Disparities in comprehensive genomic profiling in older patients with gastrointestinal malignancies.

Abstract

646 Background: Limited data guides the management of older adults with cancer, a patient population that continues to be under-represented in clinical trials. Comprehensive Genomic Profiling (CGP) drives the enrollment on biomarker-based trials and may inform treatment selection. This analysis aims to evaluate the use of CGP in older patients with gastrointestinal (GI) malignancies and to compare results of genomic profiling across age groups. Methods: Clinical CGP results derived from Next Generation Sequencing (NGS) of tumor tissue (n=92802) were reviewed for patients with GI malignancies. Genomic alterations (GAs) and complex signatures were identified, based on hybridization-captured, adapter ligation-based sequencing. Association between age group (< 65: n=51652; 65-74: n=28972; 75+: n=12178) and biomarkers of interests was evaluated using Chi-square test, adjusting for multiple testing using Bonferroni correction. Delay-adjusted incidence rates in populations included in the study were acquired from SEER Databases. Results: The majority of patients in the CGP cohort were <65 yrs (55.7%). Patients aged 75 and above were underrepresented as compared to the SEER database incidence rates (15.2% vs. 31.6%, p <0.0005). Overall, the incidence of known or likely pathogenic GAs was similar across all age groups (>99%). An analysis of specific GAs among all the GI cancers analyzed showed an age-associated increase of high tumor mutational burden (≥10 mut/Mb) (TMB-H) (5.6% vs 6.6% vs 10.7% for respective age groups, p<0.0005). The overall incidence of mismatch repair deficiency or microsatellite instability (dMMR/MSI) (3.6% vs 4.0% vs 7.5%, p<0.0005) and DNA damage repair mutations (DDR mut) (13.2% vs 13.9% vs 16.4%, p<0.0005) also increased with age. The magnitude of the CGP findings varied by GI cancer type, as summarized for select significant findings (p <0.0005) in Table. Detailed results for each GI subtype and relevant biomarkers will be presented. Conclusions: This large scale analysis of CGP done for patients with GI cancers showed that genomic profiling is under utilized in older adults who constitute the majority of patients with GI malignancies. These findings may improve access to clinical trials and guide the development of older adult-specific studies.[Table: see text]