Article Abstract

Correlation of tumor mutational burden and treatment outcomes in patients with colorectal cancer

Authors: Sachin G. Pai, Benedito A. Carneiro, Young Kwang Chae, Ricardo L. Costa, Aparna Kalyan, Hiral A. Shah, Irene Helenowski, Alfred W. Rademaker, Devalingam Mahalingam, Francis J. Giles


Background: The Cancer Genome Atlas (TCGA) showed that 16% of colorectal cancers (CRC) display DNA repair mechanisms and high tumor mutational burden (TMB). Although, there is accumulating evidence of greater benefit of immunotherapy in tumors with high-TMB, its impact on response to chemotherapy is unknown.
Methods: In this retrospective cohort study, we investigated the impact of TMB on progression-free survival (PFS) of CRC patients treated at tertiary care oncology clinics who had their tumors profiled by next-generation sequencing (NGS). Low TMB (TMB-L) and intermediate/high TMB (TMB-I/H) were defined as ≤5 mutations per base (MB) or ≥6 MB, respectively.
Results: Seventy-four CRC patients (61 colon and 13 rectal cancers) were identified from the database. In the TMB-L cohort, irinotecan-based chemotherapy treated patients had improved PFS compared to oxaliplatin-based chemotherapy treated patients (11.9 vs. 6.5 months, P<0.001). No difference in PFS was observed between the two treatment cohorts in TMB-I/H group. There was also no difference in time to recurrence in the TMB-L and TMB-I/H arms in patients treated with oxaliplatin-based therapy in perioperative setting.
Conclusions: TMB-L may be a predictive biomarker in a subset of CRC patients treated with chemotherapy but these results need to confirmed in larger studies.