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Campelo SN, Huang PH, Buie CR, Davalos RV. Recent Advancements in Electroporation Technologies: From Bench to Clinic. Annu Rev Biomed Eng 2023; 25:77-100. [PMID: 36854260 PMCID: PMC11633374 DOI: 10.1146/annurev-bioeng-110220-023800] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
Over the past decade, the increased adoption of electroporation-based technologies has led to an expansion of clinical research initiatives. Electroporation has been utilized in molecular biology for mammalian and bacterial transfection; for food sanitation; and in therapeutic settings to increase drug uptake, for gene therapy, and to eliminate cancerous tissues. We begin this article by discussing the biophysics required for understanding the concepts behind the cell permeation phenomenon that is electroporation. We then review nano- and microscale single-cell electroporation technologies before scaling up to emerging in vivo applications.
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Affiliation(s)
- Sabrina N Campelo
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, USA;
| | - Po-Hsun Huang
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Cullen R Buie
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Rafael V Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, USA;
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2
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Spiliopoulos S, Reppas L, Filippiadis D, Delvecchio A, Conticchio M, Memeo R, Inchingolo R. Irreversible electroporation for the management of pancreatic cancer: Current data and future directions. World J Gastroenterol 2023; 29:223-231. [PMID: 36687122 PMCID: PMC9846938 DOI: 10.3748/wjg.v29.i2.223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/13/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Pancreatic cancer is currently the seventh leading cause of cancer death (4.5% of all cancer deaths) while 80%-90% of the patients suffer from unresectable disease at the time of diagnosis. Prognosis remains poor, with a mean survival up to 15 mo following systemic chemotherapy. Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures, which can lead to severe adverse events. Irreversible electroporation, a promising novel non-thermal ablative modality, has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option. Experimental and initial clinical data are optimistic. This review will focus on the basic principles of IRE technology, currently available data, and future directions.
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Affiliation(s)
- Stavros Spiliopoulos
- Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens 12461, Attiki, Greece
| | - Lazaros Reppas
- Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens 12461, Attiki, Greece
| | - Dimitrios Filippiadis
- Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens 12461, Attiki, Greece
| | - Antonella Delvecchio
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Bari, Italy
| | - Maria Conticchio
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Bari, Italy
| | - Riccardo Memeo
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Bari, Italy
| | - Riccardo Inchingolo
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
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Simultaneous Gemcitabine and Percutaneous CT-Guided Irreversible Electroporation for Locally Advanced Pancreatic Cancer. JOURNAL OF ONCOLOGY 2022; 2022:3523769. [PMID: 35747123 PMCID: PMC9213186 DOI: 10.1155/2022/3523769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/19/2022] [Accepted: 05/21/2022] [Indexed: 11/24/2022]
Abstract
Background Irreversible electroporation (IRE) is a new local ablation technique for pancreatic cancer. The aim of this study is to analyse the safety and effectiveness of simultaneous gemcitabine and percutaneous CT-guided IRE for locally advanced pancreatic cancer (LAPC). Materials and Methods From October 2016 to January 2018, 61 patients with LAPC who received simultaneous gemcitabine and IRE therapy (GEM-IRE group, n = 31) or IRE alone therapy (IRE group, n = 30). Routine intravenous gemcitabine chemotherapy was performed 2 weeks after IRE in both groups. Results Technical success rates were 90.0% (27/30) and 93.3% (28/30) in the GEM-IRE and IRE groups. Compared with the IRE group, the GEM-IRE group exhibited longer overall survival (OS), local tumor progression free survival (LTPFS), and distant disease free survival (DDFS) from IRE (OS, 17.1 vs. 14.2 months, p=0.031; LTPFS, 14.6 vs. 10.2 months, p=0.045; DDFS, 15.4 vs. 11.7 months, p=0.071). Multivariate Cox regression analysis results suggested that tumor volume ≤37 cm3 and simultaneous gemcitabine with IRE were significant independent prognostic factors of OS, LTPFS, and DDFS. Four major adverse reactions occurred; all of them were resolved after symptomatic treatment. Conclusions Simultaneous gemcitabine and percutaneous CT-guided IRE therapy model was effective and well-tolerated therapeutic strategy in LAPC patients.
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Rai ZL, Ranieri V, Palmer DH, Littler P, Ghaneh P, Gurusamy K, Manas D, Pizzo E, Psarelli EE, Gilmore R, Peddu P, Bartlett DC, de Liguori Carino N, Davidson BR. Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial. BMJ Open 2022; 12:e050166. [PMID: 35551086 PMCID: PMC9109032 DOI: 10.1136/bmjopen-2021-050166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 01/17/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency. ETHICS AND DISSEMINATION The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER ISRCTN14986389.
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Affiliation(s)
- Zainab L Rai
- Division of Surgery and Interventional Science, University College London, London, UK
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS), London, UK
| | - Veronica Ranieri
- Research & Development, Tavistock and Portman NHS Foundation Trust, London, UK
- Science & Technology Studies, University College London, London, UK
| | - Daniel H Palmer
- Hepato-Pancreatco-Biliary Disease, University of Liverpool, Liverpool, Merseyside, UK
| | - Peter Littler
- Hepato-Pancreatico-Biliary Surgery, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Pauleh Ghaneh
- Hepato-Pancreatco-Biliary Disease, University of Liverpool, Liverpool, Merseyside, UK
| | - Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Derek Manas
- Hepato-Pancreatico-Biliary Surgery, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK
| | - Elena Pizzo
- Applied Health Research, University College London, London, UK
| | | | - Roopinder Gilmore
- Division of Surgery and Interventional Science, University College London, London, UK
- Oncology, Royal Free London NHS Foundation Trust, London, UK
| | - Praveen Peddu
- Department of Radiology, King's College Hospital NHS Trust, London, UK
| | - David C Bartlett
- Hepato-Pancreatico-Biliary Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, UK
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Sugumar K, Hurtado A, Naik I, Hue JJ, Rothermel LD, Ammori JB, Hardacre JM, Winter JM, Ocuin LM. Multimodal therapy with or without irreversible electroporation for unresectable locally advanced pancreatic adenocarcinoma: a systematic review and meta-analysis. HPB (Oxford) 2022; 24:586-595. [PMID: 35000842 DOI: 10.1016/j.hpb.2021.12.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 10/29/2021] [Accepted: 12/20/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Irreversible electroporation (IRE) is used as a locoregional treatment modality for patients with locally advanced pancreatic cancer (LAPC), but is non-curative and is associated with postoperative morbidity and mortality. We performed a systematic review and meta-analysis comparing survival outcomes of multimodal therapy with or without IRE. METHODS Separate searches were performed for multimodal therapy + IRE and multimodal therapy alone given the lack of comparative literature using PubMed, SCOPUS, and Cochrane Library in 3/2021. We determined overall survival (OS) and progression-free survival (PFS) from diagnosis and time of IRE. Treatment-related morbidity and mortality was determined. RESULTS Of 585 published articles, 48 met inclusion criteria for IRE (n = 27) and without IRE (n = 21) with data for 1420 (IRE) and 1348 (without IRE) patients. The 6/12/24 months OS with IRE was 99%/84%/28%. The 6/12/24 months OS without IRE was 99%/80%/12%. At 12 months from IRE, OS was 55% and PFS was 12%. The mean major complication and 90-day mortality rates for IRE were 17.95% and 2.65%. CONCLUSION Multimodal therapy alone is associated with similar OS to multimodal therapy + IRE in patients with LAPC. Most patients progress and nearly half die within 1 year of the IRE procedure. Given the lack of quality prospective data, IRE should remain experimental and be used with caution in LAPC.
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Affiliation(s)
- Kavin Sugumar
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Alex Hurtado
- Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center, Cleveland, OH, USA
| | - Ilora Naik
- Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center, Cleveland, OH, USA
| | - Jonathan J Hue
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Luke D Rothermel
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - John B Ammori
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Jordan M Winter
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA
| | - Lee M Ocuin
- University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH, USA.
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Sugumar K, Hue JJ, Hardacre JM, Ammori JB, Rothermel LD, Dorth J, Saltzman J, Mohamed A, Selfridge JE, Bajor D, Winter JM, Ocuin LM. Combined multiagent chemotherapy and radiotherapy is associated with prolonged overall survival in patients with non-operatively managed stage II-III pancreatic adenocarcinoma. HPB (Oxford) 2022; 24:433-442. [PMID: 34465529 DOI: 10.1016/j.hpb.2021.08.938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 07/25/2021] [Accepted: 08/06/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Most patients with pancreatic adenocarcinoma (PDAC) do not undergo surgical resection. The role of radiotherapy (RT) in non-operatively managed localized pancreatic adenocarcinoma is unclear. METHODS The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III PDAC treated with multiagent systemic chemotherapy (CT) +/- RT but not surgery. Factors associated with the receipt of RT and overall survival were compared after adjusting for patient demographics and clinical characteristics. RESULTS A total of 14,921 patients were included, of whom 9279 received CT and 5382 received CT + RT. Patients treated with CT + RT were more likely to be younger (65vs66yrs), treated at non-academic facilities (48.8%vs46.7%), have private insurance (40.3%vs36.5%), and have clinical T4 tumors (53.6%vs48.7%). Most patients who were treated with RT received external beam radiotherapy (89.3%), and the median dose was 5,000 cGy. Median time to start of RT was 129 days. CT + RT was associated with longer overall survival (15.9vs11.8mos,p < 0.001), and remained associated with survival on multivariable analysis (HR 0.74, 95%CI 0.70-0.78). On a 4-month conditional survival analysis, combined CT + RT remained associated with improved survival compared to CT alone (16.0vs13.1mos,p < 0.001). CONCLUSIONS In patients with non-operatively managed localized pancreatic adenocarcinoma, combined radiotherapy and multiagent systemic chemotherapy is associated with improved overall survival compared to chemotherapy alone.
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Affiliation(s)
- Kavin Sugumar
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jonathan J Hue
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - John B Ammori
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Luke D Rothermel
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jennifer Dorth
- Department of Radiology, Division of Radiation Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Joel Saltzman
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Amr Mohamed
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jennifer E Selfridge
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - David Bajor
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jordan M Winter
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Lee M Ocuin
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
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Hall WA, Erickson B, Crane CH. Evolving Concepts Regarding Radiation Therapy for Pancreatic Cancer. Surg Oncol Clin N Am 2021; 30:719-730. [PMID: 34511192 PMCID: PMC8462521 DOI: 10.1016/j.soc.2021.06.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
In todays practice most institutions individualize the use of adjuvant, neoadjuvant, and definitive RT based on their interpretation of the available data. This review highlights novel concepts and approaches to the use of RT that should be considered by the surgical oncologist.
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Affiliation(s)
- William A Hall
- Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, 8701 West Watertown Plank Road, Milwaukee, WI 53226, USA; Graduate School of Biomedical Sciences, Medical College of Wisconsin; Department of Surgery, Froedtert and the Medical College of Wisconsin.
| | - Beth Erickson
- Department of Radiation Oncology, Froedtert and the Medical College of Wisconsin, 8701 West Watertown Plank Road, Milwaukee, WI 53226, USA; Department of Surgery, Froedtert and the Medical College of Wisconsin
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Bibok A, Kim DW, Malafa M, Kis B. Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer. World J Gastroenterol 2021; 27:4322-4341. [PMID: 34366607 PMCID: PMC8316906 DOI: 10.3748/wjg.v27.i27.4322] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/21/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is a challenging malignancy with limited treatment options and poor life expectancy. The only curative option is surgical resection, but only 15%-20% of patients are resectable at presentation because more than 50% of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer (LAPC). The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation therapy. Recent developments in minimally invasive ablative techniques may add to the treatment armamentarium of LAPC. There are increasing number of studies evaluating these novel ablative techniques, including radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation. Most studies which included pancreatic tumor ablation, demonstrated improved overall survival in LAPC patients. However, the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment combinations. Patients with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%. The most common metastatic site is the liver as 90% of pancreatic cancer patients develop liver metastasis. Chemotherapy is the primary treatment option for patients with metastatic pancreatic cancer. However, when the tumor is not responding to chemotherapy or severe drug toxicity develops, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected patients. During the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer patients. These new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these procedures. This review summarizes new ablative options for patients with LAPC and percutaneous liver-directed therapies for patients with liver-dominant metastatic disease.
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Affiliation(s)
- Andras Bibok
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
- Department of Transplantation & Surgery, Radiology Unit, Semmelweis University, Budapest 1085, Hungary
| | - Dae Won Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
| | - Mokenge Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
| | - Bela Kis
- Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, United States
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Timmer FE, Geboers B, Nieuwenhuizen S, Schouten EA, Dijkstra M, de Vries JJ, van den Tol MP, de Gruijl TD, Scheffer HJ, Meijerink MR. Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy. Curr Oncol Rep 2021; 23:68. [PMID: 33864144 PMCID: PMC8052234 DOI: 10.1007/s11912-021-01057-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/11/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms, bearing a terrible prognosis. Stage III tumors, also known as locally advanced pancreatic cancer (LAPC), are unresectable, and current palliative chemotherapy regimens have only modestly improved survival in these patients. At this stage of disease, interventional techniques may be of value and further prolong life. The aim of this review was to explore current literature on locoregional percutaneous management for LAPC. RECENT FINDINGS Locoregional percutaneous interventional techniques such as ablation, brachytherapy, and intra-arterial chemotherapy possess cytoreductive abilities and have the potential to increase survival. In addition, recent research demonstrates the immunomodulatory capacities of these treatments. This immune response may be leveraged by combining the interventional techniques with intra-tumoral immunotherapy, possibly creating a durable anti-tumor effect. This multimodality treatment approach is currently being examined in several ongoing clinical trials. The use of certain interventional techniques appears to improve survival in LAPC patients and may work synergistically when combined with immunotherapy. However, definitive conclusions can only be made when large prospective (randomized controlled) trials confirm these results.
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Affiliation(s)
- Florentine E.F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Evelien A.C. Schouten
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Jan J.J. de Vries
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - M. Petrousjka van den Tol
- Department of Surgical Oncology, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Tanja D. de Gruijl
- Department of Medical Oncology, Amsterdam UMC (location VUmc)-Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC (location VUmc), De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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Rai ZL, Feakins R, Pallett LJ, Manas D, Davidson BR. Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy. J Clin Med 2021; 10:1609. [PMID: 33920118 PMCID: PMC8068938 DOI: 10.3390/jcm10081609] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 04/04/2021] [Accepted: 04/07/2021] [Indexed: 12/11/2022] Open
Abstract
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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Affiliation(s)
- Zainab L. Rai
- Centre of Surgical Innovation, Organ Regeneration and Transplantation, University College London (UCL), London NW3 2QG, UK;
- Wellcome/EPSRC Center for Interventional and Surgical Sciences (WEISS), London W1W 7TY, UK
- Royal Free NHS Foundation Trust, London NW3 2QG, UK;
| | - Roger Feakins
- Royal Free NHS Foundation Trust, London NW3 2QG, UK;
| | - Laura J. Pallett
- Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London WC1E 6BT, UK;
| | - Derek Manas
- Newcastle Upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne NE7 7DN, UK;
| | - Brian R. Davidson
- Centre of Surgical Innovation, Organ Regeneration and Transplantation, University College London (UCL), London NW3 2QG, UK;
- Royal Free NHS Foundation Trust, London NW3 2QG, UK;
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11
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Klose J, Ronellenfitsch U, Kleeff J. Management problems in patients with pancreatic cancer from a surgeon's perspective. Semin Oncol 2021; 48:76-83. [PMID: 34059343 DOI: 10.1053/j.seminoncol.2021.02.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/18/2021] [Accepted: 02/02/2021] [Indexed: 12/25/2022]
Abstract
Pancreatic cancer is one of the most lethal gastrointestinal tumor entities. Surgery is the only chance for cure; however, only a minority of patients can be offered this option. Due to the anatomic location of the gland, tumor-related problems and complications affecting the surrounding structures are common, leading to biliary and gastric outlet obstruction as well as portal vein thrombosis. This review article summarizes the management of pancreatic cancer-related problems from a surgical point of view. We further describe surgical treatment options in unresectable, metastasized and recurring pancreatic cancer, highlighting potential resection of oligometastatic disease in selected settings.
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Affiliation(s)
- Johannes Klose
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University, Halle-Wittenberg, Halle, Germany
| | - Ulrich Ronellenfitsch
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University, Halle-Wittenberg, Halle, Germany
| | - Jörg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University, Halle-Wittenberg, Halle, Germany.
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Ma YY, Leng Y, Xing YL, Li HM, Chen JB, Niu LZ. Gemcitabine plus concurrent irreversible electroporation vs gemcitabine alone for locally advanced pancreatic cancer. World J Clin Cases 2020; 8:5564-5575. [PMID: 33344547 PMCID: PMC7716311 DOI: 10.12998/wjcc.v8.i22.5564] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 08/25/2020] [Accepted: 09/26/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Locally advanced pancreatic cancer (LAPC) is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world. The prognosis of LAPC is poor even after standard treatment. Irreversible electroporation (IRE) is a novel ablative strategy for LAPC. Several studies have confirmed the safety of IRE. To date, no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine (GEM) plus concurrent IRE. AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC. METHODS From February 2016 to September 2017, a total of 68 LAPC patients were treated with GEM plus concurrent IRE n = 33) or GEM alone n = 35). Overall survival (OS), progression free survival (PFS), and procedure-related complications were compared between the two groups. Multivariate analyses were performed to identify any prognostic factors. RESULTS There were no treatment-related deaths. The technical success rate of IRE ablation was 100%. The GEM + IRE group had a significantly longer OS from the time of diagnosis of LAPC (19.8 mo vs 9.3 mo, P < 0.0001) than the GEM alone group. The GEM + IRE group had a significantly longer PFS (8.3 mo vs 4.7 mo, P < 0.0001) than the GEM alone group. Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS. CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.
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Affiliation(s)
- Yang-Yang Ma
- Central Laboratory, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Yin Leng
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Yan-Li Xing
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Hong-Mei Li
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Ji-Bing Chen
- Central Laboratory, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
| | - Li-Zhi Niu
- Department of Interventional Radiology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, Guangdong Province, China
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Hu C, Li M. In advanced pancreatic cancer: The value and significance of interventional therapy. J Interv Med 2020; 3:118-121. [PMID: 34805920 PMCID: PMC8562155 DOI: 10.1016/j.jimed.2020.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Pancreatic cancer is famous as “the king of cancer” due to its high degree of malignancy, rapid course of disease development, and poor prognosis. Relevant epidemiological studies have indicated that with improvement in people’s standard of living, the morbidity and mortality of pancreatic cancer has increased. At the same time, the disease shows an obvious upward trend worldwide. Pancreatic cancer has become a major public health problem that seriously affects the life and health of people. The present review focuses on the recent advances in interventional therapy such as transcatheter arterial infusion, radiofrequency ablation, microwave ablation, and irreversible electroporation of pancreatic cancer.
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Affiliation(s)
- Chao Hu
- Tongji University School of Medicine, No. 1239 Si Ping Road, Shanghai, 200082, China
| | - Maoquan Li
- Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No. 301 Middle Yan Chang Road, Shanghai, 200072, China.,Institute of Interventional & Vascular Surgery, Tongji University, No. 301 Middle Yan Chang Road, Shanghai, 200072, China
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14
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Timmer FEF, Geboers B, Ruarus AH, Schouten EAC, Nieuwenhuizen S, Puijk RS, de Vries JJJ, Meijerink MR, Scheffer HJ. Irreversible Electroporation for Locally Advanced Pancreatic Cancer. Tech Vasc Interv Radiol 2020; 23:100675. [PMID: 32591191 DOI: 10.1016/j.tvir.2020.100675] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Several minimally invasive image guided tumor ablation techniques have been added to the treatment spectrum for locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) might have a significant additive value in the management of this difficult-to-treat disease. As opposed to thermal ablative techniques, IRE induces cell death by the delivery of high-voltage electrical pulses. The electrical energy disrupts the cellular membrane integrity, causes loss of cellular homeostasis and ultimately results in cell death. The extracellular matrix of connective tissue in surrounding delicate structures such as bile ducts, bowel wall, and larger blood vessels is spared. The preservation of these structures makes IRE attractive for the treatment of pancreatic cancers that are unresectable due to their anatomical location (ie, LAPC and local recurrence after surgical resection). In addition to its cytoreductive abilities, evidence is emerging on IRE's capability to induce systemic immunomodulation through active in vivo vaccination against pancreatic cancer cells. These effects in combination with immunotherapy may offer a new treatment paradigm for tumors with low immunogenic potential like pancreatic ductal adenocarcinoma (PDAC). This review discusses several practical and technical issues of IRE for LAPC: clinical evaluation, indications, patient preparations, procedural steps, imaging characteristics, clinical results, and "tricks of the trade" used to improve the safety and efficacy of the treatment. Future directions such as the combination of IRE with immunotherapy will be shortly addressed.
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Affiliation(s)
- Florentine E F Timmer
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands.
| | - Alette H Ruarus
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Evelien A C Schouten
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Robbert S Puijk
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Jan J J de Vries
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Martijn R Meijerink
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
| | - Hester J Scheffer
- Department of Radiology and Nuclear Medicine at the Amsterdam University Medical Center, Vrije Universiteit-Cancer Center Amsterdam in Amsterdam, The Netherlands
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Geboers B, Scheffer HJ, Graybill PM, Ruarus AH, Nieuwenhuizen S, Puijk RS, van den Tol PM, Davalos RV, Rubinsky B, de Gruijl TD, Miklavčič D, Meijerink MR. High-Voltage Electrical Pulses in Oncology: Irreversible Electroporation, Electrochemotherapy, Gene Electrotransfer, Electrofusion, and Electroimmunotherapy. Radiology 2020; 295:254-272. [PMID: 32208094 DOI: 10.1148/radiol.2020192190] [Citation(s) in RCA: 197] [Impact Index Per Article: 39.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
This review summarizes the use of high-voltage electrical pulses (HVEPs) in clinical oncology to treat solid tumors with irreversible electroporation (IRE) and electrochemotherapy (ECT). HVEPs increase the membrane permeability of cells, a phenomenon known as electroporation. Unlike alternative ablative therapies, electroporation does not affect the structural integrity of surrounding tissue, thereby enabling tumors in the vicinity of vital structures to be treated. IRE uses HVEPs to cause cell death by inducing membrane disruption, and it is primarily used as a radical ablative therapy in the treatment of soft-tissue tumors in the liver, kidney, prostate, and pancreas. ECT uses HVEPs to transiently increase membrane permeability, enhancing cellular cytotoxic drug uptake in tumors. IRE and ECT show immunogenic effects that could be augmented when combined with immunomodulatory drugs, a combination therapy the authors term electroimmunotherapy. Additional electroporation-based technologies that may reach clinical importance, such as gene electrotransfer, electrofusion, and electroimmunotherapy, are concisely reviewed. HVEPs represent a substantial advancement in cancer research, and continued improvement and implementation of these presented technologies will require close collaboration between engineers, interventional radiologists, medical oncologists, and immuno-oncologists.
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Affiliation(s)
- Bart Geboers
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Hester J Scheffer
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Philip M Graybill
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Alette H Ruarus
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Sanne Nieuwenhuizen
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Robbert S Puijk
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Petrousjka M van den Tol
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Rafael V Davalos
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Boris Rubinsky
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Tanja D de Gruijl
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Damijan Miklavčič
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
| | - Martijn R Meijerink
- From the Departments of Radiology and Nuclear Medicine (B.G., H.J.S., A.H.R., S.N., R.S.P., M.R.M.), Surgery (P.M.v.d.T.), and Medical Oncology (T.D.d.G.), Amsterdam University Medical Centers, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands; Bioelectromechanical Systems Laboratory, Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Va (P.M.G., R.V.D.); Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, Calif (B.R.); and Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia (D.M.)
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Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy. Case Rep Gastrointest Med 2020; 2020:4138215. [PMID: 32099693 PMCID: PMC7016399 DOI: 10.1155/2020/4138215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 01/07/2020] [Accepted: 01/13/2020] [Indexed: 11/25/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.
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Aycock KN, Davalos RV. Irreversible Electroporation: Background, Theory, and Review of Recent Developments in Clinical Oncology. Bioelectricity 2019; 1:214-234. [PMID: 34471825 PMCID: PMC8370296 DOI: 10.1089/bioe.2019.0029] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Irreversible electroporation (IRE) has established a clinical niche as an alternative to thermal ablation for the eradication of unresectable tumors, particularly those near critical vascular structures. IRE has been used in over 50 independent clinical trials and has shown clinical success when used as a standalone treatment and as a single component within combinatorial treatment paradigms. Recently, many studies evaluating IRE in larger patient cohorts and alongside other novel therapies have been reported. Here, we present the basic principles of reversible electroporation and IRE followed by a review of preclinical and clinical data with a focus on tumors in three organ systems in which IRE has shown great promise: the prostate, pancreas, and liver. Finally, we discuss alternative and future developments, which will likely further advance the use of IRE in the clinic.
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Affiliation(s)
- Kenneth N Aycock
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Virginia
| | - Rafael V Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, Virginia
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