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Messaoudi N, Vanlander A, Benhadda M, Makarian R, Kortbeek K, De Haar-Holleman A, Gumbs AA. Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: Revisiting traditional techniques to explore new frontiers. World J Clin Oncol 2025; 16:101274. [PMID: 40130052 PMCID: PMC11866082 DOI: 10.5306/wjco.v16.i3.101274] [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: 09/09/2024] [Revised: 11/14/2024] [Accepted: 12/09/2024] [Indexed: 01/21/2025] Open
Abstract
Hepatic arterial infusion (HAI) chemotherapy, first introduced in the 1980s, has gained recognition as an effective locoregional treatment for colorectal liver metastasis (CRLM). Initially used for unresectable liver metastases, HAI's application has expanded to the adjuvant setting following hepatic resection, with early studies indicating improved hepatic disease-free survival. Recent research demonstrates that combining HAI with modern systemic therapies enhances conversion to resectability and prolongs both recurrence-free and overall survival, even in heavily pretreated patients with diverse RAS mutational statuses. Personalization through approaches like microsatellite instability status and dose modifications further optimize outcomes. However, the complexity of HAI requires expertise across multidisciplinary teams, limiting its widespread adoption to specialized centers. Ongoing clinical trials continue to investigate HAI's role in CRLM management, highlighting its potential to become a cornerstone of liver-directed therapy. We explore how HAI chemotherapy, in combination with personalized medicine, can advance treatment strategies for metastatic colorectal cancer.
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Affiliation(s)
- Nouredin Messaoudi
- Department of Hepatopancreatobiliary Surgery, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel and Europe Hospitals, Brussels 1090, Brussels-Capital Region, Belgium
| | - Aude Vanlander
- Department of Hepatopancreatobiliary Surgery, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel and Europe Hospitals, Brussels 1090, Brussels-Capital Region, Belgium
| | - Myriam Benhadda
- Department of Hepatopancreatobiliary Surgery, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel and Europe Hospitals, Brussels 1090, Brussels-Capital Region, Belgium
| | - Roza Makarian
- Department of Hepatopancreatobiliary Surgery, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel and Europe Hospitals, Brussels 1090, Brussels-Capital Region, Belgium
| | - Koen Kortbeek
- Department of Oncology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels 1090, Brussels-Capital Region, Belgium
| | - Amy De Haar-Holleman
- Department of Oncology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels 1090, Brussels-Capital Region, Belgium
| | - Andrew A Gumbs
- Service de Chirurgie Digestive Minimale Invasive, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Clamart 92140, France
- Department of Surgery, University of Magdeburg, Magdeburg 39130, Saxony-Anhalt, Germany
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Connor Chick R, Ruff SM, Monasterio J, Neilson T, Tsai S, Ejaz A, Tsung A, Kim AC. Implementation of Hepatic Artery Infusion Pump Therapy: Real-World Single-Center Experience. J Surg Oncol 2025; 131:212-219. [PMID: 39238425 PMCID: PMC12035665 DOI: 10.1002/jso.27859] [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: 08/14/2024] [Accepted: 08/18/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND AND OBJECTIVES Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center. METHODS Patients who underwent HAIP placement (2021-2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska-Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months. CONCLUSIONS HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.
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Affiliation(s)
- Robert Connor Chick
- Division of Surgical Oncology, The James Cancer Hospital and Solove Research InstituteThe Ohio State UniversityColumbusOhioUSA
| | - Samantha M. Ruff
- Division of Surgical Oncology, The James Cancer Hospital and Solove Research InstituteThe Ohio State UniversityColumbusOhioUSA
- Department of SurgeryUniversity of VirginiaCharlottesvilleVirginaUSA
| | | | - Taylor Neilson
- Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOhioUSA
| | - Susan Tsai
- Division of Surgical Oncology, The James Cancer Hospital and Solove Research InstituteThe Ohio State UniversityColumbusOhioUSA
| | - Aslam Ejaz
- Department of Surgery, Division of Surgical OncologyUniversity of Illinois ChicagoChicagoIllinoisUSA
| | - Allan Tsung
- Department of SurgeryUniversity of VirginiaCharlottesvilleVirginaUSA
| | - Alex C. Kim
- Department of Surgery, Division of Surgical OncologyUniversity of Texas Southwestern Medical CenterDallasTexasUSA
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Meyblum L, Faron M, Deschamps F, Kobe A, Bonnet B, Boileve A, Gelli M, Boige V, Hollebecque A, Durand-Labrunie J, Malka D, Barbé R, Ducreux M, de Baere T, Tselikas L. Safety and efficacy of percutaneous arterial port Implantation for Hepatic Arterial Infusion Chemotherapy. Eur Radiol 2025; 35:1022-1033. [PMID: 39080068 DOI: 10.1007/s00330-024-10887-1] [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: 12/20/2023] [Revised: 04/12/2024] [Accepted: 05/04/2024] [Indexed: 02/01/2025]
Abstract
OBJECTIVES Approximately 40% of patients with colorectal cancer will develop liver metastases. Hepatic arterial infusion chemotherapy (HAIC) represents a valuable treatment option, with curative, palliative, or adjuvant intent. The aim of our study was to describe technical considerations, safety, and oncological outcomes of patients receiving HAIC. MATERIALS AND METHODS All patients who underwent percutaneous hepatic arterial port placement in our institution between 2004 and 2021 were included in this retrospective analysis. Demographic, anatomical and technical data were collected. Tumor response was assessed using RECIST 1.1. Kaplan-Meier estimates were used for overall survival (OS) and hepatic progression-free survival (PFS). Adverse events (AEs) were graded using the Clavien-Dindo classification. RESULTS A total of 360 patients (median age, 58.6 years [interquartile range (IQR): 49.5-65.4]; 208 men [57.8%]) were included. Percutaneous hepatic arterial port placement was successful in 87.9% of cases, resulting in 379 port placements (431 attempts). Overall, 394 HAIC courses were delivered, mostly oxaliplatin-based (94.7%), with a median of 6 cycles per course (IQR: 3-8). AEs (all grades) were observed in 42.0% of ports (grade IIIb-V: 1.1%). Most port dysfunctions could be resolved, resulting in a 73.1% rate of HAIC resumption, without impact on OS. Median OS was 22 months (IQR: 18-24), and median hepatic PFS was 11 months (IQR: 9.5-13). Tumor downstaging allowed surgery in 35.6% of patients, with significantly longer median OS than non-operated patients (39 months [IQR: 33-79] versus 14 months [IQR: 12-16], p < 0.001). CONCLUSION This retrospective cohort study demonstrates the feasibility, safety, and efficacy of percutaneous hepatic arterial port placement with an impact on survival for selected patients. CLINICAL RELEVANCE STATEMENT Percutaneous hepatic arterial port placement is feasible, safe and effective with an impact on the survival of selected patients. KEY POINTS Hepatic arterial infusion chemotherapy provides promising tumor response and overall survival, especially in cases of resection/ablation. Total complication rate of hepatic arterial infusion chemotherapy port use is high, but serious complications are rare. Port revision is often necessary but allows the resumption of hepatic arterial infusion chemotherapy without affecting overall survival.
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Affiliation(s)
- Louis Meyblum
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
| | - Matthieu Faron
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
- OncoStat (U1018), Inserm, Université Paris Saclay, Gustave Roussy, Villejuif, F-94805, France
| | - Frédéric Deschamps
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
| | - Adrian Kobe
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
| | - Baptiste Bonnet
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
| | - Alice Boileve
- Department of Medical Oncology, Gustave Roussy, Villejuif, F-94805, France
- Dynamique des Cellules Tumorales (U-1279), Inserm, Gustave Roussy, Villejuif, F-94805, France
| | - Maximilliano Gelli
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
- Dynamique des Cellules Tumorales (U-1279), Inserm, Gustave Roussy, Villejuif, F-94805, France
| | - Valérie Boige
- Department of Medical Oncology, Gustave Roussy, Villejuif, F-94805, France
| | - Antoine Hollebecque
- Department of Medical Oncology, Gustave Roussy, Villejuif, F-94805, France
- Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Gustave Roussy, Villejuif, F-94805, France
| | | | - David Malka
- Dynamique des Cellules Tumorales (U-1279), Inserm, Gustave Roussy, Villejuif, F-94805, France
- Department of Medical Oncology, Institut Mutualiste Monstouris, Paris, 75014, France
- Université Paris Saclay, Saint Aubin, 91190, France
| | - Remy Barbé
- Department of Medical Imaging, Gustave Roussy, Villejuif, F-94805, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Villejuif, F-94805, France
- Dynamique des Cellules Tumorales (U-1279), Inserm, Gustave Roussy, Villejuif, F-94805, France
- Université Paris Saclay, Saint Aubin, 91190, France
| | - Thierry de Baere
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France
- Université Paris Saclay, Saint Aubin, 91190, France
- BIOTHERIS, Centre d'Investigation Clinique INSERM U1428, Villejuif, F-94805, France
| | - Lambros Tselikas
- Département d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, F-94805, France.
- Université Paris Saclay, Saint Aubin, 91190, France.
- BIOTHERIS, Centre d'Investigation Clinique INSERM U1428, Villejuif, F-94805, France.
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Connell LC, Kemeny NE. Intraarterial Chemotherapy for Liver Metastases. Hematol Oncol Clin North Am 2025; 39:143-159. [PMID: 39510670 DOI: 10.1016/j.hoc.2024.08.005] [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] [Indexed: 11/15/2024]
Abstract
Colorectal cancer (CRC) is one of the leading cancers globally in terms of both incidence and cancer-related mortality. Liver metastatic disease is the main prognostic driver for patients with CRC. The management options for liver metastatic CRC continue to evolve, particularly with the incorporation of locoregional therapies into the treatment paradigm. Hepatic arterial infusion (HAI) chemotherapy is one such liver directed approach used with the goal of converting patients to liver resection, reducing the risk of recurrence, treating recurrent disease, and most importantly improving overall survival. This article summarizes the role of HAI chemotherapy in the treatment of liver metastatic CRC.
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Affiliation(s)
- Louise C Connell
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA
| | - Nancy E Kemeny
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA.
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Ueberroth BE, Kriss M, Burton JR, Messersmith WA. Liver transplantation for colorectal cancer with liver metastases. Oncologist 2025; 30:oyae367. [PMID: 39834127 PMCID: PMC11753392 DOI: 10.1093/oncolo/oyae367] [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: 09/03/2024] [Accepted: 12/08/2024] [Indexed: 01/22/2025] Open
Abstract
Over the last decade, multiple clinical trials have demonstrated a survival benefit for liver transplantation in colorectal cancer with liver metastases. Additionally, advances in donor organ preservation have expanded organ availability affording the opportunity to expand indications for liver transplantation, such as colorectal cancer with unresectable liver metastases. Current data support comparable overall survival (OS) for liver transplantation for colorectal cancer with liver metastases compared with general liver transplantation recipients. Supported by this data, in the United States, allocation policy is changing to include deceased donor livers for patients with unresectable colorectal cancer liver metastases. Available studies to date demonstrate improved outcomes with primary tumor R0 resection, 6-12 months of pretransplantation chemotherapy, and careful radiologic restaging (including positron emission tomography/computed tomography) to confirm lack of extrahepatic disease. A response to pretransplantation chemotherapy is a key predictor of long-term outcomes and progression during chemotherapy appears to be a contraindication to proceeding to transplant. A carcinoembryonic antigen level ≤80 µg/L and largest liver tumor dimension <5.5 cm are both associated with improved progression-free and OS in the available literature. Liver transplantation for colorectal cancer with unresectable liver metastases is associated with longer progression-free and OS compared with chemotherapy alone. Patient selection based on imaging, laboratory, and clinical findings is critical to identify patients most likely to benefit. Liver transplantation should be considered at all centers with an active transplant program to improve outcomes for patients with advanced colorectal cancer.
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Affiliation(s)
- Benjamin E Ueberroth
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, United States
| | - Michael Kriss
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, United States
| | - James R Burton
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, United States
| | - Wells A Messersmith
- Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, United States
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Zheng J, Wang T, Wang H, Yan B, Lai J, Qiu K, Zhou X, Tan J, Wang S, Ji H, Feng M, Jiang W, Wang H, Yan J. Use of a Pathomics Nomogram to Predict Postoperative Liver Metastasis in Patients with Stage III Colorectal Cancer. Ann Surg Oncol 2024:10.1245/s10434-024-16519-8. [PMID: 39614006 DOI: 10.1245/s10434-024-16519-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/30/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Approximately 25% of patients with stage III colorectal cancer experience liver metastasis after radical resection; however, there is currently a lack of methods to predict liver metastasis. This study aims to develop and validate a pathomics nomogram to predict liver metastasis in patients with stage III colorectal cancer. METHODS A total of 318 enrolled patients were divided into three cohorts: a training cohort (n = 139), a validation cohort (n = 69), and an external cohort (n = 110). A competitive risk nomogram was established by the pathomics signature and clinicopathological characteristics and assessed by calibration, discrimination, and clinical usefulness. RESULTS A significant correlation between the pathomics signature and liver metastasis in stage III colorectal cancer was found. Multivariate Fine-Gray analysis indicated that preoperative carcinoembryonic antigen level, postoperative chemotherapy, and pathomics signature were independent predictors of liver metastasis. A competitive risk nomogram was developed to predict liver metastasis in patients with stage III colorectal cancer. The predicting nomogram shows good discrimination and calibration, with C-indexes of 0.811 (95% confidence interval [CI] 0.651-0.971), 0.759 (95% CI 0.531-0.987), and 0.845 (95% CI 0.641-0.999), with area under the receiver operating characteristic (AUROC) curves at 5 years of 0.833 (95% CI 0.742-0.925), 0.760 (95% CI 0.652-0.893), and 0.812 (95% CI 0.692-0.931) in the training, validation, and external cohorts, respectively. Compared with the clinicopathological nomogram, the nomogram combined with the pathomics signature had better performance (AUROC 0.823 [95% CI 0.764-0.881] vs. 0.678 [95% CI 0.606-0.751]; p < 0.001). CONCLUSIONS The pathomics signature is a predictive indicator for liver metastasis in patients with stage III colorectal cancer, and the integrated nomogram can be used to predict liver metastasis better than the clinicopathological nomogram alone.
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Affiliation(s)
- Jixiang Zheng
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Ting Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China
| | - Botao Yan
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Jianbo Lai
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Kemao Qiu
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Xinyi Zhou
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Jie Tan
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Shijie Wang
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Hongli Ji
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Mingyuan Feng
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Wei Jiang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
| | - Hui Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People's Republic of China.
| | - Jun Yan
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.
- Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
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Holtermann A, Gislon M, Angele M, Subklewe M, von Bergwelt-Baildon M, Lauber K, Kobold S. Prospects of Synergy: Local Interventions and CAR T Cell Therapy in Solid Tumors. BioDrugs 2024; 38:611-637. [PMID: 39080180 PMCID: PMC11358237 DOI: 10.1007/s40259-024-00669-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2024] [Indexed: 08/30/2024]
Abstract
Chimeric antigen receptor T cell therapy has been established in the treatment of various B cell malignancies. However, translating this therapeutic effect to treat solid tumors has been challenging because of their inter-tumoral as well as intratumoral heterogeneity and immunosuppressive microenvironment. Local interventions, such as surgery, radiotherapy, local ablation, and locoregional drug delivery, can enhance chimeric antigen receptor T cell therapy in solid tumors by improving tumor infiltration and reducing systemic toxicities. Additionally, ablation and radiotherapy have proven to (re-)activate systemic immune responses via abscopal effects and reprogram the tumor microenvironment on a physical, cellular, and chemical level. This review highlights the potential synergy of the combined approaches to overcome barriers of chimeric antigen receptor T cell therapy and summarizes recent studies that may pave the way for new treatment regimens.
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Affiliation(s)
- Anne Holtermann
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Lindwurmstrasse 2a, 80336, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany
| | - Mila Gislon
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Lindwurmstrasse 2a, 80336, Munich, Germany
| | - Martin Angele
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Marion Subklewe
- Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany
| | - Michael von Bergwelt-Baildon
- Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany
| | - Kirsten Lauber
- Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Sebastian Kobold
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Lindwurmstrasse 2a, 80336, Munich, Germany.
- German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany.
- Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München-German Research Center for Environmental Health Neuherberg, Munich, Germany.
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8
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Filipe WF, Buisman FE, Franssen S, Krul MF, Grünhagen DJ, Bennink RJ, Bolhuis K, Bruijnen RCG, Buffart TE, Burgmans MC, van Delden OM, Doornebosch PG, Gobardhan PD, Graven L, de Groot JWB, Grootscholten C, Hagendoorn J, Harmsen P, Homs MYV, Klompenhouwer EG, Kok NFM, Lam MGEH, Loosveld OJL, Meier MAJ, Mieog JSD, Oostdijk AHJ, Outmani L, Patijn GA, Pool S, Rietbergen DDD, Roodhart JML, Speetjens FM, Swijnenburg RJ, Versleijen MWJ, Verhoef C, Kuhlmann KFD, Moelker A, Groot Koerkamp B. Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications. HPB (Oxford) 2024; 26:919-927. [PMID: 38604828 DOI: 10.1016/j.hpb.2024.03.1158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 02/07/2024] [Accepted: 03/17/2024] [Indexed: 04/13/2024]
Abstract
INTRODUCTION This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.
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Affiliation(s)
- Wills F Filipe
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands.
| | - Florian E Buisman
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Stijn Franssen
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Myrtle F Krul
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Dirk J Grünhagen
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Roel J Bennink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Rotterdam, the Netherlands
| | - Karen Bolhuis
- Department of Medical Oncology, The Netherlands Cancer Center, Amsterdam, the Netherlands
| | - Rutger C G Bruijnen
- Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Tineke E Buffart
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Mark C Burgmans
- Department of Radiology and Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Otto M van Delden
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Rotterdam, the Netherlands
| | - Pascal G Doornebosch
- Department of Surgery, IJsselland Hospital, Capelle aan den IJssel, the Netherlands
| | | | - Laura Graven
- Department of Radiology and Nuclear Medicine, Erasmus MC, Erasmus University, Rotterdam, the Netherlands
| | | | - Cecile Grootscholten
- Department of Medical Oncology, The Netherlands Cancer Center, Amsterdam, the Netherlands
| | - Jeroen Hagendoorn
- Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Paul Harmsen
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | | | - Niels F M Kok
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Marnix G E H Lam
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Olaf J L Loosveld
- Department of Medical Oncology, Amphia Hospital, Breda, the Netherlands
| | - Mark A J Meier
- Department of Radiology and Nuclear Medicine, Isala, Zwolle, the Netherlands
| | - J Sven D Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Ad H J Oostdijk
- Department of Radiology and Nuclear Medicine, Isala, Zwolle, the Netherlands
| | - Loubna Outmani
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala, Zwolle, the Netherlands
| | - Stefan Pool
- Department of Radiology and Nuclear Medicine, Amphia Hospital, Breda, the Netherlands
| | - Daphne D D Rietbergen
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Jeanine M L Roodhart
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Frank M Speetjens
- Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - Rutger Jan Swijnenburg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, the Netherlands
| | - Michelle W J Versleijen
- Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Koert F D Kuhlmann
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, Erasmus MC, Erasmus University, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands.
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9
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Sree Ganesh B, Kazi M, Goel M, Saklani A, De Souza A, Devarmani S, Gala K, Shetty N, Kulkarni S, Ramaswamy A, Ostwal V, Bhargava P, Patkar S. Feasibility of Hepatic Artery Infusion Chemotherapy for Colorectal Liver Metastasis in an Indian Setting. Indian J Surg Oncol 2024; 15:275-280. [PMID: 38817996 PMCID: PMC11133240 DOI: 10.1007/s13193-023-01871-0] [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: 09/10/2023] [Accepted: 12/21/2023] [Indexed: 06/01/2024] Open
Abstract
Hepatic artery infusion chemotherapy (HAIC) is a popular treatment modality for the treatment of colorectal liver metastasis (CRLM). The aim of this study was to determine the feasibility of HAIC for high-risk resected CRLM delivered using repeated femoral puncture and delivering 5-fluorouracil infusional chemotherapy along with systemic adjuvant chemotherapy. The present study is a retrospective review of a prospectively maintained database. All patients who underwent HAIC for colorectal liver metastases between July 2022 and July 2023 were included. A total of 12 patients were included in the study of which 11 completed four sessions as planned. The median age was 47 (29-73) years with nine male (81%) and two female (18%) patients. Rectum (n = 7, 63%) was the most common primary location. All patients received systemic chemotherapy with 5-fluorouracil-based regimens prior to HAIC (median 12 cycles). The median number of metastasis was 2 (1-8). Eight patients had metastasis in unilobar distribution (73%). On completion of HAIC treatment, nine patients (64%) were completely disease free with a median follow-up of 8 months. None of the patients experienced any immediate adverse events during or after completion of the procedure. Conventional HAIC comes with various challenges such as unavailability of the agent floxuridine and the specialized HAIC pump. Percutaneous HAIC has a lower chance of infection. The delivery of HAIC using repeated femoral punctures and 5FU chemotherapy was successful in over 90% of the patients making it a feasible option in the treatment of CRLM.
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Affiliation(s)
- B. Sree Ganesh
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Mufaddal Kazi
- Division of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Mahesh Goel
- Division of Hepatobiliary Surgical Oncology, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Avanish Saklani
- Division of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Ashwin De Souza
- Division of Colorectal Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Sanjana Devarmani
- Department of Interventional Radiology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Kunal Gala
- Department of Interventional Radiology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Nitin Shetty
- Department of Radiodiagnosis, Tata Memorial Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, Maharashtra India
| | - Suyash Kulkarni
- Department of Radiodiagnosis, Tata Memorial Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, Maharashtra India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra India
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10
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Popescu I, Dudău AM, Dima S, Herlea V, Croitoru VM, Dinu IM, Miron M, Lupescu I, Croitoru-Cazacu IM, Dumitru R, Croitoru AE. Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:696. [PMID: 38792879 PMCID: PMC11123219 DOI: 10.3390/medicina60050696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 04/14/2024] [Accepted: 04/19/2024] [Indexed: 05/26/2024]
Abstract
Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.
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Affiliation(s)
- Ionuț Popescu
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
| | - Ana-Maria Dudău
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Simona Dima
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vlad Herlea
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Pathology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vlad M. Croitoru
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Ioana Mihaela Dinu
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Monica Miron
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Ioana Lupescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Radiology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Irina M. Croitoru-Cazacu
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
| | - Radu Dumitru
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Radiology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Adina Emilia Croitoru
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
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11
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Quénet F, Carrère S, Sgarbura O. [Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. Bull Cancer 2024; 111:285-290. [PMID: 38331695 DOI: 10.1016/j.bulcan.2023.10.006] [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: 07/18/2023] [Revised: 10/30/2023] [Accepted: 10/30/2023] [Indexed: 02/10/2024]
Abstract
After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.
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Affiliation(s)
- François Quénet
- Service de chirurgie oncologique, ICM Montpellier, 208, avenue des Apothicaires, 34000 Montpellier, France.
| | - Sébastien Carrère
- Service de chirurgie oncologique, ICM Montpellier, 208, avenue des Apothicaires, 34000 Montpellier, France
| | - Olivia Sgarbura
- Service de chirurgie oncologique, ICM Montpellier, 208, avenue des Apothicaires, 34000 Montpellier, France
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12
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Kuemmerli C, Hess V, Dutkowski P, Sinz S, Kessler U, Hess GF, Billeter AT, Müller-Stich BP, Kollmar O, Müller PC. Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence. Pharmacology 2024; 109:86-97. [PMID: 38368862 PMCID: PMC11008720 DOI: 10.1159/000537887] [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: 11/19/2023] [Accepted: 02/15/2024] [Indexed: 02/20/2024]
Abstract
BACKGROUND Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome. SUMMARY In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%. HAI in combination with systemic therapy in CRLM in the adjuvant setting shows promising long-term outcomes with up to 50% 10-year survival in a large, non-randomized single-center cohort. For hepatocellular carcinoma patients, response rates as high as 20-40% have been reported for HAI and long-term outcomes compare well to other therapies. Similarly, survival for patients with unresectable intrahepatic cholangiocarcinoma 3 years after treatment with HAI is reported as high as 34%, which compares well to trials of systemic therapy where 3-year survival is usually below 5%. However, evidence is mainly limited by highly selected, heterogenous patient groups, and outdated chemotherapy regimens. The largest body of evidence stems from small, often non-randomized cohorts, predominantly from highly specialized single centers. KEY MESSAGE In well-selected patients with primary and secondary liver malignancies, HAI might improve response rates and, possibly, long-term survival. Results of ongoing randomized trials will show whether a wider adoption of HAI is justified, particularly to increase rates of resectability in advanced malignant diseases confined to the liver.
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Affiliation(s)
- Christoph Kuemmerli
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Viviane Hess
- Department of Medical Oncology, University Hospital Basel, Basel, Switzerland
| | - Philipp Dutkowski
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Stefanie Sinz
- Department of Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Ulf Kessler
- Department of Pediatric Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Centre des Maladies Digestives, Clinique Cecil, Hirslanden, Lausanne, Switzerland
| | - Gabriel F. Hess
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Adrian T. Billeter
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Beat P. Müller-Stich
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Otto Kollmar
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Philip C. Müller
- Department of Surgery, Clarunis – University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
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13
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Kedra A, Boeken T, Di Gaeta A, Querub C, Al Ahmar M, Déan C, Sapoval M, Pellerin O. Exploring a Novel Technique to Tackle the Shortage of Devices for Hepatic Arterial Infusion Chemotherapy: Early Results of an Alternate Approach for Percutaneous Arterial Port Catheter Placement. Cancers (Basel) 2023; 15:4730. [PMID: 37835422 PMCID: PMC10571966 DOI: 10.3390/cancers15194730] [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: 08/15/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. We retrospectively included patients who underwent a percutaneous placement of a hepatic intra-arterial port catheter in a single tertiary center from February 2021 to June 2022. We examined the patient baseline characteristics, technical features of the modified procedures, technical success rates, complications and oncological outcomes. Fourteen patients (median age: 60 years; q1 = 54; q3 = 70; range: 53-81 years) underwent 15 modified procedures. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien-Dindo classification. The median liver progression free survival was 6.1 months (q1 = 2.5; q3 = 7.2; range: 1.3-11.6). Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices.
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Affiliation(s)
- Alice Kedra
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
| | - Tom Boeken
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
- Faculté de Santé, Université Paris Cité, 75006 Paris, France
- HeKA Team, INRIA, 75015 Paris, France
| | - Alessandro Di Gaeta
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
| | - Charles Querub
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
- Faculté de Santé, Université Paris Cité, 75006 Paris, France
| | - Marc Al Ahmar
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
| | - Carole Déan
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
| | - Marc Sapoval
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
- Faculté de Santé, Université Paris Cité, 75006 Paris, France
| | - Olivier Pellerin
- Vascular and Oncological Interventional Radiology Department, Assistance Publique—Hôpitaux de Paris Hôpital Européen Georges Pompidou, 75015 Paris, France; (T.B.); (A.D.G.); (C.Q.); (M.A.A.); (C.D.); (M.S.); (O.P.)
- Faculté de Santé, Université Paris Cité, 75006 Paris, France
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14
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Standring O, Gholami S. Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases. Surgery 2023; 174:747-749. [PMID: 37321884 DOI: 10.1016/j.surg.2023.04.043] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/14/2023] [Accepted: 04/27/2023] [Indexed: 06/17/2023]
Abstract
First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day. With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.
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Affiliation(s)
- Oliver Standring
- Northwell Health, North Shore/Long Island Jewish Department of Surgery, Manhasset, NY. https://twitter.com/OJStandringMD
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15
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Saito A, Kitayama J, Nagai R, Aizawa K. Anatomical Targeting of Anticancer Drugs to Solid Tumors Using Specific Administration Routes: Review. Pharmaceutics 2023; 15:1664. [PMID: 37376112 DOI: 10.3390/pharmaceutics15061664] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/02/2023] [Accepted: 06/04/2023] [Indexed: 06/29/2023] Open
Abstract
Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV) drugs by targeted tumor tissue. Although dose escalation and treatment intensification have been attempted in order to increase regional concentrations of anti-tumor drugs, these approaches have produced only marginal benefits in terms of patient outcomes, while often damaging healthy organs. To overcome this problem, local administration of anti-cancer agents can yield markedly higher drug concentrations in tumor tissue with less systemic toxicity. This strategy is most commonly used for liver and brain tumors, as well as pleural or peritoneal malignancies. Although the concept is theoretically reasonable, survival benefits are still limited. This review summarizes clinical results and problems and discusses future directions of regional cancer therapy with local administration of chemotherapeutants.
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Affiliation(s)
- Akira Saito
- Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0431, Japan
| | - Joji Kitayama
- Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0431, Japan
- Division of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Tochigi, Tochigi 329-0498, Japan
| | - Ryozo Nagai
- Department of Medicine, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
| | - Kenichi Aizawa
- Division of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Tochigi, Tochigi 329-0498, Japan
- Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
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16
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Kobe A, Deschamps F, Meyblum L, Varin E, Delpla A, Hakime A, Teriitehau C, Roux C, Boileve A, Gelli M, de Baère T, Tselikas L. Coil Embolization of Variant Hepatic Arteries During Percutaneous Arterial Port Catheter Placement for Intraarterial Chemotherapy: Analysis of Intrahepatic Perfusion Redistribution and Treatment Efficacy. Cardiovasc Intervent Radiol 2023; 46:69-79. [PMID: 36319713 DOI: 10.1007/s00270-022-03303-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 10/13/2022] [Indexed: 11/05/2022]
Abstract
PURPOSE The purpose of this study was to analyze the intrahepatic perfusion redistribution after embolization of hepatic arterial variants during percutaneous arterial port catheter placement as well as to investigate the treatment efficacy of intraarterial chemotherapy in perfusion redistribution-dependent compared to redistribution-independent liver areas. MATERIALS AND METHODS This retrospective study included 62 patients (67.7% males, mean age of 56 ± 12 years). A replaced left hepatic artery was encountered in 36/62 (58.1%), a replaced right hepatic artery in 19/62 (30.6%) and a replaced left and right hepatic artery in 7/62 of patients (11.3%), respectively. Subjective perfusion analysis was performed on digital subtracted angiography and computed tomography (CT)/cone-beam computed tomography (CBCT) images evaluating the visibility of the main, segmental and subsegmental branches of the embolized variant hepatic artery, re-perfused from intrahepatic arterial anastomoses. For objective perfusion analysis ROI measurements on CT/CBCT images were taken in the redistribution-dependent and redistribution-independent liver lobe. Response analysis according to RECIST 1.1 was separately calculated for the redistribution-dependent and redistribution-independent liver lobe. RESULTS Intrahepatic reperfusion of the embolized variant hepatic artery was observed immediately after embolization with visualization of the subsegmental branches in 95.2% of patients. ROI measurements on CT/CBCT images (right lobe mean 76 ± 30.2 HU, left lobe mean 74.4 ± 30.5, p-value 0.88) did not show any differences. Treatment response after intraarterial chemotherapy did not differ between the redistribution-dependent and redistribution-independent liver lobes. CONCLUSION Embolization of hepatic arterial variants during percutaneous arterial port catheter placement results in effective intrahepatic perfusion redistribution and does not compromise treatment efficacy of intraarterial chemotherapy in the redistribution-dependent liver lobe.
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Affiliation(s)
- Adrian Kobe
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France.
| | - Frédéric Deschamps
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Louis Meyblum
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Eloi Varin
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Alexandre Delpla
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Antoine Hakime
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Christophe Teriitehau
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Charles Roux
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Alice Boileve
- Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France
| | - Massimiliano Gelli
- Department of Surgical Oncology, Gustave Roussy Cancer Campus, Villejuif, France
| | - Thierry de Baère
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
| | - Lambros Tselikas
- Department of Interventional Radiology, Gustave Roussy Cancer Center, 114 Rue Edouard Vaillant, 94805, Villejuif, France
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Cervantes A, Adam R, Roselló S, Arnold D, Normanno N, Taïeb J, Seligmann J, De Baere T, Osterlund P, Yoshino T, Martinelli E. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34:10-32. [PMID: 36307056 DOI: 10.1016/j.annonc.2022.10.003] [Citation(s) in RCA: 741] [Impact Index Per Article: 370.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/06/2022] [Accepted: 10/06/2022] [Indexed: 02/08/2023] Open
Affiliation(s)
- A Cervantes
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - R Adam
- AP-HP Hôpital Paul Brousse, Université Paris-Saclay, ER "Chronothérapie, Cancers, Transplantation", Villejuif, France
| | - S Roselló
- Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain
| | - D Arnold
- Department of Oncology and Hematology, Asklepios Tumourzentrum Hamburg, AK Altona, Hamburg, Germany
| | - N Normanno
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumouri, 'Fondazione G. Pascale'-IRCCS, Naples, Italy
| | - J Taïeb
- Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, Assitance Publique-Hôpitaux de Paris AP-HP Paris Centre, Paris, France; Paris Cancer Institute SIRIC CARPEM, Centre de Recherche des Cordeliers, Université Paris-Cité, Paris, France
| | - J Seligmann
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - T De Baere
- Department of Interventional Radiology, Gustave Roussy, Villejuif, France; University of Paris-Saclay, UFR Médecine Le Kremlin-Bicêtre, Le Kremlin-Bicêtre, France; Centre d'Investigation Clinique BIOTHERIS, INSERM CIC1428, Villejuif, France
| | - P Osterlund
- Tampere University Hospitals and University, Tampere, Finland; Tema Cancer/GI-oncology, Karolinska Comprehensive Cancer Centre, Karolinska Institute, Solna, Sweden
| | - T Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - E Martinelli
- Department of Precision Medicine, Oncology Unit, Università della Campania "L. Vanvitelli", Naples, Italy
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Randrian V, Pernot S, Sionneau B, Smith D, Lim A, Touchefeu Y, Gallois C, Turpin A, Javed S, Guimbaud R, Rivera P, Karoui M, Auclin E, Taieb J. Hepatic Arterial Infusion Chemotherapy With Folfirinox or Oxaliplatin Alone in Metastatic Colorectal Cancer. Front Med (Lausanne) 2022; 9:830595. [PMID: 35783637 PMCID: PMC9243466 DOI: 10.3389/fmed.2022.830595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/05/2022] [Indexed: 12/04/2022] Open
Abstract
Background Hepatic arterial infusion (HAI) of chemotherapy is an option for the treatment of patients with liver metastases from colorectal cancer (LMCRC). Though HAI with oxaliplatin (HAI-Ox) is generally used, intravenous (IV) 5-fluoro-uracil (5FU)-oxaliplatin-irinotecan HAI (HAI-Folfirinox) is feasible and leads to curative-intent surgery in 30% of pretreated patients. We compared the efficacy and safety of HAI-Ox and HAI-Folfirinox. Methods Patients who underwent HAI chemotherapy for LMCRC were retrospectively included from 2008 to 2019 from six French expert centers. Results Data were collected from 273 previously treated patients with LMCRC. Patients received HAI-Folfirinox (n = 52) or HAI-Ox (n = 221) combined with IV chemotherapy. The objective response rate (ORR) was 43.2% in patients with HAI-Folfirinox and 45.9% (ns) in patients with HAI-Ox. Median overall survival (OS) was 17 months (95% CI: 15–32.3) with HAI-Folfirinox and 26.2 months (95% CI: 19.4–34.4; p = 0.1) with HAI-Ox. Median progression-free survival (PFS) was 7.9 months (95% CI: 4.9–10.3) with HAI-Folfirinox and 6.4 months (95% CI: 6.0–7.7; p = 0.6) with HAI-Ox. The secondary liver resection rate was 35.6% with HAI-Folfirinox and 16.7% with HAI-Ox (p = 0.007). Grade 2 and above toxicities were significantly more frequent with HAI-Folfirinox. In the global population, only 2 factors were prognostic for OS in multivariable analyses: liver-only disease [hazard ratio (HR): 0.4; 95% CI 0.20–0.83; p = 0.013] and local complications of the catheter (HR: 3.8; 95% CI 1.6–9.0; p = 0.002). Conclusion Hepatic arterial infusion results in high response rates, secondary resections, and long survival in pretreated patients with LMCRC.
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Affiliation(s)
- Violaine Randrian
- Department of Hepato-Gastro-Enterology, CHU Poitiers, Poitiers, France
| | - Simon Pernot
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France
| | | | - Denis Smith
- Medical Oncology, Bordeaux University Hospital, Bordeaux, France
| | - Annie Lim
- Department of Gastroenterology, Clinique Santé Atlantique, Saint-Herblain, France
| | - Yann Touchefeu
- Department of Hepatogastroenterology, Digestive Oncology, Nantes University Hospital, Nantes, France
| | - Claire Gallois
- Department of Gastrointestinal Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | | | - Sahir Javed
- Department of Oncology, CHU Lille, Lille, France
| | - Rosine Guimbaud
- Department of Digestive Oncology, IUCT-Rangueil, CHU Toulouse, Toulouse, France
| | - Pascale Rivera
- Department of Digestive Oncology, IUCT-Rangueil, CHU Toulouse, Toulouse, France
| | - Mehdi Karoui
- Department of Surgical Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | - Edouard Auclin
- Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Bourgogne Franche-Comté University, INSERM, EFS BFC, UMR 1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
- Department of Medical Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
| | - Julien Taieb
- Department of Gastrointestinal Oncology, Université de Paris, Hôpital Européen Georges Pompidou, Paris, France
- *Correspondence: Julien Taieb,
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19
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Adjuvant intra-arterial chemotherapy for patients with resected colorectal liver metastases: a systematic review and meta-analysis. HPB (Oxford) 2022; 24:299-308. [PMID: 34895829 DOI: 10.1016/j.hpb.2021.10.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/18/2021] [Accepted: 10/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The practice of adjuvant hepatic arterial infusion chemotherapy (HAIC) for colorectal liver metastasis (CRLM) varies widely. This meta-analysis investigates the effectiveness of adjuvant HAIC and the influence of variations in HAIC treatment in patients with resected CRLM. METHODS PRISMA guidelines were followed for this study. The search was limited to comparative studies (HAIC vs non-HAIC) for overall survival. Subgroup meta-analyses using random-effects were performed for type of intra-arterial drug, method of catheter insertion, use of concomitant adjuvant systemic chemotherapy, and study design. RESULTS Eighteen eligible studies were identified. After excluding overlapping cohorts, fifteen studies were included in the quantitative analysis, corresponding to 3584 patients. HAIC was associated with an improved overall survival (pooled hazard ratio (HR) 0.77; 95%CI 0.64-0.93). Survival benefit of HAIC was most pronounced in studies using floxuridine (HR 0.76; 95%CI: 0.62-0.94), surgical catheter insertion with subcutaneous pump (HR 0.71; 95%CI: 0.61-0.84), and concomitant adjuvant systemic chemotherapy (HR 0.75; 95%CI: 0.59-0.96). The pooled HR of RCTs was 0.91 (95%CI 0.72-1.14), of which only 3 used floxuridine. CONCLUSION Adjuvant HAIC is a promising treatment for patients with resectable CRLM, in particular HAIC with floxuridine using a surgically placed catheter and a subcutaneous pump, and concomitant systemic chemotherapy.
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20
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Izaaryene J, Golin M, Daidj N, Piana G, Ferre M. A study of dose indicators during intra-arterial catheter implantation for liver chemotherapy. JOURNAL OF RADIOLOGICAL PROTECTION : OFFICIAL JOURNAL OF THE SOCIETY FOR RADIOLOGICAL PROTECTION 2021; 41:495-511. [PMID: 33827058 DOI: 10.1088/1361-6498/abf570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 04/07/2021] [Indexed: 06/12/2023]
Abstract
The aim of the present study was to describe patient dose indicator levels during intra-arterial catheter (IAC) implantation for liver chemotherapy, and to determine factors affecting the dose indicators. Between January 2017 and January 2019, 61 patients with hepatic metastases from colorectal cancer were retrospectively included. Interventions were carried out in a standardised manner by three experienced radiologists on the same angiographic table without changes in protocol parameters. For each patient, clinical, radiological and dosimetry data were collected, including the air kerma area product (KAP), part of KAP due to the fluoroscopy and fluoroscopy time (FT), total kerma at the reference interventional point and peak skin dose (PSD). Local dose reference levels (RLs) were determined as the third quartile of the patient dose distributions. Univariate and multivariate analysis of factors affecting dose indicators was performed. The mean KAP was 111 Gy cm2, the mean reference point air kerma (Ka,r) was 648 mGy, the mean PSD was 613 mGy, and the mean FT was 3190 s (62% of the KAP). The mean cone beam computed tomography dose was 37.3 ± 11.8 Gy cm2, which accounted for 37% of the KAP. The RL could be proposed taking into account the third quartiles (KAP = 164.6 Gy cm2, Ka,r = 904.5 mGy, FT = 4011 s and standard deviation = 772.7 mGy). The factors affecting dose indicators were related to the patients (sex, cardiovascular risk factors, weight, body mass index), to the vascular anatomies (coeliac trunk angulation) and to the procedures (number of embolised arteries). This study allowed a better understanding of dose indicators and factors affecting these indicators during the implantation of IACs for hepatic chemotherapy, which is a long and difficult procedure. Local dose RLs were determined. Multicentre, multi-equipment studies are necessary.
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Affiliation(s)
- Jean Izaaryene
- Department of Radiology, Institut Paoli Calmettes, 232 Boulevard Sainte Marguerite, Marseille 13009, France
- Aix Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, Marseille 13007, France
| | - Melissa Golin
- Department of Radiology, Institut Paoli Calmettes, 232 Boulevard Sainte Marguerite, Marseille 13009, France
- Aix Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, Marseille 13007, France
| | - Nassima Daidj
- Department of Radiology, Institut Paoli Calmettes, 232 Boulevard Sainte Marguerite, Marseille 13009, France
- Aix Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, Marseille 13007, France
| | - Gilles Piana
- Department of Radiology, Institut Paoli Calmettes, 232 Boulevard Sainte Marguerite, Marseille 13009, France
- Aix Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, Marseille 13007, France
| | - Marjorie Ferre
- Department of Radiology, Institut Paoli Calmettes, 232 Boulevard Sainte Marguerite, Marseille 13009, France
- Aix Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, Marseille 13007, France
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21
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Donadon M, Rimassa L, Torzilli G. Unravel hepatic artery infusion chemotherapy in patients with resected colorectal liver metastases. Hepatobiliary Surg Nutr 2021; 10:257-260. [PMID: 33898571 PMCID: PMC8050568 DOI: 10.21037/hbsn-20-832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/11/2021] [Indexed: 11/06/2022]
Affiliation(s)
- Matteo Donadon
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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22
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Kwan J, Pua U. Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis. Cancers (Basel) 2021; 13:cancers13061371. [PMID: 33803606 PMCID: PMC8003062 DOI: 10.3390/cancers13061371] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/14/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.
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Percutaneous Implantation of a Microcatheter-Port System for Hepatic Arterial Infusion Chemotherapy of Unresectable Liver Tumors: Technical Feasibility, Functionality, and Complications. Diagnostics (Basel) 2021; 11:diagnostics11030399. [PMID: 33652814 PMCID: PMC7996956 DOI: 10.3390/diagnostics11030399] [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: 12/21/2020] [Revised: 02/15/2021] [Accepted: 02/23/2021] [Indexed: 02/07/2023] Open
Abstract
To evaluate the feasibility and safety of percutaneously implanted arterial port catheter systems for hepatic arterial infusion of chemotherapy (HAI) in patients with unresectable liver malignancies. From October 2010 to August 2018, arterial port catheters for HAI were percutaneously implanted in 43 patients with unresectable liver malignancies. Three different catheter placement techniques were compared: a conventional end-hole catheter placed in the common hepatic artery (technique 1, n = 16), a side-hole catheter with the tip fixed in the gastroduodenal artery (technique 2, n = 18), and a long-tapered side-hole catheter with the tip inserted distally in a segmental hepatic artery (technique 3, n = 6). Catheter implantation was successful in 40 (93%) of the 43 patients. Complications related to catheter placement were observed in 10 (23%) patients; 5 (83%) of the 6 major complications were resolved, as well as all 4 minor complications. Catheter migration and occlusion occurred in 9 (22.5%) patients. Catheter migration was more frequent with technique 1 (n = 6) than with technique 2 (n = 1), although the difference was not significant (p = 0.066). Percutaneous arterial port catheter implantation for HAI is highly feasible and carries a low risk of complications.
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24
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Connell LC, Kemeny NE. Intraarterial Chemotherapy for Liver Metastases. Surg Oncol Clin N Am 2021; 30:143-158. [PMID: 33220802 PMCID: PMC8594481 DOI: 10.1016/j.soc.2020.08.005] [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] [Indexed: 10/23/2022]
Abstract
Colorectal cancer (CRC) is one of the leading cancers globally in terms of both incidence and cancer-related mortality. Liver metastatic disease is the main prognostic driver for patients with CRC. The management options for liver metastatic CRC continue to evolve, particularly with the incorporation of locoregional therapies into the treatment paradigm. Hepatic arterial infusion (HAI) chemotherapy is one such liver directed approach used with the goal of converting patients to liver resection, reducing the risk of recurrence, treating recurrent disease, and most importantly improving overall survival. This article summarizes the role of HAI chemotherapy in the treatment of liver metastatic CRC.
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Affiliation(s)
- Louise C Connell
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA
| | - Nancy E Kemeny
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 10th floor, New York, NY 10065, USA.
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25
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Buisman FE, Grünhagen DJ, Homs MYV, Grootscholten C, Filipe WF, Kemeny NE, Cercek A, D'Angelica MI, Donswijk ML, van Doorn L, Emmering J, Jarnagin WR, Kingham TP, Klompenhouwer EG, Kok NFM, Kuiper MC, Moelker A, Prevoo W, Versleijen MWJ, Verhoef C, Kuhlmann KFD, Groot Koerkamp B. Adjuvant Hepatic Arterial Infusion Pump Chemotherapy After Resection of Colorectal Liver Metastases: Results of a Safety and Feasibility Study in The Netherlands. Ann Surg Oncol 2019; 26:4599-4607. [PMID: 31641947 PMCID: PMC6863781 DOI: 10.1245/s10434-019-07973-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Indexed: 12/27/2022]
Abstract
Background The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs. Study Design A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien–Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy. Results A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51–64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29–52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed uneventfully in all patients. Conclusion Pump implantation is safe, and administration of HAIP chemotherapy is feasible, in patients with resectable CRLMs, after training of a dedicated multidisciplinary team.
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Affiliation(s)
- Florian E Buisman
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands
| | - Dirk J Grünhagen
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands
| | - Cecile Grootscholten
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Wills F Filipe
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands
| | - Nancy E Kemeny
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Micheal I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maarten L Donswijk
- Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Leni van Doorn
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands
| | - Jasper Emmering
- Department of Radiology and Nuclear Medicine, Erasmus MC, Erasmus University, Rotterdam, The Netherlands
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Niels F M Kok
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Maria C Kuiper
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, Erasmus MC, Erasmus University, Rotterdam, The Netherlands
| | - Warner Prevoo
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Michelle W J Versleijen
- Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands
| | - Koert F D Kuhlmann
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, The Netherlands.
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26
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Saad AM, Abdel-Rahman O. Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases. Expert Opin Pharmacother 2019; 20:1767-1775. [PMID: 31314604 DOI: 10.1080/14656566.2019.1642324] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Introduction: The liver is the most common metastatic site in colorectal cancer with more than half the patients developing a liver metastasis either at the time of their diagnosis (synchronous) or later (metachronous). Surgical resection remains the principal curative approach that offers significant survival improvements. However, upfront surgery is only possible in about 10-20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential. Areas covered: In this review, the authors provide an overview of the standard approaches for the initial management of patients with colorectal cancer with liver metastases. They then provide an up-to-date discussion of first-line systemic chemotherapy/targeted therapy options in the contexts of initially resectable and unresectable disease and review toxicities and complications following these options. Expert opinion: Advances in chemotherapeutic agents and biological targeted therapies have improved the prognosis of colorectal cancer with liver metastases. However, there is still no 'single best approach', making further trials necessary to provide more evidence.
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Affiliation(s)
| | - Omar Abdel-Rahman
- Clinical Oncology Department, Ain Shams University , Cairo , Egypt.,Department of Oncology, University of Alberta, Cross Cancer Institute , Edmonton , Alberta , Canada
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27
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Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol 2019; 11:150-172. [PMID: 30820266 PMCID: PMC6393711 DOI: 10.4254/wjh.v11.i2.150] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 11/24/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.
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Affiliation(s)
| | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China.
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