Genomic mutations and histopathologic biomarkers in Y90 radioembolization for chemorefractory colorectal liver metastases

• Type of Material: Article
• Authors: Meaghan S. Dendy, Yale University; Johannes M. Ludwig, Yale University; Nima Kokabi, Emory University; Stacey M. Stein, Yale University; Jill Lacy, Yale University; Howard S. Hochster, Rutgers Cancer Institute of New Jersey; Hyun S. Kim, Yale University
• Language: English
• Date: 2018-08-21
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Dendy et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.25992
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 9
• Issue: 65
• Start Page: 32523
• End Page: 32533
• Keywords: radioembolization; biomarker; CRC; CRLM; colorectal liver metastases
• Research Categories: Health Sciences, Radiology; Health Sciences, Oncology

Abstract

Background: To investigate mutational load and histologic biomarkers as prognostic factors in patients with chemorefractory colorectal liver metastases (CRLM) treated with Y-90 radioembolization therapy. Materials and Methods: Single institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patient demographics, systemic therapy regimens, tumor characteristics and overall survival were analyzed between patients with differing histopathologic and genomic status. PIK3CA, KRAS, NRAS, AKT1, MEK1, MLH1, MSH2, MSH6 and PMS2 were analyzed. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 23 patients underwent genomic analysis prior to Y-90. Eleven (47.8%) had mutations identified (MUT), and 12 were sequenced as wild type (WT) (52.2%). Median OS of 23 patients after Y-90 was 9.6 months (95% CI 6.67-16.23). Median OS from first Y-90 was significantly greater in WT patients (16.2 mo vs 6.5 mo; p =.0054). The survival difference between poorly differentiated tumors compared to all other histologic grades was significant (poor vs. well p=0.025, HR=26.8; poor vs. moderate p=.014, HR=23.07; poor vs. moderate/poor p=0.014, HR=23.68). When separated into 3 different groups (WT vs. MUT/moderate differentiation vs. MUT/ poor differentiation) there was a difference in median OS observed (16.2 vs. 8.0 vs. 3.8 mos; p < .0001). Imaging response via RECIST criteria was significantly different between MUT and WT groups (p=0.02). Conclusions: Mutational status and histopathologic grade may predict survival after Y-90 radioembolization therapy for CRLM.