Longitudinal Natural History Study of Children and Adults with Rare Solid Tumors: Initial Results for First 200 Participants

Abstract

Understanding of tumor biology and identification of effective therapies is lacking for many rare tumors. My Pediatric and Adult Rare Tumor (MyPART) network was established to engage patients, advocates and researchers and conduct a comprehensive longitudinal Natural History Study of Rare Solid Tumors. Through remote or in-person enrollment at the NIH Clinical Center, participants with rare solid tumors ≥4 weeks old complete standardized medical and family history forms, patient reported outcomes, and provide tumor, blood and/or saliva samples. Medical records are extracted for clinical status and treatment history, and tumors undergo genomic analysis. 200 participants (65% female, 35% male, median age at diagnosis 43 years, range 2-77) enrolled from 46 US states and 9 other countries (46% remote, 55% in-person). Frequent diagnoses were neuroendocrine neoplasms (NEN), adrenocortical carcinomas (ACC), medullary thyroid carcinomas (MTC), SDH-deficient gastrointestinal stromal tumors (sdGIST), and chordomas. At enrollment, median years since diagnosis was 3.5 (range 0-36.6), 63% participants had metastatic disease and 20% had no evidence of disease. Pathogenic germline and tumor mutations included SDHA/B/C (sdGIST), RET (MTC), TP53 and CTNNB1 (ACC), MEN1 (NEN), and SMARCB1 (poorly-differentiated chordoma). Clinically significant anxiety was observed in 20%-35% of adults. Enrollment of participants and comprehensive data collection were feasible. Remote enrollment was critical during the COVID-19 pandemic. Over 30 patients were enrolled with ACC, NEN, and sdGIST, allowing for clinical/genomic analyses across tumors. Longitudinal follow-up and expansion of cohorts are ongoing to advance understanding of disease course and establish external controls for interventional trials.