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. 2022 Jan 13:11:817220.
doi: 10.3389/fonc.2021.817220. eCollection 2021.

Optimizing Patient Selection for Irreversible Electroporation of Locally Advanced Pancreatic Cancer: Analyses of Survival

Matthew R Woeste  1 , Khaleel D Wilson  1 , Edward J Kruse  2 , Matthew J Weiss  3 , John D Christein  4 , Rebekah R White  5 , Robert C G Martin 2nd  1
Affiliations

Optimizing Patient Selection for Irreversible Electroporation of Locally Advanced Pancreatic Cancer: Analyses of Survival

Matthew R Woeste et al. Front Oncol. .

Abstract

Background: Irreversible electroporation (IRE) has emerged as a viable consolidative therapy after induction chemotherapy, in which this combination has improved overall survival of locally advanced pancreatic cancer (LAPC). Optimal timing and patient selection for irreversible electroporation remains a clinically unmet need. The aim of this study was to investigate preoperative factors that may assist in predicting progression-free and overall survival following IRE.

Methods: A multi-institutional, prospectively maintained database was reviewed for patients with LAPC treated with induction chemotherapy followed by open-technique irreversible electroporation from 7/2015-5/2019. RECIST 1.1 criteria were used to assess tumor response and radiological progression. Overall survival (OS) and progression-free survival (PFS) were recorded. Survival analyses were performed using Kaplan Meier and Cox multivariable regression analyses.

Results: 187 LAPC patients (median age 62 years range, 21 - 91, 65% men, 35% women) were treated with IRE. Median PFS was 21.7 months and median OS from diagnosis was 25.5 months. On multivariable analysis, age ≤ 61 (HR 0.41, 95%CI 0.21-0.78, p<0.008) and no prior radiation (HR 0.49, 95%CI 0.26-0.94, p=0.03) were positive predictors of OS after IRE. Age ≤ 61(HR 0.53, 95%CI, 0.28-.99, p=0.046) and FOLFIRINOX followed by gemcitabine/abraxane induction chemotherapy (HR 0.37,95%CI 0.15-0.89, p=0.027) predicted prolonged PFS after IRE. Abnormal CA19-9 values at the time of surgery negatively impacted both OS (HR 2.46, 95%CI 1.28-4.72, p<0.007) and PFS (HR 2.192, 95%CI 1.143-4.201, p=0.018) following IRE.

Conclusions: Age, CA 19-9 response, avoidance of pre-IRE radiation, and FOLFIRINOX plus gemcitabine/abraxane induction chemotherapy are prominent factors to consider when referring or selecting LAPC patients to undergo IRE.

Keywords: irreversible electroporation (IRE); locally advanced pancreatic cancer; overall survival; patient selection; progression free survival; recurrence.

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Conflict of interest statement

RM II, MD, PhD, FACS is an educational consultant for AngioDynamics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Independent predictors of overall survival from diagnosis. (A) Overall survival comparison by change in CA19-9 status from diagnosis to IRE. (B) Overall survival comparison by induction chemotherapy duration.
Figure 2
Figure 2
Independent predictors of overall and progression free survival from IRE. (A) Overall survival comparison by age. (B) Overall survival comparison by prior radiation history. (C) Progression free survival comparison by age. (D) Progression free survival comparison stratified by induction chemotherapy. (E) Overall survival comparison by CA19-9 status at IRE. (F) Progression free survival comparison of CA19-9 status from diagnosis to IRE.
Figure 3
Figure 3
Patient selection algorithm. A) Optimal patient selection criteria: Age ≤ 61, normalized CA19-9 at IRE, tumor size < 3.6cm, ≤ 180° vascular involvement, less than 2 co-morbidities, and those without diabetes mellitus. B) Can continue FOLFIRINOX (per PRODIGE trial). Chemotherapy goal 12 cycles of FOLFIRINOX, 18 total doses gemcitabine/abraxane.
See this image and copyright information in PMC

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