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Journal of Contemporary Brachytherapy Feb 2021To evaluate the efficacy and vision-threatening complication rate of plaque brachytherapy with iodine-125 (I), palladium-103 (Pd), and ruthenium-106 (Ru) for treatment... (Review)
Review
PURPOSE
To evaluate the efficacy and vision-threatening complication rate of plaque brachytherapy with iodine-125 (I), palladium-103 (Pd), and ruthenium-106 (Ru) for treatment of iris and iridociliary melanoma.
MATERIAL AND METHODS
A literature review was done based on results yielded from searching PubMed, Embase, and Cochrane database, using following key words: iris melanoma, iridociliary melanoma, brachytherapy, iodine-125 brachytherapy, palladium-103 brachytherapy, and ruthenium-106 brachytherapy. Initially, relationships between mean radiation dose to apex and local recurrence and complication rate were analyzed, and then, a comparison was performed between I, Pd, and Ru studies.
RESULTS
Twelve retrospective and prospective studies were selected, with 491 patients treated primarily with plaque brachytherapy. The range of radiation dose to tumor apex were from 84 to 151.5 Gy. Ranges of mean and median of follow-up time were from 27 to 96 months. Local recurrence rate following brachytherapy ranged from 0 to 8%. A decrease in the average study dose was not associated with an increased local recurrence or metastasis rate ( = 0.373 and 0.195, respectively); however, an increase in radiation dose was associated with higher radiation-related cataract and glaucoma ( < 0.05). The rate of post-treatment glaucoma was higher in studies with I plaque brachytherapy ( = 0.004).
CONCLUSIONS
For brachytherapy of iris and iridociliary melanoma, in a range of 84 to 150 Gy, an increase in radiation dose may increase the risk of complications, while the tumor control rate does not change.
PubMed: 34025736
DOI: 10.5114/jcb.2021.103586 -
Frontiers in Immunology 2023Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs...
INTRODUCTION
Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications.
METHODS
We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification.
RESULTS
We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, β-blockers, and nonsteroidal anti-inflammatory agents.
CONCLUSION
Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, β-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.
Topics: Humans; Analgesics, Opioid; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Esophageal Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immune Checkpoint Inhibitors; Kidney Neoplasms; Liver Neoplasms; Melanoma; Metformin; Steroids; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37841249
DOI: 10.3389/fimmu.2023.1218386 -
JAMA Dermatology Oct 2022Methotrexate is widely used for the treatment of inflammatory disorders, including rheumatoid arthritis. Studies suggest that methotrexate may be associated with an... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Methotrexate is widely used for the treatment of inflammatory disorders, including rheumatoid arthritis. Studies suggest that methotrexate may be associated with an increased risk of melanoma.
OBJECTIVE
To determine whether methotrexate exposure is associated with an increased risk of cutaneous melanoma.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to May 12, 2022, for eligible studies.
STUDY SELECTION
Case-control studies, cohort studies, or randomized clinical trials (RCTs) were included if they examined the odds or risk of cutaneous melanoma in individuals exposed to low-dose methotrexate in comparison with individuals unexposed. No language limitations were applied.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed. To assess study quality, the Cochrane risk of bias tool was used for RCTs, and the Joanna Briggs Institute Checklist was used for cohort and case-control studies. Odds ratio from case-control studies and relative risk or hazard ratio from cohort studies or RCTs were pooled, and a random-effects model meta-analysis was conducted.
MAIN OUTCOMES AND MEASURES
Prespecified outcome was the odds ratio, hazard ratio, or risk ratio of cutaneous melanoma comparing low-dose methotrexate exposure with nonexposure.
RESULTS
Seventeen studies (8 RCTs, 5 cohort studies, 4 case-control studies) were eligible for inclusion, and of these, 12 studies with 16 642 cases of melanoma were pooled in the primary analysis. Indications for methotrexate included rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel disease and were unknown in 5 studies. Compared with unexposed individuals, study participants with methotrexate exposure had a small increased risk of melanoma (pooled relative risk, 1.15; 95% CI, 1.08-1.22), but this did not persist in a sensitivity analysis excluding the largest study (pooled relative risk, 1.11; 95% CI, 1.00-1.24). Subgroup analyses according to comparator group (comparing methotrexate exposure with either immunomodulator alone vs immunomodulator and methotrexate) or the indication for methotrexate being rheumatoid arthritis provided similar risk estimates. Using geographical population melanoma incidence rates, a number needed to harm of 18 630 was calculated in Australia, and 41 425 in North America.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, low-dose methotrexate exposure was associated with an increased melanoma risk, but the absolute risk increase could be considered negligible.
Topics: Humans; Methotrexate; Arthritis, Rheumatoid; Melanoma; Psoriasis; Melanoma, Cutaneous Malignant
PubMed: 36044236
DOI: 10.1001/jamadermatol.2022.3337 -
Frontiers in Oncology 2024There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma...
BACKGROUND
There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.
METHODS
Selection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using and as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.
RESULTS
A total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.
DISCUSSION
The improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.
PubMed: 38846983
DOI: 10.3389/fonc.2024.1399693 -
Frontiers in Oncology 2022More than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis.
BACKGROUND
More than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis.
OBJECTIVES
To summarize clinical outcomes and prognostic factors in MBM patients.
METHODS
A systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied.
RESULTS
A total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM.
CONCLUSION
This study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.
PubMed: 36568199
DOI: 10.3389/fonc.2022.1025664 -
Ultrasound in Medicine & Biology Nov 2022Recent technological developments in ultrasound (US) imaging and ultrasound contrast agents (UCAs) have improved diagnostic confidence in echography. In the clinical... (Review)
Review
Recent technological developments in ultrasound (US) imaging and ultrasound contrast agents (UCAs) have improved diagnostic confidence in echography. In the clinical management of melanoma, contrast-enhanced ultrasound (CEUS) imaging complements conventional US imaging (i.e., high-resolution US and Doppler imaging) for clinical examination and therapeutic follow-up. These developments have set into motion the combined use of ultrasound and UCAs as a new modality for drug delivery. This modality, called sonoporation, has emerged as a non-invasive, targeted and safe method for the delivery of therapeutic drugs into melanoma. This review focuses on the results and prospects of using US and UCAs as dual modalities for CEUS imaging and melanoma treatment.
Topics: Contrast Media; Humans; Melanoma; Microbubbles; Skin Neoplasms; Ultrasonography; Melanoma, Cutaneous Malignant
PubMed: 36050232
DOI: 10.1016/j.ultrasmedbio.2022.06.021 -
Journal of Contemporary Brachytherapy Jun 2021The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (Ru) plaque to treat uveal melanoma. (Review)
Review
PURPOSE
The aim of this study was to evaluate the efficacy and vision-threatening complications of brachytherapy with ruthenium-106 (Ru) plaque to treat uveal melanoma.
MATERIAL AND METHODS
A literature review was performed based on results from searching PubMed, Embase, Web of Science, Scopus, and Cochrane databases, using the following key words: "choroidal melanoma", "uveal melanoma", "brachytherapy", and "ruthenium-106". We included studies performed on more than 30 patients since 1986, reporting on local control rate, complications rate, mean radiation dose, and mean tumor thickness. The cumulative analysis was performed using Metaprop command of Stata v.16, and meta-regression was conducted based on mean tumor thickness and mean radiation dose to tumor's apex.
RESULTS
Twenty-one retrospective studies were selected, involving 3,913 patients treated primarily with Ru plaque brachytherapy. The range of radiation dose to tumor apex was from 70 Gy to 250 Gy. The local control rate following brachytherapy ranged from 59% to 98%, and the overall weighted mean of local control was 84%. However, the heterogeneity between studies' reports was remarkable ( = 95.40%). Meta-regression based on tumor thickness and mean dose of radiation to the apex showed that the studies' heterogeneity was minimally related to the difference in mean tumor size ( = 92%). The correlation between larger tumor size and lower local control rate was statistically significant (-value = 0.024). There was no significant correlation between the mean radiation dose and local control rate (-value = 0.679). The most commonly reported complications were cataract and radiation-related retinopathy.
CONCLUSIONS
Although the studies' heterogeneity was high, in a prescription dose ranging from 70 Gy to 250 Gy to the tumor apex, Ru brachytherapy seems to be successful in local control of uveal melanoma. The efficacy of Ru in controlling uveal melanomas decreased with the increase in tumor thickness. However, these outcomes should be verified in randomized comparative studies.
PubMed: 34122577
DOI: 10.5114/jcb.2021.106191 -
Journal of the European Academy of... May 2020Nail apparatus melanoma (NAM) is a rare dermatologic malignancy. Its prognosis is poor because it is often diagnosed late. However, progression and survival of NAM... (Meta-Analysis)
Meta-Analysis Review
Nail apparatus melanoma (NAM) is a rare dermatologic malignancy. Its prognosis is poor because it is often diagnosed late. However, progression and survival of NAM patients have only been studied among small populations. Early biopsy could help to identify suspicious lesions at a less invasive stage. While surgery is generally seen as the treatment of choice, the extent of excision margins and the use of sentinel biopsy remain debated. This systematic review aims to summarize the treatment procedures and observed prognosis in the literature during the last two decades and present pooled survival and progression rates of NAM by using meta-analysis. A systematic review on studies assessing pathology, treatment and prognosis of NAM was carried out up to end of 2018. After evaluation of eligible studies, the main emerging topics were outlined and pooled survival outcomes estimated. A total of 30 articles out of 624 identified records were included for systematic review. Finally, meta-analysis of pooled mortality rates including 18 studies was 4.6 × 100 patient-years (95% CI: 2.7, 6.8) equivalent to 5-year cumulative survival of 77.0%. Additionally, the pooled progression rate based on 17 studies was 6.3 × 100 patient-years (95% CI: 4.1, 8.9) with estimated 5-year cumulative progression-free survival of 68.5%. While the optimal extent of surgical treatment remains debated, prompt biopsy could help to identify early lesions. This is the first study to present pooled survival and progression rates by meta-analysis.
Topics: Biopsy; Humans; Melanoma; Prognosis; Progression-Free Survival
PubMed: 31788861
DOI: 10.1111/jdv.16121 -
BMJ Open Aug 2019Most skin lesions first present in primary care, where distinguishing rare melanomas from benign lesions can be challenging. Dermoscopy improves diagnostic accuracy...
OBJECTIVE
Most skin lesions first present in primary care, where distinguishing rare melanomas from benign lesions can be challenging. Dermoscopy improves diagnostic accuracy among specialists and is promoted for use by primary care physicians (PCPs). However, when used by untrained clinicians, accuracy may be no better than visual inspection. This study aimed to undertake a systematic review of literature reporting use of dermoscopy to triage suspicious skin lesions in primary care settings, and challenges for implementation.
DESIGN
A systematic literature review and narrative synthesis.
DATA SOURCES
We searched MEDLINE, Cochrane Central, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and SCOPUS bibliographic databases from 1 January 1990 to 31 December 2017, without language restrictions.
INCLUSION CRITERIA
Studies including assessment of dermoscopy accuracy, acceptability to patients and PCPs, training requirements, and cost-effectiveness of dermoscopy modes in primary care, including trials, diagnostic accuracy and acceptability studies.
RESULTS
23 studies met the review criteria, representing 49 769 lesions and 3708 PCPs, all from high-income countries. There was a paucity of studies set truly in primary care and the outcomes measured were diverse. The heterogeneity therefore made meta-analysis unfeasible; the data were synthesised through narrative review. Dermoscopy, with appropriate training, was associated with improved diagnostic accuracy for melanoma and benign lesions, and reduced unnecessary excisions and referrals. Teledermoscopy-based referral systems improved triage accuracy. Only three studies examined cost-effectiveness; hence, there was insufficient evidence to draw conclusions. Costs, training and time requirements were considered important implementation barriers. Patient satisfaction was seldom assessed. Computer-aided dermoscopy and other technological advances have not yet been tested in primary care.
CONCLUSIONS
Dermoscopy could help PCPs triage suspicious lesions for biopsy, urgent referral or reassurance. However, it will be important to establish further evidence on minimum training requirements to reach competence, as well as the cost-effectiveness and patient acceptability of implementing dermoscopy in primary care.
TRIAL REGISTRATION NUMBER
CRD42018091395.
Topics: Biopsy; Dermoscopy; Humans; Melanoma; Primary Health Care; Reproducibility of Results; Skin Neoplasms; Triage
PubMed: 31434767
DOI: 10.1136/bmjopen-2018-027529 -
Frontiers in Pharmacology 2023Multiple immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatments for high-risk resected melanoma, with unclear...
Multiple immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatments for high-risk resected melanoma, with unclear comparative efficacy and safety. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 6 June 2023. We included RCTs that assess adjuvant ICIs or targeted therapies in high-risk resected melanoma. Frequentist random-effect network meta-analyses (NMA) were performed. The primary outcome was recurrence-free survival (RFS). Eleven trials including 10,712 patients and comparing 10 treatments (nivolumab [Nivo], ipilimumab 3 mg/kg [Ipi3], Ipi10, pembrolizumab [Pemb], vemurafenib [Vemu], bevacizumab [Beva], Nivo + Ipi1, Nivo + Ipi3, dabrafenib plus trametinib [Dab + Tram], and placebo/observation [Pla/Obs]) were included. NMA showed that all treatments showed RFS benefit over placebo/observation except Ipi3 (hazard ratio [HR], 0.78; 95% CI, 0.58-1.05). Combination therapy of Nivo + Ipi3 was the most effective treatment, which significantly improved RFS compared with other treatments. NMA also showed that all treatments were associated with an increased risk of grade 3-5 adverse events over placebo/observation except Nivo (HR, 1.25; 95% CI, 0.87-1.80). NMA suggested that Nivo and Pemb were the two safest treatments except for placebo/observation. Although three combination therapies ranked as the top three in terms of RFS, they did not show significant overall survival benefits compared to monotherapies including Pemb, Nivo, Ipi3, and Ipi10. In this NMA, adjuvant Nivo and Pemb are the preferred options in patients with resected melanoma considering the benefits and harms. Combination therapy of Nivo + Ipi3 may be a promising strategy, but more evidence from phase 3 trials is needed. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438667, PROSPERO (CRD42023438667).
PubMed: 38026956
DOI: 10.3389/fphar.2023.1284240