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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: The Cancer Genome Atlas (TCGA) showed that 16% of colorectal cancers (CRCs) 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.

Original languageEnglish (US)
Pages (from-to)858-866
Number of pages9
JournalJournal of Gastrointestinal Oncology
Volume8
Issue number5
DOIs
StatePublished - Oct 1 2017

Keywords

  • Chemotherapy
  • Colorectal cancer (CRC)
  • Irinotecan
  • Next-generation sequencing (NGS)
  • Oxaliplatin
  • Tumor mutational burden (TMB)

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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