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ESMO Open Oct 2021Immune checkpoint inhibitors (i.e. anti-PD1, anti-PDL1, and anti-CTLA4) have revolutionized the therapeutic approach of several cancer types. In a subset of metastatic... (Review)
Review
Immune checkpoint inhibitors (i.e. anti-PD1, anti-PDL1, and anti-CTLA4) have revolutionized the therapeutic approach of several cancer types. In a subset of metastatic patients, the duration of the response is so long that a cure might be hypothesized, and a treatment discontinuation strategy could be proposed. Considering that long-term efficacy, some patients could also plan to have a child. Moreover, immunotherapy is moving to the early setting in several diseases including melanoma and breast cancer that are common cancers in young patients. However, there is a paucity of data about their potential detrimental effect on fertility, pregnancy, or sexuality. Herein, we conducted a systematic review with the aim to comprehensively collect the available evidence about fertility, pregnancy, and sexual adverse effects of checkpoint inhibitors in order to help clinicians in daily practice and trialists to develop future studies.
Topics: Child; Drug-Related Side Effects and Adverse Reactions; Female; Fertility; Humans; Immunologic Factors; Immunotherapy; Melanoma; Pregnancy
PubMed: 34597942
DOI: 10.1016/j.esmoop.2021.100276 -
Biomedicines Feb 2023MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and... (Review)
Review
MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and tumor suppressor genes of metabolic-related signaling pathways involved in the hallmarks of cancer. This systematic review focuses on articles describing the role, association, and/or involvement of miRNAs in regulating the mitochondrial function and metabolic reprogramming of cancer cells. Following the PRISMA guidelines, the articles reviewed were published from January 2010 to September 2022, with the search terms "mitochondrial microRNA" and its synonyms (mitochondrial microRNA, mitochondrial miRNA, mito microRNA, or mitomiR), "reprogramming metabolism," and "cancer" in the title or abstract). Thirty-six original research articles were selected, revealing 51 miRNAs with altered expression in 12 cancers: bladder, breast, cervical, colon, colorectal, liver, lung, melanoma, osteosarcoma, pancreatic, prostate, and tongue. The actions of miRNAs and their corresponding target genes have been reported mainly in cell metabolic processes, mitochondrial dynamics, mitophagy, apoptosis, redox signaling, and resistance to chemotherapeutic agents. Altogether, these studies support the role of miRNAs in the metabolic reprogramming hallmark of cancer cells and highlight their potential as predictive molecular markers of treatment response and/or targets that can be used for therapeutic intervention.
PubMed: 36979672
DOI: 10.3390/biomedicines11030693 -
Journal of Cachexia, Sarcopenia and... Oct 2021Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Progression-Free Survival; Sarcopenia
PubMed: 34337889
DOI: 10.1002/jcsm.12755 -
Oncotarget Jul 2017Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant... (Meta-Analysis)
Meta-Analysis Review
Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up to February 2017, and a random effects model was used to calculate the summary risk estimates. Five observational studies were included. Five studies reports encompassed a total of 15,979 melanoma cases occurring among 1, 188,414 participants. The pooled multivariable-adjusted RR of melanoma in patients with using PDE5 inhibitors was 1.12 (95% CI: 1.03-1.21, I2 = 0.48). Findings from this systematic review support that PDE5 inhibitor use is associated with increased risk of melanoma in ED patients, the result remains inclusive and warrants further study in the future.
Topics: Case-Control Studies; Humans; Melanoma; Phosphodiesterase 5 Inhibitors; Risk
PubMed: 28515348
DOI: 10.18632/oncotarget.17518 -
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 -
PloS One 2016Antibodies targeting programmed death 1 (PD-1) help prevent tumor cells from escaping immune-mediated destruction. We conducted this systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Antibodies targeting programmed death 1 (PD-1) help prevent tumor cells from escaping immune-mediated destruction. We conducted this systematic review and meta-analysis to gain insight into the efficacy of PD-1 antibodies for the treatment of melanoma. Five trials involving 2,828 adult patients were included in this meta-analysis. In patients with previously untreated or refractory melanoma, treatment with PD-1 antibodies significantly improved the six-month progression-free survival (PFS) (HR 0.55, 95% CI 0.50-0.60, P<0.00001) and the overall response rate (OR 3.89, 95% CI 3.12-4.83, P<0.00001). This meta-analysis indicated that anti-PD-1 treatment might provide a significant survival benefit in patients with melanoma. In addition, we found that patients treated with nivolumab reported significantly fewer treatment-related adverse events (OR 0.74, 95% CI 0.57-0.97, P = 0.03) than those treated with other agents, but there was a dose-dependent increase in the frequency of adverse events in patients treated with pembrolizumab.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Clinical Trials as Topic; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Exanthema; Fatigue; Gene Expression; Humans; Melanoma; Nausea; Nivolumab; Programmed Cell Death 1 Receptor; Pruritus; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 27483468
DOI: 10.1371/journal.pone.0160485 -
Journal of Cancer Education : the... Aug 2023Incorporation of melanoma prevention behaviors into daily lifestyles is difficult. Data suggest that high school educational programs on skin cancer prevention can be... (Review)
Review
Incorporation of melanoma prevention behaviors into daily lifestyles is difficult. Data suggest that high school educational programs on skin cancer prevention can be successful and should incorporate evidence-based teaching and learning strategies to achieve greatest impact. The goal of this systematic review is to describe evidence-based educational practices for a high-school melanoma curriculum through a comprehensive review of the literature. Ovid MEDLINE, Embase, CINAHL, and PyscINFO were searched in June 2020 for all original articles published between June 18, 1946 and June 17, 2020. All studies that used an educational curriculum to promote sun safety, skin exams, and early detection to high school students were included. A total of 25 studies with 22,683 adolescent participants were analyzed. Sixteen studies showed a significant increase in knowledge, twenty-one studies showed changes in behavior, and fifteen studies showed significant changes in attitudes. Limitations of this review include the heterogeneity of implementation and outcome reporting of educational curricula. These findings support incorporating active learning strategies as key aspects of creating an effective curriculum aimed at the prevention and early detection of melanoma.
Topics: Adolescent; Humans; Curriculum; Melanoma; Schools; Students; School Health Services
PubMed: 37043169
DOI: 10.1007/s13187-023-02294-9 -
Vascular Pharmacology Jun 2023The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and individual blood pressure lowering drugs.
METHODS
We searched Medline, Embase, Cochrane and the Web of Science and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted odds ratios (OR) using a random effects model.
RESULTS
We included 42 studies with a total of 16,670,045 subjects. Diuretics, in particular hydrochlorothiazide, were examined most frequently. Only 2 studies provided information about antihypertensive co-medication. Exposure to diuretics (OR 1.27 [1.09-1.47]) and calcium channel blockers (OR 1.06 [1.04-1.09]) was associated with an increased risk for NMSC. The increased risk for NMSC was only observed in case control studies and studies that did not correct for sun exposure, skin phototype or smoking. Studies that did correct for covariates as well as cohort studies did not show a significantly increased risk for NMSC. Egger's test revealed a significant publication bias for the subgroup of diuretics, hydrochlorothiazide and case-control studies concerning NMSC (p < 0.001).
CONCLUSION
The available studies investigating the potential skin cancer risk that is associated with antihypertensive medication have significant shortcomings. Also, a significant publication bias is present. We found no increased skin cancer risk when analyzing cohort studies or studies that corrected for important covariates. (PROSPERO (CRD42020138908)).
Topics: Humans; Antihypertensive Agents; Skin Neoplasms; Hydrochlorothiazide; Melanoma; Diuretics; Hypertension
PubMed: 37084802
DOI: 10.1016/j.vph.2023.107173 -
JAMA Oncology Aug 2015The treatment of multiple brain metastases (MBM) from melanoma is controversial and includes surgical resection, stereotactic radiosurgery (SRS), and whole-brain... (Review)
Review
IMPORTANCE
The treatment of multiple brain metastases (MBM) from melanoma is controversial and includes surgical resection, stereotactic radiosurgery (SRS), and whole-brain radiation therapy (WBRT). Several new classes of agents have revolutionized the treatment of metastatic melanoma, allowing some subsets of patients to have long-term survival. Given this, management of MBM from melanoma is continually evolving.
OBJECTIVE
To review the current evidence regarding the treatment of MBM from melanoma.
EVIDENCE REVIEW
The PubMed database was searched using combinations of search terms and synonyms for melanoma, brain metastases, radiation, chemotherapy, immunotherapy, and targeted therapy published between January 1, 1995, and January 1, 2015. Articles were selected for inclusion on the basis of targeted keyword searches, manual review of bibliographies, and whether the article was a clinical trial, large observational study, or retrospective study focusing on melanoma brain metastases. Of 2243 articles initially identified, 110 were selected for full review. Of these, the most pertinent 73 articles were included.
FINDINGS
Patients with newly diagnosed MBM can be treated with various modalities, either alone or in combination. Level 1 evidence supports the use of SRS alone, WBRT, and SRS with WBRT. Although the addition of WBRT to SRS improves the overall brain relapse rate, WBRT has no significant impact on overall survival and has detrimental neurocognitive outcomes. Cytotoxic chemotherapy has largely been ineffective; targeted therapies and immunotherapies have been reported to have high response rates and deserve further attention in larger clinical trials. Further studies are needed to fully evaluate the efficacy of these novel regimens in combination with radiation therapy.
CONCLUSIONS AND RELEVANCE
At this time, the standard management for patients with MBM from melanoma includes SRS, WBRT, or a combination of both. Emerging data exist to support the notion that SRS in combination with targeted therapies or immune therapy may obviate the need for WBRT; prospective studies are required to fully evaluate the efficacy of these novel regimens in combination with radiation therapy.
Topics: Antineoplastic Agents; Brain Neoplasms; Cranial Irradiation; Craniotomy; Disease Progression; Disease-Free Survival; Humans; Immunotherapy; Melanoma; Molecular Targeted Therapy; Radiosurgery; Radiotherapy, Adjuvant; Risk Factors; Skin Neoplasms; Time Factors; Treatment Outcome
PubMed: 26181286
DOI: 10.1001/jamaoncol.2015.1206 -
Dermatology Practical & Conceptual Nov 2022Differentiating early melanoma from other flat pigmented lesions on the head and neck is challenging both clinically and dermoscopically, partly due to the wide... (Review)
Review
INTRODUCTION
Differentiating early melanoma from other flat pigmented lesions on the head and neck is challenging both clinically and dermoscopically, partly due to the wide differential diagnosis and the lack of specific diagnostic algorithms.
OBJECTIVES
To review publications covering the dermoscopic features of pigmented macules on the head and neck.
METHODS
Embase and PubMed (Medline) database from January 2015 to January 2021 were searched using a four-step search. Keywords used were dermoscopy/dermatoscopy or epiluminescence microscopy, lentigo maligna, lentigo maligna melanoma, lichen-planus-like-keratosis, solar lentigo, seborrheic keratosis, pigmented actinic keratosis (PAK), pigmented Bowen disease (pBD), pigmented intraepidermal carcinoma (pIEC) and head and neck.
RESULTS
The commonest reported dermoscopic features of facial melanoma were irregular dots, atypical dots/globules, asymmetric pigmented follicular openings, rhomboid gray/black structures, increased vascular network, brown globules/dots and a pattern of circles. Pseudopods, radial streaming, blue white veil, irregular blotches, scar-like depigmentation and atypical pigment network were recorded in low frequencies. For PAK, pBD and pIEC perifollicular erythema, white/yellow surface scale, linear wavy vessels around hair follicles, hair follicular openings surrounded by a white halo, evident follicles or follicular or keratotic plugs, rosette sign and sharply demarcated borders were the salient features.
CONCLUSIONS
Further studies are needed to determine the dermoscopic criteria for pigmented melanocytic and non-melanocytic lesions on the head and neck. Furthermore, there is a gap in the knowledge of site-specific dermoscopic features on specific sites, namely ears, nose, cheeks, scalp and neck which will also benefit from further studies.
PubMed: 36534577
DOI: 10.5826/dpc.1204a194