillar of epidemiologic research on rare conditions and can help optimize clinical care and inform the development of novel treatments. They can also provide key information about how rare diseases develop and progress, leading to development of disease models that help make drug development more efficient and advancing the understanding of rare endocrine tumors. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.