학술논문
RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases.
Document Type
Academic Journal
Author
Bhullar D; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; O'Dwyer S; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.; Wilson M; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.; Saunders MP; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.; Kochhar R; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK.; Barriuso J; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. jorge.barriuso@manchester.ac.uk.; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK. jorge.barriuso@manchester.ac.uk.; Aziz O; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. omer.aziz2@nhs.net.; Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK. omer.aziz2@nhs.net.
Source
Publisher: Springer Country of Publication: United States NLM ID: 9420840 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1534-4681 (Electronic) Linking ISSN: 10689265 NLM ISO Abbreviation: Ann Surg Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Genetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT).
Patients and Methods: Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004-2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan-Meier curves were used to determine overall survival.
Results: One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4-184.9 months) and median OS was 38.7 months (95% CI 32.4-44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402-16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995-2.843, p = 0.052).
Conclusions: RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.
(© 2022. The Author(s).)
Patients and Methods: Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004-2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan-Meier curves were used to determine overall survival.
Results: One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4-184.9 months) and median OS was 38.7 months (95% CI 32.4-44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402-16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995-2.843, p = 0.052).
Conclusions: RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.
(© 2022. The Author(s).)