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The British Journal of Radiology Aug 2015Intra-arterial therapies (IATs) play a pivotal role in the management of patients with primary and secondary liver malignancies. The unique advantages of these... (Review)
Review
Intra-arterial therapies (IATs) play a pivotal role in the management of patients with primary and secondary liver malignancies. The unique advantages of these treatments are their ability to selectively deliver a high dose of anticancer treatment while preserving healthy liver tissue. The proven efficacy of these catheter-based locoregional therapies in a highly systemic chemoresistant cancer such as hepatocellular carcinoma (HCC), along with the minimally invasive nature of these treatments, quickly yielded wide acceptance in the medical community and revolutionized the field of Interventional Oncology. In this article, we describe the clinical rationale and background of catheter-based IATs. We provide an overview of clinical achievements of these treatments alone and in combination with sorafenib in patients with HCC.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Carcinoma, Hepatocellular; Catheter Ablation; Chemoembolization, Therapeutic; Combined Modality Therapy; Diffusion of Innovation; Embolization, Therapeutic; Female; Forecasting; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Microspheres; Niacinamide; Patient Selection; Phenylurea Compounds; Radiopharmaceuticals; Sorafenib; Yttrium Radioisotopes
PubMed: 25978585
DOI: 10.1259/bjr.20140564 -
European Journal of Surgical Oncology :... Jan 2015Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the... (Meta-Analysis)
Meta-Analysis Review
Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Disease-Free Survival; Embolization, Therapeutic; Humans; Microspheres; Radiopharmaceuticals; Treatment Outcome; Yttrium Radioisotopes
PubMed: 25449754
DOI: 10.1016/j.ejso.2014.09.007 -
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 -
Neurosurgical Review Dec 2022The literature has had some conflicting evidence regarding the effective management of lumbar spondylolisthesis (LS). Herein, we review active and prospective clinical... (Review)
Review
The literature has had some conflicting evidence regarding the effective management of lumbar spondylolisthesis (LS). Herein, we review active and prospective clinical trials to identify the emerging trends for the management of LS. A systematic search was conducted utilizing the NIH Clinical Trials database using the search term "lumbar spondylolisthesis" on February 2, 2022. Currently active and prospective clinical trials for LS were included and analyzed. All statistical analyses were performed on R 4.1.2. We identified 37 clinical trials. Nearly half the trials (n = 18, 48.6%) include novel technologies; 6 (16.2%) are comparing surgical approaches, of which 4 (67%) include decompression alone versus decompression with instrumented fusion; 6 (16.2%) are evaluating perioperative pain management protocols, of which 3 (50%) include bupivacaine or ropivacaine; 3 (8.1%) are evaluating alternative medicines in LS; 2 (5.4%) are observational studies about the natural history of LS; 1 (2.7%) involves surgical infection prophylaxis; and 1 (2.7%) is evaluating AK1320 microspheres. The 18 trials involving novel technologies include 3D-printed titanium cages (n = 3, 16.7%), interbody implants (n = 4, 22.2%), bone graft materials (n = 4, 22.2%), and miscellaneous intraoperative devices (n = 7, 38.9%). The top 3 outcomes measured were Oswestry Disability Index (n = 28, 75.7%), visual analog scale (n = 21, 56.7%), and postoperative radiographs (n = 16, 43.2%). Patient-reported outcome measures (PROMs) were included in 34 (91.9%) trials, while 23 (62.2%) trials included lumbar spine imaging. LS can often require a multifaceted approach. Novel technologies and utilization of PROMs appear to be a significant emerging trend in LS management.
Topics: Humans; Spondylolisthesis; Spinal Fusion; Prospective Studies; Lumbar Vertebrae; Lumbosacral Region; Treatment Outcome
PubMed: 36357642
DOI: 10.1007/s10143-022-01889-y -
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 -
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 -
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 -
Cardiovascular and Interventional... Jul 2017To compare the safety profiles of TheraSphere (glass) and SIR-Spheres (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was... (Comparative Study)
Comparative Study Review
To compare the safety profiles of TheraSphere (glass) and SIR-Spheres (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was conducted using the databases MEDLINE, Embase, and Cochrane Trials Register to identify all relevant studies. Baseline characteristics and adverse events of all grades related to gastrointestinal, hepatobiliary, and respiratory systems were collected along with commonly reported outcomes related to post-embolization syndrome. For all outcomes, data from each study were tabulated for each intervention. Adverse events and patients were summed across studies on TheraSphere and SIR-Spheres, respectively, and the resulting proportion of patients experiencing an outcome for both interventions was calculated. Thirty-one observational studies were included in the review. In the adverse events of all grades, more patients treated with resin microspheres reported gastric ulcers, hepatic encephalopathy, cholecystitis, hepatic failure, and pleural effusion. Patients treated with resin microspheres also had more hepatobiliary adverse events of grade 3 or higher. In the events related to post-embolization syndrome, glass microspheres exhibited a similar safety profile compared to resin microspheres. Ascites and nausea grade 3 or higher were recorded more frequently with glass microsphere treatment. Based on this review of the published literature, glass microspheres exhibit a safety profile with fewer gastrointestinal and pulmonary adverse events compared to resin microspheres in the treatment of hepatocellular carcinoma.
Topics: Adult; Brachytherapy; Carcinoma, Hepatocellular; Embolization, Therapeutic; Female; Humans; Liver Neoplasms; Male; Microspheres; Yttrium Radioisotopes
PubMed: 28246879
DOI: 10.1007/s00270-017-1594-4