|
1
|
Carrion-Alvarez L, Primavesi F, Søreide K, Sochorova D, Diaz-Nieto R, Dopazo C, Serrablo A, Edhemovic I, Stättner S. Liver metastases from colorectal cancer: A joint ESSO-EAHPBA-UEMS core curriculum collaboration. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109728. [PMID: 40023020 DOI: 10.1016/j.ejso.2025.109728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 02/22/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025]
Abstract
Colorectal liver metastases (CRLM) are a major indication for liver surgery in Europe, highlighting the need for standardized knowledge and training in surgical oncology. The European Society of Surgical Oncology (ESSO) has updated its core curriculum to provide a structured framework for education. Previous publications have addressed pancreatic, hepatocellular, and biliary tract cancers to support candidates preparing for the European Board of Surgery Qualification (EBSQ) exams in Surgical Oncology and Hepato-Pancreato-Biliary Surgery. However, a dedicated guide for CRLM remains absent. This article aims to fill that gap by offering a structured reference on CRLM, covering epidemiology, staging, genetics, and diagnosis of metastatic colorectal cancer. It also outlines multidisciplinary treatment strategies, including systemic, surgical, interventional, and palliative approaches. A structured literature review was conducted using PubMed to identify the most updated (inter)national management guidelines, prioritizing recent multicentre studies, systematic reviews, and meta-analyses published from January 2020 to January 2025. By bridging the gap between the ESSO core curriculum and detailed subspecialty training, this guide provides an essential resource for hepatobiliary surgeons and surgical oncologists. It serves as a valuable tool for those preparing for board examinations while promoting a standardized approach to CRLM education and management across Europe.
Collapse
Affiliation(s)
- Lucia Carrion-Alvarez
- HPB Unit, General Surgery Department, Fuenlabrada University Hospital, Madrid, Spain.
| | - Florian Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Dana Sochorova
- Department of Surgery, Tomas Bata Hospital Zlin, Czech Republic
| | - Rafael Diaz-Nieto
- Hepatobiliary Surgery Unit, Liverpool University Hospital, Liverpool, UK
| | - Cristina Dopazo
- Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain
| | | | - Ibrahim Edhemovic
- Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia; Faculty of Medicine Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - Stefan Stättner
- Johannes Kepler University Linz, Kepler University Hospital GmbH, Department of General and Visceral Surgery, Hepatobiliary Unit, Krankenhausstrasse 9, 4021, Linz, Austria
| |
Collapse
|
|
2
|
Wang LH, Jiang Y, Sun CH, Chen PT, Ding YN. Advancements in the application of ablative therapy and its combination with immunotherapy in anti-cancer therapy. Biochim Biophys Acta Rev Cancer 2025; 1880:189285. [PMID: 39938664 DOI: 10.1016/j.bbcan.2025.189285] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/02/2025] [Accepted: 02/04/2025] [Indexed: 02/14/2025]
Abstract
Cancer is a significant health issue impacting humans. Currently, systemic therapies such as chemotherapy have significantly increased the life expectancy of cancer patients. However, some patients are unable to endure systemic treatment due to its significant adverse effects, leading to an increased focus on local therapies including radiation and ablation therapy. Ablation therapy is a precise, low-toxicity, and minimally invasive localized therapy that is increasingly acknowledged by clinicians and cancer patients. Many cancer patients have benefited from it, with some achieving full recovery. Currently, numerous studies have shown that ablation therapy is effective due to its ability to kill cancer cells efficiently and activate the body's anti-cancer immunity. It can also convert "cold cancers" into "hot cancers" and enhance the effectiveness of immunotherapy when used in combination. In this article, we categorize ablation therapy into thermal ablation, cryoablation, photodynamic therapy (PDT), irreversible electroporation (IRE), etc. Thermal ablation is further divided into Radiofrequency ablation (RFA), microwave ablation (WMA), high-frequency focused ultrasound (HIFU), photothermal therapy (PTT), magnetic heat therapy (MHT), etc. We systematically review the most recent advancements in these ablation therapies that are either currently used in clinic or are anticipated to be used in clinic. Then, we also review the latest development of various ablative therapies combined with immunotherapy, and its future development. CLINICAL RELEVANCE STATEMENT: Ablation therapy, an invasive localized treatment, offers an alternative to systemic therapies for cancer patients who cannot tolerate their adverse effects. Its ability to kill cancer cells efficiently and activate anti-cancer immunity. This article reviews recent advancements in ablation therapies, including thermal, cryoablation, PDT, and IRE, and their potential clinical applications, both standalone and in combination with immunotherapy.
Collapse
Affiliation(s)
- Lu-Hong Wang
- Department of Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Center of Interventional Radiology & Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China; State Key Laboratory of Digital Medical Engineering, National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210009, China
| | - Yi Jiang
- Department of Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Key Laboratory of Imaging and Interventional Medicine, Hangzhou, Zhejiang 310022, China; Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Chen-Hang Sun
- Department of Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Key Laboratory of Imaging and Interventional Medicine, Hangzhou, Zhejiang 310022, China; Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Peng-Tao Chen
- Department of Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Key Laboratory of Imaging and Interventional Medicine, Hangzhou, Zhejiang 310022, China; Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Yi-Nan Ding
- Department of Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Key Laboratory of Imaging and Interventional Medicine, Hangzhou, Zhejiang 310022, China; Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
| |
Collapse
|
|
3
|
Ma YY, Wang XH, Zeng JY, Chen JB, Niu LZ. Irreversible electroporation combined with anti-programmed cell death protein 1 therapy promotes tumor antigen-specific CD8 + T cell response. World J Gastrointest Oncol 2025; 17:101991. [PMID: 40092962 PMCID: PMC11866226 DOI: 10.4251/wjgo.v17.i3.101991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/21/2024] [Accepted: 01/08/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Irreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to activate the host's immune system. However, this approach is insufficient to prevent cancer progression, and complementary approaches are required for effective immunotherapy. AIM To assess the immunomodulatory effects and mechanism of IRE combined anti-programmed cell death protein 1 (PD-1) treatment in subcutaneous pancreatic cancer models. METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups: Control group; IRE group; anti-PD-1 group; and IRE + anti-PD-1 group. Tumor-infiltrating T, B, and natural killer cell levels and plasma concentrations of T helper type 1 cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-α) were evaluated. Real-time PCR was used to determine the expression of CD8 (marker of CD8+ T cells) in tumor tissues of the mice of all groups at different points of time. The growth curves of tumors were drawn. RESULTS The results demonstrated that the IRE + anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration, including CD4+ and CD8+ T cells compared with the control group. Additionally, the IRE + anti-PD-1 group showed increased infiltration of natural killer and B cells, elevated cytokine levels, and higher CD8 mRNA expression. Tumor volume was significantly reduced in the IRE + anti-PD-1 group, indicating a more pronounced therapeutic effect. CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+ T cell immunity responses, leading to a more effective reduction in tumor volume and improved therapeutic outcomes, which provides a new direction for ablation and immunotherapy of pancreatic cancer.
Collapse
Affiliation(s)
- Yang-Yang Ma
- Central Laboratory, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
| | - Xiao-Hua Wang
- Central Laboratory, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
| | - Jian-Ying Zeng
- Central Laboratory, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
| | - Ji-Bing Chen
- Central Laboratory, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
| | - Li-Zhi Niu
- Department of Oncology, Guangzhou Fuda Cancer Hospital, Guangzhou 510665, Guangdong Province, China
| |
Collapse
|
|
4
|
Jacobs EJ, Rubinsky B, Davalos RV. Pulsed field ablation in medicine: irreversible electroporation and electropermeabilization theory and applications. Radiol Oncol 2025; 59:1-22. [PMID: 40014783 PMCID: PMC11867574 DOI: 10.2478/raon-2025-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 12/07/2024] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Focal ablation techniques are integral in the surgical intervention of diseased tissue, where it is necessary to minimize damage to the surrounding parenchyma and critical structures. Irreversible electroporation (IRE) and high-frequency IRE (H-FIRE), colloquially called pulsed-field ablation (PFA), utilize high-amplitude, low-energy pulsed electric fields (PEFs) to nonthermally ablate soft tissue. PEFs induce cell death through permeabilization of the cellular membrane, leading to loss of homeostasis. The unique nonthermal nature of PFA allows for selective cell death while minimally affecting surrounding proteinaceous structures, permitting treatment near sensitive anatomy where thermal ablation or surgical resection is contraindicated. Further, PFA is being used to treat tissue when tumor margins are not expected after surgical resection, termed margin accentuation. This review explores both the theoretical foundations of PFA, detailing how PEFs induce cell membrane destabilization and selective tissue ablation, the outcomes following treatment, and its clinical implications across oncology and cardiology. CONCLUSIONS Clinical experience is still progressing, but reports have demonstrated that PFA reduces complications often seen with thermal ablation techniques. Mounting oncology data also support that PFA produces a robust immune response that may prevent local recurrences and attenuate metastatic disease. Despite promising outcomes, challenges such as optimizing field delivery and addressing variations in tissue response require further investigation. Future directions include refining PFA protocols and expanding its application to other therapeutic areas like benign tissue hyperplasia and chronic bronchitis.
Collapse
Affiliation(s)
- Edward J Jacobs
- Wallace H Coulter School of Biomedical Engineering, Georgia Institute of Technology & Emory Medical School, Atlanta, Georgia, USA
| | - Boris Rubinsky
- Department of Bioengineering and Department of Mechanical Engineering, University of California, Berkeley, Berkeley, California, USA
| | - Rafael V Davalos
- Wallace H Coulter School of Biomedical Engineering, Georgia Institute of Technology & Emory Medical School, Atlanta, Georgia, USA
| |
Collapse
|
|
5
|
Zhao M, Li F, Tian C, Cai D, Wang C. Conventional transarterial chemoembolization followed by irreversible electroporation for hepatocellular carcinoma. BMC Cancer 2025; 25:313. [PMID: 39984913 PMCID: PMC11843783 DOI: 10.1186/s12885-025-13570-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 01/20/2025] [Indexed: 02/23/2025] Open
Abstract
OBJECTIVES This study aimed to assess the effectiveness and safety of conventional transarterial chemoembolization (c-TACE) followed by irreversible electroporation (IRE) for the treatment of hepatocellular carcinoma (HCC). METHODS From January 2019 to September 2019, 12 patients with HCC who received c-TACE followed by IRE comprised the study group. The control group comprised 15 patients who received c-TACE followed by radiofrequency ablation (RFA). The 1-month, 3-month, 6-month, and 12-month local control rates and median progression-free survival (PFS) were compared between the two groups. Additionally, postoperative complications were assessed. RESULTS The study group comprised 12 patients (median age: 57.5 years; range: 46-68 years), while the control group consisted of 15 patients (median age: 56 years; range: 31-69 years). Local control rates at 1, 3, 6, and 12 months were 91.7%, 91.7%, 83.3%, and 33.3%, respectively, for the study group, and 73.3%, 66.7%, 66.7%, and 20.0% for the control group. Statistical analysis revealed no significant differences between the two groups. In terms of survival, 9 patients (75%) in the study group and 11 patients (73.3%) in the control group were still alive at the last follow-up. The median PFS was 8 months in the study group and 7 months in the control group, with no significant difference between the two groups (p = 0.96). Notably, no severe surgery-related side effects were observed in either group, and also no significant differences were found in postoperative complications between the two groups (p = 0.64). CONCLUSIONS The long-term therapeutic outcomes of c-TACE followed by IRE were found to be similar to those of c-TACE followed by RFA in the study. The research suggests that c-TACE followed by IRE offered an effective and safe treatment option for HCC.
Collapse
Affiliation(s)
- Meng Zhao
- Department of the Interventional Medical Center, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Qingdao, Shandong, 266000, China
| | - Fubao Li
- Department of Neurosurgery, The People's Hospital of Jimo. Qingdao, Qingdao, Shandong, 266000, China
| | - Chuan Tian
- Department of the Interventional Medical Center, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Qingdao, Shandong, 266000, China
| | - Duo Cai
- Medical Animal Lab, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China
| | - Congxiao Wang
- Department of the Interventional Medical Center, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Qingdao, Shandong, 266000, China.
| |
Collapse
|
|
6
|
Narayanan G, Gentile NT, Eyshi J, Schiro BJ, Gandhi RT, Peña CS, Ucar A, Aparo S, de Zarraga FI, Joseph SN, Asbun HJ, Dijkstra M. Irreversible Electroporation in Treating Colorectal Liver Metastases in Proximity to Critical Structures. J Vasc Interv Radiol 2024; 35:1806-1813. [PMID: 39218213 DOI: 10.1016/j.jvir.2024.08.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 08/06/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024] Open
Abstract
PURPOSE To evaluate the safety, effectiveness, and oncological outcomes of irreversible electroporation (IRE) of unresectable colorectal liver metastases (CRLMs) close to critical structures. MATERIALS AND METHODS This is a single-center, institutional review board (IRB)-approved, retrospective analysis of patients who underwent percutaneous computed tomography (CT)-guided IRE of CRLM. Between August 2018 and October 2023, 26 patients had 46 tumors treated with percutaneous IRE in 30 ablation sessions. Primary end points were tumor response and local progression-free survival analyzed using Kaplan-Meier survival curves. Secondary end points were overall survival (OS), distant progression-free survival (DPFS) analyzed using Kaplan-Meier survival curves, adverse events rated according to the Common Terminology Criteria for Adverse Events (CTCAE), and length of hospital stay. RESULTS All tumors were close to critical structures, including the portal and hepatic veins, inferior vena cava, bile ducts, and gallbladder. All patients received preprocedural systemic therapy (median 10 cycles). Median length of hospital stay was 1 night. Adverse events occurred in 7 (23%) of 30 procedures, with four Grade 1 and two Grade 2 adverse events, including pleural effusions (n = 2), ileus (n = 1), small hematoma (n = 1), and pneumothorax (n = 2) requiring chest tube placements. Following IRE, the 1- and 2-year local tumor progression-free survival rates were 55.0% and 51.3%. The median DPFS was 3.5 months, with 1- and 2-year DPFS rates of 23.3% and 9.7%. Six patients (23.1%) died during follow-up, with a median OS of 40.4 months. The 1- and 2-year OS rates were 90.9% and 83.9%. CONCLUSIONS IRE is a safe and viable option in the treatment of unresectable CRLMs in locations close to critical structures, but carries a risk of local recurrence.
Collapse
Affiliation(s)
- Govindarajan Narayanan
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Nicole T Gentile
- Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Jonathan Eyshi
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Brian J Schiro
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Ripal T Gandhi
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Costantino S Peña
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida
| | - Antonio Ucar
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Santiago Aparo
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Fernando I de Zarraga
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Sarah N Joseph
- Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Horacio J Asbun
- Department of Hepatobiliary and Pancreatic Surgery, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
| | - Madelon Dijkstra
- Department of Interventional Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida; Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, Florida; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands.
| |
Collapse
|
|
7
|
Ho Chu H, Hyoung Kim J, Ha Kim G, Yeon Kim S, Jung Lee S, Jin Won H, Moon Shin Y. Percutaneous radiofrequency ablation of liver metastases from colorectal cancer: Development of a prognostic score to predict overall survival. Eur J Radiol 2024; 181:111746. [PMID: 39317001 DOI: 10.1016/j.ejrad.2024.111746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 09/10/2024] [Accepted: 09/17/2024] [Indexed: 09/26/2024]
Abstract
PURPOSE To develop a model for pretreatment prediction of overall survival (OS) after radiofrequency ablation (RFA) for colorectal liver metastasis (CRLM). METHOD This retrospective study included 491 patients (median age, 61 years; 348 men) who underwent percutaneous RFA for CRLM between 2000 and 2021. The Kaplan-Meier method was used to estimate OS rates. Independent factors affecting OS were investigated using multivariable Cox regression analysis. Risk scores were assigned to the risk factors and pretreatment prediction models were created using the risk factors. RESULTS After RFA, the 5-, 10-, and 20-year OS rates were 44 %, 31 %, and 24 %, respectively, and the median OS was 46 months. Multivariate Cox regression analysis showed that a largest tumor size ≥ 2 cm (P<0.001), positive nodal status of primary tumor (P<0.001), carcinoembryonic antigen level > 30 ng/mL (P=0.049), multiple tumors (P=0.008), and T4 stage of the primary tumor (P=0.029) were independently associated with OS. In patients with a single CRLM, tumor diameter (P<0.001), positive nodal status of primary tumor (P=0.001), disease-free interval <12 months (P=0.045), and subcapsular location (P=0.03) were risk factors affecting OS. According to our prediction models, which included the aforementioned risk factors, OS rates progressively decreased as the risk scores increased, with significantly different OS rates between contiguous groups (P<0.001). CONCLUSIONS Our prediction models can be used as a prognostic stratification tool in patients with CRLM, and can help select those candidates who will benefit most from RFA.
Collapse
Affiliation(s)
- Hee Ho Chu
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Gun Ha Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
8
|
Barbieri P, Posa A, Lancellotta V, Madoff DC, Maresca A, Cornacchione P, Tagliaferri L, Iezzi R. Electrochemotherapy in the Locoregional Treatment of Metastatic Colorectal Liver Metastases: A Systematic Review. Curr Oncol 2024; 31:7403-7413. [PMID: 39590176 PMCID: PMC11592455 DOI: 10.3390/curroncol31110546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/14/2024] [Accepted: 11/19/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND The global incidence of secondary liver cancer is rising due to multiple risk factors, presenting significant challenges in public health. Similarly, colorectal cancer (CRC) remains a leading cause of cancer-related mortality with the development of frequent liver metastases. Surgical resection of CRC liver metastases is only suitable for a limited subset of patients, necessitating alternative nonsurgical treatments such as electrochemotherapy (ECT); Methods: This review adhered to the S.P.I.D.E.R. FRAMEWORK Systematic searches of PubMed, Cochrane, and Scopus databases were conducted for studies published between 2003 and 2023, following PRISMA guidelines. Inclusion criteria were full-text clinical studies in English focusing on ECT-treated CRC liver metastases, excluding reviews, editorials, and non-clinical papers. The GRADE approach was utilized to assess evidence quality, considering study limitations, consistency, and other factors; Results: From 38 identified articles, 4 met the inclusion criteria, encompassing 78 patients and 128 treated lesions. The studies demonstrated variability in design and follow-up duration (3-11 months). Complete response (CR) rates ranged from 33.3% to 63.0%, while progression disease (PD) rates were high, ranging from 23.0% to 55.6%. Median overall survival (OS) spanned 11.3 to 29.0 months. No severe ECT-related complications were reported. CONCLUSIONS ECT appears to be a safe and effective modality for the treatment of CRC liver metastases, especially for lesions unsuitable for other ablative techniques. Further prospective and randomized studies are essential to better define the role of ECT in managing CRC liver metastases and to compare its efficacy with other ablative methods.
Collapse
Affiliation(s)
- Pierluigi Barbieri
- Department of Diagnostic Imaging and Oncologic Radiotherapy—Emergency and Interventional Radiology Unit, Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (P.B.); (A.M.); (R.I.)
| | - Alessandro Posa
- Department of Diagnostic Imaging and Oncologic Radiotherapy—Emergency and Interventional Radiology Unit, Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (P.B.); (A.M.); (R.I.)
| | - Valentina Lancellotta
- Department of Diagnostic Imaging and Oncological Radiotherapy—Gemelli ART (Advanced Radiation Therapy), Interventional Oncology Center (IOC), Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (V.L.); (P.C.); (L.T.)
| | - David C. Madoff
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA;
| | - Alessandro Maresca
- Department of Diagnostic Imaging and Oncologic Radiotherapy—Emergency and Interventional Radiology Unit, Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (P.B.); (A.M.); (R.I.)
| | - Patrizia Cornacchione
- Department of Diagnostic Imaging and Oncological Radiotherapy—Gemelli ART (Advanced Radiation Therapy), Interventional Oncology Center (IOC), Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (V.L.); (P.C.); (L.T.)
| | - Luca Tagliaferri
- Department of Diagnostic Imaging and Oncological Radiotherapy—Gemelli ART (Advanced Radiation Therapy), Interventional Oncology Center (IOC), Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (V.L.); (P.C.); (L.T.)
| | - Roberto Iezzi
- Department of Diagnostic Imaging and Oncologic Radiotherapy—Emergency and Interventional Radiology Unit, Fondazione Policlinico Universitario “Agostino Gemelli”—IRCCS, 00168 Rome, Italy; (P.B.); (A.M.); (R.I.)
- Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| |
Collapse
|
|
9
|
van den Bemd BAT, Puijk RS, Keijzers H, van den Tol PM, Meijerink MR, for the COLLISION Trial Group. Mathematical 3D Liver Model for Surgical versus Ablative Therapy Treatment Planning for Colorectal Liver Metastases: Recommendations from the COLLISION and COLDFIRE Trial Expert Panels. Radiol Imaging Cancer 2024; 6:e240068. [PMID: 39400233 PMCID: PMC11615634 DOI: 10.1148/rycan.240068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 07/24/2024] [Accepted: 09/05/2024] [Indexed: 10/15/2024]
Abstract
Purpose To further define anatomic criteria for resection and ablation using an expert panel-based three-dimensional liver model to objectively predict local treatment recommendations for colorectal liver metastases (CRLM). Materials and Methods This study analyzed data from participants with small CRLM (≤3 cm) considered suitable for resection, thermal ablation, or irreversible electroporation (IRE), according to a multidisciplinary expert panel, who were included in two prospective multicenter trials (COLLISION [NCT03088150] and COLDFIRE-2 [NCT02082782]) between August 2017 and June 2022. Ten randomly selected participants were used to standardize the model's Couinaud segments. CRLM coordinates were measured and plotted in the model as color-coded lesions according to the treatment recommendations. Statistical validation was achieved through leave-one-out cross-validation. Results A total of 611 CRLM in 202 participants (mean age, 63 [range, 29-87] years; 138 male and 64 female) were included. Superficially located CRLM were considered suitable for resection, whereas more deep-seated CRLM were preferably ablated, with the transition zone at a subsurface depth of 3 cm. Ninety-three percent (25 of 27) of perihilar CRLM treated with IRE were at least partially located within 1 cm from the portal triad. Use of the model correctly predicted the preferred treatment in 313 of 424 CRLM (73.8%). Conclusion The results suggest that CRLM can be defined as superficial (preferably resected) and deep-seated (preferably ablated) if the tumor center is within versus beyond 3 cm from the liver surface, respectively, and as perihilar if the tumor margins extend to within 1 cm from the portal triad. Keywords: Ablation Techniques, CT, MRI, Liver, Abdomen/GI, Metastases, Oncology Supplemental material is available for this article. © RSNA, 2024.
Collapse
Affiliation(s)
- Bente A. T. van den Bemd
- From the Department of Radiology and Nuclear Medicine, Amsterdam UMC,
Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the
Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Cancer Center Amsterdam, Amsterdam,
the Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Department of Surgical Oncology,
OLVG Hospital, Oost, Amsterdam, the Netherlands (B.A.T.v.d.B.); Department of
Radiology and Nuclear Medicine, OLVG Hospital, Oost, Amsterdam, the Netherlands
(R.S.P.), Department of Medical Physics and Radiation Protection, Haaglanden MC,
The Hague, the Netherlands (H. Keijzers); and Department of Surgical Oncology,
Medical Center Leeuwarden, Leeuwarden, the Netherlands (P.M.v.d.T.)
| | - Robbert S. Puijk
- From the Department of Radiology and Nuclear Medicine, Amsterdam UMC,
Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the
Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Cancer Center Amsterdam, Amsterdam,
the Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Department of Surgical Oncology,
OLVG Hospital, Oost, Amsterdam, the Netherlands (B.A.T.v.d.B.); Department of
Radiology and Nuclear Medicine, OLVG Hospital, Oost, Amsterdam, the Netherlands
(R.S.P.), Department of Medical Physics and Radiation Protection, Haaglanden MC,
The Hague, the Netherlands (H. Keijzers); and Department of Surgical Oncology,
Medical Center Leeuwarden, Leeuwarden, the Netherlands (P.M.v.d.T.)
| | - Han Keijzers
- From the Department of Radiology and Nuclear Medicine, Amsterdam UMC,
Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the
Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Cancer Center Amsterdam, Amsterdam,
the Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Department of Surgical Oncology,
OLVG Hospital, Oost, Amsterdam, the Netherlands (B.A.T.v.d.B.); Department of
Radiology and Nuclear Medicine, OLVG Hospital, Oost, Amsterdam, the Netherlands
(R.S.P.), Department of Medical Physics and Radiation Protection, Haaglanden MC,
The Hague, the Netherlands (H. Keijzers); and Department of Surgical Oncology,
Medical Center Leeuwarden, Leeuwarden, the Netherlands (P.M.v.d.T.)
| | - Petrousjka M. van den Tol
- From the Department of Radiology and Nuclear Medicine, Amsterdam UMC,
Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the
Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Cancer Center Amsterdam, Amsterdam,
the Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Department of Surgical Oncology,
OLVG Hospital, Oost, Amsterdam, the Netherlands (B.A.T.v.d.B.); Department of
Radiology and Nuclear Medicine, OLVG Hospital, Oost, Amsterdam, the Netherlands
(R.S.P.), Department of Medical Physics and Radiation Protection, Haaglanden MC,
The Hague, the Netherlands (H. Keijzers); and Department of Surgical Oncology,
Medical Center Leeuwarden, Leeuwarden, the Netherlands (P.M.v.d.T.)
| | - Martijn R. Meijerink
- From the Department of Radiology and Nuclear Medicine, Amsterdam UMC,
Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the
Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Cancer Center Amsterdam, Amsterdam,
the Netherlands (B.A.T.v.d.B., R.S.P., M.R.M.); Department of Surgical Oncology,
OLVG Hospital, Oost, Amsterdam, the Netherlands (B.A.T.v.d.B.); Department of
Radiology and Nuclear Medicine, OLVG Hospital, Oost, Amsterdam, the Netherlands
(R.S.P.), Department of Medical Physics and Radiation Protection, Haaglanden MC,
The Hague, the Netherlands (H. Keijzers); and Department of Surgical Oncology,
Medical Center Leeuwarden, Leeuwarden, the Netherlands (P.M.v.d.T.)
| | | |
Collapse
|
|
10
|
Gong J, Wang S, Wang S, Li C, Li W, Chen Y, Xia N, Wang C, Wang Z. A retrospective study of irreversible electroporation for tumors adjacent to perihepatic important structure. Front Oncol 2024; 14:1387952. [PMID: 39328209 PMCID: PMC11424374 DOI: 10.3389/fonc.2024.1387952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 08/09/2024] [Indexed: 09/28/2024] Open
Abstract
Background Irreversible electroporation has been proved as a feasible and safe method against tumor in liver. However, few studies focused on tumors adjacent to perihepatic important structure like vessels, biliary system and gall bladder. These structures limit the effectiveness of conventional treatments. The aim of this article is to analyze the clinical outcomes of patients with hepatic tumors at the special sites who received IRE treatment and provide reliable evidence for broadening the scope of IRE's clinical application. Methods The clinical information of patients who underwent IRE ablation for tumors adjacent to perihepatic important structure between February 2017 and December 2021 was collected and retrospectively analyzed. All patients underwent contrast-enhanced CT or MRI for further evaluation at the 1-month follow-up and every 3 months thereafter. Post-ablation complications, recurrence, progression-free survival and overall survival were evaluated to analyze the prognosis of IRE ablation adjacent to perihepatic important structure. Categorical variables are presented as numbers followed by percentages. Continuous data are presented as the mean ± deviation. The tumor size and IRE ablation size were evaluated by the maximum diameters. Results Thirty-two patients who underwent IRE ablation for tumor adjacent to perihepatic important structure were studied in this research. There were 39 lesions in 32 patients treated with IRE ablation. Fourteen of them (35.9%) were located adjacent to the porta hepatis, and 8 of them (20.5%) were located adjacent to the hepatocaval confluence. Subcapsular lesions accounted for 15.4% (6 of 39 lesions). The other 11 lesions were in the para gallbladder (5 of 39 lesions, 12.8%), the caudate lobe (5 of 39 lesions, 12.8%) and the colonic hepatic flexure (1 of 39 lesions, 2.6%). According to the Clavien-Dindo classification system for complications, all relative patients with cancer experienced complications below class III except one patient who developed postoperative hemorrhagic shock and improved after timely treatment. Recurrence in situ was observed in 5 of 32 (15.6%) patients. The median PFS of the patients who received IRE ablation was 384 days, and the median OS was 571 days. Conclusion IRE ablation is a feasible and safe treatment strategy for tumors adjacent to perihepatic important structure. With improved equipment, optimized therapeutic parameters and long-term clinical trials, IRE will play an increasingly important role in the treatment of tumors in liver.
Collapse
Affiliation(s)
- Ju Gong
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Shunhong Wang
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Shuting Wang
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Interventional Therapy, The Second Affiliated Hospital of Soochow University, Jiangsu, China
| | - Chaojie Li
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Wenhua Li
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yingjie Chen
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Ning Xia
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Chen Wang
- Department of Intervention Vascular, The Third Affiliated Hospital of Shihezi University, Shihezi, China
| | - Zhongmin Wang
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Intervention Vascular, The Third Affiliated Hospital of Shihezi University, Shihezi, China
- Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
|
11
|
Sutter O, Voyer D, Tasu JP, Poignard C. How Impedance Measurements and Imaging Can Be Used to Characterize the Conductivity of Tissues During the Workflow of an Electroporation-Based Therapy. IEEE Trans Biomed Eng 2024; 71:1370-1377. [PMID: 37995176 DOI: 10.1109/tbme.2023.3336193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
In this article we investigate the possibility of using needles, which the interventional radiologist inserts near a deep-seated tumor during an electroporation-based therapy, to characterize the electrical conductivity of patient's tissues. Specifically, we propose to exploit voltage/current measurements and imaging that are performed prior to the application of electroporation pulses. The approach is partly based on the concepts of electrical impedance tomography; however, imaging is used to build a specific geometric model and compensate for the lack of information resulting from the small number of electrodes available. 3D canonical and clinical examples, where a few electrodes surround a tumor, demonstrate the feasibility of this method: solving the inverse problem to estimate tissues conductivity converges in a few iterations. For a given error on the measurement, it is also possible to calculate the error on the estimated conductivities. The uncertainty error with clinical data is at best 5% for one of the tissues identified, due to the limitations of the clinical device used. Various improvements to clinical devices are discussed to make the conductivity estimation more accurate but also to extract more information.
Collapse
|
|
12
|
Vos DJW, Ruarus AH, Timmer FEF, Geboers B, Bagla S, Belfiore G, Besselink MG, Leen E, Martin II RCG, Narayanan G, Nilsson A, Paiella S, Weintraub JL, Wiggermann P, Scheffer HJ, Meijerink MR. Consensus Guidelines of Irreversible Electroporation for Pancreatic Tumors: Protocol Standardization Using the Modified Delphi Technique. Semin Intervent Radiol 2024; 41:176-219. [PMID: 38993594 PMCID: PMC11236456 DOI: 10.1055/s-0044-1787164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
Since no uniform treatment protocol for pancreatic irreversible electroporation (IRE) exists, the heterogeneity throughout literature complicates the comparison of results. To reach agreement among experts, a consensus study was performed. Eleven experts, recruited according to predefined criteria regarding previous IRE publications, participated anonymously in three rounds of questionnaires according to a modified Delphi technique. Consensus was defined as having reached ≥80% agreement. Response rates were 100, 64, and 64% in rounds 1 to 3, respectively; consensus was reached in 93%. Pancreatic IRE should be considered for stage III pancreatic cancer and inoperable recurrent disease after previous local treatment. Absolute contraindications are ventricular arrhythmias, implantable stimulation devices, congestive heart failure NYHA class 4, and severe ascites. The inter-electrode distance should be 10 to 20 mm and the exposure length should be 15 mm. After 10 test pulses, 90 treatment pulses of 1,500 V/cm should be delivered continuously, with a 90-µs pulse length. The first postprocedural contrast-enhanced computed tomography should take place 1 month post-IRE, and then every 3 months. This article provides expert recommendations regarding patient selection, procedure, and follow-up for IRE treatment in pancreatic malignancies through a modified Delphi consensus study. Future studies should define the maximum tumor diameter, response evaluation criteria, and the optimal number of preoperative FOLFIRINOX cycles.
Collapse
Affiliation(s)
- Danielle J. W. Vos
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Alette H. Ruarus
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Florentine E. F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Sandeep Bagla
- Vascular Institute of Virginia, Woodbridge, Virginia
| | - Giuseppe Belfiore
- Department of Diagnostic Imaging, S. Anna-S. Sebastiano Hospital, Caserta, Italy
| | - Marc G. Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Edward Leen
- Department of Experimental Medicine, Imperial College London, London, United Kingdom
| | | | - Govindarjan Narayanan
- Department of Interventional Radiology, Miami Cardiac and Vascular Institute, Miami, Florida
| | - Anders Nilsson
- Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, University of Verona Hospital Trust, G. B. Rossi Hospital, Verona, Italy
| | | | | | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Northwest Hospital, Alkmaar, The Netherlands
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| |
Collapse
|
|
13
|
Jacobs Iv EJ, Campelo SN, Charlton A, Altreuter S, Davalos RV. Characterizing reversible, irreversible, and calcium electroporation to generate a burst-dependent dynamic conductivity curve. Bioelectrochemistry 2024; 155:108580. [PMID: 37788520 DOI: 10.1016/j.bioelechem.2023.108580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 09/20/2023] [Accepted: 09/24/2023] [Indexed: 10/05/2023]
Abstract
The relationships between burst number, reversible, irreversible, and calcium electroporation have not been comprehensively evaluated in tumor tissue-mimics. Our findings indicate that electroporation effects saturate with a rate constant (τ) of 20 bursts for both conventional and high frequency waveforms (R2 > 0.88), with the separation between reversible and irreversible electroporation thresholds converging at 50 bursts. We find the lethal thresholds for calcium electroporation are statistically similar to reversible electroporation (R2 > 0.99). We then develop a burst-dependent dynamic conductivity curve that now incorporates electroporation effects due to both the electric field magnitude and burst number. Simulated ablation and thermal damage volumes vary significantly between finite element models using either the conventional or new burst-dependent dynamic conductivity curve (p < 0.05). Lastly, for clinically relevant protocols, thermal damage is indicated to not begin until 50 bursts, with maximum nonthermal ablation volumes at 100 bursts (1.5-13% thermal damage by volume). We find that >100 bursts generated negligible increases in ablation volumes with 40-70% thermal damage by volume at 300 bursts. Our results illustrate the need for considering burst number in minimizing thermal damage, choosing adjuvant therapies, and in modeling electroporation effects at low burst numbers.
Collapse
Affiliation(s)
- Edward J Jacobs Iv
- Bioelectromechanical Systems Laboratory, Virginia Tech - Wake Forest School of Biomedical Engineering, Blacksburg, VA, USA; Bioelectromechanical Systems Laboratory, Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech - Emory University, Atlanta, GA, USA
| | - Sabrina N Campelo
- Bioelectromechanical Systems Laboratory, Virginia Tech - Wake Forest School of Biomedical Engineering, Blacksburg, VA, USA
| | - Alyssa Charlton
- Bioelectromechanical Systems Laboratory, Virginia Tech - Wake Forest School of Biomedical Engineering, Blacksburg, VA, USA
| | - Sara Altreuter
- Bioelectromechanical Systems Laboratory, Virginia Tech - Wake Forest School of Biomedical Engineering, Blacksburg, VA, USA
| | - Rafael V Davalos
- Bioelectromechanical Systems Laboratory, Virginia Tech - Wake Forest School of Biomedical Engineering, Blacksburg, VA, USA; Bioelectromechanical Systems Laboratory, Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech - Emory University, Atlanta, GA, USA.
| |
Collapse
|
|
14
|
Wang Y, Ma R, Huang Z, Zhou Y, Wang K, Xiao Z, Guo Q, Yang D, Han M, Shen S, Qian J, Gao X, Liu Z, Zhou L, Yin S, Zheng S. Investigation of lethal thresholds of nanosecond pulsed electric field in rabbit VX2 hepatic tumors through finite element analysis and verification with a single-needle bipolar electrode: A prospective strategy employing three-dimensional comparisons. Comput Biol Med 2024; 168:107824. [PMID: 38086143 DOI: 10.1016/j.compbiomed.2023.107824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/16/2023] [Accepted: 12/04/2023] [Indexed: 01/10/2024]
Abstract
Pulsed electric field has emerged as a promising modality for the solid tumor ablation with the advantage in treatment planning, however, the accurate prediction of the lesion margin requires the determination of the lethal electric field (E) thresholds. Herein we employ the highly repetitive nanosecond pulsed electric field (RnsPEF) to ablate the normal and VX2 tumor-bearing livers of rabbits. The ultrasound-guided surgery is operated using the conventional double- and newly devised single-needle bipolar electrodes. Finite element analysis is also introduced to simulate the E distribution in the practical treatments. Two- and three-dimensional investigations are performed on the image measurements and reconstructed calcification models on micro-CT, respectively. Specially, an algorithm considering the model surface, volume and shape is employed to compare the similarities between the simulative and experimental models. Blood vessel injury, temperature and synergistic efficacy with doxorubicin (DOX) are also investigated. According to the three-dimensional calculation, the overall E threshold is 4536.4 ± 618.2 V/cm and the single-needle bipolar electrode is verified to be effective in tissue ablation. Vessels are well preserved and the increment of temperature is limited. Synergy of RnsPEF and DOX shows increased apoptosis and improved long-term tumor survival. Our study presents a prospective strategy for the evaluation of the lethal E threshold, which can be considered to guide the future clinical treatment planning for RnsPEF.
Collapse
Affiliation(s)
- Yubo Wang
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Rongwei Ma
- Institute of Industrial Ecology and Environment, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Zhiliang Huang
- Department of Ultrasound, Shulan Hospital, Hangzhou, Zhejiang Province, 310003, China
| | - Yuan Zhou
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Ke Wang
- College of Computer Science and Technology, China University of Minning and Technology, Xuzhou, Jiangsu Province, 221008, China
| | - Zhoufang Xiao
- College of Computer Science and Technology, Hangzhou Dianzi University, Hangzhou, Zhejiang Province, 310003, China
| | - Qiang Guo
- Department of Ultrasound, Shulan Hospital, Hangzhou, Zhejiang Province, 310003, China
| | - Dezhi Yang
- Department of Ultrasound, Shulan Hospital, Hangzhou, Zhejiang Province, 310003, China
| | - Mingchen Han
- College of Computer Science and Technology, China University of Minning and Technology, Xuzhou, Jiangsu Province, 221008, China
| | - Shuwei Shen
- College of Computer Science and Technology, Hangzhou Dianzi University, Hangzhou, Zhejiang Province, 310003, China
| | - Junjie Qian
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Xingxing Gao
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Zhen Liu
- Institute of Industrial Ecology and Environment, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Lin Zhou
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China
| | - Shengyong Yin
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
| | - Shunsen Zheng
- Key Laboratory of Multi-Organ Transplantation Research (Ministry of Health), First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China; Department of Ultrasound, Shulan Hospital, Hangzhou, Zhejiang Province, 310003, China.
| |
Collapse
|
|
15
|
L'Huillier R, Dumortier J, Mastier C, Cayot B, Chambon C, Benech N, Stacoffe N, Valette PJ, Milot L. Robotic-assisted percutaneous irreversible electroporation for the treatment of hepatocellular carcinoma. Diagn Interv Imaging 2023; 104:615-617. [PMID: 37679270 DOI: 10.1016/j.diii.2023.08.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/22/2023] [Accepted: 08/25/2023] [Indexed: 09/09/2023]
Affiliation(s)
- Romain L'Huillier
- Department of Diagnostic and Interventional Radiology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France; LabTAU - INSERM U1032, 69003 Lyon, France; The French Comprehensive Liver Center, Hospices Civils de Lyon, University of Lyon, 69004 Lyon, France
| | - Jérôme Dumortier
- The French Comprehensive Liver Center, Hospices Civils de Lyon, University of Lyon, 69004 Lyon, France; Department of Hepatology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France
| | - Charles Mastier
- Department of Diagnostic and Interventional Radiology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France
| | - Benedicte Cayot
- Department of Diagnostic and Interventional Radiology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France
| | - Christine Chambon
- Department of Hepatology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France
| | - Nicolas Benech
- Department of Hepatology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France
| | - Nicolas Stacoffe
- Department of Diagnostic and Interventional Radiology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, University of Lyon, 69495 Pierre-Bénite, France
| | - Pierre-Jean Valette
- Department of Diagnostic and Interventional Radiology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France
| | - Laurent Milot
- Department of Diagnostic and Interventional Radiology, Hôpital Edouard Herriot, Hospices Civils de Lyon, University of Lyon, 69003 Lyon, France; LabTAU - INSERM U1032, 69003 Lyon, France; The French Comprehensive Liver Center, Hospices Civils de Lyon, University of Lyon, 69004 Lyon, France.
| |
Collapse
|
|
16
|
Sotirchos VS, Petre EN, Sofocleous CT. Percutaneous image-guided ablation for hepatic metastases. J Med Imaging Radiat Oncol 2023; 67:832-841. [PMID: 37944085 DOI: 10.1111/1754-9485.13594] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 09/21/2023] [Indexed: 11/12/2023]
Abstract
The presence of hepatic metastases indicates advanced disease and is associated with significant morbidity and mortality, especially when the hepatic disease is not amenable to locoregional treatments. The primary tumour of origin, the distribution and extent of metastatic disease, the underlying liver reserve, the patient performance status and the presence of comorbidities are factors that determine whether a patient will benefit from hepatectomy or local curative-intent treatments. For patients with metastatic colorectal cancer, the most common primary cancer that spreads to the liver, several studies have demonstrated a survival benefit for patients who can be treated with hepatectomy and/or percutaneous ablation, compared to those treated with chemotherapy alone. Despite advances in surgical techniques increasing the percentage of patients eligible for surgery, most patients have unresectable disease or are poor surgical candidates. Percutaneous ablation can be used to provide local disease control and prolong survival for both surgical and non-surgical candidates. This is typically offered to patients with small hepatic metastases that can be ablated with optimal (≥10 mm) or at least adequate minimum ablation margins (≥5 mm), as high local tumour control rates can be achieved for these patients which are comparable to surgical resection. This review summarizes available evidence and outcomes following percutaneous ablation of the most frequently encountered types of hepatic metastases in the clinical practice of interventional oncology. Patient selection, technical considerations, follow-up protocols and oncologic outcomes are presented and discussed.
Collapse
Affiliation(s)
- Vlasios S Sotirchos
- Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Elena N Petre
- Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Constantinos T Sofocleous
- Interventional Oncology/Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| |
Collapse
|
|
17
|
Frühling P, Stillström D, Holmquist F, Nilsson A, Freedman J. Irreversible electroporation of hepatocellular carcinoma and colorectal cancer liver metastases: A nationwide multicenter study with short- and long-term follow-up. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107046. [PMID: 37716017 DOI: 10.1016/j.ejso.2023.107046] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/11/2023] [Accepted: 08/26/2023] [Indexed: 09/18/2023]
Abstract
INTRODUCTION A nationwide multicenter study was performed to examine short- and long-term effects of irreversible electroporation (IRE) for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). IRE is an alternative method when thermal ablation is contraindicated because of risk for serious thermal complications. METHODS All consecutive patients in Sweden treated with IRE because of HCC or CRCLM, were included between 2011 and 2018. We evaluated medical records and radiological imaging to obtain information regarding patient-, tumor-, and treatment characteristics. We also assessed local tumor progression, and survival. RESULTS In total 206 tumors in 149 patients were treated with IRE. Eighty-seven patients (58.4%) had colorectal cancer liver metastases, and 62 patients (41.6%) had hepatocellular carcinoma. Median tumor size was 20 mm (i.q.r. 14-26 mm). Median overall survival for CRCLM and HCC, were 27.0 months (95% CI 22.2-31.8 months), and 35.0 months (95% CI 13.8-56.2 months), respectively. Median follow-up time was 58 months (95% CI 50.6-65.4). Local ablation success at six and twelve months for HCC was 58.3% and 40.3%, and for CRCLM 37.7% and 25.4%. The median time to local tumor progression (LTP) for HCC was 21.0 months (95% CI: 9.5-32.5 months), and for CRCLM 6.0 months (95% CI: 4.5-7.5 months). At 30-day follow-up, 15.4% (n = 23) of patients suffered from a complication rated as Clavien-Dindo grade 1-3a. Three patients (2.0%) had grade 3b-5 with one death in a thromboembolic event. CONCLUSION IRE is a safe ablation modality for patients with liver tumors that are located in such a way that other treatment options are unsuitable.
Collapse
Affiliation(s)
- Petter Frühling
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
| | - David Stillström
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden
| | - Fredrik Holmquist
- Department of Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden
| | - Anders Nilsson
- Department of Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden
| | - Jacob Freedman
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden
| |
Collapse
|
|
18
|
Dijkstra M, van der Lei S, Puijk RS, Schulz HH, Vos DJW, Timmer FEF, Scheffer HJ, Buffart TE, van den Tol MP, Lissenberg-Witte BI, Swijnenburg RJ, Versteeg KS, Meijerink MR. Efficacy of Thermal Ablation for Small-Size (0-3 cm) versus Intermediate-Size (3-5 cm) Colorectal Liver Metastases: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE). Cancers (Basel) 2023; 15:4346. [PMID: 37686622 PMCID: PMC10487073 DOI: 10.3390/cancers15174346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/23/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
PURPOSE Thermal ablation is widely recognized as the standard of care for small-size unresectable colorectal liver metastases (CRLM). For larger CRLM safety, local control and overall efficacy are not well established and insufficiently validated. The purpose of this comparative series was to analyze outcomes for intermediate-size versus small-size CRLM. MATERIAL AND METHODS Patients treated with thermal ablation between December 2000 and November 2021 for small-size and intermediate-size CRLM were included. The primary endpoints were complication rate and local control (LC). Secondary endpoints included local tumor progression-free survival (LTPFS) and overall survival (OS). RESULTS In total, 59 patients were included in the intermediate-size (3-5 cm) group and 221 in the small-size (0-3 cm) group. Complications were not significantly different between the two groups (p = 0.546). No significant difference between the groups was found in an overall comparison of OS (HR 1.339; 95% CI 0.824-2.176; p = 0.239). LTPFS (HR 3.388; p < 0.001) and LC (HR 3.744; p = 0.004) were superior in the small-size group. Nevertheless, the 1-, 3-, and 5-year LC for intermediate-size CRLM was still 93.9%, 85.4%, and 81.5%, and technical efficacy improved over time. CONCLUSIONS Thermal ablation for intermediate-size unresectable CRLM is safe and induces long-term LC in the vast majority. The results of the COLLISION-XL trial (unresectable colorectal liver metastases: stereotactic body radiotherapy versus microwave ablation-a phase II randomized controlled trial for CRLM 3-5 cm) are required to provide further clarification of the role of local ablative methods for intermediate-size unresectable CRLM.
Collapse
Affiliation(s)
- Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| | - Susan van der Lei
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| | - Robbert S. Puijk
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| | - Hannah H. Schulz
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| | - Danielle J. W. Vos
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| | - Florentine E. F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
- Department of Radiology and Nuclear Medicine, Noordwest Ziekenhuisgroep, 1815 JD Alkmaar, The Netherlands
| | - Tineke E. Buffart
- Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | | | - Birgit I. Lissenberg-Witte
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Location VUmc, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | - Kathelijn S. Versteeg
- Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location VUmc, 1081 HV Amsterdam, The Netherlands; (M.D.); (M.R.M.)
| |
Collapse
|
|
19
|
Campana LG, Daud A, Lancellotti F, Arroyo JP, Davalos RV, Di Prata C, Gehl J. Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation. Cancers (Basel) 2023; 15:3340. [PMID: 37444450 PMCID: PMC10340685 DOI: 10.3390/cancers15133340] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/29/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.
Collapse
Affiliation(s)
- Luca G. Campana
- Department of Surgery, Manchester University NHS Foundation Trust, Oxford Rd., Manchester M13 9WL, UK;
| | - Adil Daud
- Department of Medicine, University of California, 550 16 Street, San Francisco, CA 94158, USA;
| | - Francesco Lancellotti
- Department of Surgery, Manchester University NHS Foundation Trust, Oxford Rd., Manchester M13 9WL, UK;
| | - Julio P. Arroyo
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (J.P.A.); (R.V.D.)
| | - Rafael V. Davalos
- Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA; (J.P.A.); (R.V.D.)
- Institute for Critical Technology and Applied Sciences, Virginia Tech, Blacksburg, VA 24061, USA
| | - Claudia Di Prata
- Department of Surgery, San Martino Hospital, 32100 Belluno, Italy;
| | - Julie Gehl
- Department of Clinical Oncology and Palliative Care, Zealand University Hospital, 4000 Roskilde, Denmark;
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark
| |
Collapse
|
|
20
|
Vulasala SSR, Sutphin PD, Kethu S, Onteddu NK, Kalva SP. Interventional radiological therapies in colorectal hepatic metastases. Front Oncol 2023; 13:963966. [PMID: 37324012 PMCID: PMC10266282 DOI: 10.3389/fonc.2023.963966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 05/19/2023] [Indexed: 06/17/2023] Open
Abstract
Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.
Collapse
Affiliation(s)
- Sai Swarupa R. Vulasala
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, United States
| | - Patrick D. Sutphin
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Samira Kethu
- Department of Microbiology and Immunology, College of Arts and Sciences, University of Miami, Coral Gables, FL, United States
| | - Nirmal K. Onteddu
- Department of Hospital Medicine, Flowers Hospital, Dothan, AL, United States
| | - Sanjeeva P. Kalva
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| |
Collapse
|
|
21
|
Selvaggi F, Catalano T, Lattanzio R, Cotellese R, Aceto GM. Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities. World J Gastroenterol 2023; 29:2764-2783. [PMID: 37274070 PMCID: PMC10237106 DOI: 10.3748/wjg.v29.i18.2764] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/28/2023] [Accepted: 04/17/2023] [Indexed: 05/11/2023] Open
Abstract
The liver is the most common site of metastases in patients with colorectal cancer. Colorectal liver metastases (CRLMs) are the result of molecular mechanisms that involve different cells of the liver microenvironment. The aberrant activation of Wingless/It (Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium, but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymal-epithelial transition interactions. In liver microenvironment, metastatic cells can also survive and adapt through dormancy, which makes them less susceptible to pro-apoptotic signals and therapies. Treatment of CRLMs is challenging due to its variability and heterogeneity. Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been re-cognized in chemoresistance. At the state of art, there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie. In this review, current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered. In addition, an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.
Collapse
Affiliation(s)
- Federico Selvaggi
- Department of Surgical, ASL2 Lanciano-Vasto-Chieti, Ospedale Clinicizzato SS Annunziata of Chieti, Chieti 66100, Italy
| | - Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Messina 98125, Italy
| | - Rossano Lattanzio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Chieti 66100, Italy
| | - Roberto Cotellese
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Chieti 66100, Italy
- Villa Serena Foundation for Research, Villa Serena - Del Dott. L. Petruzzi, Città Sant’Angelo 65013, Pescara, Italy
| | - Gitana Maria Aceto
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
| |
Collapse
|
|
22
|
Spiers HVM, Lancellotti F, de Liguori Carino N, Pandanaboyana S, Frampton AE, Jegatheeswaran S, Nadarajah V, Siriwardena AK. Irreversible Electroporation for Liver Metastases from Colorectal Cancer: A Systematic Review. Cancers (Basel) 2023; 15:cancers15092428. [PMID: 37173895 PMCID: PMC10177346 DOI: 10.3390/cancers15092428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 04/16/2023] [Accepted: 04/20/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Irreversible electroporation (IRE) is a non-thermal form of ablation based on the delivery of pulsed electrical fields. It has been used to treat liver lesions, particularly those in proximity to major hepatic vasculature. The role of this technique in the portfolio of treatments for colorectal hepatic metastases has not been clearly defined. This study undertakes a systematic review of IRE for treatment of colorectal hepatic metastases. METHODS The study protocol was registered with the PROSPERO register of systematic reviews (CRD42022332866) and reports in compliance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Ovid MEDLINE®, EMBASE, Web of Science and Cochrane databases were queried in April 2022. The search terms 'irreversible electroporation', 'colon cancer', 'rectum cancer' and 'liver metastases' were used in combinations. Studies were included if they provided information on the use of IRE for patients with colorectal hepatic metastases and reported procedure and disease-specific outcomes. The searches returned 647 unique articles and the exclusions left a total of eight articles. These were assessed for bias using the methodological index for nonrandomized studies (MINORS criteria) and reported using the synthesis without meta-analysis guideline (SWiM). RESULTS One hundred eighty patients underwent treatment for liver metastases from colorectal cancer. The median transverse diameter of tumours treated by IRE was <3 cm. Ninety-four (52%) tumours were adjacent to major hepatic inflow/outflow structures or the vena cava. IRE was undertaken under general anaesthesia with cardiac cycle synchronisation and with the use of either CT or ultrasound for lesion localisation. Probe spacing was less than 3.2 cm for all ablations. There were two (1.1%) procedure-related deaths in 180 patients. There was one (0.5%) post-operative haemorrhage requiring laparotomy, one (0.5%) bile leak, five (2.8%) post-procedure biliary strictures and a zero incidence of post-IRE liver failure. CONCLUSIONS This systematic review shows that IRE for colorectal liver metastases can be accomplished with low procedure-related morbidity and mortality. Further prospective study is required to assess the role of IRE in the portfolio of treatments for patients with liver metastases from colorectal cancer.
Collapse
Affiliation(s)
- Harry V M Spiers
- Cambridge Hepato-Pancreato-Biliary Unit, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK
- Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK
| | | | | | | | - Adam E Frampton
- Hepato-Pancreato-Biliary Surgery Unit, Royal Surrey NHS Foundation Trust, Guildford GU2 7XX, UK
- Section of Oncology, Deptartment of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7WG, UK
| | | | - Vinotha Nadarajah
- Department of Radiology, Manchester Royal Infirmary, Manchester M13 9WL, UK
| | - Ajith K Siriwardena
- Hepato-Pancreato-Biliary Unit, Manchester Royal Infirmary, Manchester M13 9WL, UK
| |
Collapse
|
|
23
|
Tasu JP, Tougeron D, Rols MP. Irreversible electroporation and electrochemotherapy in oncology: State of the art. Diagn Interv Imaging 2022; 103:499-509. [PMID: 36266192 DOI: 10.1016/j.diii.2022.09.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 01/10/2023]
Abstract
Thermal tumor ablation techniques including radiofrequency, microwave, LASER, high-intensity focused ultrasound and cryoablation are routinely used to treated liver, kidney, bone, or lung tumors. However, all these techniques are thermal and can therefore be affected by heat sink effect, which can lead to incomplete ablation, and thermal injuries of non-targeted tissues are possible. Under certain conditions, high voltage pulsed electric field can induce formation of pores in the cell membrane. This phenomenon, called electropermeabilization, is also known as "electroporation". Under certain conditions, electroporation can be irreversible, leading to cell death. Irreversible electroporation has demonstrated efficacy for the treatment of liver and prostate cancers, whereas data are scarce regarding pancreatic and renal cancers. During reversible electroporation, transient cell permeability can be used to introduce cytotoxic drugs into tumor cells (commonly bleomycin or cisplatin). Reversible electroporation used in conjunction with cytotoxic drugs shows promise in terms of oncological response, particularly for solid cutaneous and subcutaneous tumors such as melanoma. Irreversible and reversible electroporation are both not thermal ablation techniques and therefore open a new promising horizon for tumor ablation.
Collapse
Affiliation(s)
- Jean-Pierre Tasu
- Department of Diagnosis and interventional radiology, University Hospital of Poitiers, 86021 Poitiers, France; LaTim, UBO and INSERM 1101, University of Brest, 29000 Brest, France.
| | - David Tougeron
- Department of Hepatogastroenterology, University Hospital of Poitiers, 86000 Poitiers, France
| | - Marie-Pierre Rols
- Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31000 Toulouse, France
| |
Collapse
|
|
24
|
Egeland C, Baeksgaard L, Gehl J, Gögenur I, Achiam MP. Palliative Treatment of Esophageal Cancer Using Calcium Electroporation. Cancers (Basel) 2022; 14:cancers14215283. [PMID: 36358702 PMCID: PMC9655404 DOI: 10.3390/cancers14215283] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/28/2022] [Accepted: 10/25/2022] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Calcium electroporation is a new cancer therapy wherein a high, rapid influx of calcium, facilitated by electrical pulses, is used to kill cancer cells. This pilot study aimed to evaluate the safety and feasibility of this new treatment for patients with non-curable esophageal cancer. The treatment was administrated during an endoscopic examination, under general anesthesia, and in an outpatient setting. Eight patients were treated. One severe adverse event occurred (requiring a single blood transfusion) and another three mild side effects were seen. Two patients reported dysphagia relief after treatment and one patient had a partial response evaluated by CT. Six months after treatment, the same patient was still in good condition, without the need for further treatment. Calcium electroporation was conducted in eight patients with only a few side effects. More studies are warranted to evaluate clinical efficacy. Abstract Calcium electroporation (CaEP) is a novel cancer therapy wherein high intracellular calcium levels, facilitated by reversible electroporation, trigger tumor necrosis. This study aimed to establish safety with CaEP within esophageal cancer. Patients with non-curable esophageal cancer were included at Copenhagen University Hospital Rigshospitalet in 2021 and 2022. In an outpatient setting, calcium gluconate was injected intratumorally followed by reversible electroporation applied with an endoscopic electrode. The primary endpoint was the prevalence of adverse events, followed by palliation of dysphagia. All patients were evaluated with CT and upper endoscopies up to two months after treatment. The trial was registered at ClinicalTrials.gov (NCT04958044). Eight patients were treated. One serious adverse event (anemia, requiring a single blood transfusion) and three adverse events (mild retrosternal pain (two) and oral thrush (one)) were registered. Initially, six patients suffered from dysphagia: two reported dysphagia relief and four reported no change. From the imaging evaluation, one patient had a partial response, three patients had no response, and four patients had progression. Six months after treatment, the patient who responded well was still in good condition and without the need for further oncological treatment. CaEP was conducted in eight patients with only a few side effects. This study opens the way for larger studies evaluating tumor regression and symptom palliation.
Collapse
Affiliation(s)
- Charlotte Egeland
- Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- Correspondence:
| | - Lene Baeksgaard
- Department of Oncology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
| | - Julie Gehl
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Clinical Oncology and Palliative Care, Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Zealand University Hospital, 4000 Roskilde, Denmark
| | - Ismail Gögenur
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- Department of Surgery, Center for Surgical Science, Zealand University Hospital, 4600 Køge, Denmark
| | - Michael Patrick Achiam
- Department of Surgery and Transplantation, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
| |
Collapse
|
|
25
|
Xu M, Xie LT, Xiao YY, Liang P, Zhao QY, Wang ZM, Chai WL, Wei YT, Xu LF, Hu XK, Kuang M, Niu LZ, Yao CG, Kong HY, Tian G, Xie XY, Cui XW, Xu D, Zhao J, Jiang TA. Chinese clinical practice guidelines for ultrasound-guided irreversible electroporation of liver cancer (version 2022). Hepatobiliary Pancreat Dis Int 2022; 21:462-471. [PMID: 36058782 DOI: 10.1016/j.hbpd.2022.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023]
Affiliation(s)
- Min Xu
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Li-Ting Xie
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Yue-Yong Xiao
- Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing 100000, China
| | - Ping Liang
- Department of Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Qi-Yu Zhao
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Zhong-Min Wang
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wei-Lu Chai
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Ying-Tian Wei
- Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing 100000, China
| | - Lin-Feng Xu
- Department of Interventional Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
| | - Xiao-Kun Hu
- Department of the Interventional Medical Center, the Affiliated Hospital of Qingdao University, Qingdao 266000, China
| | - Ming Kuang
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Li-Zhi Niu
- Department of Oncology, Affiliated Fuda Cancer Hospital, Jinan University, Guangzhou 510665, China
| | - Chen-Guo Yao
- School of Electrical Engineering, Chongqing University, Chongqing 400033, China
| | - Hai-Ying Kong
- Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Guo Tian
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Dong Xu
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China
| | - Jun Zhao
- Department of Anatomy, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Tian-An Jiang
- Department of Ultrasound Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, Zhejiang 310003, China.
| | | | | |
Collapse
|
|
26
|
Solbiati LA, Arai Y. Interventional oncology of liver tumors: how it all started and where are we now. Br J Radiol 2022; 95:20220434. [PMID: 35776630 PMCID: PMC9815741 DOI: 10.1259/bjr.20220434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/22/2022] [Accepted: 06/28/2022] [Indexed: 01/13/2023] Open
Abstract
Liver was the very first organ for which interventional procedures were applied for the local treatment of primary and secondary malignancies. In this paper, the history of Interventional Oncology of liver, from the very beginning to the current situation, is summarized, including both percutaneous and intravascular procedures, and together with the evolution of the techniques for image guidance. The main ongoing developments, such as new techniques, combined interventional treatments and association of local interventions with new drugs are briefly described, too.
Collapse
Affiliation(s)
| | - Yasuaki Arai
- Department of Diagnostic Radiology, National Cancer Center, Tokyo, Japan
| |
Collapse
|
|
27
|
Breuer JA, Ahmed KH, Al-Khouja F, Macherla AR, Muthoka JM, Abi-Jaoudeh N. Interventional oncology: new techniques and new devices. Br J Radiol 2022; 95:20211360. [PMID: 35731848 PMCID: PMC9815742 DOI: 10.1259/bjr.20211360] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 05/20/2022] [Accepted: 05/27/2022] [Indexed: 01/13/2023] Open
Abstract
Interventional oncology is a rapidly emerging field in the treatment of cancer. Minimally invasive techniques such as transarterial embolization with chemotherapeutic and radioactive agents are established therapies and are found in multiple guidelines for the management of primary and metastatic liver lesions. Percutaneous ablation is also an alternative to surgery for small liver, renal, and pancreatic tumors. Recent research in the niche of interventional oncology has focused on improving outcomes of established techniques in addition to the development of novel therapies. In this review, we address the recent and current advancements in devices, technologies, and techniques of chemoembolization and ablation: thermal ablation, histotripsy, high-intensity focused ultrasound, embolization strategies, liquid embolic agents, and local immunotherapy/antiviral therapies.
Collapse
Affiliation(s)
| | | | | | | | | | - Nadine Abi-Jaoudeh
- Department of Radiological Sciences, University of California Irvine, Orange, USA
| |
Collapse
|
|
28
|
Justesen TF, Orhan A, Raskov H, Nolsoe C, Gögenur I. Electroporation and Immunotherapy-Unleashing the Abscopal Effect. Cancers (Basel) 2022; 14:cancers14122876. [PMID: 35740542 PMCID: PMC9221311 DOI: 10.3390/cancers14122876] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/09/2022] [Accepted: 06/09/2022] [Indexed: 01/10/2023] Open
Abstract
Simple Summary Electrochemotherapy and irreversible electroporation are primarily used for treating patients with cutaneous and subcutaneous tumors and pancreatic cancer, respectively. Increasing numbers of studies have shown that the treatments may elicit an immune response in addition to eliminating the tumor cells. The purpose of this review is to give an in-depth introduction to the electroporation-induced immune response and the local and peripheral immune systems, and to describe the various studies investigating the combination of electroporation and immunotherapy. The review may help guide and inspire the design of future clinical trials investigating the potential synergy of electroporation and immunotherapy in cancer treatment. Abstract The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells. With the dawn of the immunotherapy era, the potential of combining ECT and IRE with immunotherapy has led to the launch of numerous studies. Data from the first clinical trials are promising, and new combination regimes might change the way we treat tumors characterized by low immunogenicity and high levels of immunosuppression, such as melanoma and pancreatic cancer. In this review we will give an introduction to ECT and IRE and discuss the impact on the immune system. Additionally, we will present the results of clinical and preclinical trials, investigating the combination of electroporation modalities and immunotherapy.
Collapse
Affiliation(s)
- Tobias Freyberg Justesen
- Center for Surgical Science, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark; (A.O.); (H.R.); (I.G.)
- Correspondence:
| | - Adile Orhan
- Center for Surgical Science, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark; (A.O.); (H.R.); (I.G.)
| | - Hans Raskov
- Center for Surgical Science, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark; (A.O.); (H.R.); (I.G.)
| | - Christian Nolsoe
- Center for Surgical Ultrasound, Department of Surgery, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark;
- Copenhagen Academy for Medical Education and Simulation (CAMES), University of Copenhagen and the Capital Region of Denmark, Ryesgade 53B, 2100 Copenhagen, Denmark
| | - Ismail Gögenur
- Center for Surgical Science, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark; (A.O.); (H.R.); (I.G.)
- Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| |
Collapse
|
|
29
|
Mansur A, Garg T, Shrigiriwar A, Etezadi V, Georgiades C, Habibollahi P, Huber TC, Camacho JC, Nour SG, Sag AA, Prologo JD, Nezami N. Image-Guided Percutaneous Ablation for Primary and Metastatic Tumors. Diagnostics (Basel) 2022; 12:diagnostics12061300. [PMID: 35741109 PMCID: PMC9221861 DOI: 10.3390/diagnostics12061300] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 05/20/2022] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
Image-guided percutaneous ablation methods have been further developed during the recent two decades and have transformed the minimally invasive and precision features of treatment options targeting primary and metastatic tumors. They work by percutaneously introducing applicators to precisely destroy a tumor and offer much lower risks than conventional methods. There are usually shorter recovery periods, less bleeding, and more preservation of organ parenchyma, expanding the treatment options of patients with cancer who may not be eligible for resection. Image-guided ablation techniques are currently utilized for the treatment of primary and metastatic tumors in various organs including the liver, pancreas, kidneys, thyroid and parathyroid, prostate, lung, bone, and soft tissue. This article provides a brief review of the various imaging modalities and available ablation techniques and discusses their applications and associated complications in various organs.
Collapse
Affiliation(s)
| | - Tushar Garg
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins Hospital, Baltimore, MD 21287, USA; (T.G.); (C.G.)
| | - Apurva Shrigiriwar
- Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
| | - Vahid Etezadi
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Christos Georgiades
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins Hospital, Baltimore, MD 21287, USA; (T.G.); (C.G.)
| | - Peiman Habibollahi
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Timothy C. Huber
- Vascular and Interventional Radiology, Dotter Department of Interventional Radiology, Oregon Health and Science University, Portland, OR 97239, USA;
| | - Juan C. Camacho
- Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA;
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL 34239, USA
| | - Sherif G. Nour
- Department of Radiology and Medical Imaging, Florida State University College of Medicine, Gainesville, FL 32610, USA;
| | - Alan Alper Sag
- Division of Vascular and Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA;
| | - John David Prologo
- Division of Vascular and Interventional Radiology, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA;
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
- Correspondence: or
| |
Collapse
|
|
30
|
Koethe Y, Wilson N, Narayanan G. Irreversible electroporation for colorectal cancer liver metastasis: a review. Int J Hyperthermia 2022; 39:682-687. [PMID: 35469520 DOI: 10.1080/02656736.2021.2008025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
Irreversible electroporation (IRE) ablation is gaining popularity over the last decade as a nonthermal alternative to thermal ablation technologies such as radiofrequency ablation (RFA) and Microwave ablation (MWA). This review serves as a practical guide for applying IRE to colorectal cancer liver metastases (CRLM) for interventional radiologists, oncologists, surgeons, and anesthesiologists. It covers patient selection, procedural technique, anesthesia, imaging, and outcomes.
Collapse
Affiliation(s)
- Yilun Koethe
- Department of Interventional Radiology, Oregon Health and Science University, Portland, OR, USA
| | - Nicole Wilson
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | - Govindarajan Narayanan
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.,Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.,Miami Cardiac and Vascular, Baptist Health South Florida, Miami, FL, USA
| |
Collapse
|
|
31
|
Kardani K, Milani A, Bolhassani A. Gene delivery in adherent and suspension cells using the combined physical methods. Cytotechnology 2022; 74:245-257. [PMID: 35464169 PMCID: PMC8975990 DOI: 10.1007/s10616-022-00524-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 01/25/2022] [Indexed: 11/24/2022] Open
Abstract
UNLABELLED Physical methods are widely utilized to deliver nucleic acids into cells such as electro-transfection or heat shock. An efficient gene electro-transfection requires the best conditions including voltage, the pulse length or number, buffer, incubation time and DNA form. In this study, the delivery of pEGFP-N1 vector into two adherent cell lines (HEK-293 T and COS-7) with the same origin (epithelial cells), and also mouse bone marrow-derived dendritic cells (DCs) was evaluated using electroporation under different conditions alone and along with heat treatment. Our data showed that the highest green fluorescent protein (GFP) expression in HEK-293 T and COS-7 cells was observed in serum-free RPMI cell culture medium as electroporation buffer, voltage (200 V), the pulse number (2), the pulse length (15 ms), the circular form of DNA, and 48 h after electro-transfection. In addition, the highest GFP expression in DCs was detected in serum-free RPMI, voltage (300 V), the pulse number (1), the pulse length (5 ms), and 48 h after electro-transfection. The use of sucrose as electroporation buffer, the pulse number (2), and the pulse length (25 ms) led to further cytotoxicity and lower transfection in HEK293T and COS-7 cells than other conditions. Moreover, the high voltage (700 V) increased the cell cytotoxicity, and decreased electro-transfection efficiency in DCs. On the other hand, the best conditions of electroporation along with heat treatment could significantly augment the transfection efficiency in all the cells. These data will be useful for gene delivery in other cells with the same properties using physical methods. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10616-022-00524-4.
Collapse
Affiliation(s)
- Kimia Kardani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
| | - Alireza Milani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
| | - Azam Bolhassani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
| |
Collapse
|
|
32
|
Zhang N, Li Z, Han X, Zhu Z, Li Z, Zhao Y, Liu Z, Lv Y. Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors. Front Immunol 2022; 12:811726. [PMID: 35069599 PMCID: PMC8777104 DOI: 10.3389/fimmu.2021.811726] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/13/2021] [Indexed: 01/10/2023] Open
Abstract
Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an "in-situ tumor vaccine," inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.
Collapse
Affiliation(s)
- Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhuoqun Li
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xuan Han
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ziyu Zhu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhujun Li
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yan Zhao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhijun Liu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yi Lv
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| |
Collapse
|
|
33
|
Yu M, Li S. Irreversible electroporation for liver cancer ablation: A meta analysis. Eur J Surg Oncol 2021; 48:1321-1330. [PMID: 35012834 DOI: 10.1016/j.ejso.2021.12.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/24/2021] [Accepted: 12/11/2021] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To evaluate the efficacy and safety of IRE in the treatment of hepatic malignant tumors, especially the damage to the gastrointestinal tract, bile ducts, and vital vessels. METHODS The relevant literatures published from January 1, 2010 to July 1, 2021 were searched from PubMed and Embase databases. The following keywords were applied: "irreversible electroporation", "IRE", "unresectable Hepa∗ cancer", "ablation" and "ablation therapy". RESULTS Twenty-six studies were identified covering 807 participants and 1115 lesions. The complete ablation rate of liver cancer by IRE was 86% (95% CI: 81%-90%). The incidence of IRE-related complications was 23% (95% CI: 17%-28%), but most of them were minor, major complications such as biliary fistula, intestinal fistula and massive hemorrhage were rare. CONCLUSION Meta-analysis showed that IRE ablation is safe and effective for liver cancer treatment. Bile duct, intestine and blood vessels adjacent to the tumors are rarely damaged by IRE ablation.
Collapse
Affiliation(s)
- Maoli Yu
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China.
| | - Sheng Li
- Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China.
| |
Collapse
|
|
34
|
Torres-Jiménez J, Esteban-Villarrubia J, Ferreiro-Monteagudo R, Carrato A. Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist. Cancers (Basel) 2021; 13:5938. [PMID: 34885047 PMCID: PMC8656541 DOI: 10.3390/cancers13235938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/18/2021] [Accepted: 11/21/2021] [Indexed: 12/12/2022] Open
Abstract
For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.
Collapse
Affiliation(s)
- Javier Torres-Jiménez
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Jorge Esteban-Villarrubia
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Reyes Ferreiro-Monteagudo
- Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain; (J.E.-V.); (R.F.-M.)
| | - Alfredo Carrato
- Medical Oncology Department, Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, 28034 Madrid, Spain;
| |
Collapse
|
|
35
|
Recurrent Colorectal Liver Metastases in the Liver Remnant After Major Liver Surgery-IRE as a Salvage Local Treatment When Resection and Thermal Ablation are Unsuitable. Cardiovasc Intervent Radiol 2021; 45:182-189. [PMID: 34757483 PMCID: PMC8807435 DOI: 10.1007/s00270-021-02981-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 09/18/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To examine the safety and short-term oncologic outcomes of computer-tomography-guided (CT-guided) irreversible electroporation (IRE) of recurrent, irresectable colorectal liver metastases (CRLM) after major hepatectomy deemed unsuitable for thermal ablation. PATIENTS AND METHODS Twenty-three patients undergoing CT-guided IRE of recurrent CRLM after major hepatectomy were included in this study. All tumors were located adjacent to sole remaining intrahepatic blood vessels and bile ducts, precluding thermal ablation. Patients underwent systematic clinical and imaging follow-up, including magnetic resonance imaging of the liver at 1-month and 3-month intervals thereafter. Time to local and intrahepatic tumor progression within 12 and 36 months and associated risk factors were assessed using Kaplan Meier and Cox regression analysis, respectively. RESULTS Complete ablation with a safety margin of at least 0.5 cm was achieved in 22/23 (95.6%) patients. No vessel injury or thrombosis occurred. Five patients developed moderate biliary stenosis after a median of 4 weeks, without requiring treatment. Local tumor-progression-free rates within 12/36 months were 64%/57.4%, respectively. Intrahepatic-progression-free rate within 12/36 months was 36.4%/19.5%, respectively. Five (23%) patients were tumor-free at the end of follow-up. Multivariate Cox regression analysis did not show any association between local tumor-progression-free rates and patient age, target tumor size, primary tumor side or synchronicity of liver metastases. CONCLUSION In this highly selected patient population with local recurrences of CRLM after major surgery, IRE was shown to be a safe salvage treatment option when thermal ablation is unsuitable.
Collapse
|
|
36
|
Repeat Local Treatment of Recurrent Colorectal Liver Metastases, the Role of Neoadjuvant Chemotherapy: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study. Cancers (Basel) 2021; 13:cancers13194997. [PMID: 34638481 PMCID: PMC8507904 DOI: 10.3390/cancers13194997] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/02/2021] [Accepted: 10/03/2021] [Indexed: 01/10/2023] Open
Abstract
This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan-Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher's exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416-1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249-1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483-1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).
Collapse
|
|
37
|
Lin YM, Paolucci I, Brock KK, Odisio BC. Image-Guided Ablation for Colorectal Liver Metastasis: Principles, Current Evidence, and the Path Forward. Cancers (Basel) 2021; 13:3926. [PMID: 34439081 PMCID: PMC8394430 DOI: 10.3390/cancers13163926] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/30/2021] [Accepted: 08/02/2021] [Indexed: 02/07/2023] Open
Abstract
Image-guided ablation can provide effective local tumor control in selected patients with CLM. A randomized controlled trial suggested that radiofrequency ablation combined with systemic chemotherapy resulted in a survival benefit for patients with unresectable CLM, compared to systemic chemotherapy alone. For small tumors, ablation with adequate margins can be considered as an alternative to resection. The improvement of ablation technologies can allow the treatment of tumors close to major vascular structures or bile ducts, on which the applicability of thermal ablation modalities is challenging. Several factors affect the outcomes of ablation, including but not limited to tumor size, number, location, minimal ablation margin, RAS mutation status, prior hepatectomy, and extrahepatic disease. Further understanding of the impact of tumor biology and advanced imaging guidance on overall patient outcomes might help to tailor its application, and improve outcomes of image-guided ablation.
Collapse
Affiliation(s)
- Yuan-Mao Lin
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (Y.-M.L.); (I.P.)
| | - Iwan Paolucci
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (Y.-M.L.); (I.P.)
| | - Kristy K. Brock
- Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Bruno C. Odisio
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (Y.-M.L.); (I.P.)
| |
Collapse
|
|
38
|
Mauri G, Monfardini L, Garnero A, Zampino MG, Orsi F, Della Vigna P, Bonomo G, Varano GM, Busso M, Gazzera C, Fonio P, Veltri A, Calandri M. Optimizing Loco Regional Management of Oligometastatic Colorectal Cancer: Technical Aspects and Biomarkers, Two Sides of the Same Coin. Cancers (Basel) 2021; 13:2617. [PMID: 34073585 PMCID: PMC8198296 DOI: 10.3390/cancers13112617] [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] [Received: 02/22/2021] [Revised: 05/21/2021] [Accepted: 05/22/2021] [Indexed: 11/23/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high rate of metastatic disease which is the main cause of CRC-related death. Oligometastatic disease is a clinical condition recently included in ESMO guidelines that can benefit from a more aggressive locoregional approach. This review focuses the attention on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic locoregional strategies drawn from the current literature and consensus conferences. The different percutaneous therapies (radiofrequency ablation, microwave ablation, irreversible electroporation) as well as trans-arterial approaches (chemoembolization and radioembolization) are discussed. Ablation margins, the choice of the imaging guidance as well as characteristics of the different ablation techniques and other technical aspects are analyzed. A specific attention is then paid to the increasing role of biomarkers (in particular molecular profiling) and their role in the selection of the proper treatment for the right patient. In conclusion, in this review an up-to-date state of the art of the application of locoregional treatments on CRLM is provided, highlighting both technical aspects and the role of biomarkers, two sides of the same coin.
Collapse
Affiliation(s)
- Giovanni Mauri
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
- Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, 20122 Milan, Italy
| | | | - Andrea Garnero
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
| | - Maria Giulia Zampino
- Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy;
| | - Franco Orsi
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Paolo Della Vigna
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Guido Bonomo
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Gianluca Maria Varano
- Divisione di Radiologia Interventistica, Istituto Europeo di Oncologia, IRCCS, 20141 Milan, Italy; (G.M.); (F.O.); (P.D.V.); (G.B.); (G.M.V.)
| | - Marco Busso
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
| | - Carlo Gazzera
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Paolo Fonio
- Department of Surgical Sciences, University of Turin, 10124 Torino, Italy;
- Radiodiagnostica 1 U, A.O.U. Città della Scienza e della Salute, 10126 Torino, Italy;
| | - Andrea Veltri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
| | - Marco Calandri
- Radiodiagnostica 1 U. A.O.U., San Luigi Gonzaga di Orbassano, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; (A.G.); (M.B.); (A.V.); (M.C.)
- Department of Oncology, University of Turin, 10124 Torino, Italy
| |
Collapse
|
|
39
|
Goldberg SN. More Interventional Oncologic Fire from COLDFIRE-2. Radiology 2021; 299:481-482. [PMID: 33729013 DOI: 10.1148/radiol.2021204736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- S Nahum Goldberg
- From the Department of Radiology, Hadassah Hebrew University Medical Center, PO Box 19000, Ein Karem, Jerusalem, Israel 9112001
| |
Collapse
|