Tumor Heterogeneity as a Predictor of Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Alissa Greenbaum, David R. Martin, Thèrése Bocklage, Ji Hyun Lee, Scott A. Ness, Ashwani Rajput

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays. Patients and Methods: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral heterogeneity. Response to nCRT was pathologically scored after surgical resection. Results: Biopsy samples from 21 patient tumors were analyzed. Eight patients had disease noted to have complete response, 2 moderate, 4 minimal, and 7 poor. Higher MATH scores correlated with poorer response to treatment, demonstrating significantly increased tumor heterogeneity compared to complete response (P =.039). Conclusion: The application of MATH scores as a measure of tumor heterogeneity may provide a useful biomarker for treatment response in locally advanced rectal cancer.

Original languageEnglish (US)
Pages (from-to)102-109
Number of pages8
JournalClinical colorectal cancer
Volume18
Issue number2
DOIs
StatePublished - Jun 2019
Externally publishedYes

Keywords

  • Bioinformatics
  • Colorectal cancer
  • Personalized medicine
  • Targeted sequencing
  • Translational research

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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