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European Urology Sep 2021Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.
OBJECTIVE
To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.
EVIDENCE ACQUISITION
We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.
EVIDENCE SYNTHESIS
A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.
CONCLUSIONS
Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.
PATIENT SUMMARY
In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
Topics: Brachytherapy; Cryotherapy; High-Intensity Focused Ultrasound Ablation; Humans; Male; Neoplasm Recurrence, Local; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Radiation Dosage; Radiosurgery; Salvage Therapy
PubMed: 33309278
DOI: 10.1016/j.eururo.2020.11.010 -
European Journal of Physical and... Aug 2017This meta-analysis investigated the effectiveness of low-level laser therapy (LLLT) on pain in adult patients with musculoskeletal disorders. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This meta-analysis investigated the effectiveness of low-level laser therapy (LLLT) on pain in adult patients with musculoskeletal disorders.
EVIDENCE ACQUISITION
A systematic literature search was conducted in the Medline and PEDro databases. Two researchers independently screened titles and abstracts of the retrieved studies for eligibility. Quality assessment of the eligible studies was conducted using the PEDro rating scale. Studies that scored ≥4 were included. A random-effects model was used for this meta-analysis. Subgroup meta-analyses were conducted to evaluate the influence of the adherence of the applied LLLT to the World Association of Laser Therapy (WALT) guidelines, the anatomical site under investigation and the study design on the overall weighted mean effect size. Meta regression was used to assess the possible influence of the study quality on the individual study effect sizes.
EVIDENCE SYNTHESIS
Eighteen studies allowing for 21 head-to-head comparisons (totaling N.=1462 participants) were included. The pooled raw mean difference (D) in pain between LLLT and the control groups was -0.85 (95% CI: -1.22 to -0.48). There was high (I²=85.6%) and significant between study heterogeneity (Cochran's Q =139.2; df=20; P<0.001). The subgroup meta-analysis of the comparisons not following the WALT guidelines revealed a D=-0.68 (95% CI: -1.09 to -0.27). In this group, heterogeneity decreased to I²=72.6% (Q=51.2; df=14; P<0.001). In the WALT subgroup D equaled -1.52 (95% CI: -2.34 to -0.70). This between groups difference was clinically relevant although statistically not significant (Q=3.24; df=1; P=0.072).
CONCLUSIONS
This meta-analysis presents evidence that LLLT is an effective treatment modality to reduce pain in adult patients with musculoskeletal disorders. Adherence to WALT dosage recommendations seems to enhance treatment effectiveness.
Topics: Evidence-Based Medicine; Female; Follow-Up Studies; Humans; Low-Level Light Therapy; Male; Musculoskeletal Diseases; Pain; Pain Measurement; Risk Assessment; Treatment Outcome
PubMed: 28145397
DOI: 10.23736/S1973-9087.17.04432-X -
BMJ Open Sep 2022We investigated the effectiveness of low-level laser therapy (LLLT) in lower extremity tendinopathy and plantar fasciitis on patient-reported pain and disability. (Meta-Analysis)
Meta-Analysis
Efficacy of low-level laser therapy in patients with lower extremity tendinopathy or plantar fasciitis: systematic review and meta-analysis of randomised controlled trials.
OBJECTIVES
We investigated the effectiveness of low-level laser therapy (LLLT) in lower extremity tendinopathy and plantar fasciitis on patient-reported pain and disability.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Eligible articles in any language were identified through PubMed, Embase and Physiotherapy Evidence Database (PEDro) on the 20 August 2020, references, citations and experts.
ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES
Only randomised controlled trials involving participants with lower extremity tendinopathy or plantar fasciitis treated with LLLT were included.
DATA EXTRACTION AND SYNTHESIS
Random effects meta-analyses with dose subgroups based on the World Association for Laser Therapy treatment recommendations were conducted. Risk of bias was assessed with the PEDro scale.
RESULTS
LLLT was compared with placebo (10 trials), other interventions (5 trials) and as an add-on intervention (3 trials). The study quality was moderate to high.Overall, pain was significantly reduced by LLLT at completed therapy (13.15 mm Visual Analogue Scale (VAS; 95% CI 7.82 to 18.48)) and 4-12 weeks later (12.56 mm VAS (95% CI 5.69 to 19.42)). Overall, disability was significantly reduced by LLLT at completed therapy (Standardised Mean Difference (SMD)=0.39 (95% CI 0.09 to 0.7) and 4-9 weeks later (SMD=0.32 (95% CI 0.05 to 0.59)). Compared with placebo control, the recommended doses significantly reduced pain at completed therapy (14.98 mm VAS (95% CI 3.74 to 26.22)) and 4-8 weeks later (14.00 mm VAS (95% CI 2.81 to 25.19)). The recommended doses significantly reduced pain as an add-on to exercise therapy versus exercise therapy alone at completed therapy (18.15 mm VAS (95% CI 10.55 to 25.76)) and 4-9 weeks later (15.90 mm VAS (95% CI 2.3 to 29.51)). No adverse events were reported.
CONCLUSION
LLLT significantly reduces pain and disability in lower extremity tendinopathy and plantar fasciitis in the short and medium term. Long-term data were not available. Some uncertainty about the effect size remains due to wide CIs and lack of large trials.
PROSPERO REGISTRATION NUMBER
CRD42017077511.
Topics: Fasciitis, Plantar; Humans; Low-Level Light Therapy; Lower Extremity; Pain; Randomized Controlled Trials as Topic; Tendinopathy
PubMed: 36171024
DOI: 10.1136/bmjopen-2021-059479 -
Cancer Treatment Reviews Feb 2017Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to... (Meta-Analysis)
Meta-Analysis Review
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.
Topics: Aged; Dose Fractionation, Radiation; Hematologic Neoplasms; Humans; Middle Aged; Patient Selection; Radiotherapy; Spleen; Splenomegaly; Treatment Outcome
PubMed: 28063304
DOI: 10.1016/j.ctrv.2016.11.016 -
Lancet (London, England) Oct 2020It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced... (Comparative Study)
Comparative Study Meta-Analysis
Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data.
BACKGROUND
It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.
METHODS
We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing. RCTs were eligible if they aimed to compare immediate adjuvant radiotherapy versus early salvage radiotherapy, following radical prostatectomy in men (age ≥18 years) with intermediate-risk or high-risk, localised or locally advanced prostate cancer. We searched trial registers and conference proceedings until July 8, 2020, to identify eligible RCTs. By establishing the ARTISTIC collaboration with relevant trialists, we were able to anticipate when eligible trial results would emerge, and we developed and registered a protocol with PROSPERO before knowledge of the trial results (CRD42019132669). We used a harmonised definition of event-free survival, as the time from randomisation until the first evidence of either biochemical progression (prostate-specific antigen [PSA] ≥0·4 ng/mL and rising after completion of any postoperative radiotherapy), clinical or radiological progression, initiation of a non-trial treatment, death from prostate cancer, or a PSA level of at least 2·0 ng/mL at any time after randomisation. We predicted when we would have sufficient power to assess whether adjuvant radiotherapy was superior to early salvage radiotherapy. Investigators supplied results for event-free survival, both overall and within predefined patient subgroups. Hazard ratios (HRs) for the effects of radiotherapy timing on event-free survival and subgroup interactions were combined using fixed-effect meta-analysis.
FINDINGS
We identified three eligible trials and were able to obtain updated results for event-free survival for 2153 patients recruited between November, 2007, and December, 2016. Median follow-up ranged from 60 months to 78 months, with a maximum follow-up of 132 months. 1075 patients were randomly assigned to receive adjuvant radiotherapy and 1078 to a policy of early salvage radiotherapy, of whom 421 (39·1%) had commenced treatment at the time of analysis. Patient characteristics were balanced within trials and overall. Median age was similar between trials at 64 or 65 years (with IQRs ranging from 59 to 68 years) across the three trials and most patients (1671 [77·6%]) had a Gleason score of 7. All trials were assessed as having low risk of bias. Based on 270 events, the meta-analysis showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy (HR 0·95, 95% CI 0·75-1·21; p=0·70), with only a 1 percentage point (95% CI -2 to 3) change in 5-year event-free survival (89% vs 88%). Results were consistent across trials (heterogeneity p=0·18; I=42%).
INTERPRETATION
This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localised or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy as it offers the opportunity to spare many men radiotherapy and its associated side-effects.
FUNDING
UK Medical Research Council.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Male; Neoplasm Grading; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Salvage Therapy
PubMed: 33002431
DOI: 10.1016/S0140-6736(20)31952-8 -
Journal of Medicine and Life 2021Temporomandibular joint disorders (TMDs) encompass a wide array of ailments affecting the temporomandibular joint (TMJ), muscles of mastication, and the allied...
Temporomandibular joint disorders (TMDs) encompass a wide array of ailments affecting the temporomandibular joint (TMJ), muscles of mastication, and the allied structural framework. Myofascial pain, internal derangement of the joint, and degenerative joint diseases constitute the majority of TMDs. TMDs usually have a multifactorial etiology, and treatment modalities range from conservative therapies to surgical interventions. Low-level laser therapy (LLLT) has evolved as an efficient non-invasive therapeutic modality in TMDs. Previously conducted systematic reviews and meta-analyses have shown variable results regarding the efficiency of LLLT in TMJ disorder patients. Hence, this systematic review was carried out as an attempt to evaluate the efficacy of LLLT in the treatment of temporomandibular joint disorder patients.
Topics: Humans; Low-Level Light Therapy; Publication Bias; Risk; Software; Temporomandibular Joint Disorders
PubMed: 34104237
DOI: 10.25122/jml-2020-0169 -
Clinical Oral Investigations Oct 2021This systematic review assesses dental implant survival, calculates the incidence rate of osteoradionecrosis, and evaluates risk factors in irradiated head and neck... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This systematic review assesses dental implant survival, calculates the incidence rate of osteoradionecrosis, and evaluates risk factors in irradiated head and neck cancer patients.
MATERIALS AND METHODS
Various databases (e.g., Medline/Embase using Ovid) and gray literature platforms were searched using a combination of keywords and subject headings. When appropriate, meta-analysis was carried out using a random effects model. Otherwise, pooled analysis was applied.
RESULTS
A total of 425 of the 660 included patients received radiotherapy. In total, 2602 dental implants were placed, and 1637 were placed in irradiated patients. Implant survival after an average follow-up of 37.7 months was 97% (5% confidence interval, CI 95.2%, 95% CI 98.3%) in nonirradiated patients and 91.9% (5% CI 87.7%, 95% CI: 95.3%) after an average follow-up of 39.8 months in irradiated patients. Osteoradionecrosis occurred in 11 cases, leading to an incidence of 3% (5% CI 1.6%, 95% CI 4.9%). The main factors impacting implant survival were radiation and grafting status, while factors influencing osteoradionecrosis could not be determined using meta-analysis.
CONCLUSION
Our data show that implant survival in irradiated patients is lower than in nonirradiated patients, and osteoradionecrosis is-while rare-a serious complication that any OMF surgeon should be prepared for. The key to success could be a standardized patient selection and therapy to improve the standard of care, reduce risks and shorten treatment time.
CLINICAL RELEVANCE
Our analysis provides further evidence that implant placement is a feasible treatment option in irradiated head and neck cancer patients with diminished oral function and good long-term cancer prognosis.
Topics: Dental Implantation, Endosseous; Dental Implants; Head and Neck Neoplasms; Humans; Osteoradionecrosis
PubMed: 34401944
DOI: 10.1007/s00784-021-04065-6 -
European Urology Jul 2016To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. (Comparative Study)
Comparative Study Meta-Analysis Review
CONTEXT
To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer.
OBJECTIVE
To conduct a meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer.
EVIDENCE ACQUISITION
We searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale.
EVIDENCE SYNTHESIS
Nineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54-1.73, p<0.00001; I(2)=0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76-2.47, p < 0.00001; I(2)=48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.
CONCLUSIONS
Radiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making.
PATIENT SUMMARY
We reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery.
Topics: Brachytherapy; Humans; Male; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Survival Rate
PubMed: 26700655
DOI: 10.1016/j.eururo.2015.11.010 -
Strahlentherapie Und Onkologie : Organ... Mar 2022To seek evidence for osteoradionecrosis (ORN) after dental extractions before or after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To seek evidence for osteoradionecrosis (ORN) after dental extractions before or after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC).
METHODS
Medline/PubMed, Embase, and Cochrane Library were searched from 2000 until 2020. Articles on HNC patients treated with IMRT and dental extractions were analyzed by two independent reviewers. The risk ratios (RR) and odds ratios (OR) for ORN related to extractions were calculated using Fisher's exact test. A one-sample proportion test was used to assess the proportion of pre- versus post-IMRT extractions. Forest plots were used for the pooled RR and OR using a random-effects model.
RESULTS
Seven of 630 publications with 875 patients were eligible. A total of 437 (49.9%) patients were treated with extractions before and 92 (10.5%) after IMRT. 28 (3.2%) suffered from ORN after IMRT. ORN was associated with extractions in 15 (53.6%) patients, eight related to extractions prior to and seven cases related to extractions after IMRT. The risk and odds for ORN favored pre-IMRT extractions (RR = 0.18, 95% CI: 0.04-0.74, p = 0.031, I = 0%, OR = 0.16, 95% CI: 0.03-0.99, p = 0.049, I = 0%). However, the prediction interval of the expected range of 95% of true effects included 1 for RR and OR.
CONCLUSION
Tooth extraction before IMRT is more common than after IMRT, but dental extractions before compared to extractions after IMRT have not been proven to reduce the incidence of ORN. Extractions of teeth before IMRT have to be balanced with any potential delay in initiating cancer therapy.
Topics: Head and Neck Neoplasms; Humans; Incidence; Osteoradionecrosis; Radiotherapy, Intensity-Modulated; Tooth Extraction
PubMed: 35029717
DOI: 10.1007/s00066-021-01896-w -
Journal of Periodontal Research Feb 2017Although low-level laser therapy (LLLT) has been demonstrated to have a biomodulatory effect on periodontal tissue, no systematic review has exclusively addressed its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Although low-level laser therapy (LLLT) has been demonstrated to have a biomodulatory effect on periodontal tissue, no systematic review has exclusively addressed its effectiveness as an adjunct to non-surgical periodontal treatment. This study aimed to evaluate whether an additional benefit exists for the application of LLLT compared with scaling and root planing (SRP) alone.
MATERIAL AND METHODS
An extensive search was conducted in the Cochrane Library (Issue 8, 2015), PubMed (1997) and EMBASE (1947) before August 2015 for randomized controlled trials (RCTs). The bias risk was assessed with the Cochrane tool for risk of bias evaluation. A meta-analysis was performed using REVMAN 5.3.
RESULTS
After independent screening of 354 initial records, eight publications (seven RCTs) were included. However, six were rated as 'having a high risk of bias' as a result of major methodological weakness in 'allocation concealment' and 'blinding of key personnel'. Meta-analysis showed that LLLT-mediated SRP demonstrated significant short-term benefits over SRP monotherapy in the improvement of the probing pocket depth (p = 0.0009 at 1 mo; p = 0.03 at 2 mo) and the level of interleukin-1β in the gingival crevicular fluid (p = 0.01 at 1 mo). Nevertheless, LLLT failed to show significant additional intermediate-term (3 and 6 mo) effects in terms of clinical parameters and alveolar bone density.
CONCLUSION
These findings indicated that LLLT showed only short-term additional benefits after conventional SRP. Its long-term effects remain unclear due to substantial methodological weaknesses and an insufficient number of current studies. Future RCTs with better designs and longer follow-up periods are required to assess the effectiveness of LLLT as an adjunctive treatment strategy in patients with periodontal disease.
Topics: Combined Modality Therapy; Dental Scaling; Humans; Low-Level Light Therapy; Periodontitis; Root Planing
PubMed: 26932392
DOI: 10.1111/jre.12361