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Ocular Oncology and Pathology Oct 2019Conjunctival melanoma is rare in adults and rarer in children. We systematically reviewed the presentation, diagnostic and management strategies as well as outcomes for... (Review)
Review
BACKGROUND
Conjunctival melanoma is rare in adults and rarer in children. We systematically reviewed the presentation, diagnostic and management strategies as well as outcomes for conjunctival melanoma in children and adolescents.
METHODS
The following databases were searched: Medline, Embase, Web of Science and Scopus for cases of conjunctival melanoma occurring in children and adolescents < 18 years of age.
RESULTS
Seventeen studies with 32 patients (18 males) were identified. The median age at presentation was 11 years (range 4-18 years). Most patients were white. Most patients presented with a conjunctival mass or naevus with a recent history of growth or change. Excision biopsy provided diagnosis and management for all cases. Adjuvant chemotherapy and radiotherapy were also used. One patient had metastatic disease at diagnosis and 3 developed metastatic disease (range 1-10 months). Two patients died from disease and one was alive with metastatic disease. Two patients had disease recurrence. Outcomes were observed to be better where diagnosis was made earlier and "no-touch" excision biopsy was performed in an appropriate specialist setting.
CONCLUSIONS
Conjunctival melanoma occurs rarely in children and adolescents. Surgery is the mainstay of management. The prognosis is guarded in metastatic disease due to the small sample size and limited follow-up.
PubMed: 31768361
DOI: 10.1159/000497813 -
International Journal of Molecular... Nov 2023Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample... (Meta-Analysis)
Meta-Analysis Review
Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample should be examined in assessing drug targets. This study systematically analyzed all the literature on primary melanoma and its matched metastasis. Following PRISMA guidelines, we searched multiple medical databases for relevant publications from January 2000 to December 2022, assessed the quality of the primary-level studies using the QUIPS tool, and summarized the concordance rate of the most reported genes using the random-effects model. Finally, we evaluated the inter-study heterogeneity using the subgroup analysis. Thirty-one studies investigated the concordance of and in 1220 and 629 patients, respectively. The pooled concordance rate was 89.4% [95% CI: 84.5; 93.5] for and 97.8% [95% CI: 95.8; 99.4] for . When high-quality studies were considered, only mutation status consistency increased. Five studies reported the concordance status of c (93%, 44 patients) and promoter (64%, 53 patients). Lastly, three studies analyzed the concordance of cancer genes involved in the signaling pathways, apoptosis, and proliferation, such as (25%, four patients), (44%, nine patients), and (20%, five patients). Our study found that the concordance of known drug targets (mainly ) during melanoma progression is higher than in previous meta-analyses, likely due to advances in molecular techniques. Furthermore, significant heterogeneity exists in the genes involved in the melanoma genetic makeup; although our results are based on small patient samples, more research is necessary for validation.
Topics: Humans; Melanoma; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Mutation; Melanoma, Cutaneous Malignant
PubMed: 38003476
DOI: 10.3390/ijms242216281 -
ESMO Open Apr 2023Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown if the irAE occurrence is a valid surrogate of ICIs' efficacy.
METHODS
We identified articles reporting the results of randomized trials of experimental ICI therapy in solid tumors with a systematic search. The control arms could be placebo, cytotoxic/targeted therapy, or ICI therapy. We extracted the hazard ratios for overall survival (OS) with the number of OS events per arm and the number and percentages of overall and specific irAEs of grade 1-2 and grade 3-4 per arm. We estimated the treatment effect on the potential surrogate outcome with the odds ratio of the irAE rate between the experimental and the control arm. The statistical analysis consisted of weighted linear regression on a logarithmic scale between treatment effects on irAE rate and treatment effects on OS.
RESULTS
Sixty-two randomized trials were included for a total of 79 contrasts and 42 247 patients. The analyses found no significant association between the treatment effects for overall grade 1-2 or grade 3-4 irAE rates or specific (skin, gastrointestinal, endocrine) irAE rates. In the non-small-cell lung cancer (NSCLC) trial subset, we observed a negative association between treatment effects on overall grade 1-2 irAEs and treatment effects on OS in studies with patients selected for programmed death-ligand 1 expression (R = 0.55; 95% confidence interval 0.20-0.95; R = -0.69). In the melanoma trial subset, a negative association was shown between treatment effects on gastrointestinal grade 3-4 irAEs and treatment effects on OS in trials without an ICI-based control arm (R = 0.77; 95% confidence interval 0.24-0.99; R = -0.89).
CONCLUSIONS
We found low-strength correlations between the ICI therapy effects on overall or specific irAE rates and the treatment effects on OS in several cancer types.
Topics: Humans; Immune Checkpoint Inhibitors; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Melanoma; Antineoplastic Agents
PubMed: 36842300
DOI: 10.1016/j.esmoop.2023.100787 -
Transplantation Research 2014Cutaneous melanoma carries the potential for substantial morbidity and mortality in the solid organ transplant population. We systematically reviewed the literature... (Review)
Review
Cutaneous melanoma carries the potential for substantial morbidity and mortality in the solid organ transplant population. We systematically reviewed the literature published from January 1995 to January 2012 to determine the overall relative risk and prognosis of melanoma in transplant recipients. Our search identified 7,512 citations. Twelve unique non-overlapping studies reported the population-based incidence of melanoma in an inception cohort of solid organ transplant recipients. Compared to the general population, there is a 2.4-fold (95% confidence interval, 2.0 to 2.9) increased incidence of melanoma after transplantation. No population-based outcome data were identified for melanoma arising post-transplant. Data from non-population based cohort studies suggest a worse prognosis for late-stage melanoma developing after transplantation compared with the general population. For patients with a history of pre-transplant melanoma, one population-based study reported a local recurrence rate of 11% (2/19) after transplantation, although staging and survival information was lacking. There is a need for population-based data on the prognosis of melanoma arising pre- and post-transplantation. Increased incidence and potentially worse melanoma outcomes in this high-risk population have implications for clinical care in terms of prevention, screening and reduction of immunosuppression after melanoma development post-transplant, as well as transplantation decisions in patients with a history of pre-transplant melanoma.
PubMed: 24834346
DOI: 10.1186/2047-1440-3-10 -
Annals of Medicine and Surgery (2012) Sep 2017Congenital and infantile malignant melanomas are rare and typically carry poor prognosis. The purpose of this article was to review the data on congenital and infantile... (Review)
Review
Congenital and infantile malignant melanomas are rare and typically carry poor prognosis. The purpose of this article was to review the data on congenital and infantile malignant melanomas of the scalp in order to understand its presentation, diagnosis, management, and outcomes of congenital melanoma of scalp. We searched PubMed, CINAHL and Cochrane databases. Ten cases of congenital and 3 cases of infantile malignant melanoma of scalp were identified. The diagnosis was confirmed by biopsy and histological analysis for confirmation. The prognosis depends on the origin of disease (congenital melanocytic nevus, transplacental metastasis, or de-novo), tumor thickness, the presence of ulceration and/or necrosis, and anatomic site (scalp lesions having poor prognosis). The most commonly used treatment of the reported cases of congenital and infantile melanoma was surgical excision of the primary lesion. Further modes of treatment may be extrapolated from the treatment of childhood and adult melanomas.
PubMed: 28794873
DOI: 10.1016/j.amsu.2017.07.042 -
Clinical, Cosmetic and Investigational... 2017Rates of malignant melanoma are continuing to increase, and until recently effective treatments were lacking. However, since 2011 three immunotherapeutic agents, known... (Review)
Review
BACKGROUND AND OBJECTIVES
Rates of malignant melanoma are continuing to increase, and until recently effective treatments were lacking. However, since 2011 three immunotherapeutic agents, known as checkpoint inhibitors, have been approved. This review aims to establish whether these three drugs - ipilimumab, nivolumab, and pembrolizumab - offer greater efficacy and tolerability compared to control interventions (placebo, immunotherapy, or chemotherapy) in patients with stage III or IV unresectable cutaneous melanoma.
MATERIALS AND METHODS
A search on four major medical and scientific databases yielded 7,553 records, of which seven met the inclusion criteria, with a total study population of 3,628. Only prospective Phase II or III randomized controlled trials on checkpoint inhibitors for patients with unresectable cutaneous melanoma that reported data on survival (overall or progression-free), tumor response, or adverse events were included. Three meta-analyses were carried out.
RESULTS
The hazard ratio for progression or death was 0.54 (95% confidence interval [CI]: 0.44-0.67), and the odds ratio for best overall response rate was 4.48 (95% CI: 2.77-7.24), both in favor of checkpoint inhibitors. However, control treatments were associated with an insignificantly lower rate of discontinuation of treatment due to adverse effects or treatment-related adverse events (odds ratio =1.63 [95% CI: 0.55-4.88]).
CONCLUSION
This study finds that checkpoint inhibitors are more effective than control interventions, both in terms of survival and tumor response, and yet no less tolerable. PD1 therapies (nivolumab and pembrolizumab) appear to offer greater efficacy than CTLA4 therapy (ipilimumab). The combination of nivolumab and ipilimumab was, however, the most effective, but significantly less tolerable than monotherapy. The lack of published clinical data does, however, limit this study. Further research is needed in two areas in particular: 1) to determine the optimal use of checkpoint inhibitors, specifically in terms of combination therapy, and 2) to identify reliable biomarkers to predictive responders and guide treatment assignment.
PubMed: 28883738
DOI: 10.2147/CCID.S120877 -
Cancers Dec 2022Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not... (Review)
Review
Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not well studied, and underlying mechanisms and risk factors for MBM development are not consistently documented. We conducted a systematic literature review (SLR) including a total of 39 articles to evaluate the proportion of melanoma patients who are diagnosed with, or develop, brain metastases, and summarize the risk factors of MBM. The average proportion of MBM was calculated and weighted by the sample size of each study. Meta-analyses were conducted for the selected risk factors using a random-effects model. The proportion of MBM at diagnosis was 33% (975 with MBM out of 2948 patients) among patients with cutaneous melanoma (excluding acral) and 23% (651/2875) among patients with cutaneous mixed with other types of melanoma. The proportion at diagnosis was lower among populations with mucosal (9/96, 9%) or uveal (4/184, 2%) melanoma and among populations outside the United States and Europe. Meta-analysis demonstrated that male vs. female gender and left-sided tumors vs. right-sided were significantly associated with increased risk of melanoma brain metastases. These data may help clinicians to assess an individual patient's risk of developing melanoma brain metastases.
PubMed: 36551594
DOI: 10.3390/cancers14246108 -
Frontiers in Oncology 2022Multiple treatments of unresectable advanced or metastatic melanoma have been licensed in the adjuvant setting, causing tremendous interest in developing neoadjuvant...
Multiple treatments of unresectable advanced or metastatic melanoma have been licensed in the adjuvant setting, causing tremendous interest in developing neoadjuvant strategies for melanoma. Eligible studies included those that compared overall survival/progression-free survival/grade 3 or 4 adverse events in patients with unresectable advanced or metastatic melanoma. Seven eligible randomized trials with nine publications were included in this study. Direct and network meta-analysis consistently indicated that nivolumab+ipilimumab, nivolumab, and trametinib could significantly improve overall survival and progression-free survival compared to ipilimumab in advanced melanoma patients. Compared to ipilimumab, nivolumab, dacarbazine, and ipilimumab+gp100 had a reduced risk of grade 3/4 adverse reactions. The nivolumab+ipilimumab combination had the highest risk of adverse events, followed by ipilimumab+dacarbazine and trametinib. Combination therapy was more beneficial to improve overall survival and progression-free survival than monotherapy in advanced melanoma treatment, albeit at the cost of increased toxicity. Regarding the overall survival/progression-free survival, ipilimumab+gp100 ranked below ipilimumab+dacarbazine and nivolumab+ipilimumab, although it had a smaller rate of grade 3 or 4 AEs than other treatments (except nivolumab). Nivolumab is the optimum adjuvant treatment for unresectable advanced or metastatic melanoma with a good risk-benefit profile. In order to choose the best therapy, clinicians must consider the efficacy, adverse events, and physical status.
PubMed: 35785213
DOI: 10.3389/fonc.2022.926242 -
BMJ (Clinical Research Ed.) Oct 2012To synthesise the literature on indoor tanning and non-melanoma skin cancer. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To synthesise the literature on indoor tanning and non-melanoma skin cancer.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed (1966 to present), Embase (1974 to present), and Web of Science (1898 to present).
STUDY SELECTION
All articles that reported an original effect statistic for indoor tanning and non-melanoma skin cancer were included. Articles that presented no data, such as review articles and editorials, were excluded, as were articles in languages other than English.
DATA EXTRACTION
Two investigators independently extracted data. Random effects meta-analysis was used to summarise the relative risk of ever use versus never use of indoor tanning. Dose-response effects and exposure to indoor tanning during early life were also examined. The population attributable risk fraction for the United States population was calculated.
RESULTS
12 studies with 9328 cases of non-melanoma skin cancer were included. Among people who reported ever using indoor tanning compared with those who never used indoor tanning, the summary relative risk for squamous cell carcinoma was 1.67 (95% confidence interval 1.29 to 2.17) and that for basal cell carcinoma was 1.29 (1.08 to 1.53). No significant heterogeneity existed between studies. The population attributable risk fraction for the United States was estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma. This corresponds to more than 170 000 cases of non-melanoma skin cancer each year attributable to indoor tanning. On the basis of data from three studies, use of indoor tanning before age 25 was more strongly associated with both squamous cell carcinoma (relative risk 2.02, 0.70 to 5.86) and basal cell carcinoma (1.40, 1.29 to 1.52).
CONCLUSIONS
Indoor tanning is associated with a significantly increased risk of both basal and squamous cell skin cancer. The risk is higher with use in early life (<25 years). This modifiable risk factor may account for hundreds of thousands of cases of non-melanoma skin cancer each year in the United States alone and many more worldwide. These findings contribute to the growing body of evidence on the harms of indoor tanning and support public health campaigns and regulation to reduce exposure to this carcinogen.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cross-Sectional Studies; Humans; Neoplasms, Radiation-Induced; Odds Ratio; Proportional Hazards Models; Skin Neoplasms; Sunbathing; Ultraviolet Rays
PubMed: 23033409
DOI: 10.1136/bmj.e5909 -
Journal For Immunotherapy of Cancer Mar 2023Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects... (Review)
Review
Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.Here, we report a rare case of early-onset, mild cytokine release syndrome (CRS) in a patient who received ICIs for a metastasized renal cell carcinoma, which led to treatment discontinuation.We further provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase and the Web of Science Core Collection from inception to October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n=1866 articles, which were assessed for eligibility independently by two examiners. Of those, n=49 articles reporting on n=189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment were reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial under-reporting.The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and might be associated with fatal outcome in approximately 10% of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.
Topics: Humans; Immune Checkpoint Inhibitors; Interleukin-6; Drug-Related Side Effects and Adverse Reactions; Cytokine Release Syndrome; Lymphohistiocytosis, Hemophagocytic; Kidney Neoplasms
PubMed: 36878533
DOI: 10.1136/jitc-2022-005841