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Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) |
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| Authors: | Tonello Marco Baratti Dario Sammartino Paolo Di Giorgio Andrea Robella Manuela Sassaroli Cinzia Framarini Massimo Valle Mario Macrì Antonio Graziosi Luigina Coccolini Federico Lippolis Piero Vincenzo Gelmini Roberta Deraco Marcello Biacchi Daniele Santullo Francesco Vaira Marco Di Lauro Katia D’Acapito Fabrizio Carboni Fabio Giuffrè Giuseppe Donini Annibale Fugazzola Paola Faviana Pinuccia Sorrentino Lorena Scapinello Antonio Del Bianco Paola Sommariva Antonio |
| Affiliation: | 1.Unit of Surgical Oncology of the Esophagus and Digestive Tract, Surgical Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy ;2.Peritoneal Surface Malignancy Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy ;3.Cytoreductive Surgery and HIPEC Unit, Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, Rome, Italy ;4.Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy ;5.Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy ;6.Colorectal Surgical Oncology, Abdominal Oncology Department, Fondazione Giovanni Pascale” IRCCS, Naples, Italy ;7.General and Oncologic Surgery, Morgagni–Pierantoni Hospital, AUSL Romagna, Forlì, Italy ;8.Peritoneal Malignancies Unit, INT “Regina Elena”, Rome, Italy ;9.Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, University of Messina, Messina, Italy ;10.General and Emergency Surgery Department, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy ;11.General Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy ;12.General Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy ;13.General and Peritoneal Surgery, Department of Surgery, Hospital University Pisa (AOUP), Pisa, Italy ;14.General and Oncological Surgery Unit, AOU of Modena University of Modena and Reggio Emilia, Modena, Italy ;15.Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy ;17.Pathological Anatomy III, Laboratory Medicine Department, Hospital University Pisa (AOUP), Pisa, Italy ;18.Pathology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy ;19.Clinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy ; |
| Abstract: | Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. MethodsData were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). ResultsThe study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4–51.2 months], and the median DFS was 13.6 months (95% CI, 12.3–14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4–24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. ConclusionFor patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients. |
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