Locally Advanced Pancreatic Cancer: Work-Up, Staging, and Local Intervention Strategies

Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence.

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Irreversible electroporation for pancreatic cancer using intraprocedural cone-beam computed tomography fusion navigation: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-03152-2 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Sriram Rao ◽

Thanh-Lan Bui ◽

Ali Sasani ◽

Ben Sadeghi ◽

Anvesh Macherla ◽

...

Keyword(s):

Computed Tomography ◽

Pancreatic Cancer ◽

Radiation Therapy ◽

Cone Beam Computed Tomography ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Cone Beam ◽

Vascular Involvement

Abstract Background Patients diagnosed with locally advanced pancreatic cancer are usually not eligible for surgical resection because of significant vascular involvement. Stereotactic body radiation therapy and chemotherapy are the treatments recommended by the National Comprehensive Cancer Network criteria. For patients who do not respond to or tolerate stereotactic body radiation therapy and/or chemotherapy, a new option is irreversible electroporation. Irreversible electroporation is a nonthermal minimally invasive ablation technique that uses electrical pulses to induce apoptosis of tumor cells without damage to the extracellular matrix, thus preserving ducts and vessels. Irreversible electroporation requires very precise needle placement, which has limited its ubiquitous use. Intraprocedural cone-beam computed tomography with navigation can be fused with previous imaging to provide real-time tumor navigation capabilities during the procedure to allow for more accurate needle placement and treatment. Here, we present a patient who underwent percutaneous irreversible electroporation with intraprocedural cone-beam computed tomography fusion guidance to treat his pancreatic cancer. Case presentation The patient, an 88-year-old White male, initially presented with abdominal pain, and was ultimately diagnosed with locally advanced pancreatic cancer. He has an excellent performance status and no other comorbidities. He was started on chemotherapy and radiation therapy, with good response. However, continued vascular involvement of the tumors precluded him from safe surgical resection. The patient underwent irreversible electroporation with intraprocedural cone-beam computed tomography fusion navigation. The primary lesion demonstrates no residual tumor, and the soft tissue involvement of the adjacent vasculature has stabilized. Conclusions Although not curative on its own, irreversible electroporation holds promise as a treatment option for patients with locally advanced pancreatic cancer to increase downsizing to curative surgery or increase quality of life. Cone-beam computed tomography navigation can improve irreversible electroporation by providing guidance during needle guidance. Image fusion with previous advanced imaging can improve lesion visualization and targeting, thereby improving the effectiveness of irreversible electroporation.

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Systematic Review of Irreversible Electroporation Role in Management of Locally Advanced Pancreatic Cancer

Cancers ◽

10.3390/cancers11111718 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1718 ◽

Cited By ~ 2

Author(s):

Stefano Lafranceschina ◽

Oronzo Brunetti ◽

Antonella Delvecchio ◽

Maria Conticchio ◽

Michele Ammendola ◽

...

Keyword(s):

Pancreatic Cancer ◽

Symptomatic Relief ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Borderline Resectable ◽

Thermal Tissue Damage ◽

Oncological Results ◽

Ablative Techniques

Background: Ablative techniques provide in patients with locally advanced pancreatic cancer (LAPC) symptomatic relief, survival benefit and potential downsizing. Irreversible Electroporation (IRE) represents potentially an ideal solution as no thermal tissue damage occurs. The purpose of this review is to present an overview on safety, feasibility, oncological results, survival and quality of life improvement obtained by IRE. Methods: A systematic search was performed in PubMed, regarding the use of IRE on PC in humans for studies published in English up to March 2019. Results: 15 original studies embodying 691 patients with unresectable LAPC who underwent IRE were included. As emerged, IRE works better on tumour sizes between 3–4 cm. Oncological results are promising: median OS from diagnosis or treatment up to 27 months. Two groups investigated borderline resectable tumours treated with IRE before resection with margin attenuation, whereas IRE has proved to be effective in pain control. Conclusions: Electroporation is bringing new hopes in LAPC management. The first aim of IRE is to offer a palliative treatment. Further efforts are needed for patient selection, as well as the use of IRE for ‘margin accentuation’ during surgical resection. Even if promising, IRE needs to be validated in large, randomized, prospective series.

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Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy

Journal of Clinical Medicine ◽

10.3390/jcm10081609 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1609

Author(s):

Zainab L. Rai ◽

Roger Feakins ◽

Laura J. Pallett ◽

Derek Manas ◽

Brian R. Davidson

Keyword(s):

Pancreatic Cancer ◽

Mechanism Of Action ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Standard Of Care ◽

Locally Advanced Pancreatic Cancer ◽

Animal Data ◽

Standard Of Care Treatment ◽

Apoptosis And Necrosis

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.

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Estimation of Clinical Outcomes of Irreversible Electroporation Use During Locally Advanced Pancreatic Cancer: A Systematic Review and Meta-analysis

ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY ◽

10.37015/audt.2018.180814 ◽

2018 ◽

Vol 2 (2) ◽

pp. 143

Author(s):

Jiang, PhD Tian’an ◽

Tian, MD Guo ◽

Wu, PhD Liming ◽

Zhao, PhD Qiyu

Keyword(s):

Systematic Review ◽

Pancreatic Cancer ◽

Clinical Outcomes ◽

Meta Analysis ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer

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Improved overall survival in patients with locally advanced pancreatic cancer undergoing neoadjuvant therapy and irreversible electroporation

HPB ◽

10.1016/j.hpb.2018.02.233 ◽

2018 ◽

Vol 20 ◽

pp. S39

Author(s):

M.D. Kluger ◽

M.F. Rashid ◽

B.A. Schrope ◽

J.A. Chabot

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer

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Intraoperative Irreversible Electroporation in Locally Advanced Pancreatic Cancer: A Guide for the Interventional Radiologist

Seminars in Interventional Radiology ◽

10.1055/s-0039-1697640 ◽

2019 ◽

Vol 36 (05) ◽

pp. 386-391

Author(s):

Gregory T. Frey ◽

Carlos A. Padula ◽

John A. Stauffer ◽

Beau B. Toskich

Keyword(s):

Pancreatic Cancer ◽

Tertiary Care ◽

Multidisciplinary Treatment ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Locoregional Therapy ◽

Systemic Treatments ◽

Tertiary Care Institution

AbstractEfforts to improve mortality associated with locally advanced pancreatic cancer (LAPC) have shown minimal gains despite advances in surgical technique, systemic treatments, and radiation therapy. Locoregional therapy with ablation has not been routinely adopted due to the high risk of complications associated with thermal destruction of the pancreas. Irreversible electroporation (IRE) is an emerging, nonthermal, ablative technology that has demonstrated the ability to generate controlled ablation of LAPC while preserving pancreatic parenchymal integrity. IRE may be performed percutaneously or via laparotomy and will commonly involve multidisciplinary treatment teams. This article will describe the technical aspects of how multidisciplinary IRE is performed during laparotomy at a single tertiary care institution.

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Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00260-1 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Mao Lin ◽

Xiaoyan Zhang ◽

Shuzhen Liang ◽

Haihua Luo ◽

Mohammed Alnaggar ◽

...

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

T Cell ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Antitumor Efficacy ◽

Γδ T Cell ◽

Group A

Abstract Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits. ClinicalTrials.gov ID: NCT03180437.

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