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Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy.

Methods

This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3 months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors.

Results

Of 132 patients with LAPC, 70% (n = 93) started with chemotherapy (46% [n = 61] FOLFIRINOX). After 3 months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n = 16) of patients had Clavien–Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n = 4). With a median follow-up of 24 months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n = 30) was 34, 16, and 15 months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%.

Conclusion

Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230).

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Funding

Marc G. Besselink received a Grant (No. 2013-5842) from the Dutch Cancer Society (KWF) for studies on pancreatic cancer. Jantien A. Vogel and Marc G. Besselink received a Grant (No. 2014-7244) from the Dutch Cancer Society for studies on IRE in pancreatic cancer. Krijn P. van Lienden and Robert C. Martin are paid consultants for AngioDynamics®.

Conflict of interest

Steffi J. Rombouts, Thijs de Rooij, Otto M. van Delden, Marcel G. Dijkgraaf, Thomas M. van Gulik, Jeanin E. van Hooft, Hanneke W. van Laarhoven, Annuska Schoorlemmer, Johanna W. Wilmink, and Olivier R. Busch declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

    Jantien A. Vogel MD, MSc, Steffi J. Rombouts MD, Thijs de Rooij MSc, Thomas M. van Gulik MD, PhD, Prof, Annuska Schoorlemmer MSc, Olivier R. Busch MD, PhD, Prof & Marc G. Besselink MD, MSc, PhD

  2. Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands

    Otto M. van Delden MD, PhD, Prof & Krijn P. van Lienden MD, PhD

  3. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands

    Marcel G. Dijkgraaf MSc, PhD

  4. Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands

    Jeanin E. van Hooft MD, PhD, MBA

  5. Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands

    Hanneke W. van Laarhoven MD, PhD, Prof & Johanna W. Wilmink MD, PhD

  6. Department of Surgery, University of Louisville, Louisville, KY, USA

    Robert C. Martin MD, PhD, Prof

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  1. Jantien A. Vogel MD, MSc
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Corresponding author

Correspondence to Marc G. Besselink MD, MSc, PhD.

Appendices

Appendix 1

Tables 4, 5, and 6.

Table 4 Eligibility criteria for explorative laparotomy with potential IRE or resection
Full size table
Table 5 Complications according Clavien–Dindo grade ≥3 per treatment strategy
Full size table
Table 6 Survival from diagnosis of patients with non-progressive disease after 3 months FOLFIRINOX chemotherapy
Full size table

Appendix 2

Specification of adverse events per treatment category

Resection

Pt. 1:

Thrombosis SMV → re-laparotomy (thrombectomy, PV reconstruction) (grade IIIb) + fluid collection → drainage (grade IIIa).

Pt. 2:

GDE grade C → duodenal tube, total parenteral feeding (TPF) (grade IIIa).

Pt. 3:

Pancreas fistula grade B → drain (grade IIIa) + chyle leakage → TPF (grade IIIa).

Pt. 4:

Leakage hepaticojejunostomy (HJ) and gastrojejunostomy → death (grade V).

Pt. 5:

Fluid collection → drain (grade IIIa).

Nb.:

No intra-procedural complications occurred.

IRE

Pt. 1:

Pancreatic fistula/bile leak → drain (grade IIIa).

Pt. 2:

Thrombosis PV leading to liver failure → death (grade V).

Pt. 3:

Nausea → duodenal tube (grade IIIa).

Pt. 4:

DGE grade C → duodenal tube, parental feeding (TPF) (grade IIIa).

Pt. 5:

Bleeding gastric ulcer → wanted no treatment, death (grade V).

Pt. 6:

Bile leakage → drain (grade IIIa) and bleeding GDA → coil (grade IIIa).

Pt. 7:

Thrombosis PV with ascites → drain (grade IIIa) + Nausea → duodenal tube (grade IIIa).

Pt. 8:

Bile obstruction → ERCP (stent) (grade IIIa).

Nb.:

No intra-procedural complications occurred.

Palliative

Pt. 1:

Perforation → drain (grade IIIa).

Pt. 2:

Bleeding HJ → gastroscopy with clip placement (grade IIIa).

Pt. 3:

Intra-operative retroperitoneal bleeding → intraoperative management (grade IIIb).

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Vogel, J.A., Rombouts, S.J., de Rooij, T. et al. Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study. Ann Surg Oncol 24, 2734–2743 (2017). https://doi.org/10.1245/s10434-017-5900-9

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