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Optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent
Evidence review D2b
NICE Guideline, No. 151
National Guideline Alliance (UK).
Optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent
This evidence review supports recommendations 1.5.5 to 1.5.6.
Review question
What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Introduction
For colorectal cancer with limited liver metastases, surgical resection is typically the treatment of choice. However, many people with metastatic colorectal cancer in the liver are not candidates for surgical resection or local treatment with curative intent because of the extent of their metastases. In these circumstances, other treatment modalities should be considered. The aim of this review is to determine the optimal treatment for people with metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Summary of the protocol
Please see Table 1 for a summary of the population, intervention, comparison and outcomes (PICO) characteristics of this review.
Table 1
Summary of the protocol (PICO table).
For further details see the review protocol in appendix A.
Methods and process
This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual 2014. Methods specific to this review question are described in the review protocol in appendix A.
Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy until 31 March 2018. From 1 April 2018, declarations of interest were recorded according to NICE’s 2018 conflicts of interest policy. Those interests declared until April 2018 were reclassified according to NICE’s 2018 conflicts of interest policy (see Register of Interests).
Clinical evidence
Included studies
Eight randomised controlled trials (RCTs; reported in 7 publications) were included in this review (CLOCC trial [Ruers 2017; Ruers 2012]; DEBIRI trial [Martin 2015]; Fiorentini 2012; FOXFIRE, SIRFLOX, FOXFIRE Global trials [Wasan 2017]; Hendlisz 2010; van Hazel 2004.
The included studies are summarised in Table 2.
The included studies reported on four different comparisons. One RCT compared RFA with SACT to SACT alone (CLOCC trial [Ruers 2017; Ruers 2012]). Two RCTs studied DEBIRI, one comparing DEBIRI with SACT to SACT alone (DEBIRI trial [Martin 2015]) and one comparing DEBIRI to SACT (Fiorentini 2012). Five RCTs compared SIRT with SACT to SACT alone, 4 among chemotherapy-naïve people (FOXFIRE, SIRFLOX, FOXFIRE Global trials [Wasan 2017]; van Hazel 2004) and 1 among people refractory to chemotherapy (Hendlisz 2010).
See the literature search strategy in appendix B and study selection flow chart in appendix C.
Excluded studies
Studies not included in this review with reasons for their exclusions are provided in appendix K.
Summary of clinical studies included in the evidence review
Summaries of the studies that were included in this review are presented in Table 2.
Table 2
Summary of included studies.
See the full evidence tables in appendix D and the forest plots in appendix E.
Quality assessment of clinical outcomes included in the evidence review
See the clinical evidence profiles in appendix F.
Economic evidence
Included studies
A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.
Excluded studies
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.
Economic model
Economic analysis was planned for this topic in line with the economic plan but is not presented as part of this evidence review. For more information see appendix J.
Evidence statements
Clinical evidence statements
Comparison 1: RFA plus SACT versus SACT alone
Critical outcomes
Liver progression-free survival
No evidence was identified to inform this outcome.
Overall survival
- Moderate quality evidence from 1 RCT (N=119; median follow-up 9.7 years) showed a clinically important better overall survival for people who received RFA plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Quality of life
- Moderate quality evidence from 1 RCT (N=119) showed that health-related quality of life score (measured using EORTC QLQ-C30) temporarily dropped after RFA treatment in people who received RFA plus SACT, otherwise there was no difference in quality of life between people who received RFA plus SACT and those who received SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Important outcomes
Progression-free survival
- Moderate quality evidence from 1 RCT (N=119; median follow-up 9.7 years) showed a clinically important better progression-free survival for people who received RFA plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Treatment-related mortality
- Moderate quality evidence from 1 RCT (N=119) showed that there was 1 postoperative death in people who received RFA plus SACT and no postoperative deaths in people who received SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Resectability
No evidence was identified to inform this outcome.
Any grade 3 or 4 adverse event
- Moderate quality evidence from 1 RCT (N=119) showed no clinically important difference in risk of postoperative complications or grade 3 or 4 chemotherapy-related toxicities, apart from an increased risk of hospitalisation for more than 24 hours due to postoperative complications in people who received RFA plus SACT compared SACT alone.
Comparison 2: DEBIRI plus SACT versus SACT alone
Critical outcomes
Liver progression-free survival
- Moderate quality evidence from 1 RCT (N=71) showed that there may be a clinically important better liver progression-free survival in people who received DEBIRI plus FOLFOX plus bevacizumab compared to FOLFOX plus bevacizumab alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent but there is uncertainty around the estimate.
Overall survival
No evidence was identified to inform this outcome.
Quality of life
No evidence was identified to inform this outcome.
Important outcomes
Progression-free survival
- Moderate quality evidence from 1 RCT (N=71) showed no clinically important difference in progression-free survival in people who received DEBIRI plus FOLFOX plus bevacizumab compared to FOLFOX plus bevacizumab alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Treatment-related mortality
No evidence was identified to inform this outcome.
Resectability
No evidence was identified to inform this outcome.
Any grade 3 or 4 adverse event
- Moderate quality evidence from 1 RCT (N=71) showed no clinically important difference in risk of grade 3 or 4 adverse events in people who received DEBIRI plus FOLFOX plus bevacizumab compared to FOLFOX plus bevacizumab alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Comparison 3: DEBIRI versus SACT
Critical outcomes
Liver progression-free survival
- Moderate quality evidence from 1 RCT (N=74) showed a clinically important better liver progression-free survival in people who received DEBIRI compared to FOLFIRI for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Overall survival
- Moderate quality evidence from 1 RCT (N=74) showed a clinically important better overall survival in people who received DEBIRI compared to FOLFIRI for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Quality of life
- Low quality evidence from 1 RCT (N=74) showed that quality of life physical functioning subscale score (measured using Edmonton Symptom Assessment System [ESAS] was better at 1, 3 and 8 months in people who received DEBIRI compared to those who received FOLFIRI for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Important outcomes
Progression-free survival
- Moderate quality evidence from 1 RCT (N=74) showed a clinically important better progression-free survival in people who received DEBIRI compared to FOLFIRI for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Treatment-related mortality
No evidence was identified to inform this outcome.
Resectability
No evidence was identified to inform this outcome.
Any grade 3 or 4 adverse event
No evidence was identified to inform this outcome.
Comparison 4: SIRT plus SACT versus SACT alone
Critical outcomes
Liver progression free survival
- High quality evidence from 3 RCTs (N=1,103) showed a clinically important better liver progression-free survival in chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- Moderate quality evidence from 1 RCT (N=44) showed a clinically important better liver progression-free survival in people refractory to chemotherapy who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Overall survival
- High quality evidence from 4 RCTs (N=1,124) showed no clinically important difference in overall survival in chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- High quality evidence from 3 RCTs (N=958) showed no clinically important difference in overall survival in a subpopulation of chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for synchronous metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- Moderate quality evidence from 3 RCTs (N=139) showed no clinically important difference in overall survival in a subpopulation of chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metachronous metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- High quality evidence from 3 RCTs (N=958) showed no clinically important difference in overall survival in a subpopulation of chemotherapy-naïve people with WHO performance status 0 who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- High quality evidence from 3 RCTs (N=958) showed no clinically important difference in overall survival in a subpopulation of chemotherapy-naïve people with WHO performance status 1 who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- Moderate quality evidence from 1 RCT (N=44) showed no clinically important difference in overall survival in people refractory to chemotherapy who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Quality of life
- Moderate quality evidence from 3 RCTs (N=1,103) showed no clinically important difference in health-related quality of life (measured using EQ-5D-3L) at 2-3, 6, 12 and 24 months after randomisation in chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- Low quality evidence from 1 RCT (N=21) showed no difference in quality of life (measured using Functional Living Index [FLIC] every 3 months during follow-up) in chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Important outcomes
Progression-free survival
- High quality evidence from 3 RCTs (N=1,103) showed that there may be a clinically important better progression-free survival in chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent but there is uncertainty around the estimate.
- Moderate quality evidence from 1 RCT (N=44) showed a clinically important better progression-free survival in people refractory to chemotherapy who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Treatment-related mortality
- Moderate quality evidence from 4 RCTs (N=1,099) showed no clinically important difference in treatment-related mortality in people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Resectability
- Moderate quality evidence from 3 RCTs (N=1,103) showed no clinically important difference in resectability in people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Any grade 3 or 4 adverse event
- High quality evidence from 3 RCTs (N=1,099) showed a clinically important increase in risk of grade 3 or 4 adverse events in chemotherapy-naïve people who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
- Moderate quality evidence from 1 RCT (N=44) showed no clinically important difference in risk of grade 3 or 4 adverse events in people refractory to chemotherapy who received SIRT plus SACT compared to SACT alone for metastatic colorectal cancer in the liver not amenable to treatment with curative intent.
Economic evidence statements
No economic evidence was identified which was applicable to this review question.
The committee’s discussion of the evidence
Interpreting the evidence
The outcomes that matter most
Liver progression-free survival and overall survival were considered critical outcomes for decision making because progression of the liver metastases suggests ineffective treatment, potentially requiring further treatment and affecting overall survival. Quality of life was a critical outcome because of the impact that different treatment options can have on patients’ functioning and the potential long term adverse effects.
Progression-free survival, meaning survival without progression anywhere in the body, was an important outcome because it reflects effectiveness of treatment, and can mean additional subsequent treatments can be delivered and may affect overall survival. Resectability was also an important outcome as it indicates that a previously unresectable disease becomes resectable because of effective treatment. Additionally, treatment-related mortality and adverse events were also important outcomes, as they are indicative of the short-term side effects of treatments.
The quality of the evidence
Evidence was available for the comparisons of RFA plus SACT versus SACT alone (comparison 1), DEBIRI plus SACT versus SACT alone (comparison 2), DEBIRI versus SACT (comparison 3), SIRT plus SACT versus SACT alone (comparison 4). No evidence was identified on stereotactic body radiation therapy, stereotactic ablative radiotherapy or chemosaturation. For comparison 1, evidence was available for all of the outcomes apart from liver progression-free survival and resectability. The quality of the evidence was assessed using GRADE and was of moderate quality.
For comparison 2, evidence was available for all outcomes except overall survival, quality of life, treatment-related mortality and resectability. The quality of the evidence was assessed using GRADE and was of moderate quality.
For comparison 3, evidence was available for all outcomes except treatment-related mortality, resectability, and grade 3 or 4 adverse events. The quality of the evidence was assessed using GRADE and was mostly of moderate quality (varying from low to moderate).
Evidence was available for all of the outcomes for comparison 4. The quality of the evidence was assessed using GRADE and was mostly of moderate to high quality (although some evidence was of low quality).
The main reasons for downgrading the quality of the evidence was imprecision of the effect estimate due to small sample sizes and a lack of blinding
Benefits and harms
Surgical resection is usually the treatment of choice for colorectal liver metastases. Assessing resectability is a complex process including anatomical, functional and oncological consideration. Practice is changing and what has historically been considered unresectable might in current practice be considered resectable. Furthermore, unresectable disease might still be curable by other modes of treatment. The differentiation of resectable and unresectable disease, and curable and incurable are changing as techniques evolve.
When surgical resection of colorectal liver metastases is not possible because the metastases are unresectable or because the patient is unfit for surgery, other treatment options have been suggested, including systemic therapy, local ablative techniques, transarterial chemoembolization, selective internal radiation therapy, stereotactic ablative radiotherapy and chemosaturation. The potential benefits on survival should be balanced against potential effects on quality of life, treatment-related mortality and morbidity, and cost.
Evidence from randomised trials on local ablative techniques for colorectal liver metastases is limited. One relatively small phase II trial has compared radiofrequency ablation with systemic therapy to systemic therapy alone. This trial included patients with less than 10 liver metastases considered unresectable at the time of recruitment (between 2002 and 2007). The results showed that radiofrequency ablation combined with systemic therapy had a beneficial effect on overall survival and progression-free survival while no difference was observed in treatment-related mortality and morbidity. Evidence on quality of life was limited but suggested an initial drop in quality of life scores in the ablation group during the ablative treatment but no difference between the groups later on; however, because of the small sample size no definite conclusions on the effects on quality of life could be drawn. The committee considered this trial to be informative as it is the only trial examining the effectiveness and safety of ablative techniques for colorectal liver metastases but the clinical relevance of it was discussed: at the time of the trial the included population was considered to have unresectable liver metastases whereas at the current time these metastases might be resectable because techniques have evolved.
It was also noted that radiofrequency ablation has been largely replaced by newer local ablative techniques, mainly microwave ablation. While this review did not address the question of whether microwave ablation is comparable to radiofrequency ablation, the committee was aware of the non-randomised studies reported in the NICE interventions procedures guidance on microwave ablation for treating liver metastases (IPG553) which show that compared to radiofrequency ablation microwave ablation has similar survival rates and similar or lower local recurrence rates. For these reasons, the committee agreed that it would not be appropriate to only consider the older local ablation technique of radiofrequency ablation, but local ablative techniques more generally.
Some of the patients in both arms of the trial received bevacizumab as part of their systemic therapy. A NICE technology appraisal on bevacizumab and cetuximab for the treatment of metastatic colorectal cancer (TA118) does not recommend its use as first-line treatment for metastatic colorectal cancer because it was not found to be cost-effective. The trial included people with fewer than 10 liver metastases and in general the population had favourable disease as the survival in the palliative group (systemic treatment only) was around 30% at 5 years, higher than generally expected in people with unresectable colorectal liver metastases. Regardless, the committee agreed that for people whose colorectal liver metastases cannot be surgically resected a combination of systemic therapy and local ablative techniques should be considered.
Transarterial chemoembolization (including DEBIRI) was studied by 2 small RCTs. There was some evidence that DEBIRI improved time to progression in the liver. The committee discussed that improvement in liver progression-free survival would be valuable if it improved overall survival or could replace a course of chemotherapy and potentially hence give a benefit in terms of quality of life and cost. However, little or no benefit was observed on overall survival from DEBIRI and data on quality of life was too limited to draw conclusions. Therefore, the committee agreed that there is not enough evidence to recommend transarterial chemoembolization.
The most robust evidence was available on SIRT. Evidence on SIRT as first-line treatment was available from 4 RCTs, particularly from 3 more recent and larger RCTs where SIRT was given as first-line treatment. Even though SIRT produced a benefit in terms of liver progression there was no benefit on overall survival. There were more grade 3 or 4 adverse events among patients who underwent SIRT. No difference was observed in quality of life, resectability or treatment-related mortality. With no effect on overall survival or quality of life but increased adverse events and costs, the committee agreed that SIRT should not be offered as a first line treatment for people with colorectal liver metastases.
Evidence from one small RCT was available about SIRT for people refractory or intolerant to standard chemotherapy. The evidence was limited but suggested a benefit on liver progression-free survival and progression-free survival but not on overall survival. Because the evidence was limited, the committee was not able to make a recommendation on this. The committee were aware of the NICE interventional procedure guidance on selective internal radiation therapy for non-resectable colorectal metastases in the liver (IPG401), which recommends that SIRT should only be offered with special arrangements for clinical governance, consent, and audit or research to those patients who are chemotherapy intolerant or who have liver metastases that are refractory to chemotherapy and to other patients only in the context of research. The committee were also aware of a NHS England commissioning guidance on SIRT as third-line treatment, which used retrospective data in addition to the small RCT as their evidence base.
No evidence was identified on stereotactic ablative radiotherapy but there are several ongoing trials which have yet to publish their results but which will inform future guidance.
Cost effectiveness and resource use
The addition of RFA to SACT would increase overall survival and progression free survival with no difference to adverse events from treatment. Quality of life, despite being lower in the immediate period following ablation soon recovered to be equal to that of SACT alone. Given the greater overall survival it is likely that the addition of RFA will also increase QALYs.
There would be some initial increase in cost from the addition of RFA although it is likely that most if not all of that will be recouped by reducing or delaying the need for treatment following disease progression. RFA with SACT is already widely used across the NHS and therefore any resource impact from these recommendations are likely to be small.
Other factors the committee took into account
The committee were interested in the effectiveness of the treatments of interest stratified by performance status or comorbidity score, however, no such evidence was available, therefore, no recommendations were made based on these.
The committee was aware of the EPOCH trial of TheraSphere in patients who had failed first-line chemotherapy for metastatic colorectal cancer. The trial has not yet published any results.
Given the low quality of the published evidence the committee discussed making research recommendations about the effectiveness of chemosaturation and transarterial chemoemoblisation for people with colorectal liver metastases not amenable to local treatment. Following their discussion the committee decided not to make any research recommendations for this topic, partly because it was not a priority in comparison to the other research topics within this guideline and also because of the practical difficulties of recruiting enough participants to complete such a trial within a reasonable time.
References
CLOCC trial (Ruers 2017; Ruers 2012)
Ruers T, Van Coevorden F, Punt C, et al. (2017) Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. Journal of the National Cancer Institute 109(9) [PMC free article: PMC5408999] [PubMed: 28376151]
Ruers T, Punt C, Van Coevorden F, et al. (2012) Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: A randomized eortc intergroup phase ii study (EORTC 40004). Annals of Oncology 23(): 2619–26 [PMC free article: PMC3457746] [PubMed: 22431703]Cicero 2018
Cicero G, De Luca R and Dieli F (2018) Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer. Onco Targets and Therapy 11: 3059–3063 [PMC free article: PMC5975605] [PubMed: 29872317]DEBIRI trial (Martin 2015)
Martin R, Scoggins C, Schreeder M, et al. (2015) Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis. Cancer 121(): 3649–58 [PubMed: 26149602]Department of Health 2018
Department of Health (2018) NHS reference costs 2016 to 2017. London: The Stationery OfficeFiorentini 2012
Fiorentini G, Aliberti C, Tilli M et al. (2012) Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: Final results of a phase III study. Anticancer Research 32(): 1387–95 [PubMed: 22493375]FOXFIRE, SIRFLOX, FOXFIRE Global trials (Wasan 2017)
Wasan H, Sharma N, Francis A, et al. (2017) First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncology 18(): 1159–71 [PMC free article: PMC5593813] [PubMed: 28781171]Georghiou 2014
Georghiou T and Bardsley M. (2014) Exploring the cost of care at the end of life. Nuffield Trust. London: Nuffield TrustHendlisz 2010
Hendlisz A, Eynde M, Peeters M, et al. (2010) Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. Journal of Clinical Oncology 28(): 3687–94 [PubMed: 20567019]Mayo 2013
Mayo S, Pulitano C, Marques H, et al. (2013) Surgical management of patients with synchronous colorectal liver metastasis: A multicenter international analysis. Journal of the American College of Surgeons 216(4): 707–18 [PMC free article: PMC3994665] [PubMed: 23433970]Miller 2000
Miller A, Cantor S, Peoples G, et al (2000) Quality of life and cost effectiveness analysis of therapy for locally recurrent rectal cancer. Diseases of the Colon and Rectum 43(12): 1695–1701 [PubMed: 11156453]ONS 2018
Office for National Statistics National life tables, UK [online: accessed 25 November 2018]Rao 2017
Rao C, Sun Myint A, Athanasiou T (2017) Avoiding Radical Surgery in Elderly Patients With Rectal Cancer Is Cost-Effective. Diseases of the Colon and Rectum 60(1): 30–42 [PubMed: 27926555]van Hazel 2004
van Hazel G, Blackwell A, Anderson J et al. (2004) Randomised phase 2 trial of SIR-spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. Journal of Surgical Oncology 88(2): 78–85 [PubMed: 15499601]Woods 2017
Woods B, Sideris E, Palmer S, et al. (2017) NICE Decision Support Unit Technical Support Document 19: Partitioned Survival Analysis for Decision Modelling in Health Care: A Critical Review. Sheffield: Decision Support Unit [Available from http://www.nicedsu.org.uk]
Appendices
Appendix A. Review protocol
Review protocol for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Appendix B. Literature search strategies
Literature search strategies for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
A combined search was conducted for the following two review questions:
- What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver amenable to treatment with curative intent?
- What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Databases: Embase/Medline
Last searched on: 12/02/2019
| # | Search |
|---|---|
| 1 | (exp colorectal cancer/ or exp colon tumor/ or exp rectum tumor/) use emez |
| 2 | exp colorectal neoplasms/ use ppez |
| 3 | ((colorect* or colo rect* or colon or colonic or rectal or rectum) adj3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)).tw. |
| 4 | or/1-3 |
| 5 | liver metastasis/ use emez |
| 6 | liver/ use ppez |
| 7 | exp neoplasm metastasis/ use ppez |
| 8 | 6 and 7 |
| 9 | ((Liver or hepatic*) adj3 (disseminat* or metasta* or migrat*)).tw. |
| 10 | ((colorect* or colo rect* or colon or colonic or rectal or rectum) adj3 (liver metasta* or hepatic* metasta*)).tw. |
| 11 | 5 or 8 or 9 |
| 12 | 4 and 11 |
| 13 | 10 or 12 |
| 14 | hepatectomy/ use ppez or segmentectomy/ use emez |
| 15 | (Hepatectom* or segmentectom*).tw. |
| 16 | (exp liver resection/ or metastasis resection/) use emez |
| 17 | Metastasectomy/ use ppez |
| 18 | metastasectom*.tw. |
| 19 | ((liver or hepatic*) adj3 (excis* or metastasectom* or resect* or surg*)).tw. |
| 20 | or/14-19 |
| 21 | exp *antineoplastic agent/ use emez |
| 22 | exp antineoplastic agents/ use ppez |
| 23 | exp *Antineoplastic Protocols/ use ppez |
| 24 | multimodality cancer therapy/ use emez |
| 25 | cancer therapy/ use emez |
| 26 | exp *chemotherapy/ use emez |
| 27 | *cancer combination chemotherapy/ use emez |
| 28 | Cancer Vaccines/ use ppez |
| 29 | cancer vaccine/ use emez |
| 30 | cancer immunotherapy/ use emez |
| 31 | exp antibodies, monoclonal/ use ppez or monoclonal antibody/ use emez |
| 32 | chemosaturat*.tw. |
| 33 | ((anti canc* or anticanc* or anticancerogen* or anticarcinogen* or anti neoplas* or antineoplas* or anti tumo?r* or antitumo?r* or cytotoxic*) adj3 (agent* or drug* or protocol* or regimen* or treatment* or therap*)).ti. |
| 34 | (SACT or chemotherap* or immunotherap* or biological agent* or biological therap*).ti. |
| 35 | or/21-34 |
| 36 | 20 and 35 |
| 37 | ((combin* or delay* or simultaneous* or stage*) adj3 (resect* or surg*)).tw. |
| 38 | (liver-first or liverfirst).tw. |
| 39 | bowel first.tw. |
| 40 | or/37-39 |
| 41 | radiofrequency ablation/ use emez or ablation techniques/ use ppez |
| 42 | microwave thermotherapy/ use emez or irreversible electroporation/ use emez or electroporation/ use ppez |
| 43 | ((percutaneous* or radiofrequen* or radio-frequen* or RF or microwave*) adj3 ablat*).tw. |
| 44 | electroporat*.tw. |
| 45 | (RFA or MWA or IRE).tw. |
| 46 | or/41-45 |
| 47 | (radiosurgery/ or stereotactic body radiation therapy/ or stereotactic radiosurgery/ or cyberknife/) use emez |
| 48 | radiosurgery/ use ppez |
| 49 | (Stereotactic* adj2 (irradiation* or RT or radiation* or radioablation* or radiosurg* or radiotherap* or therap* or treat*)).tw. |
| 50 | (SBRT or SABRT or SABR or cyberknife or cyber knife).tw. |
| 51 | or/47-50 |
| 52 | chemoembolization/ use emez |
| 53 | exp embolization, therapeutic/ use ppez |
| 54 | ((transarterial or trans-arterial or transcatheter or trans-catheter) adj2 chemoemboli?ation).tw. |
| 55 | (irinotecan adj4 beads).tw. |
| 56 | (DEBIRI or TACE).tw. |
| 57 | or/52-56 |
| 58 | radioembolization/ use emez |
| 59 | radioemboli?ation.tw. |
| 60 | ((intraarterial or intra-arterial) adj3 brachytherapy).tw. |
| 61 | (SIRT or “selective internal radiation therapy”).tw. |
| 62 | or/58-61 |
| 63 | limit 35 to yr=“2000 - current” |
| 64 | limit 57 to yr=“2000 - current” |
| 65 | limit 62 to yr=“2000 - current” |
| 66 | 36 or 40 or 46 or 51 or 63 or 64 or 65 |
| 67 | 13 and 66 |
| 68 | limit 67 to (yr=“1995 - current” and english language) |
| 69 | Letter/ use ppez |
| 70 | letter.pt. or letter/ use emez |
| 71 | note.pt. |
| 72 | editorial.pt. |
| 73 | Editorial/ use ppez |
| 74 | News/ use ppez |
| 75 | exp Historical Article/ use ppez |
| 76 | Anecdotes as Topic/ use ppez |
| 77 | Comment/ use ppez |
| 78 | Case Report/ use ppez |
| 79 | case report/ or case study/ use emez |
| 80 | (letter or comment*).ti. |
| 81 | or/69-80 |
| 82 | randomized controlled trial/ use ppez |
| 83 | randomized controlled trial/ use emez |
| 84 | random*.ti,ab. |
| 85 | or/82-84 |
| 86 | 81 not 85 |
| 87 | animals/ not humans/ use ppez |
| 88 | animal/ not human/ use emez |
| 89 | nonhuman/ use emez |
| 90 | exp Animals, Laboratory/ use ppez |
| 91 | exp Animal Experimentation/ use ppez |
| 92 | exp Animal Experiment/ use emez |
| 93 | exp Experimental Animal/ use emez |
| 94 | exp Models, Animal/ use ppez |
| 95 | animal model/ use emez |
| 96 | exp Rodentia/ use ppez |
| 97 | exp Rodent/ use emez |
| 98 | (rat or rats or mouse or mice).ti. |
| 99 | or/86-98 |
| 100 | 67 not 99 |
| 101 | limit 100 to (yr=“1995 - current” and english language) |
| 102 | limit 101 to yr=“1995 - 2012” |
| 103 | limit 101 to yr=“2013-current” |
| 104 | remove duplicates from 102 |
| 105 | remove duplicates from 103 |
| 106 | 104 or 105 |
Database: Cochrane Library
Last searched on: 12/02/2019
| # | Search |
|---|---|
| 1 | MeSH descriptor: [Colorectal Neoplasms] explode all trees |
| 2 | ((colorect* or colo rect* or colon or colonic or rectal or rectum) near/3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)):ti,ab,kw |
| 3 | #1 or #2 |
| 4 | MeSH descriptor: [Neoplasm Metastasis] explode all trees |
| 5 | MeSH descriptor: [Liver] explode all trees |
| 6 | #4 and #5 |
| 7 | ((Liver or hepatic*) near/3 (disseminat* or metasta* or migrat*)):ti,ab,kw |
| 8 | ((colorect* or colo rect* or colon or colonic or rectal or rectum) near/3 (liver metasta* or hepatic* metasta*)):ti,ab,kw |
| 9 | #6 or #7 |
| 10 | #3 and #9 |
| 11 | #8 or #10 |
| 12 | MeSH descriptor: [Hepatectomy] this term only |
| 13 | (Hepatectom* or segmentectom*):ti,ab,kw |
| 14 | MeSH descriptor: [Metastasectomy] this term only |
| 15 | metastasectom*:ti,ab,kw |
| 16 | ((liver or hepatic*) near/3 (excis* or metastasectom* or resect* or surg*)):ti,ab,kw |
| 17 | MeSH descriptor: [Antineoplastic Agents] explode all trees |
| 18 | MeSH descriptor: [Antineoplastic Protocols] explode all trees |
| 19 | MeSH descriptor: [Cancer Vaccines] explode all trees |
| 20 | MeSH descriptor: [Antibodies, Monoclonal] explode all trees |
| 21 | chemosaturat*:ti,ab,kw |
| 22 | ((anti canc* or anticanc* or anticancerogen* or anticarcinogen* or anti neoplas* or antineoplas* or anti tumo?r* or antitumo?r* or cytotoxic*) near/3 (agent* or drug* or protocol* or regimen* or treatment* or therap*)):ti,ab,kw |
| 23 | (SACT or chemotherap* or chemosaturat* or immunotherap* or biological agent* or biological therap*):ti,ab,kw |
| 24 | ((combin* or delay* or simultaneous* or stage*) near/3 (resect* or surg*)):ti,ab,kw |
| 25 | (liver-first or liverfirst):ti,ab,kw |
| 26 | “bowel first”:ti,ab,kw |
| 27 | MeSH descriptor: [Ablation Techniques] explode all trees |
| 28 | ((percutaneous* or radiofrequen* or radio-frequen* or RF or microwave*) near/3 ablat*):ti,ab,kw |
| 29 | electroporat*:ti,ab,kw |
| 30 | (RFA or MWA or IRE):ti,ab,kw |
| 31 | MeSH descriptor: [Radiosurgery] this term only |
| 32 | (Stereotactic* near/2 (irradiation* or RT or radiation* or radioablation* or radiosurg* or radiotherap* or therap* or treat*)):ti,ab,kw |
| 33 | (SBRT or SABRT or SABR or cyberknife or cyber knife):ti,ab,kw |
| 34 | MeSH descriptor: [Chemoembolization, Therapeutic] this term only |
| 35 | ((transarterial or trans-arterial or transcatheter or trans-catheter) near/2 chemoemboli?ation):ti,ab,kw |
| 36 | (irinotecan near/4 beads):ti,ab,kw |
| 37 | (DEBIRI or TACE):ti,ab,kw |
| 38 | radioemboli?ation:ti,ab,kw |
| 39 | ((intraarterial or intra-arterial) near/3 brachytherapy):ti,ab,kw |
| 40 | (SIRT or “selective internal radiation therapy”):ti,ab,kw |
| 41 | {or #12-#40} |
| 42 | #11 and #41 Publication Year from 1995 to 2018 |
Appendix C. Clinical evidence study selection
Clinical study selection for: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Appendix D. Clinical evidence tables
Clinical evidence tables for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Table 4. Clinical evidence tables (PDF, 364K)
Appendix E. Forest plots
Forest plots for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Figure 2. Comparison 1: RFA plus SACT versus SACT alone – Overall survival
Figure 3. Comparison 1: RFA plus SACT versus SACT alone – Progression-free survival
Figure 4. Comparison 1: RFA plus SACT versus SACT alone – Postoperative mortality
Figure 5. Comparison 1: RFA plus SACT versus SACT alone – Postoperative complications
Figure 7. Comparison 2: DEBIRI plus SACT versus SACT alone – Grade 3 or 4 adverse events
Figure 8. Comparison 4: SIRT plus SACT versus SACT alone – Liver progression-free survival
Figure 9. Comparison 4: SIRT plus SACT versus SACT alone – Overall survival
Figure 11. Comparison 4: SIRT plus SACT versus SACT alone – Progression-free survival
Figure 12. Comparison 4: SIRT plus SACT versus SACT alone – Treatment-related mortality
Figure 13. Comparison 4: SIRT plus SACT versus SACT alone – Resectability
Figure 14. Comparison 4: SIRT plus SACT versus SACT alone – Grade 3 or 4 adverse events
Appendix F. GRADE tables
GRADE tables for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Appendix G. Economic evidence study selection
Economic evidence study selection for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.
Appendix H. Economic evidence tables
Economic evidence tables for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
No economic evidence was identified which was applicable to this review question.
Appendix I. Economic evidence profiles
Economic evidence profiles for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
No economic evidence was identified which was applicable to this review question.
Appendix J. Economic analysis
Economic evidence analysis for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Economic analysis was planned for this topic in line with the economic plan but is not presented as part of this evidence review. The planned model investigated the addition of radiofrequency ablation (RFA) to systemic anticancer therapy (SACT) compared to SACT alone. It was not possible to get consensus for the structure, inputs and structure, across the committee, for use in an economic model that was both meaningful for making recommendations and had concordance with the identified evidence. This was largely as a result of only 1 trial being identified for this comparison by the accompanying clinical evidence review (Ruers 2017). This study reported outcomes from a trial conducted between 2002 and 2007. The committee highlighted that the differentiation of resectable and unresectable disease, and curable and incurable have changed and are changing as techniques evolve. Consequently, a significant proportion of this trial population would now be eligible for treatments with curative intent either through resection or other treatment. Patients receiving the considered treatments today would likely be older and less fit. Whilst the opinion of the committee was that the addition of RFA would still be beneficial for overall and progression free survival, in line with the low HR estimates from Ruers 2017, it was difficult to estimate the direction or magnitude of any changes in the trial outcomes for use in an economic model as the result of this difference in the patient group.
Given that RFA is not prohibitively expensive and widely available it was likely any economic model would conclude it as a cost effective use of NHS resources when QALYs were valued at £20,000 each.
Appendix K. Excluded studies
Excluded clinical studies for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
Appendix L. Research recommendations
Research recommendations for review question: What is the optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent?
No research recommendations were made for this review question.
Final
Evidence reviews
Developed by the National Guideline Alliance part of the Royal College of Obstetricians and Gynaecologists
Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.
- Curative-intent treatment of recurrent colorectal liver metastases: A comparison between ablation and resection.[Eur J Surg Oncol. 2017]Curative-intent treatment of recurrent colorectal liver metastases: A comparison between ablation and resection.Dupré A, Jones RP, Diaz-Nieto R, Fenwick SW, Poston GJ, Malik HZ. Eur J Surg Oncol. 2017 Oct; 43(10):1901-1907. Epub 2017 Aug 26.
- Review Multimodal treatment strategies for colorectal liver metastases.[Swiss Med Wkly. 2021]Review Multimodal treatment strategies for colorectal liver metastases.Birrer DL, Tschuor C, Reiner C, Fritsch R, Pfammatter T, Garcia Schüler H, Pavic M, De Oliveira M, Petrowsky H, Dutkowski P, et al. Swiss Med Wkly. 2021 Feb 15; 151:w20390. Epub 2021 Feb 15.
- Review Treatment for metastatic colorectal cancer in the liver amenable to treatment with curative intent: Colorectal cancer (update): Evidence review D2a[ 2020]Review Treatment for metastatic colorectal cancer in the liver amenable to treatment with curative intent: Colorectal cancer (update): Evidence review D2aNational Guideline Alliance (UK). 2020 Jan
- Review WITHDRAWN: Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases.[Cochrane Database Syst Rev. 2007]Review WITHDRAWN: Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases.Al-Asfoor A, Fedorowicz Z. Cochrane Database Syst Rev. 2007 Oct 17; (4):CD006039. Epub 2007 Oct 17.
- Review WITHDRAWN: Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases.[Cochrane Database Syst Rev. 2007]Review WITHDRAWN: Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases.Al-asfoor A, Fedorowicz Z. Cochrane Database Syst Rev. 2007 Jul 18; (3):CD006039. Epub 2007 Jul 18.
- Optimal combination and sequence of treatments in patients presenting with metas...Optimal combination and sequence of treatments in patients presenting with metastatic colorectal cancer in the liver not amenable to treatment with curative intent
- Use of molecular biomarkers to guide systemic therapyUse of molecular biomarkers to guide systemic therapy
- Homo sapiens Rho GTPase activating protein 25 (ARHGAP25), transcript variant 5, ...Homo sapiens Rho GTPase activating protein 25 (ARHGAP25), transcript variant 5, mRNAgi|1423310397|ref|NM_001364819.1|Nucleotide
- Proteus anguinus mitochondrion, complete genomeProteus anguinus mitochondrion, complete genomegi|575669328|ref|NC_023342.1||gnl|N ENOMES|35428Nucleotide
- Wdr41 WD repeat domain 41 [Rattus norvegicus]Wdr41 WD repeat domain 41 [Rattus norvegicus]Gene ID:361879Gene
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