PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases Journal Article


Authors: Ziv, E.; Bergen, M.; Yarmohammadi, H.; Boas, F. E.; Petre, E. N.; Sofocleous, C. T.; Yaeger, R.; Solit, D. B.; Solomon, S. B.; Erinjeri, J. P.
Article Title: PI3K pathway mutations are associated with longer time to local progression after radioembolization of colorectal liver metastases
Abstract: 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.
Keywords: biomarkers; mapk; pi3k; colorectal; radioembolization
Journal Title: Oncotarget
Volume: 8
Issue: 14
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2017-04-04
Start Page: 23529
End Page: 23538
Language: English
DOI: 10.18632/oncotarget.15278
PROVIDER: scopus
PUBMED: 28206962
PMCID: PMC5410324
DOI/URL:
Notes: Article -- Export Date: 2 May 2017 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. David Solit
    551 Solit
  2. Rona Denit Yaeger
    123 Yaeger
  3. Stephen Solomon
    303 Solomon
  4. Joseph Patrick Erinjeri
    112 Erinjeri
  5. Elena Nadia Petre
    58 Petre
  6. Franz Edward Boas
    50 Boas
  7. Etay   Ziv
    39 Ziv