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

Research output: Contribution to journalArticle

12 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

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Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Pai, S. G., Carneiro, B. A., Chae, Y. K., Costa, R. L., Kalyan, A., Shah, H. A., Helenowski, I., Rademaker, A. W., Mahalingam, D., & Giles, F. J. (2017). Correlation of tumor mutational burden and treatment outcomes in patients with colorectal cancer. Journal of Gastrointestinal Oncology, 8(5), 858-866. https://doi.org/10.21037/jgo.2017.06.20