Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metast
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ORIGINAL ARTICLE – PERITONEAL SURFACE MALIGNANCY
Prognostic Impact of Primary Side and RAS/RAF Mutations in a Surgical Series of Colorectal Cancer with Peritoneal Metastases Dario Baratti, MD1, Shigeki Kusamura, PhD1, Monica Niger, MD2, Federica Perrone, PhD3, Massimo Milione, MD4, Laura Cattaneo, MD4, Marcello Guaglio, MD1, Valentina Bartolini, MD1, Filippo Pietrantonio, MD2, and Marcello Deraco, MD1 1
Peritoneal Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 3Laboratory of Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 4Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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ABSTRACT Background. Selecting patients with colorectal cancer peritoneal metastases (CRC-PMs) for surgery is still a concern. Biological features have the potential to improve prognostic stratification, but their significance in this clinical setting is still unclear. We assessed the prognostic impact of primary side and KRAS/NRAS/BRAF/PIK3CA mutations in patients treated with either cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) or CRS alone. Methods. We reviewed a prospective database of 152 CRC-PM patients selected to undergo perioperative systemic chemotherapy and CRS with or without HIPEC. Extensive mutational analysis of KRAS, NRAS, BRAF, and PIK3CA was performed by polymerase chain reaction (PCR). In 68 patients, Ion Torrent next-generation sequencing technology was used to characterize the hotspot regions of 50 genes.
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-09161-7) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2020 First Received: 12 June 2020 Accepted: 31 August 2020 D. Baratti, MD e-mail: [email protected]
Results. The primary tumor was right-sided in 61 patients (40.1%) and left-sided in 91 patients (59.9%). Right-sided primaries were associated with mutated KRAS (p = 0.01) and normal carcinoembryonic antigen (CEA; p = 0.03). KRAS was mutated in 71/152 patients (46.7%), NRAS in 7/152 patients (4.6%), BRAF in 10/152 patients (6.6%), PIK3CA in 17/78 patients (25.0%), TP53 in 37/68 patients (54.4%), APC in 25/68 patients (36.7%), SMAD4 in 13/68 patients (19.1%), and FBXW7 in 5/68 patients (7.4%). Median follow-up was 54.9 months and median survival from PM diagnosis was 45.1 months. The right-sided primary (hazard ratio [HR] 1.62, 95% confidence interval [CI] 0.43–0.89; p = 0.011), BRAF mutations (HR 2.21, 95% CI 1.05–4.63; p = 0.038), and Peritoneal Cancer Index (HR 1.47, 95% CI 1.03–2.10; p = 0.036) independently correlated with poorer survival, while APC mutations univariately correlated with better survival (p = 0.03). Conclusions. BRAF mutations and right-sided primary are adverse prognostic fac
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