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    RAS mutation status should not be used to predict outcome from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases

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    Authors
    Bhullar, Dilraj
    O'Dwyer, Sarah T
    Wilson, Malcolm S
    Saunders, Mark P
    Kochhar, Rohit
    Barriuso, Jorge
    Aziz, Omer
    Affiliation
    Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
    Issue Date
    2022
    
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    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.
    Citation
    Bhullar D, O'Dwyer S, Wilson M, Saunders MP, Kochhar R, Barriuso J, et al. RAS Mutation Status Should Not Be Used to Predict Outcome from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases. Ann Surg Oncol. 2022 Nov 18. PubMed PMID: 36400886. Epub 2022/11/19. eng.
    Journal
    Annals of Surgical Oncology
    URI
    http://hdl.handle.net/10541/625862
    DOI
    10.1245/s10434-022-12704-9
    PubMed ID
    36400886
    Additional Links
    https://dx.doi.org/10.1245/s10434-022-12704-9
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1245/s10434-022-12704-9
    Scopus Count
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