Significance of Co-expression of Epidermal Growth Factor Receptor and Ki67 on Clinical Outcome in Patients With Anal Cancer Treated With Chemoradiotherapy: An Analysis of NRG Oncology RTOG 9811.

Conference Paper

PURPOSE: To measure co-expression of EGFR and Ki67 proteins in pretreatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5-fluorouracil/mitomycin-C/radiation therapy (Arm A) versus 5-fluorouracil/cisplatin/radiation therapy (Arm B), and to correlate expression with clinical outcome. METHODS AND MATERIALS: EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis. The Ki67 score within EGFR high versus low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles, and as a continuous variable. Associations between the tumor markers and clinical endpoints (overall and disease-free survival, locoregional and colostomy failure, and distant metastases) were explored. RESULTS: A total of 282 pretreatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥median had worse overall survival (hazard ratio 2.41, 95% confidence interval 1.38-4.19, P=.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (hazard ratio 1.85, 95% confidence interval 1.18-2.92, P=.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. CONCLUSIONS: High Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR-targeted therapeutic agent.

Full Text

Duke Authors

Cited Authors

  • Doll, CM; Moughan, J; Klimowicz, A; Ho, CK; Kornaga, EN; Lees-Miller, SP; Ajani, JA; Crane, CH; Kachnic, LA; Okawara, GS; Berk, LB; Roof, KS; Becker, MJ; Grisell, DL; Ellis, RJ; Sperduto, PW; Marsa, GW; Guha, C; Magliocco, AM

Published Date

  • March 1, 2017

Published In

Volume / Issue

  • 97 / 3

Start / End Page

  • 554 - 562

PubMed ID

  • 28126304

Pubmed Central ID

  • PMC5687248

Electronic International Standard Serial Number (EISSN)

  • 1879-355X

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2016.11.021

Conference Location

  • United States