The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver

316 Pages·2014·5.74 MB·English

by  Loveman E

HEALTH TECHNOLOGY ASSESSMENT
VOLUME 18 ISSUE 7 JANUARY 2014
ISSN 1366-5278
The clinical effectiveness and cost-effectiveness
of ablative therapies in the management of
liver metastases: systematic review and
economic evaluation
Emma Loveman, Jeremy Jones, Andrew J Clegg, Joanna Picot,
Jillian L Colquitt, Diana Mendes, David J Breen, Emily Moore,
Steve George, Graeme Poston, David Cunningham,
Theo Ruers and John Primrose
DOI 10.3310/hta18070

The clinical effectiveness and
cost-effectiveness of ablative therapies
in the management of liver
metastases: systematic review and
economic evaluation
Emma Loveman,1 Jeremy Jones,1 Andrew J Clegg,1
Joanna Picot,1 Jillian L Colquitt,1 Diana Mendes,1
David J Breen,2 Emily Moore,3 Steve George,4*
Graeme Poston,5 David Cunningham,6 Theo Ruers7
and John Primrose8
1SouthamptonHealthTechnologyAssessmentsCentre,UniversityofSouthampton,
Southampton, UK
2Department of Radiology, University Hospital Southampton, Southampton, UK
3University of Southampton Clinical Trials Unit, University Hospital Southampton,
Southampton, UK
4Public Health Sciences and Medical Statistics, University of Southampton Faculty
of Medicine, University Hospital Southampton, Southampton, UK
5University of Liverpool, University Hospital Aintree, Liverpool, UK
6Gastrointestinal Unit, Royal Marsden Hospital, London, UK
7Division of Surgical Oncology, the Netherlands Cancer Institute – Antoni van
Leeuwenhoek Hospital, Amsterdam, the Netherlands
8University Surgery, University of Southampton Faculty of Medicine,
University Hospital Southampton, Southampton, UK
*Corresponding author
Declared competing interests of authors: All authors have completed the unified competing interest
formatwww.icmje.org/coi_disclosure.pdf(availableonrequestfromthecorrespondingauthor).DrDBreen
hasundertakenconsultancyforGalilMedicalLtd;ProfessorDCunningham’sinstitutionhasreceivedgrants
from Amgen Inc. and Merck & Co. Inc.; Professor G Poston has received payment for lectures from
pharmaceutical companies and royalties from books. All other authors declare (1) no financial support for
thesubmittedwork from anyoneotherthantheiremployer;(2)nofinancial relationships withcommercial
entities that might have an interest in the submitted work; (3) no spouses, partners, or children with
relationships with commercial entities that might have an interest in the submitted work; and (4) no
non-financial interests that may be relevant to the submitted work.
Published January 2014
DOI: 10.3310/hta18070

This report should be referenced as follows:
Loveman E, Jones J, Clegg AJ, Picot J, Colquitt JL, Mendes D, et al.The clinical effectiveness and
cost-effectiveness of ablative therapies in themanagement of liver metastases: systematic review
and economic evaluation. HealthTechnol Assess 2014;18(7).
Health Technology Assessment isindexed and abstractedin Index Medicus/MEDLINE, Excerpta
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Clinical Medicine.

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DOI:10.3310/hta18070 HEALTHTECHNOLOGYASSESSMENT2014 VOL. 18 NO.7
Abstract
The clinical effectiveness and cost-effectiveness of ablative
therapies in the management of liver metastases:
systematic review and economic evaluation
Emma Loveman,1 Jeremy Jones,1 Andrew J Clegg,1 Joanna Picot,1
Jillian L Colquitt,1 Diana Mendes,1 David J Breen,2 Emily Moore,3
Steve George,4* Graeme Poston,5 David Cunningham,6
Theo Ruers7 and John Primrose8
1Southampton Health Technology Assessments Centre, University of Southampton,
Southampton, UK
2Department of Radiology, University Hospital Southampton, Southampton, UK
3UniversityofSouthamptonClinicalTrialsUnit,UniversityHospitalSouthampton,Southampton,UK
4Public Health Sciences and Medical Statistics, University of Southampton Faculty of Medicine,
University Hospital Southampton, Southampton, UK
5University of Liverpool, University Hospital Aintree, Liverpool, UK
6Gastrointestinal Unit, Royal Marsden Hospital, London, UK
7Division of Surgical Oncology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek
Hospital, Amsterdam, the Netherlands
8University Surgery, University of Southampton Faculty of Medicine, University Hospital
Southampton, Southampton, UK
*Corresponding author
Background:Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary,
but survival beyond 5years of patients with untreated metastatic disease in the liver is rare. Treatment for
liver metastases has largely been surgical resection, but this isfeasible in only approximately 20–30% of
people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative
therapies and other targeted treatments.
Objectives:To evaluate the clinical effectiveness and cost-effectiveness of thedifferent ablativeand
minimally invasive therapies for treating liver metastases.
Data sources: Electronicdatabases including MEDLINE, EMBASE and The Cochrane Library were searched
from 1990 to September 2011. Experts were consulted and bibliographies checked.
Review methods:Systematicreviews of the literature wereundertakento appraise the clinical
effectiveness and cost-effectiveness of ablative therapies and minimallyinvasivetherapies used
for people with liver metastases. Studies were any prospective study with sample size greaterthan
100 participants. Aprobabilistic modelwas developed for theeconomicevaluation of the technologies
where data permitted.
Results: The evidence assessing the clinical effectiveness and cost-effectiveness of ablativeand other
minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review;
each had methodological shortcomings and few had a comparator group. Onerandomised controlled trial
(RCT) of microwave ablation versus surgical resection was identifiedand showedno improvementin
©Queen’sPrinterandControllerofHMSO2014.ThisworkwasproducedbyLovemanetal.underthetermsofacommissioningcontractissuedbytheSecretaryofStatefor
Health.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessionaljournals vii
providedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshouldbe
addressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonScience
Park,SouthamptonSO167NS,UK.
ABSTRACT
outcomescomparedwith resection.In two prospective case series studies that investigated the use of laser
ablation,mean survival ranged from 41to 58 months. One cohort study compared radiofrequency
ablationwith surgical resection and five caseseries studies also investigated theuse of radiofrequency
ablation.Across these studies themedian survival ranged from 44 to 52 months. Seven studies of
minimallyinvasivetherapies were included in thereview. Two RCTs compared chemoembolisation with
chemotherapy only. Overallsurvival was not compared betweengroups and methodological shortcomings
mean that conclusions are difficult to make. Two caseseries studies of laser ablation following
chemoembolisation were also included; however, these provide little evidenceof the use of these
technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in
tumour response and time to disease progression were demonstrated; however, benefits in terms of
survival were equivocal. An exploratory survival modelwas developed using data from the review of clinical
effectiveness. The model includes separate analyses of microwave ablation compared with surgery and
radiofrequency ablation compared with surgery and one of radioembolisation in conjunctionwith hepatic
artery chemotherapy compared with hepatic artery chemotherapy alone.Microwave ablation was
associatedwith an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year
(QALY)gained, with microwave ablationbeing associated with reduced cost but also with poorer outcome
than surgery. Radiofrequencyablation compared with surgical resection for solitary metastases <3cm
was associated with an ICER of–£266,767 perQALY gained, indicatingthat radiofrequency ablation
dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary
metastases≥3cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY
gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy
was associated with an ICER of £37,303 per QALY gained.
Conclusions: There iscurrently limited high-quality research evidence upon which to base any firm
decisionsregardingablativetherapies for liver metastases. Further trials should compare ablativetherapies
with surgery, in particular. A RCT would provide the most appropriate design for undertakingany further
evaluationand should include afull economic evaluation, but the groupto be randomised needs
carefulselection.
Source offunding:Fundingfor this study was providedby the Health Technology Assessment
programmeof the National Institute for Health Research.
viii
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