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Molecular Genetics & Genomic Medicine Oct 2023The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This... (Review)
Review
BACKGROUND
The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This review aimed to survey existing studies in gene-environment (GxE) interaction on skin cancer risk, and report on GxE effect estimates.
METHODS
We searched Embase, Medline (Ovid) and Web of Science (Core Collection) and included only primary research that reported on GxE on the risk of the three most common types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. Quality assessment followed the Newcastle-Ottawa Scale. Meta-analysis was not possible because no two studies examined the same interaction. This review was registered on PROSPERO (CRD42021238064).
RESULTS
In total 260 records were identified after exclusion of duplicates. Fifteen studies were included in the final synthesis-12 used candidate gene approach. We found some evidence of GxE interactions with sun exposure, notably, with MC1R, CAT and NOS1 genes in melanoma, HAL and IL23A in BCC and HAL and XRCC1 in SCC.
CONCLUSION
Sun exposure seems to interact with genes involved in pigmentation, oxidative stress and immunosuppression, indicating that excessive UV exposure might exhaust oxidative defence and repair systems differentially, dependent on genetic make-up. Further research is warranted to better understand skin cancer epidemiology and develop sun exposure recommendations. A genome-wide approach is recommended as it might uncover unknown disease pathways dependent on UV radiation.
PubMed: 37537768
DOI: 10.1002/mgg3.2259 -
PloS One 2023Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not... (Review)
Review
Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis.
BACKGROUND
Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not amenable to surgical resection. Despite this, no level 5 evidence exists comparing it to radiotherapy in the treatment of cutaneous malignancies. This systematic review aimed to examine the literature directly and indirectly comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies.
MATERIALS & METHODS
The protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews with the protocol ID CRD42021285415. Searches of MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov databases were undertaken from database inception to 28 December 2021. Studies in humans comparing treatment with electrochemotherapy to radiotherapy and reporting tumour response with a minimum four week follow-up were eligible. Risk of bias was assessed using the ROBINS-I tool. Results are provided as a narrative synthesis.
RESULTS
Two case series with a total of 92 patients were identified as relevant to this study. Both case series examined patients with cutaneous squamous cell carcinoma. One case series examined elderly patients with predominantly head/neck lesions. The other examined younger patients with predominantly limb lesions who had cutaneous squamous cell carcinoma directly attributable to a rare skin condition.
CONCLUSION
There is little literature presenting comparative data for electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases. Included studies were marred by serious risk of bias particularly due to confounding. The inherent bias and heterogeneity of the included studies precluded synthesis of a consolidated comparison of clinical outcomes between the two therapies. Further research is required in this domain in the form of clinical trials and observational studies to inform guidelines for electrochemotherapy treatment.
Topics: Humans; Aged; Skin Neoplasms; Carcinoma, Squamous Cell; Electrochemotherapy
PubMed: 37440502
DOI: 10.1371/journal.pone.0288251 -
Postepy Dermatologii I Alergologii Apr 2023Basal cell carcinoma (BCC) is the most common skin cancer, especially in fair-skinned adults, and the lifetime risk of its incidence in this population is estimated to... (Review)
Review
INTRODUCTION
Basal cell carcinoma (BCC) is the most common skin cancer, especially in fair-skinned adults, and the lifetime risk of its incidence in this population is estimated to be approximately 30%. We present a meta-analysis and systematic review summarizing the size of the growth rate in BCC, depending also on its subtypes.
MATERIAL AND METHODS
To find all relevant studies, online medical databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched regarding the growth rate of BCC.
RESULTS
A total of 7 studies were included in this review. Five studies contained data on the growth rate of basal cell carcinomas. The mean growth rate for the longer axis of the BCC was established to be 0.71 mm/month (standard error: 0.22).
CONCLUSIONS
The presented analysis shows that BCC is generally a slow-growing tumour, with a mean growth rate of about 0.7 mm/month. However, it was proven that this growth rate differs depending on the BCC subtype.
PubMed: 37312922
DOI: 10.5114/ada.2023.124795 -
Frontiers in Pharmacology 2023Our study aimed to identify potential correlations between anti-tumor efficacy and immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC). We...
Our study aimed to identify potential correlations between anti-tumor efficacy and immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC). We conducted a comprehensive search of online electronic databases up to March 2023 to identify any correlations between irAEs and immune checkpoint inhibitor (ICI) efficacy in NSCLC. We used meta-analysis RevMan 5.3 software to calculate pooled results. Our meta-analysis of 54 studies revealed that patients who experienced irAEs achieved a significantly higher objective response rate ( < 0.00001) and longer progression-free survival (PFS) ( < 0.00001) and overall survival (OS) ( < 0.00001) than those who did not experience irAEs. Additionally, patients with ≥2 irAEs had better PFS, whereas no significant difference was observed between patients with or without squamous cell carcinoma. Subgroup analysis of irAE types indicated that irAEs (thyroid dysfunction and gastrointestinal, skin, or endocrine irAEs) were associated with better PFS and OS. However, no significant differences were observed between patients with pneumonitis or hepatobiliary irAEs. Our study showed that the occurrence of irAEs was a strong predictor of survival efficacy in patients with NSCLC treated with ICIs. Specifically, patients with ≥2 irAEs and those with thyroid dysfunction and gastrointestinal, skin, or endocrine irAEs achieved a better survival benefit. Website: https://www.crd.york.ac.uk/prospero/, Identifier: CRD42023421690.
PubMed: 37284302
DOI: 10.3389/fphar.2023.1190001 -
International Journal of Molecular... May 2023Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their... (Review)
Review
Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.
Topics: Humans; MicroRNAs; Mesenchymal Stem Cells; Cell Differentiation; Skin Diseases; Neoplasms; Psoriasis
PubMed: 37239847
DOI: 10.3390/ijms24108502 -
Diagnostics (Basel, Switzerland) May 2023(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for... (Review)
Review
(1) Background: BCC is a sporadic disease that develops in areas of the skin not exposed to the sun. Perianal BCC, which occurs in the anorectal region, accounts for less than 0.2% of all BCC cases. There have been only a few reported cases of the disease, with fewer than 200 cases reported in total. Given the diagnostic challenges and potential for misdiagnosis, we conducted a systematic review of perianal basal cell carcinoma using real-world data to provide comprehensive and detailed information on the disease. (2) Methods: The study was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2020. Patients' clinical pathologic features, tumor characteristics, treatment modalities, and outcomes were presented. (3) Results: The results of 41 studies involving 140 patients were analyzed. The most common symptoms reported by patients at presentation were anorectal bleeding, pain, and pruritus. Ulceration was the most frequently observed tumor characteristic. The majority of patients underwent local excision as their primary treatment, with only eight patients experiencing a recurrence. Our analysis did not reveal any statistically significant differences in the outcomes of different treatment modalities. (4) Conclusions: Identifying perianal BCC poses a significant challenge as it closely resembles other anal diseases, thereby making it difficult to differentiate between the different conditions. However, a wide local excision with clear margins is considered an effective treatment option for most patients. Alternative treatments, such as radiotherapy, may be recommended for patients who are unable to undergo surgery.
PubMed: 37175041
DOI: 10.3390/diagnostics13091650 -
Cancers Apr 2023The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for... (Review)
Review
BACKGROUND
The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene expression profile (40-GEP) both independently and integrated with clinicopathologic risk factors and established staging systems (American Joint Committee on Cancer, eighth edition (AJCC8) and Brigham and Women's Hospital (BWH)).
METHODS
Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar, were systematically searched to identify cohort studies and randomized controlled trials on evaluations of the prediction value of 40-GEP in cSCC patients up to January 2023. The metastatic risk analysis of a given 40-GEP class combined with tumor stage and/or other clinicopathologic risk factors was based upon log hazard ratios (HRs) and their standard error (SE). Heterogeneity and subgroup analyses were performed, and data quality was assessed.
RESULTS
A total of 1019 patients from three cohort studies were included in this meta-analysis. The overall three-year metastatic-free survival rates were 92.4%, 78.9%, and 45.4% for class 1 (low risk), class 2A (Intermediate risk), and class 2B (high risk) 40-GEP, respectively, indicating a significant variation in survival rates between the risk classification groups. The pooled positive predictive value was significantly higher in class 2B when compared to AJCC8 or BWH. The subgroup analyses demonstrated significant superiority of integrating 40-GEP with clinicopathologic risk factors or AJCC8/BWH, especially for class 2B patients.
CONCLUSIONS
The integration of 40-GEP with staging systems can improve the identification of cSCC patients at high risk of metastasis, potentially leading to improved care and outcomes, especially in the high-risk class 2B group.
PubMed: 37173922
DOI: 10.3390/cancers15092456 -
Cureus Apr 2023Both psoriasis and methotrexate are associated with an increased risk of nonmelanoma skin cancer. The effect of methotrexate on the development of nonmelanoma skin... (Review)
Review
Both psoriasis and methotrexate are associated with an increased risk of nonmelanoma skin cancer. The effect of methotrexate on the development of nonmelanoma skin cancer in patients with psoriasis is currently unknown. To evaluate this relationship, a systematic review of the literature was conducted using databases including Ovid Medline (from 1946), Scopus (from 1970), and Embase (from 1974) through June 2019. Observational comparative and case-control studies comparing psoriasis patients treated with methotrexate to those not treated with methotrexate with data on the subsequent development of nonmelanoma skin cancer in both cohorts were included based on prespecified criteria. Two reviewers analyzed all studies for relevant data, which were analyzed using OpenMeta-Analyst statistical software. Quality was assessed with the Newcastle-Ottawa method. Nine cohort and case-control comparative studies of 1,486 screened abstracts met the inclusion criteria. Of 11,875 reported patients with psoriasis, 2,192 were taking methotrexate. A meta-analysis demonstrated an odds ratio of 2.8 (95% confidence interval = 1.47-5.39; p = 0.002) for nonmelanoma skin cancer development in patients with psoriasis taking methotrexate compared with those not taking methotrexate. Based on these findings, psoriasis patients treated with methotrexate are at a significantly increased (2.8 times higher) risk of developing nonmelanoma skin cancer. Risk counseling can improve healthcare outcomes in patients with psoriasis.
PubMed: 37153318
DOI: 10.7759/cureus.37174 -
Skin Health and Disease Apr 2023Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe)... (Review)
Review
BACKGROUND
Lichen sclerosus (LSc) is a chronic, inflammatory, destructive skin disease with a predilection for the genitalia (GLSc). An association with vulval (Vu) and penile (Pe) squamous carcinoma (SCC) is now well established but melanoma (MM) has only rarely been reported complicating GLSc.
METHODS
We have performed a systematic literature review of GLSc in patients with genital melanoma (GMM). Only articles that mentioned both GMM and LSc affecting either the penis or vulva were included.
RESULTS
Twelve studies with a total of 20 patients were included. Our review shows that an association of GLSc with GMM has been more frequently reported in women and female children than men viz, 17 cases compared with three. It is notable that five of the cases (27.8%) concerned female children aged under twelve.
DISCUSSION
These data suggest a rare association between GLSc and GMM. If proven, there arise intriguing questions about pathogenesis and consequences for counselling of patients and follow-up.
PubMed: 37013116
DOI: 10.1002/ski2.198 -
World Journal of Surgical Oncology Mar 2023Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However,... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC.
METHODS
We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio's random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs).
RESULTS
The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42).
CONCLUSIONS
Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings.
TRIAL REGISTRATION
PROSPERO registration number: CRD42022298003.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Tyrosine Kinase Inhibitors; Chemoembolization, Therapeutic; Combined Modality Therapy; Treatment Outcome
PubMed: 37004052
DOI: 10.1186/s12957-023-02961-7