Background: Rare tumors are defined as <15 cases/100,000 people/year and present an unmet need due to lack of effective medical treatments, paucity of biospecimens and research models, and difficulty accruing to clinical trials. MyPART (My Pediatric and Adult Rare Tumor Network) was established to: 1) engage patients/advocates as partners in rare tumor research, 2) provide expertise and personalized health care to children and young adults with rare tumors, and 3) build databases and tools to advance research on new treatments for rare tumors. We have developed a natural history and biospecimen acquisition study (NCT03739827), enrolling patients with rare solid tumors, their family members, and participants with germline mutations at increased rare tumor risk. Method: Participants in our natural history study enroll remotely or come to the National Institutes of Health Clinical Center. Participants complete medical and family history forms, patient reported outcomes (PROs), and provide tumor samples and blood and/or saliva for DNA/RNA analysis. For patients coming to the Clinical Center, blood samples are collected for immune phenotyping and cytokine analysis. Clinical staff extract medical records for downstream analyses. Tumors are analyzed using a 500+ gene panel and genomic analysis. Participants are followed yearly to collect data on recurrence, progression, PROs, development of additional tumors, and response to treatments such as standard of care and any treatment trials they may join. Results: We report a clinical and molecular summary of the first 200 participants (66% female, 35% male), with neuroendocrine neoplasms (NEN), adrenocortical cancer (ACC), SDH-deficient gastrointestinal stromal tumor (sdGIST), chordoma, medullary thyroid cancer (MTC), and other less commonly enrolled tumors totaling 35 different tumor types. Participants come from 46 US states and 9 countries. Early results show tumor-specific differences in mutations, treatment/management, PROs, and self-reported non-tumor health issues. The most common pathogenic germline mutations are SDHA/SDHB/SDHC in sdGIST and RET in MTC and other tumors. The most common pathogenic tumor mutations are TP53 and CTNNB1 in ACC, SDHA/B and TP53 in sdGIST, MEN1 in NEN, RET and HRAS in MTC, and SMARCB1 in chordoma. Clinically significant levels of anxiety and pain are more frequent in ACC, NEN, and sdGIST. Conclusions: By developing methods to provide value to rare tumor patients, using a large catchment area and opportunity for remote participation, and collecting data in a tumor-agnostic way, we can learn about multiple rare tumors and share findings more quickly than if each rare tumor was studied alone. We describe the MyPART cohort and challenges to overcome for successful longitudinal rare tumor natural history studies. Citation Format: Shadin Ahmed, Margarita Raygada, Robin Lockridge, Mary Frances Wedekind Malone, Jaydira Del Rivero, John W. Glod, Barbara J. Thomas, Donna Bernstein, Markku M. Miettinen, Liqiang Xi, Jung Kim, Manoj Tygagi, Mark Raffeld, Kenneth Aldape, Ashkan A. Malayeri, Abby B. Sandler, Brigitte C. Widemann, Karlyne M. Reilly. My Pediatric and Adult Rare Tumor Network (MyPART): integrating longitudinal, clinical, molecular, and patient-reported outcomes for rare tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4512.

TPS1600 Background: Rare cancers is defined as fewer than 15 cases per 100,000 people per year and account for 27% cancers diagnosed and lead to 25% of cancer-related deaths. Nearly 13% (1 in 8) of all cancers diagnosed in adults ages 20 and older are rare. All pediatric cancers are rare and approximately 12,600 children under the age of 20 years are diagnosed with cancer each year. Rarity of these diseases has caused a stagnation in understanding the tumor biology and developing newer therapies. Initiatives like Orphan Drug Act (1983) and Rare Disease Act (2002) has led to improvement in funding and research about these rare tumors. The Cancer Moonshot Research Initiative funded My Pediatric and Adult Rare Tumor (MyPART) network (cancer.gov/mypart) in the NCI Pediatric Oncology Branch and launched a longitudinal Natural History Study for Children and Adults with Rare Solid Tumors (NCT03739827). Methods: A prospective study to evaluate the natural history of rare pediatric and adult solid tumors comprehensively and longitudinally. Patients of any age with a rare solid tumor (<15 cases per 100,000 people per year) are eligible. Patients with germline mutation who are at risk of developing these tumors or relatives of participants are also eligible. Patients can participate from home or are are invited to NIH for annual evaluations. Participants complete individual medical history, family history, patient related-outcomes measurements (PROs) and provide samples (blood, saliva) for DNA analysis. Tumors are analyzed using a 500+ gene panel (TruSight500, Illumina Panel) and undergo a comprehensive genomic and epigenomic analysis. Participants invited to NIH undergo a clinical evaluation, genetic counseling, blood collection (standard clinical labs, germline DNA/RNA, immune phenotypes, cytokines, exosomes), and imaging studies, as indicated. 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 3) Develop a better understanding of these diseases in an effort to develop a) Novel therapeutic interventions, b) Preventive/screening guidelines, c) Endpoints for future clinical trials, and d) Relevant patient reported outcomes that can improve our understanding of patients psychosocial and functional needs. Subprotocols under this protocol for children and adults include adrenocortical cancer (NCT04447014), neuroendocrine neoplasms (NCT04488263) and Chordoma (NCT0391046) to gather tumor specific data. Study accrual is ongoing. Clinical trial information: NCT03739827.