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Orthopaedic Journal of Sports Medicine Jul 2021Genicular artery embolization (GAE) is an innovative technique that has been investigated as a supplementary treatment method for chronic pain secondary to knee... (Review)
Review
BACKGROUND
Genicular artery embolization (GAE) is an innovative technique that has been investigated as a supplementary treatment method for chronic pain secondary to knee osteoarthritis (OA).
PURPOSE
To evaluate the current evidence on the effectiveness and safety of GAE for OA-related knee pain.
STUDY DESIGN
Systematic review; Level of evidence, 4.
METHODS
A systematic literature search was conducted in the PubMed, Web of Science, EMBASE, and Scopus databases to identify studies related to knee OA treated with GAE. Treatment agents were categorized as Embozene, imipenem/cilastatin, resorbable microspheres, and polyvinyl alcohol. The main outcomes were the mean difference (MD) in pre- and postembolization pain based on the visual analog scale (VAS) or the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores as well as changes in the need for pain medication. Random- and fixed-effects models were applied for data analysis.
RESULTS
Of 379 initially inspected publications, 11 (N = 225 patients; 268 knees) were included in the final review. The quality of the studies was fair in 8 and poor in 3-categorized according to the National Institutes of Health quality assessment tool. Overall, 119, 72, 13, and 21 patients were treated with imipenem/cilastatin, Embozene, resorbable microspheres, and polyvinyl alcohol, respectively. Symptomatic improvement was reported in all studies. The pooled effect size, characterized by MD, showed a significant improvement in the VAS and WOMAC pain scores, with better functional status after GAE. Pre- versus postembolization MDs in VAS scores ranged from 32 within the first week to 58 after a 2-year follow-up (equivalent to 54% and 80% improvement, respectively). There was a similar trend in the overall WOMAC scores, with MDs ranging from 28.4 to 36.8 (about 58% and 85% improvement, respectively). GAE resulted in a decreased need for pain medication for knee OA, with a 27%, 65%, and 73% decline in the number of patients who used opioids, nonsteroidal anti-inflammatory drugs, and intra-articular hyaluronic acid injection, respectively ( < .00001 for all). No significant difference between embolic agents was seen with regard to post-GAE pain reduction. No severe or life-threatening complications were reported.
CONCLUSION
OA treated by GAE using different embolic particles can be considered generally safe, with good efficacy and no reported serious complications.
PubMed: 34350303
DOI: 10.1177/23259671211021356 -
Journal of Radiation Oncology 2017The purpose of this study was to review the role of radioactive microparticles (1-100 μm) for the treatment of solid tumors and provide a comprehensive overview of the... (Review)
Review
PURPOSE
The purpose of this study was to review the role of radioactive microparticles (1-100 μm) for the treatment of solid tumors and provide a comprehensive overview of the feasibility, safety, and efficacy.
METHODS
A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2017) by combining synonyms for the determinants "tumor," "injection," and "radionuclide." Data on injection technique, toxicity, tumor response, and survival were collected.
RESULTS
The search yielded 7271 studies, and 37 were included for analysis. Twelve studies were performed in human patients and 25 animal studies. The studies were heterogeneous in patient population, tumors, follow-up time, and treatment characteristics. The direct intratumoral injection of radioactive microparticles resulted in a response rate of 71% in a variety of tumors and uncomplicated procedures with high cumulative doses of >19,000 Gy were reported.
CONCLUSION
The large variety of particles, techniques, and treated tumors in the studies provided an important insight into issues concerning efficacy, safety, particle and isotope choice, and other concepts for future research. Animal studies showed efficacy and a dose response. Most studies in humans concluded that intratumoral treatment with radioactive beta-emitting microparticles is relatively safe and effective. Conflicting evidence about safety and efficacy might be explained by the considerable variation in the treatment characteristics. Larger particles had a better retention which resulted in higher anti-tumor effect. Leakage seems to follow the path of least resistance depending on anatomical structures. Subsequently, a grid-like injection procedure with small volume depots is advised over a single large infusion. Controlled image-guided treatment is necessary because inadequate local delivery and inhomogeneous dose distribution result in reduced treatment efficacy and in potential complications.
PubMed: 29213358
DOI: 10.1007/s13566-017-0315-6 -
Hepatology (Baltimore, Md.) Sep 2017Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the... (Review)
Review
Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off-target diversion of yttrium-90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization-induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969-982).
Topics: Brachytherapy; Dose-Response Relationship, Radiation; Female; Humans; Liver Neoplasms; Male; Microspheres; Practice Guidelines as Topic; Prognosis; Radiation Injuries; Radiation Pneumonitis; Retrospective Studies; Treatment Outcome; Yttrium Radioisotopes
PubMed: 28407278
DOI: 10.1002/hep.29207 -
The Cochrane Database of Systematic... Oct 2009Liver metastases are often the dominant site of metastatic disease in colorectal cancer. Selective internal radiation therapy (SIRT) involves embolising radiolabeled... (Review)
Review
BACKGROUND
Liver metastases are often the dominant site of metastatic disease in colorectal cancer. Selective internal radiation therapy (SIRT) involves embolising radiolabeled spheres (SIR-Spheres) into the arterial supply of the liver with the aim of improving the control of liver metastases.
OBJECTIVES
To assess the effectiveness and toxicity of SIRT in the treatment of metastatic colorectal cancer liver metastasis when given alone or with systemic or regional hepatic artery chemotherapy.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane library 2008 issue 2, MEDLINE (1966 to October 2008), EMBASE (1980 to October 2008), and Pubmed (October 2008). The proceedings of ASCO (1985 to 2008) and ASCO GI (2004 to 2008) were also searched. The manufacturers of SIR-Spheres were contacted and asked whether they were aware of any other unpublished studies.
SELECTION CRITERIA
Randomised controlled trials comparing SIRT and chemotherapy (systemic and/or regional) with chemotherapy alone, or comparing SIRT alone with best supportive care in patients with metastatic colorectal cancer.
DATA COLLECTION AND ANALYSIS
Two authors (AT/TP) extracted data and assessed the trial quality. The study authors were contacted and individual patient data was obtained. Results were analysed separately for patients with and without extra-hepatic disease.
MAIN RESULTS
A single study of 21 patients compared SIRT and systemic chemotherapy (fluorouracil and leucovorin) with chemotherapy alone. There was a significant improvement in progression free survival and median survival associated with SIRT, both for the total studied population and for those disease limited to the liver. There was an increase in toxicity with the use of SIRT. A second study of 63 eligible patients compared SIRT and regional chemotherapy (floxuridine) with regional chemotherapy alone. There was no significant difference in progression free survival and median survival seen with SIRT, in either the total patient group or in the 22 patients with disease limited to the liver. There was no significant increase in toxicity with the addition of SIRT to regional chemotherapy. There were no randomised studies comparing SIRT with best supportive care in patients with refractory disease, and no randomised studies assessing the effect of SIRT in patients with resectable liver metastases.
AUTHORS' CONCLUSIONS
There is a need for well designed, adequately powered phase III trials assessing the effect of SIRT when used with modern combination chemotherapy regimens. Further studies are also needed for patients with refractory disease with a particular focus on the impact on quality of life.
Topics: Antimetabolites, Antineoplastic; Colorectal Neoplasms; Combined Modality Therapy; Floxuridine; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Microspheres; Radiotherapy; Randomized Controlled Trials as Topic; Yttrium Radioisotopes
PubMed: 19821394
DOI: 10.1002/14651858.CD007045.pub2 -
ClinicoEconomics and Outcomes Research... 2021Quality of life is among the most important considerations in the treatment of hepatocellular carcinoma (HCC), arguably second only to overall survival. Measuring and... (Review)
Review
Effects of Trial Population Selection on Quality of Life and Healthcare Decision-Making: A Systematic Review and Example in the Treatment of Hepatocellular Carcinoma with Radioembolization.
BACKGROUND AND AIMS
Quality of life is among the most important considerations in the treatment of hepatocellular carcinoma (HCC), arguably second only to overall survival. Measuring and modeling patient quality of life is also crucial in the evaluation of the cost-effectiveness of health interventions. In the present study, we aimed to identify cost-utility analyses comparing selective internal radiation therapy (SIRT) with systemic therapy in patients with unresectable HCC and to compare the modeled incremental quality of life differences between the two therapies.
METHODS
A systematic literature review was conducted. PubMed, EMBASE, the Cochrane Library, and health technology assessment agency websites were searched to identify cost-utility studies of SIRT versus systemic therapies in the treatment of HCC. Key characteristics of the studies, modeled populations and incremental quality of life outcomes were extracted from the included studies.
RESULTS
The systematic literature review retrieved 1140 studies, of which four were ultimately included. Hand searches then identified two distinct analyses, and an updated version of one of the four studies identified initially. From these seven studies, 18 analyses were included. Analyses using data from the overall trial populations reported incremental quality-of-life estimates spanning -0.09 to +0.28 quality-adjusted life years (QALYs), with that range expanding to -0.09 to +0.60 QALYs when also considering post hoc sub-group analyses.
CONCLUSION
The wide range of incremental QALYs, with substantial differences between overall trial populations and subgroups, illustrates the impact that the choice of target population may have on the relative quality of life outcomes of the compared interventions, which may in turn affect clinical decision-making. The small differences also highlight both the importance of reporting measures of dispersion around the findings, and the limitations of the incremental cost-effectiveness ratio (ICER) for assessing the relative cost-effectiveness of interventions that are predicted to result in similar quality-of-life outcomes.
PubMed: 34588788
DOI: 10.2147/CEOR.S319857 -
Cancers Jan 2020Radioembolization with Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the... (Review)
Review
Radioembolization with Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the present systematic review was to summarize the evidence of contralateral liver hypertrophy and oncological outcome following unilateral treatment with radioembolization. A systematic literature search using the MEDLINE, EMBASE, and Cochrane libraries for studies published between 2008 and 2020 was performed. A total of 16 studies, comprising 602 patients, were included. The median kinetic growth rate per week of the contralateral liver lobe was 0.7% and declined slightly over time. The local tumor control was 84%. Surgical resection after radioembolization was carried out in 109 out of 362 patients (30%). Although the available data suggest that radioembolization prior to major hepatectomy is safe with a promising oncological outcome, the definitive role of radioembolization requires assessment within controlled clinical trials.
PubMed: 32012709
DOI: 10.3390/cancers12020294 -
European Journal of Nuclear Medicine... Nov 2021To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and... (Review)
Review
PURPOSE
To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer.
METHODS
A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded.
RESULTS
A total of 3038 records were identified of which 487 were screened based on the full text. Ultimately, 37 studies were included for narrative analysis. Meta-analysis could not be performed due to the large heterogeneity in study and reporting designs. Out of 37 studies, 30 reported a 'mean dose threshold' that needs to be achieved in order to expect a response. This threshold appears to be higher for hepatocellular carcinoma (HCC, 100-250 Gy) than for colorectal cancer metastases (CRC, 40-60 Gy). Reported thresholds tend to be lower for resin microspheres than when glass microspheres are used.
CONCLUSION
Although the existing evidence demonstrates a dose-response relationship in SIRT for both primary liver tumours and liver metastases, many pieces of the puzzle are still missing, hampering the definition of standardized dose thresholds. Nonetheless, most current evidence points towards a target mean dose of 100-250 Gy for HCC and 40-60 Gy for CRC. The field would greatly benefit from a reporting standard and prospective studies designed to elucidate the dose-response relation in different tumour types.
Topics: Brachytherapy; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Microspheres; Prospective Studies; Yttrium Radioisotopes
PubMed: 33839892
DOI: 10.1007/s00259-021-05340-0 -
International Journal of Surgery... Jun 2022Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective...
BACKGROUND
Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia.
MATERIALS AND METHODS
A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine.
RESULTS
The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus.
CONCLUSION
These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.
Topics: Humans; Brachytherapy; Carcinoma, Hepatocellular; Liver Neoplasms; Microspheres; Yttrium Radioisotopes
PubMed: 35662438
DOI: 10.1016/j.ijsu.2021.106094 -
Journal of Cancer Research and Clinical... Oct 2020Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). The objective was to conduct a systematic literature review (SLR)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). The objective was to conduct a systematic literature review (SLR) and exploratory network meta-analysis (NMA) to compare the tolerability and effectiveness of SIRT with Y-90 resin microspheres, regorafenib, TAS-102 (trifluridine/tipiracil), and best supportive care (BSC) as third-line treatment in patients with mCRC.
METHODS
An SLR was conducted to identify studies comparing two or more of the treatments and reporting overall survival (OS), progression-free survival, tumor response, or adverse event (AE) incidence. An exploratory NMA was conducted to compare hazard ratios (HRs) for OS using Markov chain Monte Carlo (MCMC) techniques.
RESULTS
Seven studies were identified in the SLR: two double-blind randomized-controlled trials (RCT) for each drug, one open-label RCT, and two non-randomized comparative studies for SIRT. Patient selection criteria differed between studies, with SIRT studies including patients with liver-dominant colorectal metastases. Nausea and vomiting were more frequent with TAS-102 than regorafenib or SIRT; diarrhea was more common with TAS-102 and regorafenib than SIRT. The exploratory NMA suggested that all active treatments improved OS, with HRs of 0.48 (95% CrI 0.30-0.78) for SIRT with Y-90 resin microspheres, 0.63 (0.38-1.03) for TAS-102, and 0.67 (0.40-1.08) for regorafenib each compared to BSC.
CONCLUSIONS
Regorafenib, TAS-102 and SIRT using Y-90 resin microspheres are more effective than BSC in third-line treatment of mCRC; however, study heterogeneity made comparisons between active treatments challenging. SIRT is a viable treatment for third-line mCRC and its favorable AE profile should be considered in the therapeutic decision-making process.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Colorectal Neoplasms; Double-Blind Method; Drug Combinations; Humans; Microspheres; Neoplasm Metastasis; Network Meta-Analysis; Palliative Care; Phenylurea Compounds; Progression-Free Survival; Pyridines; Pyrrolidines; Randomized Controlled Trials as Topic; Thymine; Trifluridine; Uracil; Yttrium Radioisotopes
PubMed: 32715436
DOI: 10.1007/s00432-020-03315-6 -
The Cochrane Database of Systematic... Nov 2016Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review.
OBJECTIVES
To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review.
MAIN RESULTS
One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001).
AUTHORS' CONCLUSIONS
There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.
Topics: Adult; Age Factors; Capsules; Child; Cystic Fibrosis; Delayed-Action Preparations; Enzyme Replacement Therapy; Humans; Microspheres; Nutritional Status; Pancreas; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 27878805
DOI: 10.1002/14651858.CD008227.pub3