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.
Document Type
Article
Publication Date
6-2019
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.clcc.2019.02.003
Funding Information
Supported in part by National Institutes of Health grants 5R01CA170250, 5R01DE023222, and 5P30CA118100 (to S.A.N.).
Some experiments used the facilities or services provided by the Analytical and Translational Genomics Shared Resource, which is supported by the State of New Mexico and the UNM Comprehensive Cancer Center P30CA118100.
Repository Citation
Greenbaum, Alissa; Martin, David R.; Bocklage, Therese J.; Lee, Ji-Hyun; Ness, Scott A.; and Rajput, Ashwani, "Tumor Heterogeneity as a Predictor of Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer" (2019). Pathology and Laboratory Medicine Faculty Publications. 46.
https://uknowledge.uky.edu/pathology_facpub/46
Included in
Biostatistics Commons, Internal Medicine Commons, Oncology Commons, Pathology Commons, Surgery Commons
Notes/Citation Information
Published in Clinical Colorectal Cancer, v. 18, issue 2.
© 2019 The Authors
This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).