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Li X, Bao J, Ma J. Cost-effectiveness analysis of FOLFOXIRI/FOLFOXIRI and mFOLFOX6/FOLFIRI treatment in first-line and second-line chemotherapy for metastatic colorectal cancer. BMJ Open 2025; 15:e086372. [PMID: 40132845 PMCID: PMC11934415 DOI: 10.1136/bmjopen-2024-086372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 02/28/2025] [Indexed: 03/27/2025] Open
Abstract
OBJECTIVES The aim of this study was to evaluate the cost-effectiveness of FOLFOXIRI/FOLFOXIRI compared with mFOLFOX6/FOLFIRI in first-line and second-line chemotherapy for metastatic colorectal cancer (mCRC) from the perspectives of the USA and China, respectively, and provide a decision-making basis for clinical selection of these two regimens. DESIGN The study used a decision-analytic Markov model to simulate the process of mCRC, including three distinct health states: progression-free survival, progressive disease and death. Clinical data were derived from the TRIBE2 trial.Costs and utilities were obtained from local public databases and literature. One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters' uncertainty in this study. PARTICIPANTS The main included patients were histologically confirmed colorectal adenocarcinoma. INTERVENTIONS First-line and second-line treatment with either FOLFOXIRI/FOLFOXIRI or mFOLFOX6/FOLFIRI. MAIN OUTCOME MEASURES Costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon as primary outcomes. RESULTS Patients treated with the FOLFOXIRI/FOLFOXIRI regimen produced 0.08 QALYs in the USA while 0.04 QALYs in China compared with the mFOLFOX6/FOLFIRI regimen. The final ICERs for FOLFOXIRI/FOLFOXIRI were US$5127.70 per QALY and US$30 478.33 per QALY in the USA and China, which are below the willingness-to-pay (WTP) thresholds. In the USA, when the WTP was US$100 000 for each QALY gained, the probability was nearly 99.6% that the FOLFOXIRI/FOLFOXIRI treatment was cost-effective. In China, when the WTP was US$36 053.01 (3 × GDP) for each QALY gained, the probability was nearly 54.7% that FOLFOXIRI/FOLFOXIRI treatment was cost-effective. CONCLUSION Patients with mCRC treated with FOLFOXIRI/FOLFOXIRI as first-line and second-line chemotherapy may improve health outcomes and expend financial resources more efficiently than mFOLFOX6/FOLFIRI whether in China or the USA, which benefits not only individual survival but also the health care system from a value perspective.
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Affiliation(s)
- Xianglian Li
- The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jianan Bao
- The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jingjing Ma
- The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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2
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Rajendran L, Sapisochin G, Cattral M. The role of living donor liver transplantation in colorectal cancer liver metastases. Curr Opin Organ Transplant 2025; 30:12-20. [PMID: 39607024 DOI: 10.1097/mot.0000000000001188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
PURPOSE OF REVIEW Despite technical and therapeutic advances, only 20-40% of patients with colorectal liver metastases (CRLM) have resectable disease. Historically, the remaining patients with unresectable, liver-only CRLM would receive palliative chemotherapy, with a median survival of 8 months. RECENT FINDINGS Liver transplantation has emerged as a viable option for selected patients with CRLM. This advancement stems from improved understanding of tumour genomics and biology and better patient selection criteria. The results of recent prospective clinical trials have further ignited enthusiasm for liver transplantation as a viable therapeutic option. Living donor liver transplantation (LDLT) offers several advantages over deceased donor liver transplantation (DDLT) for this disease, including reduced wait-time and optimized timing and coordination of oncologic therapy. On-going LDLT clinical trials have demonstrated favourable outcomes as compared with other liver transplantation indications. However, there is no established consensus or standardization in the implementation of LDLT for CRLM, beyond trials and centre-specific protocols. SUMMARY LDLT is an excellent therapeutic option in highly selected patients with CRLM. Refining prognostic factors and selection criteria will help to further optimize the utility and broaden the acceptance and implementation of LDLT for patients with CRLM.
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Affiliation(s)
- Luckshi Rajendran
- Division of General Surgery, Department of Surgery, University of Toronto
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Division of General Surgery, Department of Surgery, University of Toronto
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Mark Cattral
- Division of General Surgery, Department of Surgery, University of Toronto
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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3
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Chávez-Villa M, Pope-Collins E, Dokus K, Martens J, Keller E, Nickels M, Byrne M, Hernandez-Alejandro R, Al-Judaibi B. Public Acceptance of Living Donor Liver Transplant for Colorectal Liver Metastases: A Web-Based Survey. Clin Transplant 2024; 38:e70013. [PMID: 39460631 DOI: 10.1111/ctr.70013] [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: 04/10/2024] [Revised: 09/08/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024]
Abstract
BACKGROUND Recent advancements in cancer treatment and post-transplant management have expanded the population of living donor liver transplant (LDLT) candidates. We aimed to examine variations in public acceptance of LDLT based on patient diagnosis, including unresectable colorectal liver metastases (uCRLM). METHODS A web-based survey collected demographic information and general perceptions about organ donation in different settings. Respondents indicated their likelihood of being a living liver donor for a family member with genetic liver disease, alcohol-related liver disease (ALD), and uCRLM. Differences in the likelihood of donation between scenarios were compared. RESULTS There were 491 survey respondents (female [76.5%], Caucasians [87.4%], and had at least a college degree [98.2%]). Most (82.4%) were aware of the option of living liver donation before the study and 95% supported living organ donation in general. Over 80% were registered as organ donors. Ninety percent indicated that they would be likely to donate to a family member with a genetic liver disease if they qualified as a living donor; significantly more than ALD (59%) and uCRLM (71%) (p < 0.001). Willingness to donate to patients with uCRLM was significantly higher (p < 0.001) than the hypothetical patient with ALD with a clinically accepted recovery period of 6 months. CONCLUSIONS This study is the first of its kind to assess the public acceptance of living liver donation for uCRLM. Respondents were as or more supportive of donating to uCRLM as they were of generally accepted indications for LT. Further surveys with a broader respondent pool are warranted.
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Affiliation(s)
- Mariana Chávez-Villa
- Department of Surgery, Transplant Institute, University of Rochester Medical Center, Rochester, New York, USA
| | - Elizabeth Pope-Collins
- Department of Medicine, University of Rochester Medical Center, Rochester, New York, USA
| | - Katherine Dokus
- Department of Surgery, Transplant Institute, University of Rochester Medical Center, Rochester, New York, USA
| | - John Martens
- Department of Surgery, Transplant Institute, University of Rochester Medical Center, Rochester, New York, USA
| | - Elizabeth Keller
- Center for Community Health & Prevention, University of Rochester Medical Center, Rochester, New York, USA
| | - Mark Nickels
- Department of Psychiatry, University of Rochester Medical Center, Rochester, New York, USA
| | - Matthew Byrne
- Department of Surgery, Transplant Institute, University of Rochester Medical Center, Rochester, New York, USA
| | - Roberto Hernandez-Alejandro
- Department of Surgery, Transplant Institute, University of Rochester Medical Center, Rochester, New York, USA
| | - Bandar Al-Judaibi
- Liver and Small Bowel Health Centre, King Faisal Special Hospital, Riyadh, Saudi Arabia
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Varnier R, Toullec C, Philonenko S, Dupré A, Artru P, Hafliger E, Drouillard A, Torregrosa C, Pernot S, McLellan P, Lecomte T, Moulin V, Lécaille C, Touchefeu Y, Locher C, Taieb J, Coutzac C. Triplet chemotherapy with or without bevacizumab as first line treatment for metastatic colorectal cancer: An AGEO multicenter real-world study. Dig Liver Dis 2024; 56:1605-1613. [PMID: 38403514 DOI: 10.1016/j.dld.2024.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/03/2024] [Accepted: 02/11/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND Prior trials validated triplet chemotherapy (Tri-CT) with bevacizumab as first line treatment for metastatic colorectal cancer (mCRC) but real-world data are scarce and practices remain heterogeneous. AIMS To evaluate Tri-CT +/- bevacizumab efficacy and safety, and to identify factors influencing treatment decisions. METHODS The COLOTRIP retrospective study enrolled mCRC patients treated from 2014 to 2019 in 14 French centers. RESULTS Of 299 patients (81% PS 0-1, 58% RAS-mutated and 19% BRAF-mutated), 51% received Tri-CT and 49% Tri-CT + bevacizumab. Metastatic disease was classified as resectable (6.5%), potentially resectable (40%), and unresectable (54%). Bevacizumab use was associated with primary tumor location, mutational status and number of metastases. Median overall survival was 33.5 months in the Tri-CT group and 23.9 months in the Tri-CT + bevacizumab group, with median progression-free survival being 14.5 and 11.4 months. After adjusting for initial characteristics, no difference in survival was noted. Around 30% of patients experienced grade ≥3 adverse events. CONCLUSIONS This study highlights several factors influencing Tri-CT use +/- bevacizumab decision and confirms the real-world good oncological outcomes and tolerability of these regimens in mCRC patients. Our results suggest that Tri-CT alone may by an appropriate option for specific subgroups of patients.
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Affiliation(s)
- R Varnier
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France; Research on Healthcare Performance (RESHAPE, Inserm U1290), Université Claude Bernard Lyon 1, Lyon, France
| | - C Toullec
- Department of Digestive Oncology, Institut du Cancer Avignon-Provence, Avignon, France
| | - S Philonenko
- Department of Gastroenterology and Digestive Oncology, Hôpital Pitié Salpêtrière, Paris, France
| | - A Dupré
- Department of Surgery, Centre Léon Bérard, Lyon, France
| | - P Artru
- Department of Gastroenterology and Digestive Oncology, Hôpital Privé Jean Mermoz, Lyon, France
| | - E Hafliger
- Department of Gastroenterology and Digestive Oncology, Hôpital Privé Jean Mermoz, Lyon, France
| | - A Drouillard
- Department of Hepato-Gastroenterology and Digestive Oncology, Centre Hospitalier Universitaire de Dijon, Dijon, France
| | - C Torregrosa
- Department of Medical Oncology, Institut Curie, Paris, France
| | - S Pernot
- Department of Digestive Oncology, Institut Bergonié, Bordeaux, France
| | - P McLellan
- Department of Hepato-Gastroenterology and Digestive Oncology, Hôpital Saint-Louis, Paris, France
| | - T Lecomte
- Department of Hepato-Gastroenterology and Digestive Oncology, Centre Hospitalier Universitaire de Tours, Tours, France
| | - V Moulin
- Department of Hepato-Gastroenterology and Digestive Oncology, Centre Hospitalier de La Rochelle, La Rochelle, France
| | - C Lécaille
- Department of Hepato-Gastroenterology and Digestive Oncology, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France
| | - Y Touchefeu
- Department of Hepato-Gastroenterology and Digestive Oncology, Centre Hospitalier Universitaire de Nantes, Nantes, France
| | - C Locher
- Department of Hepato-Gastroenterology, Centre Hospitalier de Meaux, Meaux, France
| | - J Taieb
- Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, AP-HP, Paris-Cité University, SIRIC CARPEM Comprehensive Cancer Center, Paris, France
| | - C Coutzac
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France; Association des Gastro-Entérologues Oncologues (AGEO), France.
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Sjule HM, Vinter CN, Dueland S, Line PD, Burger EA, Bjørnelv GMW. The Spillover Effects of Extending Liver Transplantation to Patients with Colorectal Liver Metastases: A Discrete Event Simulation Analysis. Med Decis Making 2024; 44:529-542. [PMID: 38828508 PMCID: PMC11283734 DOI: 10.1177/0272989x241249154] [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: 02/09/2023] [Accepted: 03/11/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND Liver transplantation is an alternative treatment for patients with nonresectable colorectal cancer liver-only metastases (CRLM); however, the potential effects on wait-list time and life expectancy to other patients on the transplant waiting list have not been considered. We explored the potential effects of expanding liver transplantation eligibility to include patients with CRLM on wait-list time and life expectancy in Norway. METHODS We developed a discrete event simulation model to reflect the Norwegian liver transplantation waiting list process and included 2 groups: 1) patients currently eligible for liver transplantation and 2) CRLM patients. Under 2 alternative CRLM-patient transplant eligibility criteria, we simulated 2 strategies: 1) inclusion of only currently eligible patients (CRLM patients received standard-of-care palliative chemotherapy) and 2) expanding waiting list eligibility to include CRLM patients under 2 eligibility criteria. Model outcomes included median waiting list time, life expectancy, and total life-years. RESULTS For every additional CRLM patient listed per year, the overall median wait-list time, initially 52 d, increased by 8% to 11%. Adding 2 additional CRLM patients under the most restrictive eligibility criteria increased the CRLM patients' average life expectancy by 10.64 y and decreased the average life expectancy for currently eligible patients by 0.05 y. Under these assumptions, there was a net gain of 149.61 life-years over a 10-y programmatic period, which continued to increase under scenarios of adding 10 CRLM patients to the wait-list. Health gains were lower under less restrictive CRLM eligibility criteria. For example, adding 4 additional CRLM patients under the less restrictive eligibility criteria increased the CRLM patients' average life expectancy by 5.64 y and decreased the average life expectancy for currently eligible patients by 0.12 y. Under these assumptions, there was a net gain of 96.36 life-years over a 10-y programmatic period, which continued to increase up to 7 CRLM patients. CONCLUSIONS Our model-based analysis enabled the consideration of the potential effects of enlisting Norwegian CRLM patients for liver transplantation on wait-list time and life expectancy. Enlisting CRLM patients is expected to increase the total health effects, which supports the implementation of liver transplantation for CRLM patients in Norway. HIGHLIGHTS Given the Norwegian donor liver availability, adding patients with nonresectable colorectal cancer liver-only metastases (CRLM) to the liver transplantation waiting list had an overall modest, but varying, impact on total waiting list time.Survival gains for selected CRLM patients treated with liver transplantation would likely outweigh the losses incurred to patients listed currently.To improve the total life-years gained in the population, Norway should consider expanding the treatment options for CRLM patients to include liver transplantation.Other countries may also have an opportunity to gain total life-years by extending the waiting list eligibility criteria; however, country-specific analyses are required.
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Affiliation(s)
- Hanna Meidell Sjule
- Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
| | - Caroline N. Vinter
- Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
| | - Svein Dueland
- Research group for Transplant Oncology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Pål-Dag Line
- Research group for Transplant Oncology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Emily A. Burger
- Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
- Center for Health Decision Science, Harvard T.H. Chan School of Public Health
| | - Gudrun Marie Waaler Bjørnelv
- Department of Health Management and Health Economics, University of Oslo, Oslo, Norway
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
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Battistella S, Grasso M, Catanzaro E, D’Arcangelo F, Corrà G, Germani G, Senzolo M, Zanetto A, Ferrarese A, Gambato M, Burra P, Russo FP. Evolution of Liver Transplantation Indications: Expanding Horizons. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:412. [PMID: 38541138 PMCID: PMC10972065 DOI: 10.3390/medicina60030412] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/22/2024] [Accepted: 02/26/2024] [Indexed: 01/03/2025]
Abstract
Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 Padua, Italy; (S.B.); (E.C.); (F.D.); (G.C.); (G.G.); (M.S.); (A.Z.); (A.F.); (M.G.); (P.B.)
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7
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Chávez-Villa M, Ruffolo LI, Line PD, Dueland S, Tomiyama K, Hernandez-Alejandro R. Emerging Role of Liver Transplantation for Unresectable Colorectal Liver Metastases. J Clin Oncol 2024:JCO2301781. [PMID: 38408289 DOI: 10.1200/jco.23.01781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 12/05/2023] [Accepted: 12/19/2023] [Indexed: 02/28/2024] Open
Affiliation(s)
- Mariana Chávez-Villa
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY
| | - Luis I Ruffolo
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY
| | - Pål-Dag Line
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Koji Tomiyama
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY
| | - Roberto Hernandez-Alejandro
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Rochester Medical Center, Rochester, NY
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Chai Y, Liu JL, Zhang S, Li N, Xu DQ, Liu WJ, Fu RJ, Tang YP. The effective combination therapies with irinotecan for colorectal cancer. Front Pharmacol 2024; 15:1356708. [PMID: 38375031 PMCID: PMC10875015 DOI: 10.3389/fphar.2024.1356708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 01/19/2024] [Indexed: 02/21/2024] Open
Abstract
Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.
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Affiliation(s)
- Yun Chai
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Jing-Li Liu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Shuo Zhang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Na Li
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Ding-Qiao Xu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Wen-Juan Liu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Rui-Jia Fu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Yu-Ping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
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Dueland S, Smedman TM, Syversveen T, Grut H, Hagness M, Line PD. Long-Term Survival, Prognostic Factors, and Selection of Patients With Colorectal Cancer for Liver Transplant: A Nonrandomized Controlled Trial. JAMA Surg 2023; 158:e232932. [PMID: 37494056 PMCID: PMC10372758 DOI: 10.1001/jamasurg.2023.2932] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 05/06/2023] [Indexed: 07/27/2023]
Abstract
Importance Liver transplant for colorectal cancer with liver metastases was abandoned in the 1990s due to poor overall survival. From 2006, liver transplant for in nonresectable colorectal liver metastases has been reexamined through different prospective trials. Objective To determine predictive factors for transplant long-term survival and cure after liver transplant. Design, Setting, and Participants This was a prospective, nonrandomized controlled cohort study derived from different clinical trials on liver transplant for colorectal liver metastases from 2006 to 2020 at Oslo University Hospital. The trials differed in prognostic inclusion criteria, but the design was otherwise identical regarding follow-up scheme to determine disease recurrence, overall survival, and survival after relapse. Final data analysis was performed on December 31, 2021. All patients with colorectal liver metastases from comparable prospective liver transplant studies were included. Exposure Liver transplant. Main outcomes and measures Disease-free survival, overall survival, and survival time after recurrence were determined in all participants. Results A total of 61 patients (median [range] age, 57.8 [28.7-71.1] years; 35 male [57.4%]) underwent liver transplant at Oslo University Hospital. Posttransplant observation time ranged from 16 to 165 months, and no patient was lost to follow-up. Median disease-free period, overall survival, and survival after relapse were 11.8 (95% CI, 9.3-14.2) months, 60.3 (95% CI, 44.3-76.4) months, and 37.1 (95% CI, 4.6-69.5) months, respectively. Negative predictive factors for overall survival included the following: largest tumor size greater than 5.5 cm (median OS, 25.3 months; 95% CI, 15.8-34.8 months; P <.001), progressive disease while receiving chemotherapy (median OS, 39.8 months; 95% CI, 28.8-50.7 months; P = .02), plasma carcinoembryonic antigen values greater than 80 μg/L (median OS, 26.6 months; 95% CI, 22.7-30.6 months; P <.001), liver metabolic tumor volume on positron emission tomography of greater than 70 cm3 (26.6 months; 95% CI, 11.8-41.5 months; P <.001), primary tumor in the ascending colon (17.9 months; 95% CI, 0-37.5 months; P <.001), tumor burden score of 9 or higher (23.3 months; 95% CI, 19.2-27.4 months; P = .02), and 9 or more liver lesions (42.5 months; 95% CI, 17.2-67.8 months; P = .02). An Oslo score of 0 or Fong Clinical Risk Score of 1 yielded 10-year survival of 88.9% and 80.0%, respectively. Conclusions and relevance Results of this nonrandomized controlled trial suggest that selected patients with liver-only metastases and favorable pretransplant prognostic scoring had long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care.
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Affiliation(s)
- Svein Dueland
- Transplant Oncology Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Tor Magnus Smedman
- Transplant Oncology Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Department of Oncology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trygve Syversveen
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Harald Grut
- Department of Radiology, Vestre Viken Hospital Trust, Drammen, Norway
| | - Morten Hagness
- Transplant Oncology Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Pål-Dag Line
- Transplant Oncology Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Section for Transplantation Surgery, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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10
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Chávez-Villa M, Ruffolo LI, Hernandez-Alejandro R. Liver transplantation for unresectable colorectal liver metastasis. Curr Opin Organ Transplant 2023; 28:245-253. [PMID: 37339517 DOI: 10.1097/mot.0000000000001083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/22/2023]
Abstract
PURPOSE OF REVIEW To summarize the current state of liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM), and to address future directions. RECENT FINDINGS The Norwegian secondary cancer (SECA) I and SECA II studies demonstrated that after LT the 5-year survival of a highly selected group of patients with uCRLM could be as high as 60% and 83%, respectively. After long-term follow-up, the 5- and 10-year survival was shown to be 43% and 26%, respectively. Furthermore, data has accumulated in other countries and a North American study reported a 1.5-year survival of 100%. In addition, steady growth has been demonstrated in the US, with 46 patients transplanted to date and 19 centers enrolling patients for this indication. Lastly, although recurrence is almost universal in patients with a high tumor burden, it has not been an accurate surrogate for survival, reflecting the relatively indolent nature of recurrence after LT. SUMMARY Growing evidence has shown that excellent survival and even cure can be achieved in highly selected patients with uCRLM, with survival rates far superior than in patients treated with chemotherapy. The next step is to create national registries to standardize selection criteria and establish the optimal approach and best practices for incorporating LT for uCRLM into the treatment armamentarium.
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Affiliation(s)
- Mariana Chávez-Villa
- Department of Surgery, Division of Transplantation, University of Rochester Medical Center, Rochester, New York, USA
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Ros J, Salva F, Dopazo C, López D, Saoudi N, Baraibar I, Charco R, Tabernero J, Elez E. Liver transplantation in metastatic colorectal cancer: are we ready for it? Br J Cancer 2023; 128:1797-1806. [PMID: 36879000 PMCID: PMC10147684 DOI: 10.1038/s41416-023-02213-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 02/10/2023] [Accepted: 02/17/2023] [Indexed: 03/08/2023] Open
Abstract
Colorectal cancer (CRC) is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Five-year overall survival remains modest among patients with metastatic CRC (mCRC) treated with conventional therapies however, liver transplantation in a highly selected population can improve clinical outcomes with an impressive 5-year overall survival of 83%. Despite liver transplantation appearing to be a promising therapeutical option for well-selected patients with mCRC with the liver-limited disease, these data come from small monocentric trials which included a heterogeneous population. Currently, several clinical trials are evaluating liver transplantation in this scenario, aiming for a more accurate patient selection by integrating liquid biopsy, tissue profiling, and nuclear medicine to the already known clinical biomarkers that eventually may lead to a survival improvement. In this paper, the clinical outcomes and inclusion criteria from the most relevant clinical trials and clinical series involving liver transplantation in patients with liver-limited disease colorectal cancer are reviewed as well as the trials currently recruiting.
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Affiliation(s)
- Javier Ros
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain.
- Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, 80131, Naples, Italy.
| | - Francesc Salva
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain
| | - Cristina Dopazo
- Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Daniel López
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain
| | - Nadia Saoudi
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain
| | - Iosune Baraibar
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain
| | - Ramon Charco
- Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Josep Tabernero
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain
| | - Elena Elez
- Department of Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), 08035, Barcelona, Spain
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Kitasaki N, Abe T, Inoue M, Kohata A, Toyota K. Pathological complete response of multiple liver metastases from colon cancer successfully treated with conversion surgery: A case report. Int J Surg Case Rep 2023; 104:107935. [PMID: 36801767 PMCID: PMC9969276 DOI: 10.1016/j.ijscr.2023.107935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/16/2023] [Indexed: 02/19/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE Recently, the successful long-term survival of patients with unresectable distant metastases from colorectal cancer, who underwent conversion surgery after systemic chemotherapy, have been documented. Herein, we present a patient afflicted with ascending colon cancer and multiple unresectable liver metastases, who underwent conversion surgery, resulting in the complete disappearance of the pathological liver metastases. PRESENTATION OF CASE A 70-year-old woman visited our hospital with a chief complaint of weight loss. A diagnosis of ascending colon cancer (cT4aN2aM1a [H3]: TNM classification 8th edition) stage IVa with RAS/BRAF wild-type mutation was made (four liver metastases up to 60 mm in diameter were observed in both lobes). After 2 years and 3 months of systemic chemotherapy (capecitabine, oxaliplatin, and bevacizumab), the tumor marker levels had decreased to normal ranges and all liver metastases showed partial responses with remarkable shrinkage. After confirmation of a liver function and a preserved future liver remnant volume, the patient finally underwent hepatectomy, involving partial resection of S4 and subsegmentectomy of S8, along with a right hemicolectomy. Histopathologic examination revealed that all liver metastases had completely disappeared, while regional lymph node metastases had changed into scar tissue. However, the primary tumor failed to respond to chemotherapy, resulting in ypT3N0M0 ypStage IIA. The patient was discharged from the hospital on the 8th postoperative day without any postoperative complications. She is currently on the 6th month of follow-up without any recurring metastasis. CLINICAL DISCUSSION Curative surgery is recommended for resectable liver metastases of colorectal cancer (CRLM), be it synchronous or heterochronous. Up until now, the efficacy of perioperative chemotherapy for CRLM is limited. Chemotherapy has a double-edged aspect, where some cases have shown successful improvement in the treatment stage. CONCLUSION To obtain the maximum benefit from conversion surgery, it is critical to incorporate the appropriate surgical technique, at the correct stage, in order avoid the progression to chemotherapy-associated steatohepatitis (CASH) in the patient.
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Affiliation(s)
- Nao Kitasaki
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan.
| | - Tomoyuki Abe
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan.
| | - Masashi Inoue
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan.
| | - Akihiro Kohata
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan.
| | - Kazuhiro Toyota
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan.
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Menon K, Vijayashanker A, Murphy J, Line PD, Isaac J, Adair A, Prasad R, Thorburn D. Liver transplantation for isolated unresectable colorectal liver metastases - Protocol for a service evaluation in the United Kingdom - UKCoMET study. HPB (Oxford) 2023:S1365-182X(23)00049-7. [PMID: 36948901 DOI: 10.1016/j.hpb.2023.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/13/2023] [Accepted: 02/13/2023] [Indexed: 03/24/2023]
Abstract
BACKGROUND Liver transplantation (LT) for unresectable colorectal liver metastases (CRCLM) demonstrates good overall survival for selected patients in contemporary studies, with 5-year survival of 80%. A Fixed Term Working Group (FTWG), set up by NHS Blood and Transplant (NHSBT) Liver Advisory Group (LAG), advised whether CRCLM should be considered for LT in United Kingdom. Their recommendation was that LT may be undertaken for isolated and unresectable CRCLM using strict selection criteria as a national clinical service evaluation. METHODS Opinions were sought from colorectal cancer/LT patient representatives, experts in colorectal cancer surgery/oncology, LT surgery, hepatology, hepatobiliary radiology, pathology, and nuclear medicine, and appropriate patient selection criteria, referral and transplant listing pathways were identified. RESULTS This paper summarises selection criteria for LT in United Kingdom for isolated and unresectable CRCLM patients, and highlights referral framework and pre-transplant assessment criteria. Finally, oncology-specific outcome measures to be utilised for assessing applicability of LT are described. CONCLUSION This service evaluation represents a significant development for colorectal cancer patients in United Kingdom and a meaningful step forward in the field of transplant oncology. This paper details the protocol for the pilot study, scheduled to begin in the fourth quarter of 2022 in United Kingdom.
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Affiliation(s)
- Krishna Menon
- Institute of Liver Studies, King's College Hospital, London, UK; Digestive Diseases and Surgery Institute, Cleveland Clinic London, UK.
| | | | - Jamie Murphy
- Department of Surgery and Cancer, Imperial College London, UK; Digestive Diseases and Surgery Institute, Cleveland Clinic London, UK
| | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - John Isaac
- Liver Unit, Queen Elizabeth Hospital, Birmingham, UK
| | - Anya Adair
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, UK
| | - Raj Prasad
- Liver Transplantation and HPB Surgery, Leeds Teaching Hospitals, Leeds, UK
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre and UCL Institute for Liver & Digestive Health, Royal Free Hospital, London, UK
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Villard C, Abdelrafee A, Habib M, Ndegwa N, Jorns C, Sparrelid E, Allard MA, Adam R. Prediction of survival in patients with colorectal liver metastases- development and validation of a prognostic score model. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2432-2439. [PMID: 35786533 DOI: 10.1016/j.ejso.2022.06.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 05/10/2022] [Accepted: 06/17/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Metastatic spread of colorectal cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information. METHODS The retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013-2018. Independent prognostic factors for OS were identified, based on which a score model was generated. The model was validated on patients treated for CRLM at Hôpital Universitaire Paul Brousse, Villejuif, France, 2007-2018. Calibration and discrimination methods were used for internal and external validation. RESULTS The Swedish development cohort included 1013 patients, the French validation cohort 391 patients. Poor OS was significantly associated with age>60years (hazard ratio (HR) 3.57 (95%CI 2.18-9.94)), number of CRLM (HR 4.59 (2.83-12.20)), diameter of largest CRLM>5 cm (HR 2.59 (1.74-5.03)), right-sided primary tumour (HR 2.98 (2.00-5.80)), extrahepatic disease (HR 4.14 (2.38-15.87)) and non-resectability (HR 0.77 (0.66-0.90)). The C-statistic for prediction of OS was .74, in the development cohort and 0.69 in the validation cohort. CONCLUSION The presented predictive score model can adequately predict OS for patients at the initial diagnosis of CRLM. The prognostic model could be of clinical value in the management of all patients with CRLM, by predicting individualized survival and thereby facilitating treatment recommendations.
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Affiliation(s)
- Christina Villard
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | - Ahmed Abdelrafee
- Gastrointestinal Surgery Center, Department of Surgery, Mansoura University, Mansoura, Egypt
| | - Miriam Habib
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche « Chronothérapie, Cancers et Transplantation » Université Paris-Saclay, Villejuif, France
| | - Nelson Ndegwa
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Carl Jorns
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Ernesto Sparrelid
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | - Marc-Antoine Allard
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche « Chronothérapie, Cancers et Transplantation » Université Paris-Saclay, Villejuif, France
| | - René Adam
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche « Chronothérapie, Cancers et Transplantation » Université Paris-Saclay, Villejuif, France
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15
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Chávez-Villa M, Ruffolo LI, Tomiyama K, Hernandez-Alejandro R. Where Are We Now With Liver Transplant for Colorectal Metastasis? CURRENT TRANSPLANTATION REPORTS 2022. [DOI: 10.1007/s40472-022-00373-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Smedman TM, Guren TK, Tveit KM, Thomsen M, Andersen MH, Line PD, Dueland S. Health-Related Quality of Life in Colorectal Cancer Patients Treated With Liver Transplantation Compared to Chemotherapy. Transpl Int 2022; 35:10404. [PMID: 35707633 PMCID: PMC9189292 DOI: 10.3389/ti.2022.10404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/12/2022] [Indexed: 11/13/2022]
Abstract
Liver transplantation (LT) for patients with non-resectable colorectal liver metastases (CRLM) offers improved survival and has gained increased interest internationally the last years. The aim of this study was to describe the health-related quality of life (HRQoL) in patients with non-resectable CRLM receiving LT and how baseline HRQoL factors affect overall survival (OS). HRQoL data in the SECA (SEcondary CAncer) LT cohort was compared to data obtained from colorectal cancer patients starting first-line chemotherapy for metastatic disease in a clinical trial and data from a Norwegian normal population. HRQoL data from the QLQ-C30 questionnaire used in the SECA LT study and the NORDIC- VII study were reported. The relationship between patient-reported symptom burden at baseline and OS was investigated. In the SECA study longitudinal HRQoL assessment was used to describe the time until definitive deterioration as well as mean values at different time points. Patients in the SECA and NORDIC-VII studies reported similar baseline HRQoL. The median time until definitive deterioration in the transplanted patients was estimated to 36 months. In the SECA study appetite loss and pain at baseline had negative impact on OS (25.3 versus 71.7 months, p = 0.002 and 39.7 versus 71.7 months, p = 0.038, respectively). Despite a relapse in most of the LT patients the Global Health Score (GHS) remained good. Pain, and especially appetite loss at time of transplantation is associated with poor outcome after LT.
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Affiliation(s)
- Tor Magnus Smedman
- Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- *Correspondence: Tor Magnus Smedman,
| | | | | | | | | | - Pål-Dag Line
- Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Liver Transplant for Non-Hepatocellular Malignancies: A Review for Radiologists. AJR Am J Roentgenol 2022; 219:590-603. [PMID: 35544376 DOI: 10.2214/ajr.22.27783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Although traditionally only performed for hepatocellular carcinoma (HCC), the last decade has seen a resurgence in the use of liver transplant (LT) for non-HCC malignancies, likely due to improvements in neoadjuvant treatment regimens as well as the establishment of well-defined eligibility criteria. Given promising survival results, patients with perihilar cholangiocarcinoma, neuroendocrine liver metastases, and hepatic hemangioendothelioma are eligible to receive Model for End Stage Liver Disease (MELD) exception for tumors that meet well-defined criteria. Additional tumors such as colorectal cancer liver metastases, intrahepatic cholangiocarcinoma, and hepatocholangiocarcinoma may undergo transplant at specialized centers with well-defined protocols, although are not yet eligible for MELD exception. Transplant eligibility criteria commonly incorporate imaging findings, yet due to the relatively novel and evolving nature of LT for non-HCC malignancies, radiologists may be unaware of relevant criteria or of the implications of their imaging interpretations. Knowledge of the allocation process, background, and liver transplant selection criteria facilitates the radiologist' active participation in multidisciplinary discussion, leading to better and more equitable care for transplant candidates with non-HCC malignancy. This review provides an overview of transplant allocation and selection criteria in patients with non-HCC malignancy, with an emphasis on imaging features and the role of the radiologist.
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18
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Cawich SO, Phillips E, Moore S, Ramkissoon S, Padmore G, Griffith S. Colorectal cancer in an Eastern Caribbean nation: are we missing an opportunity for secondary prevention? Rev Panam Salud Publica 2022; 46:e18. [PMID: 35432501 PMCID: PMC9004695 DOI: 10.26633/rpsp.2022.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 11/24/2021] [Indexed: 11/24/2022] Open
Abstract
Objective. To establish whether there was any difference in disease stage in patients with screening-detected colorectal cancer (CRC) in a Caribbean country. Methods. The mode of presentation (elective vs. emergent), method of diagnosis (screening vs. symptomatic), and disease stage were retrospectively compared in all consecutive patients who had resections for CRC over a five-year period. Early CRC was defined as disease that could be completely resected with no involvement of adjacent organs, lymph nodes, or distant sites. Locally advanced CRC was disease that involved contiguous organs without distant metastases that was still amenable to curative resection. Results. There were 97 patients at a mean age of 64.9 ± 12.2 years treated for CRC, and only 21 (21.6%) had their diagnoses made through screening. Significantly more screening-detected lesions were early-stage CRCs (21.7% vs. 9.3%; p < 0.001). At the time of diagnosis, patients who did not have screening-detected lesions had a greater proportion of locally advanced (42.3% vs. 0) and metastatic (26.8% vs. 0) CRC. Those who did not have screening-detected lesions had a greater incidence of emergency presentations at diagnosis (26.8% vs. 0). Conclusions. The incidence of screening-detected CRC in this Caribbean nation was low. Consequently, most patients presented with locally advanced or metastatic CRC, for which there is less opportunity to achieve a cure. Significantly more screening-detected lesions were early-stage CRCs. It is time for policymakers to develop a national CRC screening program.
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Affiliation(s)
- Shamir O. Cawich
- Port of Spain General Hospital, Port of Spain, Trinidad and Tobago
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Jin H, Amonkar M, Aguiar-Ibáñez R, Thosar M, Chase M, Keeping S. Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, microsatellite instability-high or mismatch repair-deficient colorectal cancer. Future Oncol 2022; 18:2155-2171. [PMID: 35332802 DOI: 10.2217/fon-2021-1633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To compare pembrolizumab with competing interventions for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. Method: Trials were identified via a systematic literature review and synthesized using a Bayesian network meta-analysis with time-varying hazard ratios (HRs). Results: Using intention-to-treat data, HRs for overall survival were generally in favor of pembrolizumab but not statistically significant; however, statistical significance was reached versus all comparators by month 16 when accounting for crossover. Estimated HRs for progression-free survival significantly favored pembrolizumab versus all comparators by month 12. Pembrolizumab was also superior to all comparators in terms of grade ≥3 adverse events. Conclusion: These analyses suggest that pembrolizumab is a highly efficacious and safe treatment in this population.
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Affiliation(s)
- He Jin
- PRECISIONheor, New York, NY 10165, USA
| | | | | | | | | | - Sam Keeping
- PRECISIONheor, Vancouver, BC, V6H 3Y4, Canada
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Bazarbashi S, Alghabban A, Aseafan M, Aljubran AH, Alzahrani A, Elhassan TAM. Prognostic significance of peritoneal metastasis from colorectal cancer treated with first-line triplet chemotherapy. World J Clin Cases 2022; 10:2429-2438. [PMID: 35434075 PMCID: PMC8968618 DOI: 10.12998/wjcc.v10.i8.2429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 12/03/2021] [Accepted: 01/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Peritoneal metastasis from colorectal cancer (CRC) carries a poor prognosis in most studies. The majority of those studies used either a single-agent or doublet chemotherapy regimen in the first-line setting.
AIM To investigate the prognostic significance of peritoneal metastasis in a cohort of patients treated with triplet chemotherapy in the first-line setting.
METHODS We retrospectively evaluated progression-free survival (PFS) and overall survival (OS) in 51 patients with metastatic CRC treated in a prospective clinical trial with capecitabine, oxaliplatin, irinotecan, and bevacizumab in the first-line setting according to the presence and absence of peritoneal metastasis. Furthermore, univariate and multivariate analyses for PFS and OS were performed to assess the prognostic significance of peritoneal metastasis at the multivariate level.
RESULTS Fifty-one patients were treated with the above triplet therapy. Fifteen had peritoneal metastasis. The patient characteristics of both groups showed a significant difference in the sidedness of the primary tumor (left-sided primary tumor in 60% of the peritoneal group vs 86% in the nonperitoneal group, P = 0.03) and the presence of liver metastasis (40% for the peritoneal group vs 75% for the nonperitoneal group, P = 0.01). Univariate analysis for PFS showed a statistically significant difference for age less than 65 years (P = 0.034), presence of liver metastasis (P = 0.046), lung metastasis (P = 0.011), and those who underwent metastasectomy (P = 0.001). Only liver metastasis and metastasectomy were statistically significant for OS, with P values of 0.001 and 0.002, respectively. Multivariate analysis showed that age (less than 65 years) and metastasectomy were statistically significant for PFS, with P values of 0.002 and 0.001, respectively. On the other hand, the absence of liver metastasis and metastasectomy were statistically significant for OS, with P values of 0.003 and 0.005, respectively.
CONCLUSION Peritoneal metastasis in patients with metastatic CRC treated with first-line triple chemotherapy does not carry prognostic significance at univariate and multivariate levels. Confirmatory larger studies are warranted.
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Affiliation(s)
- Shouki Bazarbashi
- Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Riyadh, Saudi Arabia
| | - Abdulrahman Alghabban
- Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Riyadh, Saudi Arabia
| | - Mohamed Aseafan
- Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Riyadh, Saudi Arabia
| | - Ali H Aljubran
- Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Riyadh, Saudi Arabia
| | - Ahmed Alzahrani
- Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Riyadh, Saudi Arabia
| | - Tusneem AM Elhassan
- Oncology Center, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Riyadh, Saudi Arabia
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21
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Strömberg C, Martinez de la Maza L, Fernández Moro C, Gerling M, Jorns C, Sparrelid E, Löhr J, Villard C. Prognostic impact of inter-metastatic heterogeneity of viable tumour cells in colorectal liver metastases. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1656-1663. [DOI: 10.1016/j.ejso.2022.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/03/2022] [Accepted: 03/08/2022] [Indexed: 11/16/2022]
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22
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Hoang T, Sohn DK, Kim BC, Cha Y, Kim J. Efficacy and Safety of Systemic Treatments Among Colorectal Cancer Patients: A Network Meta-Analysis of Randomized Controlled Trials. Front Oncol 2022; 11:756214. [PMID: 35223449 PMCID: PMC8864322 DOI: 10.3389/fonc.2021.756214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 12/31/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Systemic treatments, namely, either monotherapy or combination therapy, are commonly administered to patients with advanced or metastatic colorectal cancer (CRC). This study aimed to provide the complete efficacy and safety profiles and ranking of systemic therapies for the treatment of unresectable advanced or metastatic CRC. METHODS We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until June 30, 2021, and also the bibliographies of relevant studies. Randomized controlled trials comparing two or more treatments, namely, at least capecitabine, 5-fluorouracil, leucovorin, irinotecan, bevacizumab, cetuximab, oxaliplatin, or panitumumab were investigated. A network meta-analysis using the Bayesian approach was performed to compare the efficacy and safety of treatments. The surface under the cumulative ranking curve (SUCRA) was calculated for the probability of each treatment as the most effective. The overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), adverse events (AEs) grade ≥3, and serious adverse events (SAEs) were evaluated. RESULTS One hundred two publications with 36,147 participants were assigned to 39 different treatments. Among 11 treatments with full information on six outcomes, FOLFIRI/FOLFOX/FOLFOXIRI + bevacizumab significantly improved both the ORR and DCR, compared to FOLFIRI. Although FOLFOX and FOLFIRI/FOLFOX + cetuximab significantly prolonged both OS and PFS, treatments were comparable in terms of AEs grade ≥3 and SAEs. The top highest SUCRA values were observed in the FOLFOXIRI + panitumumab group for ORR (96%) and DCR (99%), FOLFIRI + bevacizumab + panitumumab group for OS (62%) and PFS (54%), and FOLFOXIRI + bevacizumab group for AEs grade ≥3 (59%) and SAEs (59%) outcomes. CONCLUSIONS These findings suggest an available range of systemic treatment therapies with different efficacy and safety profiles with patients. Further investigations of the side effects and mutation status are required to confirm our findings. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier CRD42019127772.
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Affiliation(s)
- Tung Hoang
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, South Korea
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Byung Chang Kim
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Yongjun Cha
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, South Korea
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23
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Temraz S, Nasr F, Kattan J, Abigerges D, Moukadem W, Farhat F, Maatouk L, Chahine G, Shamseddine A. A Non-Interventional Multicenter Study of First-Line Bevacizumab in Combination with Chemotherapy in Patients with Metastatic Colorectal Cancer in Lebanon. Biologics 2022; 16:7-15. [PMID: 35221671 PMCID: PMC8881008 DOI: 10.2147/btt.s340525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/23/2021] [Indexed: 11/30/2022]
Abstract
Purpose When combined with chemotherapy, bevacizumab improves progression-free survival (PFS) in metastatic colorectal cancer (mCRC). This observational trial was designed to assess the safety and efficacy of bevacizumab plus first-line chemotherapy in a real-world setting in Lebanon. Patients and Methods A non-interventionaL multicenter study of first-LIne AVastin® (bevacizumab) in combination with chEmotherapy in patients with metastatic colorectal cancer (LLIVE) is a multicenter, prospective, Lebanon-based, observational study that enrolled mCRC patients who received first-line bevacizumab plus chemotherapy combination. The primary end point of the study was PFS. Secondary endpoints comprised the overall response rate (ORR) and the safety and tolerability of bevacizumab. Results A total of 196 patients were enrolled between July 2010 and August 2013. The median duration of follow-up was 11 months. Median duration of bevacizumab treatment was 4 months with FOLFOX being the chiefly chemotherapy regimen used in the first-line setting (26%). Median PFS was 8.22 months (95% confidence interval (CI): 7.005–9.443). The ORR was 50.3% (complete response 7.5%, partial response 42.8%). The most common adverse event encountered was hypertension (28%) followed by epistaxis (4.8%), diarrhea (4%), anemia (4%) and headache (4%). Grade 3/4 adverse events occurred in 15.2% of patients. Conclusion The trial further substantiated the efficacy and safety of bevacizumab and chemotherapy in the first-line treatment of mCRC patients in Lebanon.
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Affiliation(s)
- Sally Temraz
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fadi Nasr
- Department of Hematology and Oncology, Mount Lebanon Hospital, Beirut, Lebanon
| | - Joseph Kattan
- Department of Hematology and Oncology, Saint- Joseph University, Beirut, Lebanon
| | - Dany Abigerges
- Department of Hematology and Oncology, Middle East Institute of Health, Bsalim, Lebanon
| | - Walid Moukadem
- Department of Hematology and Oncology, Haykal Hospital, Tripoli, Lebanon
| | - Fadi Farhat
- Department of Hematology and Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon
| | | | - Georges Chahine
- Department of Hematology and Oncology, Hôtel-Dieu de France University Hospital, Beirut, Lebanon
| | - Ali Shamseddine
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
- Correspondence: Ali Shamseddine, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon, Tel +961 1 374374, Fax +961 1 370814, Email
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24
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Ychou M, Rivoire M, Thezenas S, Guimbaud R, Ghiringhelli F, Mercier-Blas A, Mineur L, Francois E, Khemissa F, Chauvenet M, Kianmanesh R, Fonck M, Houyau P, Aparicio T, Galais MP, Audemar F, Assenat E, Lopez-Crapez E, Jouffroy C, Adenis A, Adam R, Bouché O. Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial. Br J Cancer 2022; 126:1264-1270. [PMID: 34992255 DOI: 10.1038/s41416-021-01644-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 10/01/2021] [Accepted: 11/17/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. METHODS PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. RESULTS Patients (n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48-66) with the 3-CTx versus 48.4% (95% CI: 39-57) with the 2-CTx (P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. CONCLUSION We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
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Affiliation(s)
- Marc Ychou
- Department of Digestive Oncology, Institut du Cancer de Montpellier, Montpellier, France.
| | - Michel Rivoire
- Department of Surgical Oncology, Léon Bérard Cancer Center, Lyon, France
| | - Simon Thezenas
- Biometrics Unit, Institut du Cancer de Montpellier, Montpellier, France
| | - Rosine Guimbaud
- Department of Digestive Oncology - IUCT Rangueil-Larrey, CHU de Toulouse, Toulouse, France
| | | | - Anne Mercier-Blas
- Department of Medical Oncology, Centre Hospitalier Privé de Saint-Grégoire, Saint-Grégoire, France
| | - Laurent Mineur
- Department of Digestive Oncology, Institut Sainte Catherine, Avignon, France
| | - Eric Francois
- Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France
| | - Faiza Khemissa
- Gastroenterology unit, Centre Hospitalier Saint-Jean, Perpignan, France
| | - Marion Chauvenet
- Department of Hepato-gastroenterology and Digestive Oncology, Hôpital Lyon Sud, Lyon, France
| | - Reza Kianmanesh
- Department of Digestive and Endocrine Surgery, Hôpital Robert Debré, Reims, France
| | - Marianne Fonck
- Department of Digestive Oncology, Institut Bergonié, Bordeaux, France
| | - Philippe Houyau
- Department of Medical Oncology, Clinique Claude Bernard, Albi, France
| | - Thomas Aparicio
- Department of Gastroenterology and Digestive Oncology, Hôpital Saint Louis, APHP, Paris, France
| | | | - Franck Audemar
- Gastroenterology unit, Centre hospitalier Côte Basque, Bayonne, France
| | - Eric Assenat
- Department of Digestive Oncology, CHU Saint Eloi, Montpellier, France
| | - Evelyne Lopez-Crapez
- Translational Research Unit, Institut du Cancer de Montpellier, Montpellier, France and IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France
| | | | - Antoine Adenis
- Department of Digestive Oncology, Institut du Cancer de Montpellier, Montpellier, France
| | - René Adam
- Hepatobiliary Centre, Paul Brousse Hospital, AP-HP, Villejuif, France
| | - Olivier Bouché
- Department of Hepatogastroenterology and Digestive Oncology, Hôpital Robert Debré, Reims, France
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25
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Tasoudis PT, Ziogas IA, Alexopoulos SP, Fung JJ, Tsoulfas G. Role of liver transplantation in the management of colorectal liver metastases: Challenges and opportunities. World J Clin Oncol 2021; 12:1193-1201. [PMID: 35070738 PMCID: PMC8716993 DOI: 10.5306/wjco.v12.i12.1193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/29/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the most common site of colorectal cancer metastasis. Complete resection of the metastatic tumor is currently the only treatment modality available with a potential for cure. However, only 20% of colorectal liver metastases (CRLM) are considered resectable at the time of presentation. Liver transplantation (LT) has been proposed as an alternative oncologic treatment for patients with unresectable CRLM. This review summarizes the published experiences of LT in the setting of unresectable CRLM from the previous decades and discusses the challenges and future horizons in the field. Contemporary experiences that come mostly from countries with broader access to liver grafts are also explored and their promising findings in terms of overall survival (OS) and disease-free survival (DFS) are outlined along with their study design and methods. The rationale of establishing specific patient selection criteria and the dilemmas around immunosuppressive regimens in patients undergoing LT for CRLM are also highlighted. Additionally, this review describes the findings of studies comparing LT vs chemotherapy alone and LT vs portal vein embolization plus resection for CRLM in terms of OS and DFS. Last but not least, we present current perspectives and ongoing prospective trials that try to elucidate the role of LT for CRLM.
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Affiliation(s)
| | - Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, United States
| | - John J Fung
- Department of Surgery, University of Chicago Medicine Transplant Institute, Chicago, IL 60637, United States
| | - Georgios Tsoulfas
- Department of Transplant Surgery, Aristotle University School of Medicine, Thessaloniki 54622, Greece
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26
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Bonney GK, Chew CA, Lodge P, Hubbard J, Halazun KJ, Trunecka P, Muiesan P, Mirza DF, Isaac J, Laing RW, Iyer SG, Chee CE, Yong WP, Muthiah MD, Panaro F, Sanabria J, Grothey A, Moodley K, Chau I, Chan ACY, Wang CC, Menon K, Sapisochin G, Hagness M, Dueland S, Line PD, Adam R. Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines. Lancet Gastroenterol Hepatol 2021; 6:933-946. [PMID: 34506756 DOI: 10.1016/s2468-1253(21)00219-3] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/02/2021] [Accepted: 06/07/2021] [Indexed: 12/13/2022]
Abstract
Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.
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Affiliation(s)
- Glenn K Bonney
- Division of Hepatobiliary and Pancreatic Surgery, National University Hospital, Singapore.
| | - Claire Alexandra Chew
- Division of Hepatobiliary and Pancreatic Surgery, National University Hospital, Singapore
| | - Peter Lodge
- Department of Transplantation and Hepatobiliary Surgery, Leeds Teaching Hospital NHS Trust, Leeds, UK
| | - Joleen Hubbard
- Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA
| | - Karim J Halazun
- Division of Liver Transplantation and Hepato-Pancreato-Biliary Surgery, Department of Surgery, Weill Cornell Medicine, New York City, NY, USA
| | - Pavel Trunecka
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Paolo Muiesan
- Department of Hepatobiliary Surgery, Careggi University Hospital, Florence, Italy
| | - Darius F Mirza
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - John Isaac
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Richard W Laing
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Shridhar Ganpathi Iyer
- Division of Hepatobiliary and Pancreatic Surgery, National University Hospital, Singapore
| | - Cheng Ean Chee
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Wei Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Mark Dhinesh Muthiah
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore
| | - Fabrizio Panaro
- Division of Hepato-Pancreato-Biliary Surgery and Transplantation, Department of Surgery, Saint Eloi Hospital, Montpellier University Hospital-School of Medicine, Montpellier, France
| | - Juan Sanabria
- Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Axel Grothey
- Department of Medical Oncology, West Cancer Center and Research Institute, Germantown, TN, USA
| | - Keymanthri Moodley
- The Centre of Medical Ethics and Law, Department of Medicine, Stellenbosch University, Stellenbosch, South Africa
| | - Ian Chau
- Department of Medicine, Royal Marsden Hospital, London, UK
| | - Albert C Y Chan
- Division of Liver Transplantation, Hepatobiliary & Pancreatic Surgery, Queen Mary Hospital, Hong Kong
| | - Chih Chi Wang
- Department of Surgery, Liver Transplantation Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Krishna Menon
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Gonzalo Sapisochin
- Abdominal Transplant and Hepato-Pancreato-Biliary Surgical Oncology, Multi-Organ Transplant Program, Division of General Surgery, University of Toronto, Toronto, ON, Canada
| | - Morten Hagness
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - René Adam
- Hepato Biliary Surgery, Cancer and Transplantation Unit, AP-HP Paul Brousse Hospital, University Paris-Saclay, Villejuif, France
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27
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Guo M, Jin N, Pawlik T, Cloyd JM. Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature. World J Gastrointest Oncol 2021; 13:1043-1061. [PMID: 34616511 PMCID: PMC8465453 DOI: 10.4251/wjgo.v13.i9.1043] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/17/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide, and up to 50% of patients with CRC develop colorectal liver metastases (CRLM). For these patients, surgical resection remains the only opportunity for cure and long-term survival. Over the past few decades, outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy, as well as improvements in operative technique and perioperative care. Chemotherapy in the modern era of oxaliplatin- and irinotecan-containing regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents. The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery. Consequently, the use of neoadjuvant strategies is becoming progressively more established. For patients with CRLM, the primary advantage of neoadjuvant chemotherapy (NCT) is the potential to down-stage metastatic disease in order to facilitate hepatic resection. On the other hand, the routine use of NCT for patients with resectable metastases remains controversial, especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy. Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk, reserving NCT for patients with borderline resectable or unresectable disease and high operative risk. Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability. In light of the growing number of treatment options available to patients with metastatic CRC, it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.
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Affiliation(s)
- Marissa Guo
- Department of Surgery, The Ohio State University Medical Center, Columbus, OH 43210, United States
| | - Ning Jin
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
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28
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Frühling P, Urdzik J, Strömberg C, Isaksson B. Composite Score: prognostic tool to predict survival in patients undergoing surgery for colorectal liver metastases. BJS Open 2021; 5:6410111. [PMID: 34697642 PMCID: PMC8545612 DOI: 10.1093/bjsopen/zrab104] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Several existing scoring systems predict survival of patients with colorectal liver metastases. Many lack validation, rely on old clinical data, and have been found to be less accurate since the introduction of chemotherapy. This study aimed to construct and validate a clinically relevant preoperative prognostic model for patients with colorectal liver metastases. METHODS A predictive model with data available before surgery was developed. Survival was analysed by Cox regression analysis, and the quality of the model was assessed using discrimination and calibration. The model was validated using multifold cross-validation. RESULTS The model included 1212 consecutive patients who underwent liver resection for colorectal liver metastases between 2005 and 2015. Prognostic factors for survival included advanced age, raised C-reactive protein level, hypoalbuminaemia, extended liver resection, larger number of metastases, and midgut origin of the primary tumour. A Composite Score was developed based on the prognostic variables. Patients were classified into those at low, medium, and high risk. Survival differences between the groups were significant; median overall survival was 87.4 months in the low-risk group, 50.1 months in the medium-risk group, and 22.6 months in the high-risk group. The discriminative performance, assessed by the concordance index, was 0.71, 0.67, and 0.67 respectively at 1, 3, and 5 years. Calibration, assessed graphically, was close to perfect. A multifold cross-validation of the model confirmed its internal validity (C-index 0.63 versus 0.62). CONCLUSION The Composite Score categorizes patients into risk strata, and may help identify patients who have a poor prognosis, for whom surgery is questionable.
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Affiliation(s)
- Petter Frühling
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Jozef Urdzik
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Cecilia Strömberg
- Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Bengt Isaksson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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29
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Zanetto A, Shalaby S, Gambato M, Germani G, Senzolo M, Bizzaro D, Russo FP, Burra P. New Indications for Liver Transplantation. J Clin Med 2021; 10:3867. [PMID: 34501314 PMCID: PMC8432035 DOI: 10.3390/jcm10173867] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/20/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, clinical conditions historically considered exclusion criteria for LT, have been considered new indications for LT, showing survival advantages for patients. In this review, we provide an updated overview of the principal newer indications for LT, with particular attention to alcoholic hepatitis, acute-on-chronic liver failure (ACLF), cholangiocarcinoma and colorectal cancer metastases.
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Affiliation(s)
| | | | | | | | | | | | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (M.S.); (D.B.); (F.P.R.)
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30
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Lanari J, Hagness M, Sartori A, Rosso E, Gringeri E, Dueland S, Cillo U, Line PD. Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score. Transpl Int 2021; 34:1722-1732. [PMID: 34448271 DOI: 10.1111/tri.13981] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 07/13/2021] [Accepted: 07/14/2021] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.
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Affiliation(s)
- Jacopo Lanari
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy.,Department of Transplantation Medicine, Oslo universitetssykehus Rikshospitalet, Oslo, Norway
| | - Morten Hagness
- Department of Transplantation Medicine, Oslo universitetssykehus Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, Oslo universitetssykehus Rikshospitalet, Oslo, Norway
| | - Alessandra Sartori
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Eugenia Rosso
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Enrico Gringeri
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Svein Dueland
- Institute of Clinical Medicine, Oslo universitetssykehus Rikshospitalet, Oslo, Norway
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Pål-Dag Line
- Department of Transplantation Medicine, Oslo universitetssykehus Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, Oslo universitetssykehus Rikshospitalet, Oslo, Norway.,Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo universitetssykehus Rikshospitalet, Oslo, Norway
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31
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Lang SA, Bednarsch J, Czigany Z, Joechle K, Kroh A, Amygdalos I, Strnad P, Bruns T, Heise D, Ulmer F, Neumann UP. Liver transplantation in malignant disease. World J Clin Oncol 2021; 12:623-645. [PMID: 34513597 PMCID: PMC8394155 DOI: 10.5306/wjco.v12.i8.623] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.
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Affiliation(s)
- Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Andreas Kroh
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
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Villard C, Westman J, Frank J, Jynge O, Sparrelid E, Jorns C. The potential use of extended criteria donors and eligible recipients in liver transplantation for unresectable colorectal liver metastases in Central Sweden. Hepatobiliary Surg Nutr 2021; 10:476-485. [PMID: 34430526 PMCID: PMC8350992 DOI: 10.21037/hbsn.2020.03.10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 03/03/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Unresectable colorectal liver metastases (CRLM) is a condition with poor prognosis. A recent treatment alternative improving survival in patients with unresectable CRLM, has emerged with the introduction of liver transplantation (LT), yet not uncontroversial with the current organ shortage. This study aimed to retrospectively investigate the potential of declined donors with acceptable risk as liver graft donors and patients with unresectable CRLM as potential recipients. METHODS All declined donors in central Sweden and all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, January 2013-October 2018, were identified. Donors were classified according to the European Committee Guide to the quality and safety of organs for transplantation and potential recipients were evaluated by selection criteria, based on studies on the Norwegian Secondary Cancer study database. RESULTS Out of 1,462 evaluated potential donors, 62 (2.7 pmp) donors were identified, corresponding to 6-18% of the utilized donor pool. Out of 1,008 included patients with CRLM, 25 (2.1 pmp) potential recipients were recognized. Eligibility for LT and left-sided colon cancer were favorable prognostic factors. CONCLUSIONS Today's donor pool could increase with the use of extended criteria donors, which is sufficient and display an acceptable risk-benefit ratio for patients with unresectable CRLM. With current selection criteria a small subset of patients with unresectable CRLM are eligible recipients. This subset of patients has a better survival compared to patients ineligible for LT.
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Affiliation(s)
- Christina Villard
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | | | | | - Oystein Jynge
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Ernesto Sparrelid
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden;,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Carl Jorns
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden;,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Dueland S, Syversveen T, Hagness M, Grut H, Line PD. Liver transplantation for advanced liver-only colorectal metastases. Br J Surg 2021; 108:1402-1405. [PMID: 34117498 DOI: 10.1093/bjs/znab196] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 05/05/2021] [Indexed: 11/14/2022]
Abstract
Liver transplantation provided a 5-year overall survival rate of 100 per cent in patients with colorectal cancer who had undergone liver resection previously. Patients with extensive liver metastases (over 20 lesions) and a left-sided primary tumour had long survival, whereas those with an ascending colonic primary tumour had inferior survival after liver transplantation.
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Affiliation(s)
- S Dueland
- Division of Surgery, Inflammatory Diseases and Transplantation, Experimental Transplantation and Malignancy Research Group, Oslo University Hospital, Oslo, Norway
| | - T Syversveen
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - M Hagness
- Department of Transplantation Medicine, Section for Transplantation Surgery, Oslo University Hospital, Oslo, Norway
| | - H Grut
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.,Department of Radiology, Vestre Viken Hospital Trust, Drammen, Norway
| | - P-D Line
- Division of Surgery, Inflammatory Diseases and Transplantation, Experimental Transplantation and Malignancy Research Group, Oslo University Hospital, Oslo, Norway.,Department of Transplantation Medicine, Section for Transplantation Surgery, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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34
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Min ST, Roohullah A, Tognela A, Jalali A, Lee M, Wong R, Shapiro J, Burge M, Yip D, Nott L, Zimet A, Lee B, Dean A, Steel S, Wong HL, Gibbs P, Lim SHS. Patient demographics and management landscape of metastatic colorectal cancer in the third-line setting: Real-world data in an australian population. Asia Pac J Clin Oncol 2021; 18:e56-e63. [PMID: 33870631 DOI: 10.1111/ajco.13553] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 12/02/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. AIMS This analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting. METHODS We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression. RESULTS Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third-line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)-oxaliplatin combination was the most common choice (51%), followed by FP-irinotecan (15%), trifluridine/tipiracil (11%), mono-chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP-doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP-doublet (18%), mono-chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4-41.2), and median time on third-line treatment was 3 months (range 0.1-40). CONCLUSIONS In real-world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.
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Affiliation(s)
- Sandy Tun Min
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia
| | - Aflah Roohullah
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.,School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
| | - Annette Tognela
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.,School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
| | - Azim Jalali
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.,Department of Medicine, Monash University, Clayton, Victoria, Australia.,Epworth Health Care, Box Hill, Victoria, Australia
| | - Jeremy Shapiro
- Department of Medicine, Monash University, Clayton, Victoria, Australia.,Cabrini Haematology and Oncology Centre, Malvern, Victoria, Australia
| | - Matthew Burge
- Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.,Faculty of Medicine, University of Queensland, St Lucia, Queensland, Australia
| | - Desmond Yip
- Department of Medical Oncology, Canberra and Calvary Hospitals, Garran, Australia Capital Territory, Australia
| | - Louise Nott
- Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Allan Zimet
- Epworth HealthCare, Richmond, Victoria, Australia
| | - Belinda Lee
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,The Northern Hospital, Epping, Victoria, Australia
| | - Andrew Dean
- Department of Medical Oncology, St John of God Hospital, Subiaco, Western Australia, Australia
| | - Simone Steel
- Peninsula Private Hospital, Frankston, Victoria, Australia
| | - Hui-Li Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.,Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia.,Faculty of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Stephanie Hui-Su Lim
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.,School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.,Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
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Kubal C, Mihaylov P, Holden J. Oncologic indications of liver transplantation and deceased donor liver allocation in the United States. Curr Opin Organ Transplant 2021; 26:168-175. [PMID: 33650998 DOI: 10.1097/mot.0000000000000866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy. RECENT FINDINGS Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT). SUMMARY With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.
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Affiliation(s)
| | | | - John Holden
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Bhatti T, Moser M, Tan KT, Chalchal H, Souied O, Le D, Shaw J, Zaidi A, Gill D, Ahmed S. Rate of Curative Surgery in Real-world Patients with Unresectable Metastatic Colorectal Cancer Treated with FOLFOXIRI ± Bevacizumab: A Western Canadian Province Experience. J Gastrointest Cancer 2021; 53:427-433. [PMID: 33779898 DOI: 10.1007/s12029-021-00634-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Recent evidence from randomized trials suggests that FOLFOXIRI (fluorouracil, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates, with the potential for conversion of unresectable to resectable disease in metastatic colorectal cancer (mCRC). However, limited evidence is available on the efficacy and safety of this regimen in real-world patients with mCRC. The current study aims to evaluate the conversion rate and safety of FOLFOXIRI ± bevacizumab in real-world patients with unresectable mCRC. METHODS In this retrospective multicenter population-based cohort study, patients who were diagnosed with unresectable mCRC between January 2015 and December 2018 in Saskatchewan and received FOLFOXIRI ± bevacizumab were assessed. Kaplan-Meier survival methods and the log-rank test were performed. RESULTS A total of 28 eligible patients with a median age of 51 years (interquartile range 39-60) and a male:female ratio of 11:17 were identified; 39% had rectal cancer, 46% had extrahepatic disease, and 46% had bilobar liver metastases. Overall, 63% of the patients had a positive response to FOLFOXIRI ± bevacizumab and 53% underwent metastasectomy. Of all patients 60% had grade 3/4 toxicity and 32% required hospital admission. No treatment-related mortality was noted. After 4 years, 50% of the patients were alive. Median progression-free survival of patients who underwent surgery was 18 months (95% CI 11.3-24.7) versus 11 months (4-18.1) without surgery (p = 0.28). Median overall survival of patients with surgery was 33 months (17.5-48.5) versus 16 months (8.3-23.7) without surgery (p = 0.03). CONCLUSION The current study suggests that FOLFOXIRI ± bevacizumab therapy in real-world patients with mCRC is associated with a high rate of conversion from unresectable to resectable metastatic disease. Patients with metastasectomy had better survival.
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Affiliation(s)
- Tayyaba Bhatti
- College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Michael Moser
- Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada
| | | | | | | | - Duc Le
- Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada
| | - John Shaw
- Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada
| | - Adnan Zaidi
- Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada
| | - Dilip Gill
- Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada
| | - Shahid Ahmed
- Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada.
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Puia-Negulescu S, Lebossé F, Mabrut JY, Muller X, Rossignol G, Antonini T, Erard D, Radenne S, Guillet M, Souquet JC, Mohkam K, Lesurtel M. Liver Transplantation for Colorectal Liver Metastases: Current Management and Future Perspectives. Int J Mol Sci 2021; 22:ijms22063093. [PMID: 33803503 PMCID: PMC8002956 DOI: 10.3390/ijms22063093] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/07/2021] [Accepted: 03/10/2021] [Indexed: 12/25/2022] Open
Abstract
Patients with nonresectable liver metastases from colorectal cancer have few therapeutic options and a dismal prognosis. Although liver transplantation for this indication has historically a poor reputation, recent advances in the field of chemotherapy and immunosuppression have paved the way to revisit the concept. New data have shown promising results that need to be validated in several ongoing clinical trials. Since liver grafts represent a scarce resource, several new tools are being explored to expand the donor pool for this indication. The purpose of this review is to present all current available data and perspectives about liver transplantation for nonresectable liver metastases from colorectal cancer.
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Affiliation(s)
- Serban Puia-Negulescu
- Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (S.P.-N.); (J.-Y.M.); (X.M.); (K.M.)
| | - Fanny Lebossé
- Department of Hepatology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (F.L.); (T.A.); (D.E.); (S.R.)
- Cancer Research Center of Lyon, INSERM U1052, 69008 Lyon, France
| | - Jean-Yves Mabrut
- Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (S.P.-N.); (J.-Y.M.); (X.M.); (K.M.)
- Cancer Research Center of Lyon, INSERM U1052, 69008 Lyon, France
| | - Xavier Muller
- Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (S.P.-N.); (J.-Y.M.); (X.M.); (K.M.)
- Cancer Research Center of Lyon, INSERM U1052, 69008 Lyon, France
| | - Guillaume Rossignol
- Department of Pediatric Surgery, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, University of Lyon I, 69500 Lyon, France;
| | - Teresa Antonini
- Department of Hepatology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (F.L.); (T.A.); (D.E.); (S.R.)
| | - Domitille Erard
- Department of Hepatology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (F.L.); (T.A.); (D.E.); (S.R.)
| | - Sylvie Radenne
- Department of Hepatology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (F.L.); (T.A.); (D.E.); (S.R.)
- Department of Hepatogastroenterology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (M.G.); (J.-C.S.)
| | - Marielle Guillet
- Department of Hepatogastroenterology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (M.G.); (J.-C.S.)
| | - Jean-Christophe Souquet
- Department of Hepatogastroenterology, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (M.G.); (J.-C.S.)
| | - Kayvan Mohkam
- Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (S.P.-N.); (J.-Y.M.); (X.M.); (K.M.)
- Cancer Research Center of Lyon, INSERM U1052, 69008 Lyon, France
| | - Mickael Lesurtel
- Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, University of Lyon I, 69004 Lyon, France; (S.P.-N.); (J.-Y.M.); (X.M.); (K.M.)
- Cancer Research Center of Lyon, INSERM U1052, 69008 Lyon, France
- Correspondence: ; Tel.: +33-472-071100; Fax: +33-472-072927
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Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Farkas L, Garrido-Laguna I, Grem JL, Gunn A, Hecht JR, Hoffe S, Hubbard J, Hunt S, Johung KL, Kirilcuk N, Krishnamurthi S, Messersmith WA, Meyerhardt J, Miller ED, Mulcahy MF, Nurkin S, Overman MJ, Parikh A, Patel H, Pedersen K, Saltz L, Schneider C, Shibata D, Skibber JM, Sofocleous CT, Stoffel EM, Stotsky-Himelfarb E, Willett CG, Gregory KM, Gurski LA. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:329-359. [PMID: 33724754 DOI: 10.6004/jnccn.2021.0012] [Citation(s) in RCA: 880] [Impact Index Per Article: 220.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
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Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Alan P Venook
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | | | | | - Stacey Cohen
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | - Linda Farkas
- UT Southwestern Simmons Comprehensive Cancer Center
| | | | | | | | | | | | | | - Steven Hunt
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - Smitha Krishnamurthi
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | - Eric D Miller
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Mary F Mulcahy
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | | | - Katrina Pedersen
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Villard C, Habib M, Nordenvall C, Nilsson PJ, Jorns C, Sparrelid E. Conversion therapy in patients with colorectal liver metastases. Eur J Surg Oncol 2021; 47:2038-2045. [PMID: 33640172 DOI: 10.1016/j.ejso.2021.02.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/25/2021] [Accepted: 02/16/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The occurrence of colorectal liver metastases (CRLM) impairs prognosis, yet long-term survival can be achieved by enabling liver resection. This study aims to describe factors associated with conversion therapy leading to liver surgery and treatment outcome. METHODS A retrospective cohort study was conducted including all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with conversion therapy and outcome following conversion therapy were analysed with logistic regression and survival analyses. RESULTS Out of 1023 patients with CRLM, 100 patients (10%) received conversion chemotherapy, out of whom 31 patients (31%) subsequently underwent liver resection. Patients in whom conversion chemotherapy resulted in liver resection were younger (median age 61 vs. 66 years, p = .024), less likely to have a KRAS/NRAS-mutated primary tumours (25% vs. 53%, p = .039) and more likely to have received anti-EGFR agents (32% vs. 4%, p = .001) than patients progressing during conversion chemotherapy. The median OS for patients treated with conversion chemotherapy leading to liver resection was 24 months, compared to 14 months for patients progressing during conversion chemotherapy, p < .001. The OS for patients progressing during conversion chemotherapy was similar to patients given palliative chemotherapy, approximately 13 months. CONCLUSION Conversion therapy offers a survival benefit in selected patients. Despite treatment advances, the majority of patients undergoing conversion chemotherapy never become eligible for curative treatment.
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Affiliation(s)
- C Villard
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | - M Habib
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche, Chronothérapie, Cancers et Transplantation, Université Paris-Saclay, Villejuif, France
| | - C Nordenvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - P J Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - C Jorns
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Transplantation Surgery, Karolinska University, Stockholm, Sweden
| | - E Sparrelid
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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40
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Abstract
IMPORTANCE Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases. OBSERVATIONS Colorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves overall survival. Genomic profiling to detect somatic variants is important because it identifies the treatments that may be effective. For the 50% of patients with metastatic CRC with KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor [EGFR]), in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations (formerly termed mutations), effective targeted therapies are not yet available. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extended overall survival to 9.3 months, compared to 5.9 months for those receiving standard chemotherapy. For the 5% with microsatellite instability (the presence of numerous insertions or deletions at repetitive DNA units) or mismatch repair deficiency, immunotherapy may be used in the first or subsequent line and has improved treatment outcomes with a median overall survival of 31.4 months in previously treated patients. CONCLUSIONS AND RELEVANCE Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.
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Affiliation(s)
- Leah H Biller
- Division of Gastrointestinal Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
- Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts
| | - Deborah Schrag
- Division of Gastrointestinal Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
- Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts
- Division of Population Sciences, Dana Farber Cancer Institute, Boston, Massachusetts
- Associate Editor, JAMA
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41
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Pan DC, Krishnan V, Salinas AK, Kim J, Sun T, Ravid S, Peng K, Wu D, Nurunnabi M, Nelson JA, Niziolek Z, Guo J, Mitragotri S. Hyaluronic acid-doxorubicin nanoparticles for targeted treatment of colorectal cancer. Bioeng Transl Med 2021; 6:e10166. [PMID: 33532580 PMCID: PMC7823125 DOI: 10.1002/btm2.10166] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 05/04/2020] [Accepted: 05/09/2020] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer, common in both men and women, occurs when tumors form in the linings of the colon. Common treatments of colorectal cancer include surgery, chemotherapy, and radiation therapy; however, many colorectal cancer treatments often damage healthy tissues and cells, inducing severe side effects. Conventional chemotherapeutic agents such as doxorubicin (Dox) can be potentially used for the treatment of colorectal cancer; however, they suffer from limited targeting and lack of selectivity. Here, we report that doxorubicin complexed to hyaluronic acid (HA) (HA-Dox) exhibits an unusual behavior of high accumulation in the intestines for at least 24 hr when injected intravenously. Intravenous administrations of HA-Dox effectively preserved the mucosal epithelial intestinal integrity in a chemical induced colon cancer model in mice. Moreover, treatment with HA-Dox decreased the expression of intestinal apoptotic and inflammatory markers. The results suggest that HA-Dox could effectively inhibit the development of colorectal cancer in a safe manner, which potentially be used a promising therapeutic option.
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Affiliation(s)
- Daniel C. Pan
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Vinu Krishnan
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Alyssa K. Salinas
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Jayoung Kim
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Tao Sun
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Sagi Ravid
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Kevin Peng
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Debra Wu
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Md Nurunnabi
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Jeffery A. Nelson
- Faculty of Arts and Sciences, Division of SciencesHarvard UniversityCambridgeMassachusettsUSA
| | - Zachary Niziolek
- Faculty of Arts and Sciences, Division of SciencesHarvard UniversityCambridgeMassachusettsUSA
| | - Junling Guo
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
| | - Samir Mitragotri
- School of Engineering & Applied Sciences, Harvard UniversityWyss Institute of Biologically Inspired EngineeringCambridgeMassachusettsUSA
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Line PD, Dueland S. Liver transplantation for secondary liver tumours: The difficult balance between survival and recurrence. J Hepatol 2020; 73:1557-1562. [PMID: 32896581 DOI: 10.1016/j.jhep.2020.08.015] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/05/2020] [Accepted: 08/07/2020] [Indexed: 12/13/2022]
Abstract
Assessing the balance between survival and recurrence after transplantation for secondary liver tumours should be based on the type of cancer in question. For neuroendocrine liver metastases, high recurrence rates are clearly related to reduced long-term survival. For colorectal liver metastases, experience to date indicates that pulmonary recurrence alone has a modest impact on survival outcomes. Further studies focusing on this group of patients will be important for the development of this field of transplant oncology. Liver transplantation for secondary liver tumours should be implemented in accordance with stringent transplant criteria and preferably in the context of prospective trials. Expansion of the donor pool by utilising extended criteria donors and partial liver transplantation could be considered for this indication.
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Affiliation(s)
- Pål-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Svein Dueland
- Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Abstract
Abstract
Purpose of Review
Accumulating evidence suggest that selected patients with nonresectable liver only metastases from colorectal cancer can be offered liver transplantation with acceptable outcome. This review provides an update on the scientific literature.
Recent Findings
The SECA-I study showed an estimated 5-year survival of 60% in a heterogenous patient population and guided the development of the first clinical selection criteria. In the sequel SECA-II trial, an estimated 5-year survival of 83% was obtained. A recent study shows that an Oslo score of 0–2, a metabolic tumor volume below 70 cm3 on PET-CT or Fong score of 0–2 at time of listing, can stratify patients with superior survival. Recurrence is common, but about 70% are slow-growing lung metastases, whereof the majority are resectable.
Summary
Liver transplantation for colorectal liver metastasis is an option in highly selected patients. Futile use of grafts can be avoided by applying stringent selection criteria.
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Hoang T, Kim J. Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments. Cancers (Basel) 2020; 12:E2663. [PMID: 32961943 PMCID: PMC7565292 DOI: 10.3390/cancers12092663] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/31/2020] [Accepted: 09/13/2020] [Indexed: 12/24/2022] Open
Abstract
This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73-0.98; HR = 0.76, 95% CrI = 0.62-0.94; HR = 0.80, 95% CrI = 0.66-0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51-0.94 and HR = 0.73, 95% CrI = 0.54-0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01-4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09-3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51-5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.
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Affiliation(s)
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea;
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Bhudia J, Glynne-Jones R, Smith T, Hall M. Neoadjuvant Chemotherapy without Radiation in Colorectal Cancer. Clin Colon Rectal Surg 2020; 33:287-297. [PMID: 32968364 PMCID: PMC7500967 DOI: 10.1055/s-0040-1713746] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In colon cancer, primary surgery followed by postoperative chemotherapy represents the standard of care. In rectal cancer, the standard of care is preoperative radiotherapy or chemoradiation, which significantly reduces local recurrence but has no impact on subsequent metastatic disease or overall survival. The administration of neoadjuvant chemotherapy (NACT) before surgery can increase the chance of a curative resection and improves long-term outcomes in patients with liver metastases. Hence, NACT is being explored in both primary rectal and colon cancers as an alternative strategy to shrink the tumor, facilitate a curative resection, and simultaneously counter the risk of metastases. Yet, this lack of clarity regarding the precise aims of NACT (downstaging, maximizing response, or improving survival) is hindering progress. The appropriate cytotoxic agents, the optimal regimen, the number of cycles, or duration of NACT prior to surgery or in the postoperative setting remains undefined. Several potential strategies for integrating NACT are discussed with their advantages and disadvantages.
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Affiliation(s)
- Jyotsna Bhudia
- Department of Radiotherapy, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, United Kingdom
| | - Rob Glynne-Jones
- Department of Radiotherapy, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, United Kingdom
| | - Thomas Smith
- Department of Radiotherapy, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, United Kingdom
| | - Marcia Hall
- Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, United Kingdom
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Kalanxhi E, Meltzer S, Ree AH. Immune-Modulating Effects of Conventional Therapies in Colorectal Cancer. Cancers (Basel) 2020; 12:E2193. [PMID: 32781554 PMCID: PMC7464272 DOI: 10.3390/cancers12082193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/03/2020] [Accepted: 08/05/2020] [Indexed: 12/22/2022] Open
Abstract
Biological heterogeneity and low inherent immunogenicity are two features that greatly impact therapeutic management and outcome in colorectal cancer. Despite high local control rates, systemic tumor dissemination remains the main cause of treatment failure and stresses the need for new developments in combined-modality approaches. While the role of adaptive immune responses in a small subgroup of colorectal tumors with inherent immunogenicity is indisputable, the challenge remains in identifying the optimal synergy between conventional treatment modalities and immune therapy for the majority of the less immunogenic cases. In this context, cytotoxic agents such as radiation and certain chemotherapeutics can be utilized to enhance the immunogenicity of an otherwise immunologically silent disease and enable responsiveness to immune therapy. In this review, we explore the immunological characteristics of colorectal cancer, the effects that standard-of-care treatments have on the immune system, and the opportunities arising from combining immune checkpoint-blocking therapy with immune-modulating conventional treatments.
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Affiliation(s)
- Erta Kalanxhi
- Department of Oncology, Akershus University Hospital, 1478 Lørenskog, Norway; (E.K.); (S.M.)
| | - Sebastian Meltzer
- Department of Oncology, Akershus University Hospital, 1478 Lørenskog, Norway; (E.K.); (S.M.)
| | - Anne Hansen Ree
- Department of Oncology, Akershus University Hospital, 1478 Lørenskog, Norway; (E.K.); (S.M.)
- Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway
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Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment. Molecules 2020; 25:molecules25112614. [PMID: 32512790 PMCID: PMC7321123 DOI: 10.3390/molecules25112614] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 05/30/2020] [Accepted: 06/01/2020] [Indexed: 12/24/2022] Open
Abstract
The combination of folinic acid, 5-fluorouracil, oxaliplatin and/or irinotecan (FOLFOXIRI) is the standard of care for metastatic colorectal cancer (CRC). This strategy inhibits tumor growth but provokes drug resistance and serious side effects. We aimed to improve FOLFOXIRI by optimization of the dosing and the sequence of drug administration. We employed an orthogonal array composite design and linear regression analysis to obtain cell line-specific drug combinations for four CRC cell lines (DLD1, SW620, HCT116, LS174T). Our results confirmed the synergy between folinic acid and 5-fluorouracil and additivity, or even antagonism, between the other drugs of the combination. The drug combination administered at clinical doses resulted in significantly higher antagonistic interactions compared to the low-dose optimized drug combination (ODC). We found that the concomitant administration of the optimized drug combination (ODC) was comparatively active to sequential administration. However, the administration of oxaliplatin or the active metabolite of irinotecan seemed to sensitize the cells to the combination of folinic acid and 5-fluorouracil. ODCs were similarly active in non-cancerous cells as compared to the clinically used doses, indicating a lack of reduction of side effects. Interestingly, ODCs were inactive in CRC cells chronically pretreated with FOLFOXIRI, suggesting the occurrence of resistance. We were unable to improve FOLFOXIRI in terms of efficacy or specificity. Improvement of CRC treatment should come from the optimization of targeted drugs and immunotherapy strategies.
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Comparing Late-line Treatment Sequence of Regorafenib and Reduced-intensity FOLFOXIRI for Refractory Metastatic Colorectal Cancer. Am J Clin Oncol 2020; 43:28-34. [PMID: 31693507 DOI: 10.1097/coc.0000000000000637] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Both regorafenib and reduced-intensity FOLFOXIRI (riFOLFOXIRI) prolong survival in patients with metastatic colorectal cancer (mCRC). However, the sequence in which they should be administrated first in late-line treatment for refractory mCRC remains unclear. PATIENTS AND METHODS This study was a single-center retrospective cohort study that reviewed data from patients at Taipei Veterans General Hospital, Taiwan, with mCRC refractory to fluorouracil, irinotecan, oxaliplatin, cetuximab (wild-type RAS), and bevacizumab. Patients were divided into 2 groups: a regorafenib-first group and a riFOLFOXIRI-first group. The Kaplan-Meier method and log-rank test were used to analyze survival, and a Cox proportional hazards model was used for univariate, multivariate, and subgroup analyses. RESULTS A total of 136 and 55 patients followed a regorafenib-first or riFOLFOXIRI-first treatment strategy, respectively. At baseline, patient characteristics were similar between the groups, except for younger age in the riFOLFOXIRI-first group. The regorafenib-first group had better overall survival (13.8 vs. 10.7 mo, P=0.038), whereas patients in the riFOLFOXIRI-first group had a better partial response rate (P=0.005) but a higher rate of discontinuation due to adverse effects (P=0.004) and cross-over to regorafenib (P<0.001). Thus, no significant difference was observed in progression-free survival (regorafenib-first strategy: 3.17 mo; riFOLFOXIRI-first strategy: 4.97 mo; P=0.624). Regorafenib-first strategy, sex, and pathology were identified as independent prognostic factors. Subgroup analysis indicated that younger age, better performance status, stage IV disease, and mutant RAS gene favored the regorafenib-first strategy. CONCLUSION Treatment with regorafenib-first followed by riFOLFOXIRI resulted in better overall survival when given as late-line treatment for patients with refractory mCRC.
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49
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Smedman TM, Line PD, Hagness M, Syversveen T, Grut H, Dueland S. Liver transplantation for unresectable colorectal liver metastases in patients and donors with extended criteria (SECA-II arm D study). BJS Open 2020; 4:467-477. [PMID: 32333527 PMCID: PMC7260412 DOI: 10.1002/bjs5.50278] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 12/14/2022] Open
Abstract
Background Patients with metastatic colorectal cancer receiving palliative chemotherapy have a 5‐year survival rate of approximately 10 per cent. Liver transplantation using strict selection criteria in patients with colorectal cancer and unresectable liver‐only disease will result in a 5‐year survival rate of 56–83 per cent. The aim of this study was to evaluate survival of patients with colorectal liver metastases (CRLM) after liver transplantation using extended criteria for both patients and donors. Methods This was a prospective single‐arm study. Patients with synchronous unresectable CRLM who were not suitable for arms A, B or C of the SEcondary CAncer (SECA) II study who had undergone radical resection of the primary tumour and received chemotherapy were included; they underwent liver transplantation with extended criteria donor grafts. Patients who had resectable pulmonary metastases were eligible for inclusion. The main exclusion criteria were BMI above 30 kg/m2 and liver metastases larger than 10 cm. Survival was estimated using Kaplan–Meier analysis. Results Ten patients (median age 54 years; 3 women) were included. They had an extensive liver tumour load with a median of 20 (range 1–45) lesions; the median size of the largest lesion was 59 (range 15–94) mm. Eight patients had (y)pN2 disease, six had poorly differentiated or signet ring cell‐differentiated primary tumours, and five had primary tumour in the ascending colon. The median Fong clinical risk score was 3 (range 2–5) and the median Oslo score was 1 (range 1–4). The median plasma carcinoembryonic antigen level was 4·3 (range 2–4346) μg/l. Median disease‐free and overall survival was 4 and 18 months respectively. Conclusion Patients with unresectable liver‐only CRLM undergoing liver transplantation with extended patient and donor criteria have relatively short overall survival.
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Affiliation(s)
- T M Smedman
- Department of Oncology, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - P-D Line
- Department of Transplantation Medicine, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - M Hagness
- Department of Transplantation Medicine, Oslo, Norway
| | | | - H Grut
- Radiology and Nuclear Medicine, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - S Dueland
- Department of Oncology, Oslo, Norway.,Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
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Liver transplantation for non-resectable colorectal liver metastasis: where we are and where we are going. Langenbecks Arch Surg 2020; 405:255-264. [PMID: 32333096 DOI: 10.1007/s00423-020-01883-2] [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: 10/27/2019] [Accepted: 04/15/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed. METHODS A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials. RESULTS Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results. CONCLUSION LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern.
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