Salvatore Paiella1, Giuseppe Malleo2, Ivana Cataldo3, Clizia Gasparini2, Matteo De Pastena2, Giulia De Marchi4, Giovanni Marchegiani2, Borislav Rusev3,4,5, Aldo Scarpa3,4,5, Roberto Girelli6, Alessandro Giardino6, Isabella Frigerio6, Mirko D'Onofrio7, Erica Secchettin2, Claudio Bassi2, Roberto Salvia2. 1. General and Pancreatic Surgery Department, Pancreas Institute, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. salvatore.paiella@aovr.veneto.it. 2. General and Pancreatic Surgery Department, Pancreas Institute, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. 3. Department of Pathology and Diagnostics, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. 4. Gastroenterology B Department, Pancreas Institute, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. 5. ARC-Net Research Centre, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. 6. HPB Unit, Casa di Cura Pederzoli, Via Monte Baldo, Peschiera del Garda, Verona, Italy. 7. Department of Radiology, Pancreas Institute, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy.
Abstract
PURPOSE: SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. METHODS: Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). CONCLUSIONS: Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation.
PURPOSE:SMAD4 mutational status correlates with pancreatic ductal adenocarcinoma (PDAC) failure pattern. We investigated in a subset of locally advanced patients submitted to radiofrequency ablation (RFA) whether the assessment of SMAD4 status is a useful way to select the patients. METHODS: Clinical, radiological, and follow-up details of patients submitted to RFA for locally advanced pancreatic cancer (LAPC), in whom cytohistological material was available at our institution, were retrospectively retrieved. SMAD4 expression was evaluated by immunohistochemistry (IHC) and considered "negative" or "positive." The survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: The study population consisted of 30 patients. Thirteen patients (43.3%) received RFA upfront, whereas 17 (56.7%) after induction treatments. SMAD4 was mutant in 18 out of 30 patients (60%). The overall estimated post-RFA disease-specific survival (DSS) was 15 months (95% CI 11.64-18.35). The estimated post-RFA DSS of patients with wild-type and mutant SMAD4 was 22 and 12 months, respectively (log-rank p < 0.05). At the multivariate analysis, SMAD4 was the only independent predictor of survival (p = 0.05). The pattern of failure was not associated with SMAD4 status (p = 0.4). CONCLUSIONS: Within patients undergoing RFA for LAPC, SMAD4 analysis could segregate a subgroup of subjects with improved survival, who likely benefited from tumor ablation.
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