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Past
Despite improving median and 5-year survival in patients with peritoneal surface malignancy originating from the large bowel, a substantial proportion experience rapid disease progression after seemingly radical cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Some of these patients have low Peritoneal Cancer Index (PCI). Various more or less fruitful attempts have been undertaken to predict outcome but, to date, reliable measures are insufficient. Among useful predictive tools are extent of peritoneal dissemination, signet cell differentiation, and colorectal peritoneal (COREP) score.1,2,–3
Present
Our study identified BRAF mutation as a potential predictive tool in one-tenth of patients scheduled for CRS and HIPEC.4 In fact, no patients with BRAF mutation experienced long-term survival. Mutated KRAS did not influence survival in patients undergoing CRS and HIPEC. The predictive importance of BRAF mutation also remained in multivariate analysis adjusted for PCI, CCS, and signet cell differentiation.
Future
The present results need to be verified in an independent and larger patient sample. If BRAF mutation can be confirmed to have this poor prognosis after CRS and HIPEC, BRAF-mutated subjects may need alternative therapeutic strategies, such as systemic chemotherapy or targeted therapies with BRAF inhibitors, combined with CRS and HIPEC. The efforts to select the most suitable group for CRS and HIPEC should be continued, and even increased, in view of the results of a recent controlled trial5 where unselected patients were included.
References
Goéré D, Souadka A, Faron M, Cloutier AS, Viana B, Honoré C, et al. Extent of colorectal peritoneal carcinomatosis: attempt to define a threshold above which HIPEC does not offer survival benefit: a comparative study. Ann Surg Oncol. 2015;22:2958–64.
Solomon D, DeNicola N, Feingold D, Liu PH, Aycart S, Golas BJ, et al.Signet ring cell features with peritoneal carcinomatosis in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are associated with poor overall survival. J Surg Oncol. 2019;119(6):758–65.
Cashin PH, Graf W, Nygren P, Mahteme H. Patient selection for cytoreductive surgery in colorectal peritoneal carcinomatosis using serum tumor markers: an observational cohort study. Ann Surg. 2012;256(6):1078–83.
Graf W, Cashin PH, Ghanipour L, Enblad M, Botling J, Terman A, et al. Prognostic impact of BRAF and KRAS mutation in patients with colorectal and appendiceal peritoneal metastases scheduled for CRS and HIPEC. Ann Surg Oncol. 2019. https://doi.org/10.1245/s10434-019-07452-2.
Quenet F, Elias D, Roca L, Goere D, Ghouti L, Pocard M, et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7 [abstract]. J Clin Oncol. 2018;36:18.
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Wilhelm Graf and Helgi Birgisson have no conflicts of interest to disclose.
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ASO Author Reflections is a brief invited commentary on the article “Prognostic impact of BRAF and KRAS mutation in patients with colorectal and appendiceal peritoneal metastases scheduled for CRS and HIPEC”, Ann Surg Oncol. 2019. https://doi.org/10.1245/s10434-019-07452-2.
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Graf, W., Birgisson, H. ASO Author Reflections: Can Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy be Improved?. Ann Surg Oncol 27, 301–302 (2020). https://doi.org/10.1245/s10434-019-07664-6
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DOI: https://doi.org/10.1245/s10434-019-07664-6