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Expert Review of Anticancer Therapy Nov 2020Neuroendocrine tumors (NETs) are a heterogeneous group of cancers arising from neuroendocrine cells. The aim was to evaluate objective response rate (ORR) as a predictor... (Comparative Study)
Comparative Study
Association between objective response rate and overall survival in metastatic neuroendocrine tumors treated with radioembolization: a systematic literature review and regression analysis.
OBJECTIVES
Neuroendocrine tumors (NETs) are a heterogeneous group of cancers arising from neuroendocrine cells. The aim was to evaluate objective response rate (ORR) as a predictor of overall survival (OS) in patients with metastatic NETs (mNETs) treated with radioembolization (RE).
METHODS
Randomized controlled trials and observational studies of RE treatment of mNETs were identified by systematic literature review (SLR). Pooled ORR and OS estimates were calculated and a weighted generalized linear model (GLM) of ORR as a predictor of OS was derived, stratified by ORR assessment criteria and RE type (Yttrium-90 resin or glass microspheres).
RESULTS
The SLR identified 32 observational studies. Mean ORR was 41% (95% confidence interval 38-45%). The Yttrium-90 resin and glass microsphere GLMs accounted for 59% and 57% of OS deviance, respectively. ORR was a significant predictor of OS in the resin microspheres model (p < 0.001), but not the glass microspheres model (p = 0.11).
CONCLUSIONS
A weighted GLM showed a significant relationship between ORR and OS in patients with mNETs treated with Yttrium-90 resin microspheres. ORR could therefore potentially be an OS surrogate in future trials of Yttrium-90 resin microspheres. Further research is needed to confirm the relationship between ORR and OS and the difference between resin and glass microspheres.
Topics: Combined Modality Therapy; Embolization, Therapeutic; Glass; Humans; Microspheres; Neoplasm Metastasis; Neuroendocrine Tumors; Randomized Controlled Trials as Topic; Regression Analysis; Survival Rate; Treatment Outcome; Yttrium Radioisotopes
PubMed: 32930618
DOI: 10.1080/14737140.2020.1814748 -
Journal of Cardiovascular and Thoracic... 2023The present review sought to evaluate by meta-analysis the efficacy of bariatric arterial embolization (BAE) in promoting weight loss in patients with body mass index... (Review)
Review
The present review sought to evaluate by meta-analysis the efficacy of bariatric arterial embolization (BAE) in promoting weight loss in patients with body mass index (BMI) ranging from 25-40 kg/m. This study was performed and reported according to Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines. A systematic literature search of MEDLINE, Embase Google Scholar, and World Health Organization Library database was done for studies evaluating BAE for promoting weight loss in patients with BMI ranging from 25-40 kg/ m published up to March 10, 2021. Primary outcome measure included weight loss after the embolisation procedure. Three single-arm studies comprising of a total of 28 patients (BMI: 25- 40 kg/m) were found eligible for meta-analysis. All patients underwent embolization with either Embosphere microspheres or PVA particles. The predominant artery embolised was left gastric artery (in all patients). Additional arteries embolised included gastroepiploic artery (8 patients), or accessory left gastric artery (1 patient), or short gastric artery (1 patient). Pooled absolute mean weight loss was 7.854 kg (95% CI: 6.103-9.605). No significant statistical heterogeneity was detected (I=51.75%, =0.126) among pooled studies. In conclusion, limited single-arm studies report BAE as an effective, and relatively safe procedure for promoting weight loss in patients with BMI ranging from 25-40 kg/m, although the number of patients included is very small. Initial results of BAE in promoting weight loss are promising with no major/severe complications reported; however, long term follow-up is required to see the sustainability of the effects.
PubMed: 38357559
DOI: 10.34172/jcvtr.2023.32900 -
The Cochrane Database of Systematic... Jan 2020Hepatocellular carcinoma is the most common liver neoplasm and the sixth most common cancer worldwide. Its incidence has increased dramatically since the mid-2000s.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatocellular carcinoma is the most common liver neoplasm and the sixth most common cancer worldwide. Its incidence has increased dramatically since the mid-2000s. Although surgical resection and liver transplantation are the main curative treatments, only about 20% of people with early hepatocellular carcinoma may benefit from these interventions. Treatment options for unresectable hepatocellular carcinoma include ablative and transarterial interventions - selective yttrium-90 microsphere transarterial radioembolisation - in addition to the drug sorafenib.
OBJECTIVES
To determine the benefits and harms of yttrium-90 (Y-90) microsphere transarterial radioembolisation given as monotherapy or in combination with other systemic or locoregional interventions versus placebo, no treatment, or other similar systemic or locoregional interventions for people with unresectable hepatocellular carcinoma.
SEARCH METHODS
We performed electronic searches in the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), Science Citation Index - Expanded, and Conference Proceedings Citation Index - Science until September 2019. We manually checked the reference lists of primary studies and review articles.
SELECTION CRITERIA
We searched for randomised clinical trials.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We extracted information on participants, interventions, outcomes, trial design, and trial methods. We assessed risk of bias of the included trials using pre-defined domains and the certainty of evidence using GRADE. Our primary review outcomes were all-cause mortality, quality of life, and serious adverse events; our secondary outcomes were cancer-related mortality, time to progression of the tumour, tumour response, non-serious adverse events, and liver transplantation. For dichotomous variables, we calculated risk ratio (RR), and for continuous variables, we planned to calculate mean difference (MD) or standardised mean difference (SMD), with 95% confidence intervals (CIs). We based time-to-event data analyses on hazard ratios (HRs).
MAIN RESULTS
Six randomised trials with 1340 participants in total fulfilled the review inclusion criteria and provided data for one or more of our analysed outcomes. All trials were at high risk of bias. We assessed the certainty of evidence as low to very low. One trial compared radioembolisation plus sorafenib versus sorafenib alone in people with advanced hepatocellular carcinoma. All-cause mortality, health-related quality of life, cancer-related mortality, time to progression, and tumour response rates were not reported. Serious adverse events were reported in 63 trial participants (39.6%) in the radioembolisation plus sorafenib group versus 70 trial participants (38.5%) in the sorafenib group (very low-certainty evidence). Hyperbilirubinaemia was approximately three times more common in the radioembolisation plus sorafenib group versus the sorafenib group (14.5% versus 4.4%; very low-certainty evidence). Fatigue was more common in the radioembolisation plus sorafenib group than in the sorafenib group, at 35.2% versus 24.2% of trial participants. Two trials compared radioembolisation versus sorafenib for unresectable hepatocellular carcinoma in people with locally advanced hepatocellular carcinoma. From the data we could extract, one-year all-cause mortality was 62.7% in the radioembolisation group versus 53.0% in the sorafenib group (1 trial; n = 360; very low-certainty evidence). There were no differences in the quality of life between radioembolisation and sorafenib groups (1 trial). Global health status subscore was better in the radioembolisation group than in the sorafenib group (P = 0.0048; 1 trial). Fewer participants had serious adverse events in the radioembolisation group than in the sorafenib group (27 (20.8%) in the radioembolisation group versus 57 (35.2%) in the sorafenib group; 1 trial). Median time to progression of the tumour in the radioembolisation group was 6.1 months versus 5.4 months in the sorafenib group (1 trial). The RR for disease control rate was 0.94 (95% CI 0.84 to 1.05; n = 748; 2 trials; very low-certainty evidence), favouring neither radioembolisation nor sorafenib. In two trials with 734 participants, radioembolisation seemed to be less likely to be associated with hand-foot skin reaction (RR 0.02, 95% CI 0.00 to 0.06; P < 0.001; low-certainty evidence), skin rash (RR 0.11, 95% CI 0.04 to 0.34; low-certainty evidence), diarrhoea (RR 0.11, 95% CI 0.04 to 0.34; low-certainty evidence), and hypertension (RR 0.10, 95% CI 0.01 to 0.88; low-certainty evidence). No trial reported cancer-related mortality. Three trials compared radioembolisation versus chemoembolisation in people with intermediate-stage hepatocellular carcinoma. From the data we could extract, none of these trials reported all-cause mortality and cancer-related mortality. The RR for serious adverse events was 1.41 (95% CI 0.63 to 3.14; n = 97; very low-certainty evidence), favouring neither radioembolisation nor chemoembolisation. One trial reported quality of life and noted no differences between intervention groups with regard to this outcome at week 12 (very low-certainty evidence). Median time to progression was not reached in the radioembolisation group and was 6.8 months in the chemoembolisation group (HR 0.122, 95% CI 0.027 to 0.557; 1 trial). Median time to progression of the tumour in the radioembolisation group was 371 days versus 336 days in the chemoembolisation group (P = 0.5764; 1 trial). Disease control rates (complete response + partial response + stable disease) were 73.3% with radioembolisation versus 76.9% with chemoembolisation (1 trial). According to World Health Organization (WHO) criteria, tumour response was reported in 52% of participants who received radioembolisation versus 63% of those who received chemoembolisation (1 trial). Patients in the chemoembolisation group experienced diarrhoea (P = 0.031; 1 trial) and hypoalbuminaemia (P < 0.001; 1 trial) more frequently. Four trials were sponsored by industry, and two by University. We found two ongoing trials.
AUTHORS' CONCLUSIONS
Evidence showing effects of radioembolisation with or without sorafenib compared with sorafenib alone in people with unresectable hepatocellular carcinoma is highly insufficient. We cannot determine if radioembolisation plus sorafenib compared with sorafenib alone affects all-cause mortality or the occurrence of adverse events. Radioembolisation compared with sorafenib seemed to achieve equivalent survival and to cause fewer adverse effects, but our certainty was very low. Evidence showing effects of radioembolisation versus chemoembolisation in people with unresectable hepatocellular carcinoma is also highly insufficient. Radioembolisation did not seem to differ from chemoembolisation in terms of serious adverse events and quality of life, but the certainty of evidence was very low. Further high-quality placebo-controlled randomised clinical trials are needed to assess patient-centred outcomes.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Humans; Liver Neoplasms; Microspheres; Randomized Controlled Trials as Topic; Yttrium Radioisotopes
PubMed: 31978267
DOI: 10.1002/14651858.CD011313.pub3 -
Tissue Engineering. Part B, Reviews Jun 2024Developing an model of gingival connective tissue that mimics the original structure and composition of gingiva for clinical grafting is relevant for personalized... (Review)
Review
Developing an model of gingival connective tissue that mimics the original structure and composition of gingiva for clinical grafting is relevant for personalized treatment of missing gingiva. Using tissue engineering techniques allows bypassing limitations encountered with existing solutions to increase oral soft tissue volume. This review aims to systematically analyze the different currently existing cellularized materials and technologies used to engineer gingival substitutes for applications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. An electronic search on PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted to identify suitable studies. studies about gingival substitutes and grafts containing oral cells compared with a control to investigate the graft remodeling were included. Risk of bias in the included studies was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) 10-item checklist. Out of 631 screened studies, 19 were included. Animal models were mostly rodents, and the most used implantation was subcutaneous. According to the SYRCLE tool, low-to-unclear risk of bias was prevalent. Studies checked vascularization and extracellular remodeling up to 60 days after implantation of the cellularized biomaterial. Cells used were mostly fibroblasts and stem cells from oral origin. Grafts presenting vascularization potential after implantation were produced by tissue engineering technologies including cell seeding or embedding for 14, cell sheets for 2, microsphere for 1, and extrusion 3D bioprinting for 2. Components used to build the scaffold containing the cells are all naturally derived and are mainly fibrin, gelatin, collagen, agarose, alginate, fibroin, guar gum, hyaluronic acid, and decellularized extracellular matrix. The most recurring crosslinking method was using chemicals. All studies except one reported vascularization of the graft after implantation, and some detailed extracellular matrix remodeling. Current solutions are not efficient enough. By assessing the relevant studies on the subject, this systematic review showed that a diversity of cellularized biomaterials substituting gingival connective tissue enables vascularization and extracellular remodeling. Taking the results of this review into account could help improve current bio-inks used in 3D bioprinting for applications compensating for gingival loss.
PubMed: 38756084
DOI: 10.1089/ten.TEB.2024.0031 -
Current Oncology (Toronto, Ont.) May 2022Selective internal radiation therapy (SIRT) with yttrium-90 (Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC).... (Review)
Review
Selective internal radiation therapy (SIRT) with yttrium-90 (Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC). Dosimetry verifications post-treatment are required for a valid assessment of any dose-response relationship. We performed a systematic review of the literature to determine how often clinics conducted post-treatment dosimetry verification to measure the actual radiation doses delivered to the tumor and to the normal liver in patients who underwent SIRT for ICC, and also to explore the corresponding dose-response relationship. We also investigated other factors that potentially affect treatment outcomes, including the type of microspheres used and concomitant chemotherapy. Out of the final 47 studies that entered our study, only four papers included post-treatment dosimetry studies after SIRT to quantitatively assess the radiation doses delivered. No study showed that one microsphere type provided a benefit over another, one study demonstrated better imaging-based response rates associated with the use of glass-based TheraSpheres, and two studies found similar toxicity profiles for different types of microspheres. Gemcitabine and cisplatin were the most common chemotherapeutic drugs for concomitant administration with SIRT. Future studies of SIRT for ICC should include dosimetry to optimize treatment planning and post-treatment radiation dosage measurements in order to reliably predict patient responses and liver toxicity.
Topics: Humans; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemoradiotherapy; Cholangiocarcinoma; Yttrium Radioisotopes
PubMed: 35735415
DOI: 10.3390/curroncol29060306 -
BMC Gastroenterology Jul 2022Transarterial radioembolization (TARE) with yttrium-90 microspheres is a clinically effective therapy for hepatocellular carcinoma (HCC) treatment. This study aimed to...
BACKGROUND
Transarterial radioembolization (TARE) with yttrium-90 microspheres is a clinically effective therapy for hepatocellular carcinoma (HCC) treatment. This study aimed to perform a systematic review of the available economic evaluations of TARE for the treatment of HCC.
METHODS
The Preferred Reported Items for Systematic reviews and Meta-Analyses guidelines was followed by applying a search strategy across six databases. All studies identified as economic evaluations with TARE for HCC treatment in English or Spanish language were considered. Costs were adjusted using the 2020 US dollars based on purchasing-power-parity ($US PPP).
RESULTS
Among 423 records screened, 20 studies (6 cost-analyses, 3 budget-impact-analyses, 2 cost-effectiveness-analyses, 8 cost-utility-analyses, and 1 cost-minimization analysis) met the pre-defined criteria for inclusion. Thirteen studies were published from the European perspective, six from the United States, and one from the Canadian perspectives. The assessed populations included early- (n = 4), and intermediate-advanced-stages patients (n = 15). Included studies were evaluated from a payer perspective (n = 20) and included both payer and social perspective (n = 2). TARE was compared with transarterial chemoembolization (TACE) in nine studies or sorafenib (n = 11). The life-years gained (LYG) differed by comparator: TARE versus TACE (range: 1.3 to 3.1), and TARE versus sorafenib (range: 1.1 to 2.53). Of the 20 studies, TARE was associated with lower treatment costs in ten studies. The cost of TARE treatment varied widely according to Barcelona Clinic Liver Cancer (BCLC) staging system and ranged from 1311 $US PPP/month (BCLC-A) to 71,890 $US PPP/5-years time horizon (BCLC-C). The incremental cost-utility ratio for TARE versus TACE resulted in a 17,397 $US PPP/Quality-adjusted-Life-Years (QALY), and for TARE versus sorafenib ranged from dominant (more effectiveness and lower cost) to 3363 $US PPP/QALY.
CONCLUSIONS
Economic evaluations of TARE for HCC treatment are heterogeneous. Overall, TARE is a cost-effective short- and long-term therapy for the treatment of intermediate-advanced HCC.
Topics: Canada; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cost-Benefit Analysis; Female; Humans; Liver Neoplasms; Microspheres; Pregnancy; Sorafenib
PubMed: 35780112
DOI: 10.1186/s12876-022-02396-6 -
Expert Review of Anticancer Therapy Mar 2021Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. First-line treatment options for unresectable HCC include sorafenib, lenvatinib,... (Comparative Study)
Comparative Study Meta-Analysis
A systematic literature review and network meta-analysis of first-line treatments for unresectable hepatocellular carcinoma based on data from randomized controlled trials.
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. First-line treatment options for unresectable HCC include sorafenib, lenvatinib, selective internal radiation therapy (SIRT), and transarterial chemoembolization (TACE). The present study reviewed randomized controlled trials (RCTs) of first-line therapies for unresectable HCC in TACE-ineligible patients.
RESEARCH DESIGN AND METHODS
A systematic literature review (SLR) was conducted to identify RCTs of first-line treatments for TACE-ineligible patients with unresectable HCC. Data on overall survival (OS) and progression-free survival were extracted and a contrast-based Bayesian network meta-analysis (NMA) was conducted using Markov Chain Monte Carlo techniques.
RESULTS
The SLR identified three RCTs: two comparing Y-90 resin microspheres with sorafenib, and one comparing sorafenib with lenvatinib. No RCTs were identified comparing other SIRT technologies with any other approved first-line HCC therapies. The NMA showed no significant OS differences between Y-90 resin microspheres and sorafenib (hazard ratio [HR] 0.92, 95% credible interval [CrI]: 0.79-1.08) or lenvatinib (HR: 0.88, 95% CrI: 0.63-1.22).
CONCLUSIONS
An SLR and NMA showed no significant differences between sorafenib, lenvatinib, and Y-90 resin microspheres in treating unresectable HCC. RCT evidence was not available for any other SIRT technologies and an evaluation of their relative efficacy was therefore not possible.
Topics: Antineoplastic Agents; Brachytherapy; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Humans; Liver Neoplasms; Progression-Free Survival; Randomized Controlled Trials as Topic; Survival Rate; Yttrium Radioisotopes
PubMed: 33131346
DOI: 10.1080/14737140.2021.1842204 -
Advances in Therapy Apr 2024This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC).
METHODS
In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques.
RESULTS
Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI.
CONCLUSION
Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.
Topics: Adult; Humans; Yttrium Radioisotopes; Colorectal Neoplasms; Network Meta-Analysis; Microspheres; Colonic Neoplasms; Pyrrolidines; Antineoplastic Combined Chemotherapy Protocols; Phenylurea Compounds; Pyridines
PubMed: 38407790
DOI: 10.1007/s12325-024-02800-5 -
Turkish Journal of Obstetrics and... Mar 2023To identify the preferred agent by comparing the therapeutic efficacy, degree of infarction, and side effects of polyvinyl alcohol particles (PVA) and tris-acryl gelatin...
OBJECTIVE
To identify the preferred agent by comparing the therapeutic efficacy, degree of infarction, and side effects of polyvinyl alcohol particles (PVA) and tris-acryl gelatin embolization (TAGM) agents in uterine artery embolization.
MATERIALS AND METHODS
We included available articles comparing PVA with TAGM embolization agents in the management of fibroids. The primary outcomes included the decrease in uterine volume (%), decrease in dominant tumor volume (%), fibroid infarction rate, complete infarction fibroid, complications, pain score after 24 h, procedure time (minutes), duration of hospital stay, fluoroscopy time (minutes), and the change in symptom severity score.
RESULTS
Eight articles that met our inclusion criteria were included in this study. Our analysis yielded an overall superiority of PVA compared to TAGM regarding complete fibroid infarction rate at the first 24 h. However, TAGM was better than PVA concerning <90% infarction rate outcome. While both embolization techniques showed similar effects regarding the change in symptom severity score, the percentage of decrease in uterine volume, percentage of decrease of dominant tumor volume, 90-99% infarction rate, complete infarction rate when assessed after the first 24 h, pain score after the first 24 h, procedure time, fluoroscopy time, minor, and major complications.
CONCLUSION
Both PVA and TAGM embolization agents are effective and safe modalities in treating patients with fibroids, with no significant variation of both agents in most outcomes.
PubMed: 36908106
DOI: 10.4274/tjod.galenos.2023.43778 -
The Cochrane Database of Systematic... Mar 2020The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic...
BACKGROUND
The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of people; therefore, other treatments have to be considered. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents, and can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. This can also be performed without chemotherapy, which is called bland transarterial embolisation (TAE).
OBJECTIVES
To assess the beneficial and harmful effects of TAE or TACE compared with no intervention or placebo in people with liver metastases.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and four more databases (December 2019). We also searched two trials registers and the US Food and Drug Administration database (September 2019).
SELECTION CRITERIA
Randomised clinical trials assessing beneficial and harmful effects of TAE or TACE compared with no intervention or placebo for liver metastases.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence with GRADE. We resolved disagreements by discussion.
MAIN RESULTS
We included one randomised clinical trial with 61 participants (43 male and 18 female) with colorectal cancer with liver metastases: 22 received transarterial embolisation (TAE; hepatic artery embolisation), 19 received transarterial chemoembolisation (TACE; 5-fluorouracil hepatic artery infusion chemotherapy with degradable microspheres), and 20 received 'no active therapeutic intervention' as a control. Most tumours were synchronous, unresectable metastases involving up to 75% of the liver. Participants were followed for a minimum of seven months. The trial was at high risk of bias. Very-low-certainty evidence found inconclusive results for mortality at 44 months between the TAE and TACE versus no intervention groups (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06; 61 participants). Local recurrence was reported in 10 participants without any details about the group allocation. Very-low-certainty evidence found little or no difference in mortality between the TAE and no intervention groups (RR 0.91, 95% CI 0.75 to 1.10; 42 participants). Median survival was 7 months from trial entry (range 2 to 44 months) in the TAE group and 7.9 months (range 1 to 26 months) in the control group, and 8.7 months after diagnosis (range 2 to 49 months) in the TAE group and 9.6 months (range 1 to 27 months) in the control group. The trial authors reported the differences were not statistically significant. There were no reported side effects in the control group. In the TAE group, 18 participants experienced short-term symptoms of 'post-embolisation syndrome', which were relieved with symptomatic treatment; one participant also had a local puncture site haematoma. Very-low-certainty evidence found little or no difference in mortality between the TACE and no intervention groups (RR 0.83, 95% CI 0.65 to 1.07; 39 participants). Median survival in the TACE group was 10.7 months (range 3 to 38 months) from trial entry, and 13.0 months (range 3 to 38 months) after diagnosis. The trial authors reported that differences between groups were not statistically significant. All participants experienced short-term nausea, with or without vomiting, immediately after treatment; one participant developed a wound infection, and one developed deep vein thrombosis. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Cancer Research Campaign, a non-profit organisation, provided a grant for the trial; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. We identified one ongoing trial comparing TACE plus chemotherapy versus chemotherapy alone in people with unresectable colorectal liver metastases who failed with first-line chemotherapy (NCT03783559).
AUTHORS' CONCLUSIONS
Based on one, small randomised trial at high risk of bias, the evidence is very uncertain about the effect of TAE or TACE versus no active therapeutic intervention on mortality for people with liver metastases as the true effect may be substantially different. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Short-term, minor adverse events were recorded in the intervention groups only. Large trials, following current standards of conduct and reporting, are required to explore the benefits and harms of TAE or TACE compared with no intervention or placebo in people with resectable and unresectable liver metastasis.
Topics: Antimetabolites, Antineoplastic; Chemoembolization, Therapeutic; Colorectal Neoplasms; Embolization, Therapeutic; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Microspheres; Randomized Controlled Trials as Topic
PubMed: 32163181
DOI: 10.1002/14651858.CD009498.pub4