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Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients

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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.

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Acknowledgements

The authors thank Ossian Elkington for his kind English language editing of the manuscript.

Funding

AIRC 5xmille (grant no. 12182), European Community FP7 Grant (Cam-PaC, agreement no: 602783), FIMP-Ministero Salute (CUP_J33G13000210001). The funding agencies had no role in the collection, analysis, and interpretation of data and in the writing of the manuscript.

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Authors and Affiliations

  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, Giuseppe Malleo, Clizia Gasparini, Matteo De Pastena, Giovanni Marchegiani, Erica Secchettin, Claudio Bassi & Roberto Salvia

  2. Department of Pathology and Diagnostics, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

    Ivana Cataldo, Borislav Rusev & Aldo Scarpa

  3. Gastroenterology B Department, Pancreas Institute, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

    Giulia De Marchi, Borislav Rusev & Aldo Scarpa

  4. ARC-Net Research Centre, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

    Borislav Rusev & Aldo Scarpa

  5. HPB Unit, Casa di Cura Pederzoli, Via Monte Baldo, Peschiera del Garda, Verona, Italy

    Roberto Girelli, Alessandro Giardino & Isabella Frigerio

  6. Department of Radiology, Pancreas Institute, University of Verona Hospital Trust, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

    Mirko D’Onofrio

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  1. Salvatore Paiella
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  2. Giuseppe Malleo
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  3. Ivana Cataldo
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  4. Clizia Gasparini
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  9. Aldo Scarpa
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  10. Roberto Girelli
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  15. Claudio Bassi
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  16. Roberto Salvia
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Contributions

Study conception and design: SP, GDM, RS, MDM, CB, AS; acquisition of data: CG, ES, GDM, IC, AG, IF, BR; analysis and interpretation of data: SP GM, GM, RG, RS, MDO; drafting of the manuscript: SP, GM, MDP, GM, AG, RS, IC; critical revision of the manuscript: SP, GM, IC, GDM, MDP, GM, RS, AG, IF, RG, AS, RS, CB, MDO.

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Correspondence to Salvatore Paiella.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was available for all the patients.

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Paiella, S., Malleo, G., Cataldo, I. et al. Radiofrequency ablation for locally advanced pancreatic cancer: SMAD4 analysis segregates a responsive subgroup of patients. Langenbecks Arch Surg 403, 213–220 (2018). https://doi.org/10.1007/s00423-017-1627-0

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