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Multimodality Treatment of Locally Advanced Pancreatic Cancer Including FOLFIRINOX Chemotherapy, Surgical Exploration and Irreversible Electroporation: Prospective Series of 132 Consecutive Patients
Jantien Vogel*1, Thijs de Rooij1, Krijn P. van Lienden6, Johanna Wilmink2, Hanneke van Laarhoven2, Jeanin E. van Hooft3, Otto van Delden6, Marcel Dijkgraaf4, Robert C. Martin5, Olivier R. Busch1, Marc Besselink1
1Surgery, Academic Medical Center Amsterdam, Amsterdam, Netherlands; 2Medical Oncology, Academic Medical Center Amsterdam, Amsterdam, Netherlands; 3Gastroenterology, Academic Medical Center Amsterdam, Amsterdam, Netherlands; 4Clinical Research Unit, Academic Medical Center Amsterdam, Amsterdam, Netherlands; 5Surgery, University of Louisville, Louisville, KY; 6Radiology, Academic Medical Center Amsterdam, Amsterdam, Netherlands

Introduction
Pancreatic cancer has a poor prognosis. However, since the introduction of FOLFIRINOX, several recent studies on LAPC patients have reported resection-rates after this chemotherapy exceeding 20%. Secondly, the addition of irreversible electroporation (IRE) to standard treatment has led to a median overall survival (mOS) after IRE exceeding 20 months. Most studies, however, exclude patients who receive no chemotherapy or have progressive disease during. Prospective series on large cohorts of all consecutive patients with LAPC are lacking. The aim of this study is to describe outcomes of multimodality treatment of LAPC with chemotherapy, surgical exploration and IRE in a consecutive cohort.
Methods
A prospective, single center, consecutive cohort study (September 2013 - March 2015) including all patients with histologically proven LAPC (>90° arterial or >270° venous involvement). After 3 months of chemotherapy, restaging was performed to assess RECIST 1.1 response, resectability and IRE-eligibility (i.e. tumor ≤ 5 cm). All patients with non-progressive, IRE-eligible tumors underwent explorative laparotomy. Outcomes included (R0-)resection-rate, IRE-rate, Clavien-Dindo grade ≥ 3 complications and survival.
Results
Of 132 patients with LAPC, 70% (n=93) received chemotherapy, of which 65% (n=60) FOLFIRINOX. After 3 months, 45% (n=59/132) had non-progressive disease. Of all 132 patients, 27% (n=36) underwent laparotomy with a resection-rate of 11% (n=14/132, R0 8/14) and an IRE-rate of 11% (n=15/132). After laparotomy, the Clavien-Dindo grade ≥ 3 complication-rate was 39% (6/14 resection, 7/15 IRE, 1/7 other) and 90-day mortality 11% (1/14 resection, 2/15 IRE, 1/7 other). In the 60 patients who received FOLFIRINOX chemotherapy, the resection-rate was 20% (n=12) and IRE-rate 15% (n=9). mOS from diagnosis was 10 months for all patients, 19 months for patients with non-progressive disease after 3 months, was not reached in resected patients (median follow-up 14 months, 1 death) and was 16 months in IRE-patients.
Conclusions
Multimodality treatment in a cohort of consecutive patients with LAPC resulted in 11% resections and 11% IRE with acceptable complication-rates. Final survival data will have to be awaited but appear promising, especially for resection after chemotherapy. This study highlights the importance of reporting on the outcomes of complete, rather than selected, cohorts of LAPC.


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