Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Liver resection surgery versus thermal ablation for colorectal LiVer MetAstases (LAVA): study protocol for a randomised controlled trial

Authors: Kurinchi Gurusamy, Neil Corrigan, Julie Croft, Maureen Twiddy, Stephen Morris, Nick Woodward, Steve Bandula, Daniel Hochhauser, Vicky Napp, Alison Pullan, Nicholas Jakowiw, Raj Prasad, Steven Olde Damink, C. J. H. M. van Laarhoven, Johannes H. W. de Wilt, Julia Brown, Brian R. Davidson

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

Although surgical resection has been considered the only curative option for colorectal liver metastases (CLM), thermal ablation has recently been suggested as an alternative curative treatment. A prospective randomised trial is required to define the efficacy of resection vs ablation for the treatment of colorectal liver metastases.

Methods

Design and setting: This is a multicentre, open, randomised controlled non-inferiority trial design with internal pilot and will be performed in tertiary liver centres in UK and The Netherlands.
Participants: Eligible patients will be those with colorectal liver metastases at high surgical risk because of their age, co-morbidities or tumour burden and who would be suitable for liver resection or thermal ablation.
Intervention: Thermal ablation as per local policy.
Control: Surgical liver resection performed as per centre protocol.
Co-interventions: Further chemotherapy will be offered to patients as per current practice.
Outcomes
Pilot study: Same as main study and in addition patients and clinicians’ acceptability of the trial to assist in optimisation of recruitment.
Primary outcome: Disease-free survival (DFS) at two years post randomisation.
Secondary outcomes: Overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, DFS measured from end of intervention.
Follow-up: 24 months from randomisation; five-year follow-up for overall survival.
Sample size: 330 patients to demonstrate non-inferiority of thermal ablation.

Discussion

This trial will determine the effectiveness and cost-effectiveness of thermal ablation vs surgical resection for high-risk people with colorectal liver metastases, and guide the optimal treatment for these patients.

Trial registration

ISRCTN Registry, ISRCTN52040363. Registered on 9 March 2016.
Appendix
Available only for authorised users
Literature
1.
2.
3.
van der Geest LG, Lam-Boer J, Koopman M, Verhoef C, Elferink MA, de Wilt JH. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015;32(5):457–65.CrossRefPubMed
4.
Elferink MA, de Jong KP, Klaase JM, Siemerink EJ, de Wilt JH. Metachronous metastases from colorectal cancer: a population-based study in north-East Netherlands. Int J Color Dis. 2015;30(2):205–12.CrossRef
5.
Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 2006;93(4):465–74.CrossRefPubMed
6.
Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244(2):254–9.CrossRefPubMedPubMedCentral
7.
Morris EJ, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L, et al. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg. 2010;97(7):1110–8.CrossRefPubMed
8.
Robertson DJ, Stukel TA, Gottlieb DJ, Sutherland JM, Fisher ES. Survival after hepatic resection of colorectal cancer metastases: a national experience. Cancer. 2009;115(4):752–9.CrossRefPubMedPubMedCentral
9.
Eshmuminov D, Raptis DA, Linecker M, Wirsching A, Lesurtel M, Clavien PA. Meta-analysis of associating liver partition with portal vein ligation and portal vein occlusion for two-stage hepatectomy. Br J Surg. 2016;103(13):1768–82.CrossRefPubMed
10.
Ironside N, Bell R, Bartlett A, McCall J, Powell J, Pandanaboyana S. Systematic review of perioperative and survival outcomes of liver resections with and without preoperative portal vein embolization for colorectal metastases. HPB (Oxford). 2017;19:559–66.CrossRef
11.
Lam VW, Laurence JM, Johnston E, Hollands MJ, Pleass HC, Richardson AJ. A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases. HPB (Oxford). 2013;15(7):483–91.CrossRef
12.
Gurusamy KS, Imber C, Davidson BR. Management of the hepatic lymph nodes during resection of liver metastases from colorectal cancer: a systematic review. HPB Surg. 2008;2008:684150.CrossRefPubMed
13.
Spelt L, Andersson B, Nilsson J, Andersson R. Prognostic models for outcome following liver resection for colorectal cancer metastases: a systematic review. Eur J Surg Oncol. 2012;38(1):16–24.CrossRefPubMed
14.
Kanas GP, Taylor A, Primrose JN, Langeberg WJ, Kelsh MA, Mowat FS, et al. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol. 2012;4:283–301.PubMedPubMedCentral
15.
Guenette JP, Dupuy DE. Radiofrequency ablation of colorectal hepatic metastases. J Surg Oncol. 2010;102(8):978–87.CrossRefPubMed
16.
Crocetti L, de Baere T, Lencioni R. Quality improvement guidelines for radiofrequency ablation of liver tumours. Cardiovasc Intervent Radiol. 2010;33(1):11–7.CrossRefPubMed
17.
Lubner MG, Brace CL, Ziemlewicz TJ, Hinshaw JL, Lee FT Jr. Microwave ablation of hepatic malignancy. Semin Interv Radiol. 2013;30(1):56–66.CrossRef
18.
Liang P, Yu J, Lu MD, Dong BW, Yu XL, Zhou XD, et al. Practice guidelines for ultrasound-guided percutaneous microwave ablation for hepatic malignancy. World J Gastroenterol. 2013;19(33):5430–8.CrossRefPubMedPubMedCentral
19.
Ong SL, Gravante G, Metcalfe MS, Strickland AD, Dennison AR, Lloyd DM. Efficacy and safety of microwave ablation for primary and secondary liver malignancies: a systematic review. Eur J Gastroenterol Hepatol. 2009;21(6):599–605.CrossRefPubMed
20.
Ierardi AM, Floridi C, Fontana F, Chini C, Giorlando F, Piacentino F, et al. Microwave ablation of liver metastases to overcome the limitations of radiofrequency ablation. La Radiologia medica. 2013;118(6):949–61.CrossRefPubMed
21.
Nishiwada S, Ko S, Mukogawa T, Ishikawa H, Matsusaka M, Nakatani T, et al. Comparison between percutaneous radiofrequency ablation and surgical hepatectomy focusing on local disease control rate for colorectal liver metastases. Hepato-Gastroenterology. 2014;61(130):436–41.PubMed
22.
Tanis E, Nordlinger B, Mauer M, Sorbye H, van Coevorden F, Gruenberger T, et al. Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983. Eur J Cancer. 2014;50(5):912–9.CrossRefPubMed
23.
Vogl TJ, Farshid P, Naguib NN, Darvishi A, Bazrafshan B, Mbalisike E, et al. Thermal ablation of liver metastases from colorectal cancer: radiofrequency, microwave and laser ablation therapies. Radiol Med. 2014;119:451–61.CrossRefPubMed
24.
Chok KS, Cheung TT, Lo RC, Chu FS, Tsang SH, Chan AC, et al. Pilot study of high-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients wait-listed for liver transplantation. Liver Transpl. 2014;20:912–21.CrossRefPubMed
25.
Loveman E, Jones J, Clegg AJ, Picot J, Colquitt JL, Mendes D, et al. The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation. Health Technol Assess. 2014;18(7):vii–viii. 1–283CrossRefPubMedPubMedCentral
26.
Kim KH, Yoon YS, Yu CS, Kim TW, Kim HJ, Kim PN, et al. Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases. J Korean Surg Soc. 2011;81(1):25–34.CrossRefPubMedPubMedCentral
27.
Shibata T, Niinobu T, Ogata N, Takami M. Microwave coagulation therapy for multiple hepatic metastases from colorectal carcinoma. Cancer. 2000;89(2):276–84.CrossRefPubMed
28.
Ko S, Jo H, Yun S, Park E, Kim S, Seo HI. Comparative analysis of radiofrequency ablation and resection for resectable colorectal liver metastases. World J Gastroenterol. 2014;20(2):525–31.CrossRefPubMedPubMedCentral
29.
van Amerongen MJ, Jenniskens SFM, van den Boezem PB, Futterer JJ, de Wilt JHW. Radiofrequency ablation compared to surgical resection for curative treatment of patients with colorectal liver metastases - a meta-analysis. HPB (Oxford). 2017;19(9):749–56.CrossRef
30.
Mulier S, Ni Y, Jamart J, Michel L, Marchal G, Ruers T. Radiofrequency ablation versus resection for resectable colorectal liver metastases: time for a randomized trial? Ann Surg Oncol. 2008;15(1):144–57.CrossRefPubMed
31.
Gomez D, Sangha VK, Morris-Stiff G, Malik HZ, Guthrie AJ, Toogood GJ, et al. Outcomes of intensive surveillance after resection of hepatic colorectal metastases. Br J Surg. 2010;97(10):1552–60.CrossRefPubMed
32.
Chan A, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krieza-Jeric K, et al. Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7.CrossRefPubMedPubMedCentral
33.
Khoo E, O’Neill S, Brown E, Wigmore SJ, Harrison EM. Systematic review of systemic adjuvant, neoadjuvant and perioperative chemotherapy for resectable colorectal-liver metastases. HPB (Oxford). 2016;18(6):485–93.CrossRef
34.
Dupre A, Jones RP, Diaz-Nieto R, Fenwick SW, Poston GJ, Malik HZ. Curative-intent treatment of recurrent colorectal liver metastases: a comparison between ablation and resection. Eur J Surg Oncol. 2017;43(10):1901–7.CrossRefPubMed
35.
Lam VW, Pang T, Laurence JM, Johnston E, Hollands MJ, Pleass HC, et al. A systematic review of repeat hepatectomy for recurrent colorectal liver metastases. J Gastrointest Surg. 2013;17(7):1312–21.CrossRefPubMed
36.
Vigano L, Capussotti L, Lapointe R, Barroso E, Hubert C, Giuliante F, et al. Early recurrence after liver resection for colorectal metastases: risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6,025 patients. Ann Surg Oncol. 2014;21(4):1276–86.CrossRefPubMed
37.
Blazeby JM, Fayers P, Conroy T, Sezer O, Ramage J, Rees M, et al. Validation of the European Organization for Research and Treatment of cancer QLQ-LMC21 questionnaire for assessment of patient-reported outcomes during treatment of colorectal liver metastases. Br J Surg. 2009;96(3):291–8.CrossRefPubMed
38.
39.
40.
Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.CrossRefPubMed
41.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral
42.
43.
Dakin H, Wordsworth S. Cost-minimisation analysis versus cost-effectiveness analysis, revisited. Health Econ. 2013;22(1):22–34.CrossRefPubMed
44.
Briggs AH, O’Brien BJ. The death of cost-minimization analysis? Health Econ. 2001;10(2):179–84.CrossRefPubMed
45.
Briggs AH, Wonderling DE, Mooney CZ. Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation. Health Econ. 1997;6(4):327–40.CrossRefPubMed
46.
Briggs A, Sculpher M, Claxton K. Decision modelling for health economic evaluation. Oxford: Oxford University Press; 2006.
47.
McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, et al. What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies. Trials. 2006;7:9.CrossRefPubMedPubMedCentral
48.
Wade J, Donovan JL, Lane JA, Neal DE, Hamdy FC. It’s not just what you say, it’s also how you say it: opening the ‘black box’ of informed consent appointments in randomised controlled trials. Soc Sci Med. 2009;68(11):2018–28.CrossRefPubMed
49.
Paramasivan S, Huddart R, Hall E, Lewis R, Birtle A, Donovan JL. Key issues in recruitment to randomised controlled trials with very different interventions: a qualitative investigation of recruitment to the SPARE trial (CRUK/07/011). Trials. 2011;12:78.CrossRefPubMedPubMedCentral
50.
Collinson FJ, Gregory WM, McCabe C, Howard H, Lowe C, Potrata D, et al. The STAR trial protocol: a randomised multi-stage phase II/III study of Sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic renal cancer. BMC Cancer. 2012;12:598.CrossRefPubMedPubMedCentral
51.
Hamilton DW, de Salis I, Donovan JL, Birchall M. The recruitment of patients to trials in head and neck cancer: a qualitative study of the EaStER trial of treatments for early laryngeal cancer. Eur Arch Otorhinolaryngol Suppl. 2013;270(8):2333–7.CrossRef
52.
53.
Joffe H, Yardley L. Content and thematic analysis. In: Marks DF, Yardle L, editors. Research methods for clinical and health psychology. London: SAGE Publications Ltd; 2004;56–68.
54.
Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101.CrossRef
Metadata
Title
Liver resection surgery versus thermal ablation for colorectal LiVer MetAstases (LAVA): study protocol for a randomised controlled trial
Authors
Kurinchi Gurusamy
Neil Corrigan
Julie Croft
Maureen Twiddy
Stephen Morris
Nick Woodward
Steve Bandula
Daniel Hochhauser
Vicky Napp
Alison Pullan
Nicholas Jakowiw
Raj Prasad
Steven Olde Damink
C. J. H. M. van Laarhoven
Johannes H. W. de Wilt
Julia Brown
Brian R. Davidson
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2499-5

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Mesenchymal stem cells in the treatment of Cesarean section skin scars: study protocol for a randomized, controlled trial

Study protocol

The impact of manual rotation of the occiput posterior position on spontaneous vaginal delivery rate: study protocol for a randomized clinical trial (RMOS)

Study protocol

Effectiveness of a transdiagnostic individually tailored Internet-based and mobile-supported intervention for the indicated prevention of depression and anxiety (ICare Prevent) in Dutch college students: study protocol for a randomised controlled trial

Study protocol

Restrictive Versus Massive Fluid Resuscitation Strategy (REFILL study), influence on blood loss and hemostatic parameters in obstetric hemorrhage: study protocol for a randomized controlled trial

Study protocol

Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial

Study protocol

A customized home-based computerized cognitive rehabilitation platform for patients with chronic-stage stroke: study protocol for a randomized controlled trial