Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin.

Details

Serval ID
serval:BIB_C6F070AE0FBC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin.
Journal
Annals of surgery
Author(s)
Schneider M.A., Eden J., Pache B., Laminger F., Lopez-Lopez V., Steffen T., Hübner M., Kober F., Roka S., Campos P.C., Roth L., Gupta A., Siebenhüner A., Kepenekian V., Passot G., Gertsch P., Glehen O., Lehmann K.
ISSN
1528-1140 (Electronic)
ISSN-L
0003-4932
Publication state
Published
Issued date
11/2018
Peer-reviewed
Oui
Volume
268
Number
5
Pages
845-853
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear.
Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction.
Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes.
RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.
Pubmed
Web of science
Create date
17/10/2018 11:28
Last modification date
20/08/2019 16:42
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