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

2018; Impact Journals LLC; Volume: 9; Issue: 65 Linguagem: Inglês

10.18632/oncotarget.25992

1949-2553

Meaghan Dendy, Johannes Ludwig, Nima Kokabi, Stacey Stein, Jill Lacy, Howard S. Höchster, Hyun S. Kim,

Genetic factors in colorectal cancer

// Meaghan S. Dendy 1 , Johannes M. Ludwig 1, 2 , Nima Kokabi 1, 3 , Stacey M. Stein 4, 5 , Jill Lacy 4, 5 , Howard S. Hochster 6 and Hyun S. Kim 1, 4, 5 1 Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA 2 Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany 3 Division of Interventional Radiology and Image Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA 4 Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT, USA 5 Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA 6 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA Correspondence to: Hyun S. Kim, email: kevin.kim@yale.edu Keywords: radioembolization; CRC; biomarker; colorectal liver metastases; CRLM Received: January 04, 2018 Accepted: August 02, 2018 Published: August 21, 2018 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.