PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases
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Etay Ziv1, Michael Bergen2, Hooman Yarmohammadi1, F. Ed Boas1, E. Nadia Petre1, Constantinos T. Sofocleous1, Rona Yaeger3, David B. Solit4,5,6, Stephen B. Solomon1, Joseph P. Erinjeri1
1Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
2Department of Radiology, Mount Sinai Hospital, New York, USA
3Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
4Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USA
5Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA
6Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
Etay Ziv, email: [email protected]
Keywords: biomarkers, colorectal, PI3K, radioembolization, MAPK
Received: August 25, 2016 Accepted: January 16, 2017 Published: February 11, 2017
Purpose: To establish the relationship between common mutations in the MAPK and PI3K signaling pathways and local progression after radioembolization.
Materials and Methods: Retrospective review of a HIPAA-compliant institutional review-board approved database identified 40 patients with chemo-refractory colorectal liver metastases treated with radioembolization who underwent tumor genotyping for hotspot mutations in 6 key genes in the MAPK/PI3K pathways (KRAS, NRAS, BRAF, MEK1, PIK3CA, and AKT1). Mutation status as well as clinical, tumor, and treatment variables were recorded. These factors were evaluated in relation to time to local progression (TTLP), which was calculated from time of radioembolization to first radiographic evidence of local progression. Predictors of outcome were identified using a proportional hazards model for both univariate and multivariate analysis with death as a competing risk.
Results: Sixteen patients (40%) had no mutations in either pathway, eighteen patients (45%) had mutations in the MAPK pathway, ten patients (25%) had mutations in the PI3K pathway and four patients (10%) had mutations in both pathways. The cumulative incidence of progression at 6 and 12 months was 33% and 55% for the PI3K mutated group compared with 76% and 92% in the PI3K wild type group. Mutation in the PI3K pathway was a significant predictor of longer TTLP in both univariate (p=0.031, sHR 0.31, 95% CI: 0.11-0.90) and multivariate (p=0.015, sHR=0.27, 95% CI: 0.096-0.77) analysis. MAPK pathway alterations were not associated with TTLP.
Conclusions: PI3K pathway mutation predicts longer time to local progression after radioembolization of colorectal liver metastases.
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