Electrochemotherapy with Irreversible Electroporation and FOLFIRINOX Improves Survival in Murine Models of Pancreatic Adenocarcinoma

Bhutiani, Neal; Li, Yan; Zheng, Qianqian; Pandit, Harshul; Shi, Xiaorui; Chen, Yujia; Yu, Youxi; Pulliam, Zachary; Tan, Min; Martin, Robert C.G.

doi:10.1245/s10434-020-08782-2

Cited by 15 publications

(9 citation statements)

References 27 publications

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“…44 Finally, there is an emerging body of literature supporting synergistic antitumor activity of combined IRE +chemotherapy, under the term "electrochemotherapy," that shows superiority of the combined treatment compared with either treatment modality used alone in terms of increased tumor cell apoptosis and decreased tumor cell proliferation and improved OS in patients with LAPC. [45][46][47][48][49] The current study had several limitations. Given the nature of retrospective data analysis, this study is nonetheless subject to bias.…”

Section: Discussionmentioning

confidence: 92%

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC)

Oikonomou

Karamouzis

Moris

et al. 2021

American Journal of Clinical Oncology

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Objectives: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy.Materials and Methods: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy.Results: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have > 24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. Conclusion:The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.

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Section: Discussionmentioning

confidence: 92%

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC)

Oikonomou

Karamouzis

Moris

et al. 2021

American Journal of Clinical Oncology

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“…Furthermore, the delivery of electroporation with these chemotherapeutics (i.e. electrochemotherapy) improves the delivery of such agents to a complex tumor microenvironment (TME) with synergistic anti-tumor activity ( 70 , 71 ). With respect to radiation, use of radiotherapy in the setting of LAPC has historically been controversial, however current NCCN guidelines recommend its use.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…30 In the last 10 years, several studies have been conducted to evaluate the potential adjunctive role of ECT and IRE in patients affected by locally advanced pancreatic cancer, who currently have a poor prognosis, with a 5-year survival rate of approximately 12%. 31 Preclinical studies were performed to evaluate ECT's role: the results of an animal study conducted on 10 mice with orthotropic human pancreatic carcinoma suggested that ECT might allow increased drug delivery in tumor cells, increasing gemcitabine efficacy and potentially reducing local tumor recurrence. 32 IRE's role has been evaluated in clinical studies: results of a multicenter prospective trial published in 2014 conducted on 200 patients with pancreatic can-cer demonstrated that the addition of irreversible electroporation (IRE) to systemic chemotherapy could prolong survival.…”

Section: Literature Reviewmentioning

confidence: 99%

Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach

Schipilliti

Onorato²,

Arrivi

et al. 2022

Radiology and Oncology

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Background Electrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected. Conclusions Clinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life.

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Electrochemotherapy with Irreversible Electroporation and FOLFIRINOX Improves Survival in Murine Models of Pancreatic Adenocarcinoma

Cited by 15 publications

References 27 publications

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC)

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC)

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

Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach

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