Mentor Name: Julia Glade-Bender

There is clear evidence that the incidence of “early onset” colorectal and gastric carcinoma, defined as occurring under the age of 50, is on the rise in the United States and, in some cases, biologically distinct from late onset disease; however, recent reviews are limited to patients over the age of 18 years. Several trends have been noted in early onset disease including an increased incidence of germline cancer predisposition, personal or family history of inflammatory bowel disease, more advanced stage at diagnosis, and an increase in signet ring histology. The recommendations for treating early onset gastrointestinal (GI) carcinomas are to follow paradigms for late onset carcinoma, although younger patients tend to receive more intensive therapies to obtain similar outcomes. There are currently no established treatment guidelines for “very young onset” GI carcinomas, and no pediatric-specific clinical trials or adult trials allowing for the inclusion of patients under age 18 years. This gap is particularly significant given the increasing use of targeted therapies, many of which are recently approved exclusively for adult populations. Current NCCN guidelines recommend immunohistochemical testing and/or molecular testing for HER2/ ERBB2 overexpression/amplification, MSI or MMR status, PD-L1 expression, CLDN18.2 positivity, tumor mutational burden-high (TMB-H) status; NTRK gene fusion, RET gene fusion; and POLE/POLD1, RAS and BRAF mutation. At MSK patients have access to disease specific expertise from collaborating GI oncologists, surgeons and gastroenterologists who have helped shape the modern biomarker driven approach to the treatment of advanced GI carcinomas. Despite the local expertise, the clinical trends and molecular characteristics of GI carcinomas diagnosed in individuals aged 20 years and younger are largely uncharacterized, and the extent to which very young patients might benefit from novel therapeutics unknown. Sam will be working on a retrospective review of patients under the age of 20 treated at MSK for gastroesophageal and colorectal carcinoma. He will perform a chart review to characterize patient characteristics, extent of disease evaluation, pathologic diagnosis, stage, molecular profile and germline predisposition (for patients consented to IRB 12-245), therapy, surgical approach and outcomes in collaboration with me and the multidisciplinary GI malignancy disease management team. The aim of this research will be to develop standardized, evidence-based guidelines for screening, evaluation and treatment and future clinical trials with appropriate targeted drug development for very young onset GI malignancy.