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Leigh J, Ahmed A, Aubin F, Berry S, Boucher M, Campeau MP, Colwell B, Connors S, Corbett J, Dadwal S, Dudani S, Elimova E, Falkson C, Galvis L, Goel R, Gotfrit J, Hyde A, Febbraro M, Laidley DT, Locke G, Mahmud A, Baccili Cury Megid T, Michael J, Nair VJ, Quigley S, Ramjeesingh R, Samimi S, Seal M, Snow S, Spadafora S, Stuckless T, Wilson B, Asmis T, Goodwin R, Vickers M. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2024. Curr Oncol 2025; 32:175. [PMID: 40136379 PMCID: PMC11941643 DOI: 10.3390/curroncol32030175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/05/2025] [Accepted: 03/13/2025] [Indexed: 03/27/2025] Open
Abstract
The Eastern Canadian Gastrointestinal Cancer Consensus Conference was an annual meeting that was held in St. John's, Newfoundland and Labrador, from 26 to 28 September 2024. This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers.
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Affiliation(s)
| | - Arwa Ahmed
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Francine Aubin
- Centre Hospitalier de l’Universite de Montreal, Montreal, QC H2X 3E4, Canada
| | - Scott Berry
- Trillium Health Partners, Mississauga, ON L5A 4G1, Canada
| | - Melanie Boucher
- Prince Edward Island Cancer Treatment Center, Charlottetown, PE C1A 8T5, Canada
| | | | - Bruce Colwell
- Queen Elizabeth II Health Sciences Center, Halifax, NS B3H 3A7, Canada
| | | | - Jessica Corbett
- Prince Edward Island Cancer Treatment Center, Charlottetown, PE C1A 8T5, Canada
| | | | - Shaan Dudani
- William Osler Health System, Brampton, ON L6R 3J7, Canada
| | - Elena Elimova
- Princess Margaret Cancer Center, Toronto, ON M5G 2M9, Canada
| | - Conrad Falkson
- Kingston Health Sciences Center, Kingston, ON K7L 2V7, Canada
| | - Luisa Galvis
- Horizon Health Network, Fredericton, NB E3B 4R3, Canada
| | - Rakesh Goel
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Joanna Gotfrit
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Angela Hyde
- Dr. H. Bliss Murphy Cancer Center, St. John’s, NL A1B 3X5, Canada
| | - Michela Febbraro
- Algoma District Cancer Program, Sault Ste. Marie, ON P6B 0A8, Canada
| | | | - Gordon Locke
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Aamer Mahmud
- Kingston Health Sciences Center, Kingston, ON K7L 2V7, Canada
| | | | - James Michael
- Saint John Regional Hospital Oncology Center, Saint John, NB E2L 4L2, Canada
| | - Vimoj J. Nair
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Stephen Quigley
- Health Sciences Center-Eastern Health, St. John’s, NL A1B 3V6, Canada
| | - Ravi Ramjeesingh
- Queen Elizabeth II Health Sciences Center, Halifax, NS B3H 3A7, Canada
| | - Setareh Samimi
- Hopital du Sacre-Coeur de Montreal, Montreal, QC H4J 1C5, Canada
| | - Melanie Seal
- Dr. H. Bliss Murphy Cancer Center, St. John’s, NL A1B 3X5, Canada
| | - Stephanie Snow
- Queen Elizabeth II Health Sciences Center, Halifax, NS B3H 3A7, Canada
| | - Silvana Spadafora
- Algoma District Cancer Program, Sault Ste. Marie, ON P6B 0A8, Canada
| | - Teri Stuckless
- Dr. H. Bliss Murphy Cancer Center, St. John’s, NL A1B 3X5, Canada
| | - Brooke Wilson
- Kingston Health Sciences Center, Kingston, ON K7L 2V7, Canada
| | - Timothy Asmis
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Rachel Goodwin
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
| | - Michael Vickers
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
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Pat Fong W, Li ZJ, Ren C, Guan WL, Zuo MX, Zhang TQ, Li BK, Zheng Y, Wu XJ, Ding PR, Chen G, Pan ZZ, Yuan YF, Tan Q, Wang ZQ, Li YH, Wang DS. Percutaneous hepatic artery infusion chemotherapy with oxaliplatin and fluoropyrimidines in treatment-resistant colorectal cancer patients with unresectable liver metastases: a retrospective cohort study. HPB (Oxford) 2025; 27:289-298. [PMID: 39668070 DOI: 10.1016/j.hpb.2024.11.008] [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: 06/20/2024] [Revised: 11/19/2024] [Accepted: 11/25/2024] [Indexed: 12/14/2024]
Abstract
BACKGROUND Subsequent lines of therapy for chemotherapy-resistant metastatic colorectal cancer (CRC) have shown limited efficacy. Herein, we retrospectively investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) using oxaliplatin plus 5-FU/FUDR in patients with unresectable colorectal liver metastases (CRLM) who progressed following standard chemotherapy regimens. METHODS From March 2017 to April 2023, CRC patients with unresectable CRLM who progressed following standard chemotherapy and subsequently received HAIC oxaliplatin plus 5-FU/FUDR were evaluated. Objective response rate (ORR), disease control rate (DCR), median depth of tumor response (DpR), no evidence of disease (NED) rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. RESULTS A total of 21 patients who progressed after a median of two (range: 1-4) lines of standard systemic chemotherapy were included. The ORR and DCR were 28.6 % and 95.2 %, respectively, with six patients reaching partial response. Additionally, the median DpR was 10.6 %, and seven patients underwent successful conversion surgery. Stratification revealed significantly better PFS in patients with liver-limited metastases compared to those with concurrent hepatic and extrahepatic metastases (P = 0.0003). CONCLUSION HAIC oxaliplatin plus 5-FU/FUDR is a robust regimen for treatment-resistant CRC patients with unresectable CRLM, particularly those with liver-limited disease.
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Affiliation(s)
- William Pat Fong
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zi-Jing Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Chao Ren
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wen-Long Guan
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Meng-Xuan Zuo
- Department of Minimally Invasive & Interventional Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Tian-Qi Zhang
- Department of Minimally Invasive & Interventional Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bin-Kui Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yun Zheng
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao-Jun Wu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yun-Fei Yuan
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qiong Tan
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Qiang Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yu-Hong Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
| | - De-Shen Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Hematol Oncol Clin North Am 2025; 39:1-24. [PMID: 39510667 DOI: 10.1016/j.hoc.2024.08.011] [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
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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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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Ayala-de Miguel C, Jiménez-Castro J, Sánchez-Vegas A, Díaz-López S, Chaves-Conde M. Third-line treatment and beyond in metastatic colorectal cancer: What do we have and what can we expect? Crit Rev Oncol Hematol 2024; 202:104454. [PMID: 39043356 DOI: 10.1016/j.critrevonc.2024.104454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 07/11/2024] [Accepted: 07/13/2024] [Indexed: 07/25/2024] Open
Abstract
Colorectal cancer remains the third most common cancer worldwide and the second cause of cancer-related death. Treatment advances and precision oncological medicine for these tumours have been stalled in comparison to those for other common tumours such as lung and breast cancer. However, the recent publication of the SUNLIGHT trial results with the trifluridine/tipiracil (TAS-102)-bevacizumab combination and the irruption of new molecular targets with guided treatments have opened new possibilities in third-line metastatic colorectal cancer management. Anti-EGFR rechallenge, anti-HER2 targeted therapies or the promising results of Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC), are some of the available options that may modify what is presumably third-line colorectal treatment. Hereby, we present the evidence of the different treatment options in third-line colorectal cancer and beyond, as well as the possibilities of sequencing them.
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Affiliation(s)
- Carlos Ayala-de Miguel
- Servicio Oncología Médica, Hospital Universitario Virgen de Valme, Ctra, de Cádiz Km 548,9, Seville C.P. 41014, Spain.
| | - Jerónimo Jiménez-Castro
- Servicio Oncología Médica, Hospital Universitario Virgen de Valme, Ctra, de Cádiz Km 548,9, Seville C.P. 41014, Spain.
| | - Adrián Sánchez-Vegas
- Servicio Oncología Médica, Hospital Universitario Virgen de Valme, Ctra, de Cádiz Km 548,9, Seville C.P. 41014, Spain.
| | - Sebastián Díaz-López
- Servicio Oncología Médica, Hospital Universitario Virgen de Valme, Ctra, de Cádiz Km 548,9, Seville C.P. 41014, Spain.
| | - Manuel Chaves-Conde
- Servicio Oncología Médica, Hospital Universitario Virgen de Valme, Ctra, de Cádiz Km 548,9, Seville C.P. 41014, Spain.
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Valéry M, Tanguy ML, Gelli M, Smolenschi C, Hollebecque A, Boilève A, de Sevilla EF, Tselikas L, Bonnet B, Goéré D, Taïeb J, Boige V, Ducreux M, Malka D. Oxaliplatin-induced peripheral neuropathy with hepatic arterial versus intravenous infusion in metastatic colorectal cancer. Support Care Cancer 2024; 32:660. [PMID: 39283505 DOI: 10.1007/s00520-024-08807-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 08/13/2024] [Indexed: 10/20/2024]
Abstract
BACKGROUND Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with the intravenous (IV) route has not been specifically explored so far. METHODS We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000-05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE, and FFCD 2000-05 trials and through a review of Gustave Roussy patients' electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grades 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. RESULTS A total of 363 patients were included (IV, 300; HAI, 63). In total, 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN either (p = 0.23). CONCLUSION The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not reduce the incidence, precocity, and severity of PN.
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Affiliation(s)
- Marine Valéry
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Marie-Laure Tanguy
- Service de Biostatistique et d'Épidémiologie, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- Équipe Labellisée Ligue Contre Le Cancer, Oncostat U1018, INSERM, Université Paris-Saclay, Villejuif, France
| | - Maximiliano Gelli
- Département de Chirurgie Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Cristina Smolenschi
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- Département d'Innovation Thérapeutique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Antoine Hollebecque
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- Département d'Innovation Thérapeutique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Alice Boilève
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- INSERM Unité Dynamique Des Cellules Tumorales, Université Paris-Saclay, Gustave Roussy, 94805, Villejuif, France
| | | | - Lambros Tselikas
- Département d'Imagerie Médicale et de Radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Baptiste Bonnet
- Département d'Imagerie Médicale et de Radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Diane Goéré
- Service de Chirurgie Viscérale, Cancérologique et Endocrinienne, Hôpital Universitaire Saint-Louis, Paris, France
| | - Julien Taïeb
- Service d'Oncologie Digestive, Hôpital Européen Georges Pompidou, Paris, France
| | - Valérie Boige
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
| | - Michel Ducreux
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France
- INSERM Unité Dynamique Des Cellules Tumorales, Université Paris-Saclay, Gustave Roussy, 94805, Villejuif, France
| | - David Malka
- INSERM Unité Dynamique Des Cellules Tumorales, Université Paris-Saclay, Gustave Roussy, 94805, Villejuif, France.
- Département d'Oncologie Médicale, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014 Paris, France.
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Dumont F, Kepenekian V, Passot C, Ezanno-Manasterski AC, Pocard M, Raoul JL, Lelièvre B, Hiret S, Senellart H, Pein F, Raimbourg J, Campion L, Thibaudeau E, Paul J, Glehen O. PIPAC in patients with peritoneal metastases from gastrointestinal tract (PIPOX01): An open label, non-comparative phase 1/2 dose escalation and expansion trial. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108468. [PMID: 38878757 DOI: 10.1016/j.ejso.2024.108468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/20/2024] [Accepted: 06/04/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND Despite modern systemic chemotherapy, survival remains poor for patients with advanced isolated peritoneal metastases from the gastrointestinal tract. We aimed to assess the safety and efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin. PATIENTS AND METHODS We conducted a phase 1/2, open label, non-comparative, dose escalation and expansion trial of PIPAC with oxaliplatin in patients with a peritoneal cancer index (PCI) of more than 5, 13 and 15 for respectively a gastric, small bowel and colorectal primary cancer, and who had received at least three months of systemic chemotherapy. PIPAC cycle lengths were 4-6 weeks with systemic chemotherapy allowed 15 days after each PIPAC. PCI and oxaliplatin tumor concentration were assessed every PIPAC cycle. The main endpoints were tolerability, tumor response, and survival. RESULTS Between 2017 and 2020, 34 patients were enrolled in three centers, in this phase 1/2 study, of whom 25 were evaluable at the recommended dose determined in the phase I trial (90 mg/m2 plus systemic 5-FU). Before inclusion, patients received a median of 2 [1-4] chemotherapy lines and had a median PCI of 22.5 [7-29]. At this dose, the safety profile showed acceptable tolerability. Eight patients (32 %) had grade 3/4 treatment-related adverse events. Minor (grade 1/2) adverse events were mainly abdominal pain (n = 19, 76 %) and nausea (n = 16, 64 %). Median PFS was 6.1 months and median OS was 13 months. CONCLUSION In patients with advanced and refractory peritoneal metastasis, PFS of 6.1 months is encouraging. A prospective randomized phase II study is required.
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Affiliation(s)
- Frédéric Dumont
- Department of Surgical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France.
| | - Vahan Kepenekian
- Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France
| | - Christophe Passot
- Oncopharmacology - Pharmacogenetics, Institut de Cancérologie de l'Ouest, Site d'Angers, France
| | | | - Marc Pocard
- Department of Surgery, Hôpital d'Instruction des armées Begin, Saint-Mande, France
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Bénédicte Lelièvre
- Laboratory of Pharmacology and Toxicology, Centre Hospitalier et Universitaire, Angers, France
| | - Sandrine Hiret
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Hélène Senellart
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Francois Pein
- Department of Clinical Research and Innovation, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Judith Raimbourg
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Loic Campion
- Department of Biostatistics and Methodology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Emilie Thibaudeau
- Department of Surgical Oncology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Julie Paul
- Department of Biostatistics and Methodology, Institut de Cancérologie de l'Ouest, Site de Saint Herblain, France
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France
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Karaoğlan BB, Öz DK, Araz MS, Akyol C, Utkan G. Advancements in the Management of Synchronous Colorectal Liver Metastases: A Comprehensive Review of Surgical, Systemic, and Local Treatment Modalities. Curr Oncol Rep 2024; 26:791-803. [PMID: 38776011 PMCID: PMC11224077 DOI: 10.1007/s11912-024-01548-z] [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] [Accepted: 05/11/2024] [Indexed: 07/05/2024]
Abstract
PURPOSE OF REVIEW This review addresses the current landscape of colorectal cancer (CRC) with a focus on liver metastases, the third most common cancer globally. It explores recent findings in treatment strategies, emphasizing the dynamic interplay between surgery, systemic chemotherapy, and local therapies for synchronous colorectal liver metastases (CRLMs). RECENT FINDINGS Highlighting the role of advanced imaging, the review underscores the significance of contrast-enhanced MRI in surgical planning for CRLMs. Surgical resection remains a primary choice for resectable cases, with considerations for oncologic scoring systems and tumor biology. Perioperative systemic chemotherapy plays a pivotal role, especially in conversion therapy for initially unresectable CRLMs. The review also explores various local therapies, including radiofrequency ablation, microwave ablation, stereotactic body radiotherapy, hepatic arterial infusional chemotherapy, selective internal radiation therapy, and transarterial chemoembolization for unresectable cases. A comprehensive approach, integrating surgery, systemic chemotherapy, and local therapies, is crucial for managing synchronous CRLMs. Surgical resection and perioperative chemotherapy are key players, guided by considerations of tumor biology and scoring systems. For unresectable cases, local therapies offer viable alternatives, emphasizing the need for tailored treatments. Multidisciplinary collaboration among medical oncologists, surgeons, and radiologists is essential. Ongoing research will refine treatment approaches, while emerging technologies hold promise for further advancements in managing colorectal liver metastases.
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Affiliation(s)
- Beliz Bahar Karaoğlan
- Department of Medical Oncology, Faculty of Medicine, Ankara University, 06100, Ankara, Turkey.
| | - Diğdem Kuru Öz
- Department of Radiology, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Mine Soylu Araz
- Department of Nuclear Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Cihangir Akyol
- Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Güngör Utkan
- Department of Medical Oncology, Faculty of Medicine, Ankara University, 06100, Ankara, Turkey
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10
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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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11
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Cherchenko K, Lukashenko A, Ostapenko Y, Patsko V, Vinohradova M, Valikhnovska K, Pamanska S. INTRA-ARTERIAL CHEMOTHERAPY AS A CLINICAL OPTION FOR METASTATIC COLORECTAL CANCER: CONVERSION OF INOPERABLE LIVER METASTASES TO OPERABLE ILLUSTRATED WITH A CLINICAL CASE. Exp Oncol 2024; 45:515-522. [PMID: 38328838 DOI: 10.15407/exp-oncology.2023.04.515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Indexed: 02/09/2024]
Abstract
Colorectal cancer exerts a very high level of liver metastases, even on primary diagnosis, with 80%-90% unresectable nodules. At the same time, the possibility of resection has a significant impact on survival: 5-year survival is 6%-10% without liver surgery and up to 30% upon resection of liver metastases. Finding ways to improve resectability is a topical search for doctors all over the world. One of the promising methods to convert unresectable liver metastases of colorectal cancer into resectable ones is a hepatic artery infusion, or intra-arterial chemotherapy allowing for the delivery of cytotoxic drugs directly to the common hepatic artery via catheter or pump with decreased systemic toxicity and increased local drug concentration. In this article, we discuss the literature data on the impact of intra-arterial chemotherapy on the resectability of colorectal metastases in the liver and present the results of the successful clinical case. The literature shows a positive impact of the hepatic artery infusion on the resectability of hepatic metastases of colorectal cancer. The National Cancer Institute (Ukraine) has its own experience in hepatic artery infusion with further resection of primary-unresectable colorectal metastases in the liver. In our clinical case, a patient with liver-limited metastasis of colorectal cancer was initially inoperable due to the size of tumor lesions and an insufficient residual volume of the liver. Hepatic artery infusion tactics was chosen for this patient. The patient received six cycles of intra-arterial chemotherapy, namely five FOLFOX cycles and one 5-FU cycle, and then met the resectability criteria. Also, it is important to notice that the case demonstrates chemoresistance overcoming, since the patient had disease progression before, following systemically administered XELOX, and the period until readmission of the drugs was less than 6 months. So, hepatic artery infusion can be considered a promising method to convert unresectable liver metastases of colorectal cancer into resectable ones for highly selected patients.
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Affiliation(s)
- K Cherchenko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - A Lukashenko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - Yu Ostapenko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - V Patsko
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - M Vinohradova
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - K Valikhnovska
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
| | - S Pamanska
- State Non-commercial Enterprise "National Cancer Institute", Kyiv, Ukraine
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12
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Zhang H, Wu C, Chen M, Sun Y, Han J. Drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional transarterial chemoembolization (cTACE) in colorectal liver metastasis: Efficacy, safety, and prognostic factors. J Cancer Res Ther 2023; 19:1525-1532. [PMID: 38156918 DOI: 10.4103/jcrt.jcrt_2143_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 09/04/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVE To comparatively evaluate drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) for efficacy, safety, and related prognostic factors in the treatment of colorectal liver metastasis (CRLM). MATERIALS AND METHODS This study retrospectively analyzed 75 patients with CRLM-administered DEB-TACE (n = 36) or cTACE (n = 39) between January 2016 and December 2017. Local control, survival outcome, and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and overall survival (OS) were performed. RESULTS The median follow-up in the two groups was 10.5 months (range, 0.5-22). Median PFS and OS in the DEB-TACE group were 10.0 and 13.0 months, respectively, and 6.0 and 8.5 months in the cTACE group, respectively (P = 0.009 and P = 0.008). The 3-, 6-, and 12-month OS rates in the DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively, and 92.3%, 71.8%, and 35.9% in the cTACE group, respectively. The 3-month OS rate (P = 0.083) showed no significant difference between the two groups, but significant differences were found in the 6- and 12-month OS rates (P = 0.008 and P = 0.030). Univariate and multivariate survival analyses showed that treatment method, tumor size, and tumor number were independent prognostic factors affecting PFS and OS. CONCLUSION DEB-TACE has advantages over cTACE in prolonging PFS and OS in patients with CRLM. Treatment method, tumor number, and tumor size are important prognostic factors affecting PFS and OS. However, further multicenter and prospective trials are needed to confirm a deeper comparison between DEB-TACE and cTACE in patients with CRLM.
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Affiliation(s)
- Hao Zhang
- Interventional Radiology Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, China
| | - Chunxue Wu
- Interventional Radiology Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, China
| | - Miaoling Chen
- Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, China
| | - Yuandong Sun
- Interventional Radiology Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, China
| | - Jianjun Han
- Interventional Radiology Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, China
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13
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Malka D, Verret B, Faron M, Guimbaud R, Caramella C, Edeline J, Galais MP, Bengrine-Lefevre L, Smith D, Dupont-Bierre E, De Baere T, Goéré D, Dartigues P, Lacroix L, Boige V, Gelli M, Pignon JP, Ducreux M. Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial. Eur J Cancer 2023; 195:113400. [PMID: 37922632 DOI: 10.1016/j.ejca.2023.113400] [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: 08/14/2023] [Revised: 10/17/2023] [Accepted: 10/19/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. METHODS In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). RESULTS 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death. CONCLUSION HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.
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Affiliation(s)
- David Malka
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Département d'Oncologie Médicale, Institut Mutualiste Montsouris, Paris, France.
| | - Benjamin Verret
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Matthieu Faron
- Service de Biostatistique et Epidémiologie, Gustave Roussy, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France; Département de Chirurgie Générale et Digestive, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | | | - Caroline Caramella
- Département d'Imagerie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | | | | | | | - Denis Smith
- Centre Hospitalier Universitaire Saint-André, Bordeaux, France
| | | | - Thierry De Baere
- Département d'Imagerie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Diane Goéré
- Département de Chirurgie Générale et Digestive, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Peggy Dartigues
- Département de Pathologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Ludovic Lacroix
- Département de Biologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Valérie Boige
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Maximiliano Gelli
- Département de Chirurgie Générale et Digestive, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Jean-Pierre Pignon
- Service de Biostatistique et Epidémiologie, Gustave Roussy, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France
| | - Michel Ducreux
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Centre Hospitalier Universitaire Paul Brousse, Villejuif, France
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14
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Kim JS, Kim H, Lee SY, Han YD, Han K, Min BS, Kim MD, Won JY, Beom SH, Shin SJ, Kim HS, Han DH, Ahn JB. Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study - (NCT05103020) - study protocol. BMC Cancer 2023; 23:691. [PMID: 37481515 PMCID: PMC10363309 DOI: 10.1186/s12885-023-11085-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 06/16/2023] [Indexed: 07/24/2023] Open
Abstract
BACKGROUND Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis. METHODS This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate. DISCUSSION This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate. TRIAL REGISTRATION ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.
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Affiliation(s)
- Ji Su Kim
- Division of Hepatobiliary and Pancreas Surgery, Incheon St. Mary's Hospital, The Catholic University College of Medicine, Incheon, Korea
| | - Hyunwook Kim
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Seo Young Lee
- Department of Medical Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Dae Han
- Department of Colorectal Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kichang Han
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Soh Min
- Department of Colorectal Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Man-Deuk Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Yun Won
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Hoon Beom
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Sang Joon Shin
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Han Sang Kim
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
- Graduate School of Medical Science, Brain Korea 21 Project, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
| | - Dai Hoon Han
- Department of Hepatobiliary and Pancreatic Surgery, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
| | - Joong Bae Ahn
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
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15
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Dong F, Cao G, Lu Z. HAIC as a potential therapy for esophageal cancer patients with liver metastasis: a retrospective cohort study. Front Med (Lausanne) 2023; 10:1143617. [PMID: 37215706 PMCID: PMC10196257 DOI: 10.3389/fmed.2023.1143617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/27/2023] [Indexed: 05/24/2023] Open
Abstract
Methods This was a single-arm historical cohort study of ESCC patients with synchronous or heterochronous LM between December 2014 and July 2021 at the Department of Gastrointestinal Oncology. The patients were treated with HAIC for LM, and regular image assessments were performed according to the judgment of the interventional physician. Liver progression-free survival (PFS), liver objective response rate (ORR), liver disease control rate (DCR), overall survival (OS), adverse events (AEs), treatment information, and basic characteristics were observed retrospectively. Results Overall, a total of 33 patients were enrolled in this study. All included patients received catheterized HAIC therapy, with a median of three (ranging from 2 to 6) sessions. The treatment response of liver metastatic lesions included partial response (PR) in 16 (48.5%) patients, stable disease (SD) in 15 (45.5%) patients, and progressive disease (PD) in two (6.1%) patients, for an ORR of 48.5% and a DCR of 93.9%. The median liver PFS was 4.8 months (95% confidence interval (CI): 3.0-6.6 months), and the median OS was 6.4 months (95% CI: 6.1-6.6 months). Patients who achieved PR at the liver metastasis site after HAIC were more likely to have a longer OS than those who achieved SD or PD. Grade 3 AEs occurred in 12 patients. The most common grade 3 AE was nausea, occurring in 10 (30.0%) patients, followed by abdominal pain in three (9.1%) patients. Only one patient showed grade 3 elevation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and one patient suffered from grade 3 embolism syndrome AEs. Grade 4 adverse events, followed by abdominal pain, occurred in one patient. Conclusion Hepatic arterial infusion chemotherapy might be an option as a regional therapy for ESCC patients with LM, as it is acceptable and tolerable.
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Affiliation(s)
- Fengxiao Dong
- Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Guang Cao
- Department of Interventional Therapy, Peking University Cancer Hospital, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhihao Lu
- Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
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A Case of Heavily Pretreated HER2+ Colorectal Liver Metastases Responsive to Hepatic Arterial Infusion Chemotherapy. Clin Colorectal Cancer 2023; 22:245-249. [PMID: 36931913 DOI: 10.1016/j.clcc.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/14/2023] [Accepted: 02/21/2023] [Indexed: 03/02/2023]
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17
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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: 749] [Impact Index Per Article: 374.5] [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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Rigault E, Lacas B, Glehen O, Smith D, Dupont-Bierre E, Guimbaud R, Malka D, Boige V, Fuerea A, Pignon JP, Ducreux M. Intra-arterial hepatic bevacizumab and systemic chemotherapy in hepatic metastasis of colorectal cancer: A phase II multicentric trial in second-line treatment. Cancer Treat Res Commun 2023; 34:100674. [PMID: 36565566 DOI: 10.1016/j.ctarc.2022.100674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/07/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Intra-arterial hepatic (IAH) treatment has shown promising results in the management of patients with unresectable colorectal liver metastases (CRLM) the prognosis of which is poor. Bevacizumab adjunction to standard chemotherapy has been shown to improve survival of this patient population. This prospective study was conducted to assess the efficacy and safety of IAH bevacizumab combined to systemic chemotherapy after first-line treatment failure in patients with CRLM. METHODS Included patients had dominant or isolated unresectable CRLM progressing after standard first-line treatment for metastases of colorectal cancer. Three patients had less than 30% liver invasion, three patients between 30 and 50%, two more than 50% and data was missing in two patients. An intra-hepatic catheter was implanted surgically or percutaneously. Bevacizumab 7.5 mg/kg was administered once every 3 weeks in combination with capecitabine 2000 mg/m² per day for 2 weeks and oxaliplatin 130 mg/m² or irinotecan 200 mg/m² once every 3 weeks. The primary end-point was the objective response rate. RESULTS Between June 2013 and February 2015, 10 patients were included. The trial was prematurely closed because of the lack of financial support and poor accrual. The patients had a median of 6 [1-9] cycles of treatment. Partial response was achieved in 2 patients (20%) and a R0 liver metastases resection in one another. All patients died of disease progression. The median overall and progression-free survival rates were respectively 14.0 (95% IC [4.8 - 25.8] and 5.4 months (95% IC [1.6 - 6.2]). Four patients had severe side effects but no toxic death occurred. CONCLUSION IAH bevacizumab combined to systemic chemotherapy is feasible and safe in patients with unresectable isolated or dominant CRLM progressing after a first-line systemic treatment. Based on the low number of patients included in our study, our results suggest that this treatment does not increase dramatically the response rate versus an adapted systemic treatment. However, considering the safety data provided in this study, arterial infusion of bevacizumab in adjunction to chemotherapeutic agents could be evaluated in the future.
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Affiliation(s)
- Eugénie Rigault
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France
| | - Benjamin Lacas
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Center, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Gustave Roussy, Villejuif, France
| | - Olivier Glehen
- Département de Chirurgie Digestive, Hospices Civils de Lyon, Université Lyon Rhône, France
| | - Denis Smith
- Département d'Hépato-Gastro-Enterologie et d'oncologie digestive, Hôpital Haut-Lévêque, Bordeaux, France
| | | | - Rosine Guimbaud
- Département d'oncologie médicale, Université de Toulouse, Toulouse, France
| | - David Malka
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France; Unité Dynamique des Cellules Tumorales - Inserm U1279, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Valérie Boige
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France
| | - Alina Fuerea
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France
| | - Jean-Pierre Pignon
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Center, Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Université Paris-Saclay, Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France; Unité Dynamique des Cellules Tumorales - Inserm U1279, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Université Paris-Saclay, Saint Aubin, France.
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19
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Feng AW, Guo JH, Gao S, Kou FX, Liu SX, Liu P, Chen H, Wang XD, Xu HF, Cao G, Zhu X. A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases. Front Oncol 2022; 12:913017. [PMID: 36212504 PMCID: PMC9532863 DOI: 10.3389/fonc.2022.913017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 08/29/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). METHODS Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. RESULTS 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838-6.762]) and 4.6 months [95% CI, 3.419-5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828-21.372] and 13.1 months [95% CI, 11.215-14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. CONCLUSION HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/, identifier NCT02557490.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Xu Zhu
- Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
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20
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Cao G, Wang X, Chen H, Gao S, Guo J, Liu P, Xu H, Xu L, Zhu X, Yang R. Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal cancer: a real-world retrospective study. BMC Gastroenterol 2022; 22:328. [PMID: 35788189 PMCID: PMC9251591 DOI: 10.1186/s12876-022-02344-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 05/20/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy. METHODS This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle. RESULTS Among 47 patients, 32 (68%) were males. The median age was 61 (29-75). With a median follow-up of 22.2 months (3.7-50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0-13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events. CONCLUSIONS Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy.
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Affiliation(s)
- Guang Cao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
| | - Xiaodong Wang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hui Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Song Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Jianhai Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Peng Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Haifeng Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Liang Xu
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xu Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
| | - Renjie Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
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21
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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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22
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Papamichail M, Pizanias M, Heaton ND, M P, M P, Nd H. Minimizing the risk of small-for-size syndrome after liver surgery. Hepatobiliary Pancreat Dis Int 2022; 21:113-133. [PMID: 34961675 DOI: 10.1016/j.hbpd.2021.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 12/06/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Primary and secondary liver tumors are not always amenable to resection due to location and size. Inadequate future liver remnant (FLR) may prevent patients from having a curative resection or may result in increased postoperative morbidity and mortality from complications related to small-for-size syndrome (SFSS). DATA SOURCES This comprehensive review analyzed the principles, mechanism and risk factors associated with SFSS and presented current available options in the evaluation of FLR when planning liver surgery. In addition, it provided a detailed description of specific modalities that can be used before, during or after surgery, in order to optimize the conditions for a safe resection and minimize the risk of SFSS. RESULTS Several methods which aim to reduce tumor burden, preserve healthy liver parenchyma, induce hypertrophy of FLR or prevent postoperative complications help minimize the risk of SFSS. CONCLUSIONS With those techniques the indications of radical treatment for patients with liver tumors have significantly expanded. The successful outcome depends on appropriate patient selection, the individualization and modification of interventions and the right timing of surgery.
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Affiliation(s)
- Michail Papamichail
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK.
| | - Michail Pizanias
- Department of General Surgery, Whittington Hospital, London N19 5NF, UK
| | - Nigel D Heaton
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Papamichail M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Pizanias M
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
| | - Heaton Nd
- Department of Hepato-Pancreato-Biliary Surgery, Royal Blackburn Hospital, Blackburn BB2 3HH, UK; Department of General Surgery, Whittington Hospital, London N19 5NF, UK; Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver Studies, Kings Health Partners at King's College Hospital NHS Trust, London SE5 9RS, UK
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Liu P, Zhu H, Zhu H, Zhang X, Feng A, Zhu X, Sun Y. Predicting Survival for Hepatic Arterial Infusion Chemotherapy of Unresectable Colorectal Liver Metastases: Radiomics Analysis of Pretreatment Computed Tomography. J Transl Int Med 2022; 10:56-64. [PMID: 35702189 PMCID: PMC8997799 DOI: 10.2478/jtim-2022-0004] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE Hepatic arterial infusion chemotherapy (HAIC) is an effective treatment for advanced unresectable colorectal cancer liver metastases (CRLM). This study was conducted to predict the efficacy of HAIC in patients with unresectable CRLM by radiomics methods based on pretreatment computed tomography (CT) examinations and clinical data. MATERIALS AND METHODS A total of 63 patients were included in this study (41 in the training group and 22 in the validation group). All these patients underwent CT examination before HAIC. During the follow-up period, CT scans and laboratory examinations were performed regularly. Eighty-five radiological features were extracted from the regions of interest (ROIs) of CT images using the PyRadiomics program. The t-test and correlation were applied to select features. These features were analyzed using LASSO-Cox regression, and a linear model was developed to predict overall survival (OS). RESULTS After reducing features by t-test and correlation test, seven features remained. After LASSO-Cox cross-validation, four features remained at λ = 0.232. They were gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), neighborhood gray tone difference matrix (NGTDM), and the location of the primary tumor. The C-index was 0.758 in the training group and 0.743 in the test group. Nomograms predicting 1-, 2-, and 3-year survival were established. CONCLUSION Our study demonstrates that a radiomics approach based on pretreatment CT texture analysis has the ability to predict early the outcome of HAIC in patients with advanced unresectable colorectal cancer with a high degree of accuracy and feasibility.
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Affiliation(s)
- Peng Liu
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing100142, China
- Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing100142, China
| | - Haitao Zhu
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing100142, China
| | - Haibin Zhu
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing100142, China
| | - Xiaoyan Zhang
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing100142, China
| | - Aiwei Feng
- Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing100142, China
| | - Xu Zhu
- Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing100142, China
| | - Yingshi Sun
- Department of Radiology, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing100142, China
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24
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Pernot S, Pellerin O, Mineur L, Monterymard C, Smith D, Lapuyade B, Gallois C, Khemissa Akouz F, De Baere T, Tougeron D, Thirot-Bidault A, Audemar F, Simon M, Lecaille C, Louafi S, Lepage C, Ducreux M, Taieb J. Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin, combined with LV5FU2 +/- irinotecan and a targeted therapy, in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49. Dig Liver Dis 2022; 54:324-330. [PMID: 35027324 DOI: 10.1016/j.dld.2021.12.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/14/2021] [Accepted: 12/17/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION In patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We incorporated HAI-ox in doublet or triplet + targeted therapy to validate its efficacy. AIM The OSCAR study is an ongoing randomized phase III trial comparing FOLFOX + targeted therapy according to RAS status, or FOLFOXIRI + bevacizumab in patients eligible for triplet therapy, with the same regimen but with HAI-ox instead of IV-ox as the first-line treatment for CRCLM. MATERIALS AND METHODS Main eligibility criteria are colorectal cancer, unresectable liver metastasis, no extra-hepatic metastases except pulmonary nodules if ≤3 and <10 mm, ECOG performance status 0 or 1. ENDPOINT The primary endpoint is progression-free survival (PFS). A difference of 4 months for the median PFS in favor of HAI-ox is expected (HR = 0.73). Secondary endpoints include overall survival, overall response rate, secondary liver resection, safety, and quality of life. CONCLUSION This study is planned to include 348 patients to demonstrate the superiority of HAI-ox over systemic oxaliplatin in first-line CRCLM treatment (NCT02885753).
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Affiliation(s)
- Simon Pernot
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
| | - Olivier Pellerin
- Department of Interventional Radiology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France
| | - Laurent Mineur
- Department of Medical Oncology, Institut Sainte Catherine, Avignon, France
| | - Carole Monterymard
- Federation Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Denis Smith
- Department of Gastroenterology and GI Oncology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France
| | - Bruno Lapuyade
- Department of Interventional Radiology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France
| | - Claire Gallois
- Department of Gastroenterology and GI Oncology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France
| | - Faiza Khemissa Akouz
- Department of Gastroenterology and GI Oncology, CH Saint-Jean, Perpignan, France
| | - Thierry De Baere
- Department of Interventional Radiology, Gustave Roussy, BIOTHERIS, Université Paris-Saclay, Villejuif, France
| | - David Tougeron
- Université de Poitiers, Department of Gastroenterology and Hepatology, CHU La Milétrie, Poitiers, France
| | | | - Franck Audemar
- Department of Gastroenterology and GI Oncology, CH de la Côte-Basque, Bayonne, France
| | - Mireille Simon
- Department of Gastroenterology and GI Oncology, CH Pau, Pau, France
| | - Cedric Lecaille
- Department of Gastroenterology and GI Oncology, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France
| | - Sami Louafi
- Department of Medical Oncology, CH Corbeille Essonne, France
| | - Come Lepage
- Federation Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France; Department of Gastroenterology and GI Oncology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France; Department of Interventional Radiology, CHU Haut-Leveque, Université de Bordeaux, Pessac, France; Department of Gastroenterology and GI Oncology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France; Department of Gastroenterology and GI Oncology, CH Saint-Jean, Perpignan, France; Department of Interventional Radiology, Gustave Roussy, BIOTHERIS, Université Paris-Saclay, Villejuif, France; Université de Poitiers, Department of Gastroenterology and Hepatology, CHU La Milétrie, Poitiers, France; Department of Medical Oncology, Hôpital Privé d'Antony, Antony, France; Department of Gastroenterology and GI Oncology, CH de la Côte-Basque, Bayonne, France; Department of Gastroenterology and GI Oncology, CH Pau, Pau, France; Department of Gastroenterology and GI Oncology, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France; Department of Medical Oncology, CH Corbeille Essonne, France; Department of Gastroenterology and GI oncology, CHU Le Bocage, University of Burgundy and Franche Comté, Dijon, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Inserm U1279, Université Paris-Saclay, Villejuif, France
| | - Julien Taieb
- Department of Gastroenterology and GI Oncology, Hopital Européen Georges-Pompidou, Université de Paris, SIRIC CARPEM, France
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Zhao J, Zheng Y, Liu T, Chang J, Shan H, Cong K. Comparison between fluoropyrimidine-hepatic arterial infusion and systemic chemotherapy for unresectable liver metastases: A protocol for systematic review and meta-analysis based on 16 observational studies. Medicine (Baltimore) 2021; 100:e27483. [PMID: 34731127 PMCID: PMC8519215 DOI: 10.1097/md.0000000000027483] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 09/01/2021] [Accepted: 09/16/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The benefit of loco-regional treatments such as hepatic arterial infusion (HAI) in terms of survival and response rate is unclear. The aim of this work is to quantitatively summarize the results of both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing fluoropyrimidine-HAI (F-HAI) to systemic chemotherapy (SCT) for the treatment of colorectal liver metastases (CRLMs). METHODS We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to July 1, 2021. The outcome measures were tumor response rate and overall survival (OS). Both RCTs and NRSIs comparing HAI to SCT for patients with unresectable CRLMs were included. The outcome measures were tumor response rate and OS. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS A total of 16 studies including 11 RCTs and 5 NRSIs were identified for the present meta-analysis. Nine RCTs compared F-HAI to SCT for patients with unresectable CRLMs and the pooled result indicated that patients who received F-HAI experienced more than twofold response rate than SCT, with a pooled risk ratio of 2.10 (95%CI 1.59-2.79; P < .00001). In addition, the pooled result based on RCTs showed that F-HAI had a significant benefit regarding OS, with a pooled HR of 0.83 (95% CI 0.70-0.99; P = .04). Similarly, the benefit of F-HAI in terms of OS was also observed in the results of NRSIs. CONCLUSIONS Our results indicated that the F-HAI regimen had a greater tumor response rate and survival advantage than SCT for patients with unresectable CRLMs. Future propensity score-matched analyses with a large sample size should be conducted to support the evidence of our results based on RCTs and NRSIs.
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Fohlen A, Bordji K, Assenat E, Gongora C, Bazille C, Boulonnais J, Naveau M, Breuil C, Pérès EA, Bernaudin M, Guiu B. Anticancer Drugs for Intra-Arterial Treatment of Colorectal Cancer Liver Metastases: In-Vitro Screening after Short Exposure Time. Pharmaceuticals (Basel) 2021; 14:ph14070639. [PMID: 34358065 PMCID: PMC8308869 DOI: 10.3390/ph14070639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 12/24/2022] Open
Abstract
To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC50 and IC90 were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI90 = C Max/IC90) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
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Affiliation(s)
- Audrey Fohlen
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
- Urodigestive Imagery and Interventional Radiology Department, University Hospital of Caen, CEDEX, 14000 Caen, France
- Correspondence: ; Tel.: +33-616702414
| | - Karim Bordji
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Eric Assenat
- Medical Oncology Department, Montpellier School of Medicine, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295 Montpellier, France;
| | - Céline Gongora
- IRCM, Montpellier Cancerology Research Center, INSERM U1194, Montpellier University, Montpellier Regional Institute of Cancer, 34298 Montpellier, France;
| | - Céline Bazille
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
- Department of Pathology, University Hospital of Caen, CEDEX, 14000 Caen, France
| | - Jérémy Boulonnais
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Mikaël Naveau
- UNICAEN, CNRS, UMS 3408, GIP CYCERON, Normandie University, 14000 Caen, France;
| | - Cécile Breuil
- Pharmacy Department, University Hospital of Caen, CEDEX, 14000 Caen, France;
| | - Elodie A. Pérès
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Myriam Bernaudin
- UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Normandie University, 14000 Caen, France; (K.B.); (C.B.); (J.B.); (E.A.P.); (M.B.)
| | - Boris Guiu
- Radiology Department, Montpellier School of Medicine, Saint-Eloi University Hospital, 80 Avenue Augustin Fliche, 34295 Montpellier, France;
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Zhao JJ, Tan E, Sultana R, Syn NL, Da Zhuang K, Leong S, Tai DWM, Too CW. Intra-arterial therapy for unresectable colorectal liver metastases: A meta-analysis. J Vasc Interv Radiol 2021; 32:1536-1545.e38. [PMID: 34166803 DOI: 10.1016/j.jvir.2021.05.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 05/09/2021] [Accepted: 05/31/2021] [Indexed: 11/19/2022] Open
Abstract
PURPOSE To evaluate the efficacy of hepatic arterial infusion (HAI), conventional trans-arterial chemoembolization (cTACE), drug-eluting embolic trans-arterial chemoembolization (DEE-TACE), trans-arterial radioembolization (TARE) and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases. METHODS A search was conducted on EMBASE, Scopus, PubMed and Web of Science for prospective non-randomized studies and randomized controlled trials (RCTs) from inception to 20th June 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for median overall survival (OS), survival rates (SR), and restricted mean survival time (RMST), while two-stage meta-analyses of proportions were conducted to determine response rates (RR) and conversion-to-resection rates (CRR). RESULTS 71 prospective non-randomized studies and 21 RCTs were identified comprising 6,695 patients. Among patients treated beyond first line, DEE-TACE+SCT (n=152) had the best survival outcomes of median OS of 26.5 (95%-CI: 22.5-29.1) months and 3-year RMST of 23.6 (95%-CI: 21.8-25.5) months. Upon further stratification by publication year, DEE-TACE+SCT appears to consistently have the highest pooled survival rates at 1-year (81.9%) and 2-years (66.1%) in recent publications (2015-2020). DEE-TACE+SCT and HAI+SCT had the highest pooled-RRs of 56.7% (I2=0.90) and 62.6% (I2=0.87) respectively and pooled-CRRs of 35.5% (I2=0.00) and 30.3% (I2=0.80) respectively. CONCLUSION Albeit significant heterogeneity, paucity of high-quality evidence and the non-comparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE+SCT may have the best oncological outcomes and greatest potential to be converted for resection.
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Affiliation(s)
- Joseph J Zhao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Eelin Tan
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore
| | - Rehena Sultana
- Centre for Quantitative Medicine, Duke-National University of Singapore Graduate Medical School, Singapore
| | - Nicholas L Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kun Da Zhuang
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore
| | - Sum Leong
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore
| | - David W M Tai
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Chow Wei Too
- Department of Vascular and Interventional Radiology, Division of Radiological Sciences; Radiological Sciences Academic Clinical Program, SingHealth- Duke-National University of Singapore Academic Medical, Singapore General Hospital, Singapore.
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Ghiringhelli F. Hype and hope of hepatic arterial infusion for colorectal cancer. Hepatobiliary Surg Nutr 2021; 10:235-237. [PMID: 33898565 DOI: 10.21037/hbsn-20-756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- François Ghiringhelli
- Centre de Recherche INSERM LNC-UMR1231, Dijon, France.,University of Burgundy Franche-Comté, Dijon, France.,Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France.,Cancer Biology Transfer Platform, Centre Georges-François Leclerc, Dijon, France.,Genetic and Immunology Medical Institute, Dijon, France
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29
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Deschamps F, Tselikas L, Tasaki M, Motoyama S, Isoardo T, Ducreux M, Paunovic D, Moine L, de Baere T. Sustained-hepatic arterial infusion of oxaliplatin: pharmacokinetic advantages over hepatic arterial infusion using a preclinical animal tumour model. Drug Deliv Transl Res 2021; 11:2144-2150. [PMID: 33432522 DOI: 10.1007/s13346-020-00881-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2020] [Indexed: 11/28/2022]
Abstract
Hepatic arterial infusion (HAI) of oxaliplatin allows greater liver tumour drug exposure compared to systemic infusion. However, the therapeutic index of HAI oxaliplatin remains poor. Using Pickering emulsion technology, we developed a platform able to provide sustained releases of oxaliplatin. The goal of this study was to evaluate the pharmacokinetic advantages of sustained-HAI oxaliplatin over HAI using a preclinical animal tumour model. Injections of 0.6 mg oxaliplatin in 20 min were selectively done in left hepatic arteries of 20 rabbits bearing a VX2 liver tumour in the middle left-lobe, using HAI (n = 10) or sustained-HAI (n = 10). In each group, half of the rabbits were sacrificed at 24 h and half at 72 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and oxaliplatin concentrations in tumour tissues, right- and middle left-liver lobes, spleen and lung. Compared to HAI, sustained-HAI of oxaliplatin resulted in lower plasmatic peak (Cmax: 275 ± 41 vs. 416 ± 133 ng/mL, p = 0.02) and higher concentration in the tumour at 24 h (2118 ± 2107 vs. 210 ± 93 ng/g, p = 0.008). After HAI, oxaliplatin concentration in tumours was significantly higher than in lung at 24 h (p = 0.03) but no other difference was found between oxaliplatin concentrations in tumours and in liver lobes, spleen or lung, neither at 24 h nor at 72 h. On the opposite, sustained-HAI resulted in higher concentrations of oxaliplatin in tumour compared to oxaliplatin concentrations in the middle left lobe (163 ± 86 ng/g at 24 h, p = 0.01, and 90 ± 15 ng/g at 72 h, p = 0.04), right lobe (174 ± 112 ng/g at 24 h, p = 0.01, and 112 ± 35 ng/g, p = 0.04 at 72 h), spleen (142 ± 21 ng/g at 24 h, p = 0.01, and 98 ± 12 ng/g at 72 h, p = 0.04), and lung (85 ± 11 ng/g at 24 h, p = 0.01, and 52 ± 4 ng/g at 72 h, p = 0.03). Sustained-HAI improves the therapeutic index of HAI oxaliplatin and offers a great potential for patients suffering from unresectable colorectal liver metastases or hepatocellular carcinoma.
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Affiliation(s)
| | - Lambros Tselikas
- Interventional Radiology Department, Gustave Roussy, Villejuif, France.,Laboratory of Translational Research in Immunology (LTRI), UMR 1015, Gustave Roussy, Villejuif, France
| | | | | | - Thomas Isoardo
- Interventional Radiology Department, Gustave Roussy, Villejuif, France.,Laboratory of Translational Research in Immunology (LTRI), UMR 1015, Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Oncology department, Gustave Roussy, Villejuif, France.,Université Paris-Saclay, Saint-Aubin, France
| | - Dragica Paunovic
- Global Medical Affairs, Terumo Corporation, Interventional Systems, Tokyo, Japan
| | - Laurence Moine
- Institut Galien, CNRS. Paris-Sud University, Châtenay-Malabry, France
| | - Thierry de Baere
- Interventional Radiology Department, Gustave Roussy, Villejuif, France.,Université Paris-Saclay, Saint-Aubin, France
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30
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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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31
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Surg Oncol Clin N Am 2021; 30:1-25. [PMID: 33220799 DOI: 10.1016/j.soc.2020.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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32
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Muaddi H, D'Angelica M, Wiseman JT, Dillhoff M, Latchana N, Roke R, Ko YJ, Carpizo D, Spencer K, Fields RC, Williams G, Aucejo F, Acevedo-Moreno LA, Billingsley KG, Walker BS, Mayo SC, Karanicolas PJ. Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study. J Surg Oncol 2020; 123:252-260. [PMID: 33095919 DOI: 10.1002/jso.26270] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 10/06/2020] [Accepted: 10/08/2020] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.
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Affiliation(s)
- Hala Muaddi
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jason T Wiseman
- Arthur G. James Comprehensive Cancer Center Cancer Cachexia Program, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Mary Dillhoff
- Arthur G. James Comprehensive Cancer Center Cancer Cachexia Program, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Nicholas Latchana
- Department of Surgery, Novant Health Carolina Surgical, Charlotte, North Carolina, USA
| | - Rachel Roke
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada
| | - Yoo-Joung Ko
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.,St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Darren Carpizo
- Department of Surgery, Division of Surgical Oncology, Rochester's School of Medicine and Dentistry and Wilmot Cancer Center, Rochester, New York, USA
| | - Kristen Spencer
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine and the Alvin J. Siteman Comprehensive Cancer Center, St. Louis, Missouri, USA
| | - Gregory Williams
- Department of Surgery, Washington University School of Medicine and the Alvin J. Siteman Comprehensive Cancer Center, St. Louis, Missouri, USA
| | - Federico Aucejo
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Lou-Anne Acevedo-Moreno
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Kevin G Billingsley
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA
| | - Brett S Walker
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA
| | - Skye C Mayo
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA
| | - Paul J Karanicolas
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada
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Dumont F, Passot C, Raoul JL, Kepenekian V, Lelièvre B, Boisdron-Celle M, Hiret S, Senellart H, Pein F, Blanc-Lapierre A, Raimbourg J, Thibaudeau E, Glehen O. A phase I dose-escalation study of oxaliplatin delivered via a laparoscopic approach using pressurised intraperitoneal aerosol chemotherapy for advanced peritoneal metastases of gastrointestinal tract cancers. Eur J Cancer 2020; 140:37-44. [PMID: 33039812 DOI: 10.1016/j.ejca.2020.09.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 08/28/2020] [Accepted: 09/02/2020] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers. METHODS PIPAC was applied every 4-6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m2 with planned increases of 50 mg/m2 per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov (NCT03294252). RESULTS Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m2 and two at 140 mg/m2. The MTD was therefore set at 90 mg/m2. Overall treatment included a median number of three PIPAC sessions (range: 1-5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I-II and 11 grade III-IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m2, the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC)0-48h of 1035 μg/l and 9028 μg h/L, respectively. CONCLUSIONS The MTD of oxaliplatin during PIPAC is 90 mg/m2. PK data demonstrate a high tumour concentration and a significant systemic absorption.
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Affiliation(s)
- Frédéric Dumont
- Department of Surgical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France.
| | - Christophe Passot
- Oncopharmacology - Pharmacogenetics, Institut de Cancérologie de L'Ouest, Angers, France
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Vahan Kepenekian
- Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France
| | - Bénédicte Lelièvre
- Laboratory of Pharmacology and Toxicology, Centre Hospitalier et Universitaire, Angers, France
| | | | - Sandrine Hiret
- Department of Medical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Hélène Senellart
- Department of Medical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Francois Pein
- Department of Clinical Research and Innovation, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Audrey Blanc-Lapierre
- Department of Biostatistics and Methodology, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Judith Raimbourg
- Department of Medical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Emilie Thibaudeau
- Department of Surgical Oncology, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Bénite, France
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Hepatic arterial infusion of oxaliplatin plus systemic chemotherapy and targeted therapy for unresectable colorectal liver metastases. Eur J Cancer 2020; 138:89-98. [PMID: 32871526 DOI: 10.1016/j.ejca.2020.07.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 07/19/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatic arterial infusion (HAI) combined with systemic chemotherapy has shown promising results in patients with unresectable colorectal liver metastases (CRLM), even after failure to systemic therapy. Addition of systemic targeted therapies has been investigated with controversial results regarding tolerance, especially with HAI-floruxidine when combined with systemic bevacizumab. Our study aimed to analyse feasibility, safety and efficacy of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies. METHODS Between 2005 and 2016, single-centre consecutive patients with unresectable CRLM who received at least one cycle of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies (cetuximab/panitumumab or bevacizumab) were analysed. RESULTS A total of 89 patients (median age 55 years (range, 26-76 years) who previously received a median number of one systemic chemotherapy regimen (range, 0-5) including oxaliplatin in 78% of cases were included. Median number of HAI-oxaliplatin cycles was 9 (range, 1-28) combined with systemic chemotherapy and targeted therapies (LV5FU2 [63%], FOLFIRI [36%]) plus anti-EGFR (30%), or bevacizumab (70%). Grade 3/4 toxicities included neutropenia (40%), HAI-related abdominal pain (43%) and neurotoxicity (12%). The intent-to-treat objective response rate was 42%, and 45% had stable disease, allowing complete CRLM resection/ablation in 27% of patients. After a median follow-up of 72 months, median overall and progression-free survival was 20 and 9 months, respectively. CONCLUSION Addition of targeted therapy to systemic chemotherapy combined with HAI-oxaliplatin is feasible, safe and shows promising activity, even after systemic chemotherapy failure.
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Long GB, Xiao CW, Zhao XY, Zhang J, Li X. Effects of hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2020; 99:e20745. [PMID: 32590750 PMCID: PMC7328911 DOI: 10.1097/md.0000000000020745] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The potential benefits and safety of hepatic arterial infusion chemotherapy (HAIC) for the treatment of patients with hepatocellular carcinoma (HCC) remains inconsistent. Therefore, we conducted this meta-analysis of evaluate the efficacy and safety of HAIC in the treatment of HCC. METHODS A comprehensive literature search was performed using PubMed, Embase, Web of Science, and the Cochrane library to identify eligible studies that compared HAIC with other therapies for patients with HCC. The main outcomes of our interest, including overall survival (OS), disease free survival (DFS), objective response rate (ORR), disease control rate (DCR), and adverse events, were calculated using the meta-analysis. The pooled estimates were expressed with hazard ratio (HR) with 95%confidence intervals (95%CIs) or risk ratio (RR) with 95%CIs. RESULTS A total of 13 studies met the inclusion criteria and were included in this meta-analysis. Pooled estimates showed that, HAIC was associated with significantly improved OS (HR = 0.61, 95%CI: 0.48, 0.77; P < .001) and DFS (HR = 0.66, 95%CI: 0.52, 0.84; P = .001) as compared with other therapies. The ORR (RR = 2.28, 95%CI: 1.77, 2.94; P < .001) and DCR (RR = 1.47, 95%CI: 1.23, 1.77; P < .001) were also significantly higher in HAIC group than in control group. Most of the common adverse events were comparably occurred in the 2 groups, except for nausea/vomiting, hypoalbuminemia, pain, anemia and hepatic toxicity. Subgroup analysis suggested that, the improved OS and DFS associated with HAIC were only observed in patients with colorectal liver metastases (CRLM), or advanced HCC, but not in those with unresectable HCC or pancreatic liver metastases. CONCLUSION Based on the present data, HAIC showed benefit effect in HCC patients, with pronged OS and DFS, as well as increased ORR and DCR. These benefit effects were more obvious in CRLM or advanced HCC patients. However, considering the potential limitations, more large-scale, randomized trials are needed to verify our findings.
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Sato Y, Inaba Y, Aramaki T, Sone M, Morita Y, Nishiofuku H, Tanaka T, Miyazaki M, Matsueda K, Arai Y. Hepatic Arterial Infusion Chemotherapy of 5-Fluorouracil for Patients with Unresectable Liver Metastases from Colorectal Cancer Refractory to Standard Systemic Chemotherapy: A Multicenter Retrospective Study. Oncology 2020; 98:267-272. [PMID: 32092755 DOI: 10.1159/000505520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 12/17/2019] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Hepatic arterial infusion chemotherapy (HAIC) is a feasible treatment for patients with colorectal cancer (CRC) with unresectable liver metastases. OBJECTIVE The aim of this retrospective study was to assess HAIC of 5-fluorouracil (5FU) in patients with unresectable liver metastases from CRC refractory to standard systemic chemotherapy. METHODS A total of 137 patients (85 men, 52 women; median age, 62 years; with KRAS mutation, n = 57) were recruited from seven institutions from September 2008 to December 2015. These patients were refractory to systemic chemotherapy including three cytotoxic agents (fluoropyrimidine, oxaliplatin, and irinotecan) with two molecular-targeted agents (bevacizumab and epidermal growth factor receptor antibody [cetuximab or panitumumab]). All patients underwent HAIC of continuous 5FU for unresectable liver metastases. Overall survival time, time to treatment failure, objective response rate, disease control rate, and incidence of adverse events to HAIC were assessed retrospectively. RESULTS The median overall survival time was 4.8 months (95% confidence interval [CI], 4.0-5.7 months), whereas time to treatment failure was 2.4 months (95% CI, 2.0-2.8 months). The objective overall response rate and disease control rate were 12.4 and 64%, respectively. Grade 3 or 4 adverse events were observed in 2.9% of the patients (hyperbilirubinemia in 2, liver abscess in 1, and myelosuppression in 1). CONCLUSIONS There were few incidences of severe adverse events to HAIC of 5FU for liver metastases from CRC refractory to standard systemic chemotherapy. Therefore, it might present as a treatment option as last-line chemotherapy.
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Affiliation(s)
- Yozo Sato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan,
| | - Yoshitaka Inaba
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takeshi Aramaki
- Division of Interventional Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Miyuki Sone
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshitaka Morita
- Department of Diagnostic Radiology, Kobe Medical Center, Kobe, Japan
| | | | - Toshihiro Tanaka
- Department of Radiology, Nara Medical University, Kashihara, Japan
| | - Masaya Miyazaki
- Department of Interventional Radiology and Clinical Ultrasound Center, Gunma University Hospital, Maebashi, Japan
| | - Kiyoshi Matsueda
- Diagnostic Imaging Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yasuaki Arai
- Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan
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Boilève A, Maillard A, Wagner M, Dromain C, Laurent C, Dupont Bierre E, Le Sourd S, Audemar F, Ulusakarya A, Guerin-Meyer V, Smisth D, Pezzella V, De Baere T, Goere D, Gelli M, Taieb J, Boige V. Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy - a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol. BMC Cancer 2020; 20:74. [PMID: 32000724 PMCID: PMC6990591 DOI: 10.1186/s12885-020-6571-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 01/23/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10-15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as a salvage treatment in patients with CRLM unresectable after at least 2 months of first-line induction sys-CT. OBJECTIVES AND ENDPOINTS OF THE PHASE II STUDY Our main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0). METHODS This study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients. TRIAL REGISTRATION ClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.
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Affiliation(s)
- Alice Boilève
- Department of Medical Oncology, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.
| | - Aline Maillard
- Department of statistics and epidemiology, Villejuif, France.,Centre for Research in Epidemiology and Population Health (team 2), INSERM U1018, Paris-Saclay University, Villejuif, France
| | - Mathilde Wagner
- Department of radiology, CHU Pitié Salpétrière, Paris, France
| | - Clarisse Dromain
- Department of radiology, Centre Hospitalier et Universitaire Vaudois, Lausanne, Switzerland
| | - Christophe Laurent
- Department of hepatogastroenterology, Hôpital Haut Levêque, Pessac, France
| | - Eric Dupont Bierre
- Department of digestive surgery, CHP Saint Grégoire, Saint-Grégoire, France
| | - Samuel Le Sourd
- Department of medical oncology, Centre Eugène-Marquis, Rennes, France
| | - Franck Audemar
- Department of hepatogastroenterology, Centre hospitalier Côte Basque, Bayonne, France
| | - Ayhan Ulusakarya
- Department of medical oncology, Hôpital Paul Brousse, Villejuif, France
| | | | - Denis Smisth
- Department of hepatogastroenterology, Hôpital Haut Levêque, Pessac, France
| | | | - Thierry De Baere
- Department of interventional radiology, Gustave Roussy, Villejuif, France
| | - Diane Goere
- Department of Surgical Oncology, Hôpital Saint Louis, Paris, France
| | | | - Julien Taieb
- Department of digestive oncology, Hôpital Européen Georges-Pompidou, Sorbonne Paris Cite/Paris Descartes University, Paris, France
| | - Valérie Boige
- Department of Medical Oncology, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France
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Ghiringhelli F, Vincent J, Bengrine L, Borg C, Jouve JL, Loffroy R, Guiu B, Blanc J, Bertaut A. Hepatic arterial chemotherapy with raltitrexed and oxaliplatin versus standard chemotherapy in unresectable liver metastases from colorectal cancer after conventional chemotherapy failure (HEARTO): a randomized phase-II study. J Cancer Res Clin Oncol 2019; 145:2357-2363. [PMID: 31273511 DOI: 10.1007/s00432-019-02970-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 07/01/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Hepatic arterial infusion (HAI) of chemotherapy could be used in patients with liver-only metastatic colorectal cancer (mCRC) to fight against chemoresistance. We previously reported the efficacy of raltitrexed plus oxaliplatin (HAI) in a retrospective series. We performed a randomized two-stage phase-II study to evaluate the efficacy of HAI of the combination of raltitrexed and oxaliplatin in refractory mCRC with only liver metastases in comparison with standard of care. PATIENTS AND METHODS Eligible patients had unresectable mCRC and were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type KRAS). Patients were randomized between HAI raltitrexed (3 mg/m2 over 1 h) followed by oxaliplatin (130 mg/m2 over 2 h) every 3 weeks and standard of care in a 2:1 ratio. A total of 57 patients (38 in the experimental arm and 19 in the standard of care arm) were to be included. The main objective was to demonstrate 6-month PFS of 45% by intention-to-treat analysis in the experimental arm, compared to theoretical PFS of 20%, with a unilateral alpha risk of 5% and beta risk of 10%. RESULTS After inclusion of 27 patients, the trial was terminated due to insufficient accrual. In the experimental arm, 11 and 4 patients experienced grade 3 and 4 toxicities, respectively. The most frequent grade 3-4 toxicities were neutropenia, liver toxicity, and abdominal pain. Median progression-free survival was 6.7 months (95% Confidence Interval; 3.9-7.2) in the HAI group and 2.2 months (95% CI 1.2-4.3) with standard of care [HR 0.32 (95% CI 0.14-0.76), p = 0.01]. Median overall survival did not differ between the two groups, at 11.2 months (95% CI 4.8-17.6) for the HAI group and 11.9 months (95% CI 2.8-14.3) for standard of care [HR 0.86 (95% CI 0.36-2.04), p = 0.73]. CONCLUSION Although stopped prematurely, this randomized trial provides evidence for the benefit and safety of HAI of a combination of raltitrexed and oxaliplatin in liver-only mCRC with chemoresistant disease.
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Affiliation(s)
- Francois Ghiringhelli
- Department of Medical Oncology, Centre Georges-François Leclerc, University of Bourgogne Franche Comté, 7 Boulevard Jeanne d'Arc, 21000, Dijon, France.
- University of Burgundy and Franche Comté, Dijon, France.
| | - Julie Vincent
- Department of Medical Oncology, Centre Georges-François Leclerc, University of Bourgogne Franche Comté, 7 Boulevard Jeanne d'Arc, 21000, Dijon, France
| | - Leila Bengrine
- Department of Medical Oncology, Centre Georges-François Leclerc, University of Bourgogne Franche Comté, 7 Boulevard Jeanne d'Arc, 21000, Dijon, France
| | - Christophe Borg
- University of Burgundy and Franche Comté, Dijon, France
- University Hospital of Besançon and CIC-BT506, Besançon, France
| | | | - Romaric Loffroy
- University of Burgundy and Franche Comté, Dijon, France
- University Hospital of Dijon, Dijon, France
| | - Boris Guiu
- University Hospital of Montpellier, Montpellier, France
| | - Julie Blanc
- Unit of Methodology and Biostatistics, Centre Georges-François Leclerc, Dijon, France
| | - Aurélie Bertaut
- Unit of Methodology and Biostatistics, Centre Georges-François Leclerc, Dijon, France
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Larsen FO, Jensen BV, Nørgaard HH, Hermann HK, Larsen PN, Markussen A, Hogdall E, Nielsen D. Intrahepatic Oxaliplatin and Systemic 5-FU +/- Cetuximab in Chemo-Naïve Patients with Liver Metastases from Colorectal Cancer. Oncology 2019; 96:299-308. [PMID: 30999314 DOI: 10.1159/000499314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 02/28/2019] [Indexed: 01/26/2023]
Abstract
BACKGROUND In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. METHODS Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. RESULTS The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0-44.3) and 12.9 months (95% CI 10.2-15.6), respectively. CONCLUSIONS Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained.
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Affiliation(s)
- Finn Ole Larsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark,
| | - Benny V Jensen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Hans Henrik Nørgaard
- Department of Radiology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Bispebjerg and Frederiksberg, Denmark
| | - Helle Kirstine Hermann
- Department of Radiology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Peter N Larsen
- Department of Liver Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Alice Markussen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Estrid Hogdall
- Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
| | - Dorte Nielsen
- Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark
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Oxaliplatin-Based Intra-arterial Chemotherapy in Colo-Rectal Cancer Liver Metastases: A Review from Pharmacology to Clinical Application. Cancers (Basel) 2019; 11:cancers11020141. [PMID: 30682873 PMCID: PMC6406804 DOI: 10.3390/cancers11020141] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 01/18/2019] [Accepted: 01/22/2019] [Indexed: 01/04/2023] Open
Abstract
Liver metastases (LM) are often consequences of colo-rectal cancer (CRC)and the majority of patients have unresectable LM. Oxaliplatin-based intravenous chemotherapy represents the gold standard treatment for CRC. Intravenous oxaliplatin has several side effects i.e., nephrologic, hematologic and neurological toxicity. Moreover, hepatic arterial infusion (HAI) of antitumor drugs deeply modifies the treatment of LMCRC due to the knowledge that LM are perfused by the hepatic artery network, whereas healthy tissue is perfused by the portal vein. Therefore, oxaliplatin-based HAI becomes an interesting possibility to treat LMCRC. The aim of this review is to shed light on the important impact of the oxaliplatin-based chemotherapy from a non-conventional clinical point of view, considering that, being universally accepted its antitumor effect if administered intravenously, fragmentary information are known about its clinical applications and benefits deriving from intra-arterial administration in loco-regional chemotherapy.
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Fountzilas E, Krishnan E, Janku F, Fu S, Karp DD, Naing A, Subbiah V, Hong DS, Piha-Paul SA, Vining DJ, Tsimberidou AM. A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement. Cancer Chemother Pharmacol 2018; 82:877-885. [PMID: 30182147 DOI: 10.1007/s00280-018-3680-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 08/27/2018] [Indexed: 01/25/2023]
Abstract
BACKGROUND We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/- bevacizumab in advanced cancer with predominant liver involvement. METHODS Patients received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase. RESULTS From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20-88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1-12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2 capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2). CONCLUSION HAI oxaliplatin combined with capecitabine +/- bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.
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Affiliation(s)
- Elena Fountzilas
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Elangovan Krishnan
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Filip Janku
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Siqing Fu
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Daniel D Karp
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Aung Naing
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Vivek Subbiah
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - David S Hong
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - Sarina A Piha-Paul
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA
| | - David J Vining
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Apostolia-Maria Tsimberidou
- Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
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Pernot S, Velut G, Kourie RH, Amouyal G, Sapoval M, Pointet AL, Landi B, Zaimi Y, Lepère C, Pellerin O, Taieb J. 5-FU or mitomycin C hepatic arterial infusion after failure of arterial oxaliplatin in patients with colorectal cancer unresectable liver metastases. Clin Res Hepatol Gastroenterol 2018; 42:255-260. [PMID: 29233520 DOI: 10.1016/j.clinre.2017.11.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 10/27/2017] [Accepted: 11/13/2017] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Hepatic arterial infusion (HAI) chemotherapy with oxaliplatin is an accepted option in the management of colorectal cancer (CRC) with dominant liver metastases (LM). However, despite prolonged control, some patients experience disease progression. On the other hand, oxaliplatin leads to dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. We evaluated treatment outcomes in patients receiving second-line HAI with 5-FU or mitomycin C, after first-line HAI of oxaliplatin in heavily pretreated patients. MATERIAL AND METHODS Between March 2010 and June 2016, this observational study included 24 patients with unresectable CRC LM and treated with HAI of 5-FU (17 patients) or mitomycin C (7 patients), after HAI of oxaliplatin. RESULTS Mean age was 61.7 years. Forty-two percent of patients (10/24) had extra-hepatic metastases and 75% (18/24) at least 8 liver metastases. Including HAI of oxaliplatin, all patients had previously received at least 2 lines of chemotherapy±targeted agents (100%) and 96% (23/24) received concomitant systemic therapies together with HAI of 5-FU or mitomycin C. The overall objective response rate and disease control rate were, respectively, 42% (10/24) and 71% (17/24). Median progression-free survival and overall survival (OS) were, respectively, 5.6 and 25.8 months; hepatic progression-free survival was 8.5months. Thirteen percent (3/24) of the patients received further curative intent treatment after HAI 5-FU and mitomycin C. No toxic death occurred and the toxicity profile was acceptable. CONCLUSIONS HAI of 5-FU or mitomycin C is an alternative option in patients with predominant CRC LM, when they experience disease progression or do not tolerate HAI of oxaliplatin.
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Affiliation(s)
- Simon Pernot
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Guillaume Velut
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Rapahel Hampig Kourie
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Gregory Amouyal
- Department of interventional radiology, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Marc Sapoval
- Department of interventional radiology, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Anne Laure Pointet
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Bruno Landi
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Yosra Zaimi
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Céline Lepère
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Olivier Pellerin
- Department of interventional radiology, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - Julien Taieb
- Department of gastroenterology and digestive oncology depart, université Paris Descartes, Sorbonne Paris-cité, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France.
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Chapelle N, Matysiak-Budnik T, Douane F, Metairie S, Rougier P, Touchefeu Y. Hepatic arterial infusion in the management of colorectal cancer liver metastasis: Current and future perspectives. Dig Liver Dis 2018; 50:220-225. [PMID: 29290599 DOI: 10.1016/j.dld.2017.12.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 12/04/2017] [Accepted: 12/06/2017] [Indexed: 12/11/2022]
Abstract
The technique of hepatic arterial infusion (HAI) for the treatment of liver metastases from colorectal cancer has been developed over more than 30 years. Although the indications and protocols for this technique have evolved with time, HAI is not routinely performed in clinical practice. Studies have been heterogeneous, with different regimens of intra-arterial drugs, associated or not with systemic chemotherapy, and with unconvincing outcomes. Technical difficulties for catheter placement have limited the implementation of this method in routine practice. The aim of this review is to present recent studies, highlighting technical improvements and promising combinations of oxaliplatin-based HAI with systemic treatments. HAI is being investigated in both the metastatic setting - in the first line and beyond - and in the adjuvant setting, and we will discuss its potential place in current and future patient management.
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Affiliation(s)
- Nicolas Chapelle
- University of Nantes, Nantes, France; Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France.
| | - Tamara Matysiak-Budnik
- University of Nantes, Nantes, France; Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
| | | | | | - Philippe Rougier
- Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
| | - Yann Touchefeu
- Nantes University Hospital, Hôtel-Dieu, Digestive Disease Institute, Gastro-Enterology, Hepatology and Digestive Oncology Unit, France
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Deschamps F, Harris KR, Moine L, Li W, Tselikas L, Isoardo T, Lewandowski RJ, Paci A, Huang N, de Baere T, Salem R, Larson AC. Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin. Cardiovasc Intervent Radiol 2018; 41:781-788. [PMID: 29468287 DOI: 10.1007/s00270-018-1899-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 02/07/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. MATERIALS/METHODS Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. RESULTS Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). CONCLUSION Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.
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Affiliation(s)
- Frederic Deschamps
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France. .,CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France.
| | | | - Laurence Moine
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | - Weiguo Li
- Department of Radiology, Northwestern University, Chicago, USA
| | - Lambros Tselikas
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France
| | - Thomas Isoardo
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | | | - Angelo Paci
- CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France
| | - Nicolas Huang
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | - Thierry de Baere
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France
| | - Riad Salem
- Department of Radiology, Northwestern University, Chicago, USA
| | - Andrew C Larson
- Department of Radiology, Northwestern University, Chicago, USA
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Brozou V, Vadalouca A, Zis P. Pain in Platin-Induced Neuropathies: A Systematic Review and Meta-Analysis. Pain Ther 2017; 7:105-119. [PMID: 29196945 PMCID: PMC5993684 DOI: 10.1007/s40122-017-0092-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Indexed: 01/01/2023] Open
Abstract
Introduction Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. Methods A systematic computer-based literature search was conducted on the PubMed database. Results This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. Conclusion Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment.
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Affiliation(s)
| | | | - Panagiotis Zis
- Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
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Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study. Clin Colorectal Cancer 2017; 16:308-315. [DOI: 10.1016/j.clcc.2017.03.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 02/19/2017] [Accepted: 03/01/2017] [Indexed: 01/05/2023]
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Fiorentini G, Sarti D, Aliberti C, Carandina R, Mambrini A, Guadagni S. Multidisciplinary approach of colorectal cancer liver metastases. World J Clin Oncol 2017; 8:190-202. [PMID: 28638789 PMCID: PMC5465009 DOI: 10.5306/wjco.v8.i3.190] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 04/27/2017] [Accepted: 05/03/2017] [Indexed: 02/06/2023] Open
Abstract
Large bowel cancer is a worldwide public health challenge. More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases. Selection criteria for early diagnosis, chemotherapy and surgery have been recently expanded. The definition of resectability remains unclear. The presence of metastases is the most significant prognostic factor. For this reason the surgical resection of hepatic metastases is the leading treatment. The most appropriate resection approach remains to be defined. The two step and simultaneous resection processes of both primary and metastases have comparable survival long-term outcomes. The advent of targeted biological chemotherapeutic agents and the development of loco-regional therapies (chemoembolization, thermal ablation, arterial infusion chemotherapy) contribute to extend favorable results. Standardized evidence-based protocols are missing, hence optimal management of hepatic metastases should be single patient tailored and decided by a multidisciplinary team. This article reviews the outcomes of resection, systemic and loco-regional therapies of liver metastases originating from large bowel cancer.
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Adam R, Yi B, Innominato PF, Barroso E, Laurent C, Giuliante F, Capussotti L, Lapointe R, Regimbeau JM, Lopez-Ben S, Isoniemi H, Hubert C, Lin JK, Gruenberger T, Elias D, Skipenko OG, Guglielmi A. Resection of colorectal liver metastases after second-line chemotherapy: is it worthwhile? A LiverMetSurvey analysis of 6415 patients. Eur J Cancer 2017; 78:7-15. [DOI: 10.1016/j.ejca.2017.03.009] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 02/20/2017] [Accepted: 03/05/2017] [Indexed: 12/27/2022]
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50
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Wang X, Hu J, Cao G, Zhu X, Cui Y, Ji X, Li X, Yang R, Chen H, Xu H, Liu P, Li J, Li J, Hao C, Xing B, Shen L. Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma. Radiology 2017; 283:580-589. [PMID: 27820684 DOI: 10.1148/radiol.2016160572] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose To evaluate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma (PCC) in this prospective phase II study. Materials and Methods The protocol was approved by the local ethics committee, and all patients gave informed consent. Patients with nonresectable PCC were included in a prospective, open phase II study investigating HAI through interventionally implanted port catheters. HAI consisted of infusions of oxaliplatin 40 mg/m2 for 2 hours, followed by 5-fluorouracil 800 mg/m2 for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern. © RSNA, 2016.
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Affiliation(s)
- Xiaodong Wang
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Jungang Hu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Guang Cao
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Xu Zhu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Yong Cui
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Xinqiang Ji
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Xuan Li
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Renjie Yang
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Hui Chen
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Haifeng Xu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Peng Liu
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Jian Li
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Jie Li
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Chunyi Hao
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Baocai Xing
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
| | - Lin Shen
- From the Department of Interventional Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) (X.W., J.H., G.C., X.Z., R.Y., H.C., H.X., P.L.), Departments of Radiology (Y.C.), Medical Statistics (X.J.), and GI Oncology (Jian Li, Jie Li, L.S.), and Department of Hepatic, Biliary & Pancreatic Surgery (C.H., B.X.), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China; and Department of Mathematics and Statistics, University of Minnesota-Duluth, Duluth, Minn (X.L.)
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