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

Clin Colorectal Cancer

Division of Surgical Oncology, Department of Surgery, University of New Mexico, Albuquerque, NM; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM. Electronic address:

Published: June 2019

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556409PMC
http://dx.doi.org/10.1016/j.clcc.2019.02.003DOI Listing

Publication Analysis

Top Keywords

tumor heterogeneity
16
locally advanced
16
advanced rectal
12
math scores
12
rectal cancer
8
patients disease
8
response ncrt
8
intratumoral heterogeneity
8
biopsy samples
8
complete response
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!