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

Abstract

BackgroundIrreversible 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.MethodsA 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.Results187 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.ConclusionsAge, 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.

Treatment of pancreatic cancer with irreversible electroporation and intratumoral CD40 antibody stimulates systemic immune responses that inhibit liver metastasis in an orthotopic model

“…7 Specific to PC, the acellular structural components of blood vessels are not damaged by IRE, 8 which permits safe treatment of tumors with vascular involvement. Multiple individual institutions [9][10][11] and a few multicenter studies [12][13][14][15] have published clinical experiences with IRE for locally advanced PC. These nonrandomized studies suggest that IRE is associated with longer survival than standard therapy alone.…”

Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies

“…To optimize the patient criteria for IRE, a recent multi-institutional study concluded that patients with normal Carbohydrate Antigen 19-9 levels before surgery and avoiding radiation therapy before IRE, in addition to administering FOLFIRINOX plus GEM or abraxane induction chemotherapy, are good interpreters of better survival rate after IRE [ 196 ]. Moreover, IRE is contraindicated with cardiac arrhythmia pacemakers [ 179 ].…”

Irreversible electroporation of the pancreas – A decade on

“…Patient selection for IRE is essential. 23 , 24 , 25 Narayanan proposed that patients should be reviewed in a multidisciplinary tumour board to determine if they are suitable candidates for IRE. 23 Some proposed criteria include having an Eastern Cooperative Oncology Group (ECOG) status of 0–1, with Stage 3 LAPC or low volume Stage 4 metastatic disease that has been stable over time.…”

“…The authors found that younger patients (60 years and below), patients without more than two comorbidities, and patients without diabetes display superior post-IRE outcomes. 24 On top of these, anatomic tumour characteristics need to be considered, with smaller tumours generally having prolonged survival outcomes. Vascular involvement of ≤180° of their affected structure is also more likely to have significantly longer overall survival.…”