2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T416,Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide-sphingosine-1-phosphate-STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion.31:T45f,Abstract Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion.32:T51b,Teledermatology has become increasingly relevant for skin cancer diagnosis, particularly following the COVID-19 pandemic. This retrospective study assessed whether teledermatology enables earlier diagnosis of cutaneous squamous cell carcinoma (cSCC) compared with conventional face-to-face consultation. Clinical and histopathological data from 224 patients (101 in 2019; 123 in 2022) were analysed. Referral delays decreased from 55 to 3 days and surgical wait times from 28.7 to 12.3 days. Tumours diagnosed via teledermatology had significantly smaller minor diameters (0.56 ± 0.3 cm vs 1.09 ± 0.5 cm; p < 0.001). Al-though maximum diameter and tumour depth did not differ significantly, the smaller tumour surface area in the teledermatology group suggests diagnosis at an earlier clinical stage. In multivariate analysis, minor diameter was the strongest independent predictor of teledermatology-based diagnosis (OR = 0.01, 95% CI: 0.001-0.02). These findings suggest that teledermatology facilitates earlier diagnosis of cSCC, allowing timely treatment and potentially reducing the need for extensive surgical procedures. Teledermatology should be considered a valuable triage tool for skin cancer detection, particularly in health systems with limited access to dermatological care.33:T531,Teledermatology has become increasingly relevant for skin cancer diagnosis, particularly following the COVID-19 pandemic. This retrospective study assessed whether teledermatology enables earlier diagnosis of cutaneous squamous cell carcinoma (cSCC) compared with conventional face-to-face consultation. Clinical and histopathological data from 224 patients (101 in 2019; 123 in 2022) were analysed. Referral delays decreased from 55 to 3 days and surgical wait times from 28.7 to 12.3 days. Tumours diagnosed via teledermatology had significantly smaller minor diameters (0.56 ± 0.3 cm vs 1.09 ± 0.5 cm; p < 0.001). Al-though maximum diameter and tumour depth did not differ significantly, the smaller tumour surface area in the teledermatology group suggests diagnosis at an earlier clinical stage. In multivariate analysis, minor diameter was the strongest independent predictor of teledermatology-based diagnosis (OR = 0.01, 95% CI: 0.001–0.02). These findings suggest that teledermatology facilitates earlier diagnosis of cSCC, allowing timely treatment and potentially reducing the need for extensive surgical procedures. Teledermatology should be considered a valuable triage tool for skin cancer detection, particularly in health systems with limited access to dermatological care.34:T517,Cosibelimab-ipdl, a high-affinity, programmed death-ligand 1-blocking antibody, is approved by the US Food and Drug Administration for treatment of adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or radiation. To report long-term efficacy and safety outcomes from a pivotal study of cosibelimab in mCSCC or laCSCC. Patients received intravenous cosibelimab 800 mg every 2 weeks (mCSCC and laCSCC cohorts) or 1200 mg every 3 weeks (mCSCC cohort). The primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DOR) and safety. With a median follow-up duration of 29.3 months for the mCSCC cohort (n = 78), ORR was 50.0% (complete response [CR], 12.8%), median DOR was not reached, and estimated 24-month DOR was 72.1%. With a median follow-up duration of 24.1 months for the laCSCC cohort (n = 31), ORR was 54.8% (CR, 25.8%), median DOR was not reached, and the estimated 24-month DOR was 80.2%. Immune-related adverse event rate was 27.6%; 3.6% grade 3, no grade ≥4 events. Nonrandomized; limited biomarker analysis. Cosibelimab demonstrated robust and durable ORRs with increasing CR rates in advanced CSCC and low rates of severe immune-related adverse events.35:T9a3,While UV radiation is a known carcinogen associated with cutaneous squamous cell carcinoma (cSCC), sunburn's specific role remains less clear. To quantitatively assess the association between sunburn history and the risk of developing cSCC. A comprehensive search of Embase, PubMed, and Cochrane Library (CENTRAL) was conducted from inception up to May 6, 2025, with no language or date restrictions. Search terms included Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease and Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays. The study included analytical investigations of the general population that assessed the association between cSCC and any type of sunburn history at any age. The initial screening of 9310 titles and abstracts by 3 masked independent reviewers resulted in 279 articles for full-text review, with 43 ultimately meeting eligibility criteria. This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Two reviewers worked independently to extract relevant data. The random effects DerSimonian-Laird method was used to pool data. The main outcome was the risk of developing cSCC. Main measures included sunburn frequency (both undefined and painful, blistering, and/or severe) in any life period, categorized into ordinal variables: none, low, medium, and high. The primary analysis was the most adjusted measure of association, standardized to odds ratio (OR). This incorporated adjusted measures of association when available and unadjusted measures when adjusted measures were absent. Seventeen studies with a combined 321 473 participants were included in the meta-analysis. Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79). This meta-analysis supports an association between painful, blistering, and/or severe sunburns and cSCC.36:T10d0, Importance While UV radiation is a known carcinogen associated with cutaneous squamous cell carcinoma (cSCC), sunburn’s specific role remains less clear. Objective To quantitatively assess the association between sunburn history and the risk of developing cSCC. Data Sources A comprehensive search of Embase, PubMed, and Cochrane Library (CENTRAL) was conducted from inception up to May 6, 2025, with no language or date restrictions. Search terms included Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease and Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays . Study Selection The study included analytical investigations of the general population that assessed the association between cSCC and any type of sunburn history at any age. The initial screening of 9310 titles and abstracts by 3 masked independent reviewers resulted in 279 articles for full-text review, with 43 ultimately meeting eligibility criteria. Data Extraction and Synthesis This study follows the Meta-analysis of Observational Studies in Epidemiology ( MOOSE ) reporting guideline. Two reviewers worked independently to extract relevant data. The random effects DerSimonian-Laird method was used to pool data. Main Outcome and Measures The main outcome was the risk of developing cSCC. Main measures included sunburn frequency (both undefined and painful, blistering, and/or severe) in any life period, categorized into ordinal variables: none, low, medium, and high. The primary analysis was the most adjusted measure of association, standardized to odds ratio (OR). This incorporated adjusted measures of association when available and unadjusted measures when adjusted measures were absent. Results Seventeen studies with a combined 321 473 participants were included in the meta-analysis. Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79). Conclusions and Relevance This meta-analysis supports an association between painful, blistering, and/or severe sunburns and cSCC. 37:T598,There were 12 287 patients (mean [SD] age, 77.2 [8.9] years; 241 women [2.0%]; 31 [0.3%] American Indian or Alaska Native, 3 [<0.1%] Asian, 13 [0.1%] Black or African American, 59 [0.5%] Native Hawaiian or other Pacific Islander, and 11 662 [94.9%] White individuals) exposed to oral nicotinamide, 500 mg, twice daily for longer than 30 days who were matched to 21 479 unexposed patients (mean [SD] age, 76.9 [8.7] years; 374 women [2.0%]; 49 [0.2%] American Indian or Alaska Native, 3 [<0.1%] Asian, 16 [0.1%] Black or African American, 88 [0.4%] Native Hawaiian or other Pacific Islander, and 20 517 [95.3%] White individuals). Within the matched dataset, there were 10 994 instances of basal cell carcinoma after nicotinamide exposure and 12 551 cutaneous squamous cell carcinoma (cSCC). A total of 1334 (3.9%) in the matched cohort were solid organ transplant recipients. Overall, there was a significant 14% reduction in skin cancer risk. When nicotinamide was initiated after a first skin cancer, the risk reduction rose to 54%, although this benefit declined with initiation following subsequent skin cancers. This risk reduction was seen for skin cancers overall, basal cell carcinoma, and cSCC, with the greatest risk reduction seen for cSCC. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced cSCC incidence.38:Tb42,Nicotinamide supplementation has been studied as a chemopreventive medication for reducing skin cancer risk, but large-scale data are limited. To determine the clinical efficacy of nicotinamide supplementation for skin cancer prevention in the general population and among solid organ transplant recipients. A retrospective cohort study was conducted using electronic health record data (October 1, 1999, to December 31, 2024) from the Veterans Affairs Corporate Data Warehouse (CDW) of 33 822 patients. Analyses were conducted from January 17, 2025, to May 9, 2025. Patients who were exposed to nicotinamide were propensity score matched based on the number and year of skin cancers after which treatment with nicotinamide was initiated, age, sex, self-reported race, exposure to acitretin, exposure to field therapy, history of chronic lymphocytic leukemia, and history of solid organ transplant. The index date was the first prescription of nicotinamide filled within the VA system. Stratified Cox models were used to investigate the association of nicotinamide with skin cancer development. Nicotinamide, 500 mg, twice daily for longer than 30 days as documented in the electronic health record. Time to the next skin cancer after baseline. There were 12 287 patients (mean [SD] age, 77.2 [8.9] years; 241 women [2.0%]; 31 [0.3%] American Indian or Alaska Native, 3 [<0.1%] Asian, 13 [0.1%] Black or African American, 59 [0.5%] Native Hawaiian or other Pacific Islander, and 11 662 [94.9%] White individuals) exposed to oral nicotinamide, 500 mg, twice daily for longer than 30 days who were matched to 21 479 unexposed patients (mean [SD] age, 76.9 [8.7] years; 374 women [2.0%]; 49 [0.2%] American Indian or Alaska Native, 3 [<0.1%] Asian, 16 [0.1%] Black or African American, 88 [0.4%] Native Hawaiian or other Pacific Islander, and 20 517 [95.3%] White individuals). Within the matched dataset, there were 10 994 instances of basal cell carcinoma after nicotinamide exposure and 12 551 cutaneous squamous cell carcinoma (cSCC). A total of 1334 (3.9%) in the matched cohort were solid organ transplant recipients. Overall, there was a significant 14% reduction in skin cancer risk. When nicotinamide was initiated after a first skin cancer, the risk reduction rose to 54%, although this benefit declined with initiation following subsequent skin cancers. This risk reduction was seen for skin cancers overall, basal cell carcinoma, and cSCC, with the greatest risk reduction seen for cSCC. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced cSCC incidence. The results of this cohort study suggest that there is a decreased risk of skin cancer among patients treated with nicotinamide, with the greatest effect seen when initiated after the first skin cancer.39:T102c, Importance Nicotinamide supplementation has been studied as a chemopreventive medication for reducing skin cancer risk, but large-scale data are limited. Objective To determine the clinical efficacy of nicotinamide supplementation for skin cancer prevention in the general population and among solid organ transplant recipients. Design, Setting, and Participants A retrospective cohort study was conducted using electronic health record data (October 1, 1999, to December 31, 2024) from the Veterans Affairs Corporate Data Warehouse (CDW) of 33 822 patients. Analyses were conducted from January 17, 2025, to May 9, 2025. Patients who were exposed to nicotinamide were propensity score matched based on the number and year of skin cancers after which treatment with nicotinamide was initiated, age, sex, self-reported race, exposure to acitretin, exposure to field therapy, history of chronic lymphocytic leukemia, and history of solid organ transplant. The index date was the first prescription of nicotinamide filled within the VA system. Stratified Cox models were used to investigate the association of nicotinamide with skin cancer development. Exposures Nicotinamide, 500 mg, twice daily for longer than 30 days as documented in the electronic health record. Main Outcomes and Measures Time to the next skin cancer after baseline. Results There were 12 287 patients (mean [SD] age, 77.2 [8.9] years; 241 women [2.0%]; 31 [0.3%] American Indian or Alaska Native, 3 [&lt;0.1%] Asian, 13 [0.1%] Black or African American, 59 [0.5%] Native Hawaiian or other Pacific Islander, and 11 662 [94.9%] White individuals) exposed to oral nicotinamide, 500 mg, twice daily for longer than 30 days who were matched to 21 479 unexposed patients (mean [SD] age, 76.9 [8.7] years; 374 women [2.0%]; 49 [0.2%] American Indian or Alaska Native, 3 [&lt;0.1%] Asian, 16 [0.1%] Black or African American, 88 [0.4%] Native Hawaiian or other Pacific Islander, and 20 517 [95.3%] White individuals). Within the matched dataset, there were 10 994 instances of basal cell carcinoma after nicotinamide exposure and 12 551 cutaneous squamous cell carcinoma (cSCC). A total of 1334 (3.9%) in the matched cohort were solid organ transplant recipients. Overall, there was a significant 14% reduction in skin cancer risk. When nicotinamide was initiated after a first skin cancer, the risk reduction rose to 54%, although this benefit declined with initiation following subsequent skin cancers. This risk reduction was seen for skin cancers overall, basal cell carcinoma, and cSCC, with the greatest risk reduction seen for cSCC. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced cSCC incidence. Conclusions and Relevance The results of this cohort study suggest that there is a decreased risk of skin cancer among patients treated with nicotinamide, with the greatest effect seen when initiated after the first skin cancer. 3a:T72d,Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCC) which represent the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC. To evaluate the anti-tumor activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator initiated open-label, single arm phase 2 studies were opened in Europe and the United States and enrolled five RDEB patients diagnosed with locally advanced and/or metastatic SCCs that had failed prior standard of care. Using a common protocol, patients were offered either oral or intravenous administration of rigosertib with consultation from the treating physician. Patients were monitored with clinical photography, biopsy, PET-CT scans and quality of life questionnaires over the 12 months duration of the trial. Pharmacokinetics of drug absorption was monitored in 4 patients. Patients on intravenous or oral therapy showed anti-tumor efficacy with acceptable toxicity and two patients had a complete response within six months of treatment. Quality of life was not negatively impacted by treatment and drug absorption exceeded previous patient populations presumably due to the relatively high dosing in an underweight patient cohort. These data identify rigosertib as a promising drug therapy for RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumors arise on the background of a unique fibrotic and inflammatory environment characterized by germline mutations in COL7A1 that promote development of homogenous primary tumors with aberrant PLK1 activity.3b:Tae5,Abstract Background Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC. Objectives To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced and/or metastatic SCCs whose disease had not previously responded successfully to standard care. Methods Using a common protocol, patients were offered either oral or intravenous (IV) administration of rigosertib with consultation from the treating physician. Patients were monitored with clinical photography, biopsy, positron emission tomography/computed tomography scans and quality of life (QoL) questionnaires over the 12-month duration of the trial. The pharmacokinetics of drug absorption was monitored in four patients. Results Antitumour efficacy with acceptable toxicity was seen in patients on IV or oral therapy and two patients had a complete response within 6 months of treatment. Their QoL was not negatively impacted by treatment and drug absorption exceeded that seen in previous patient populations presumably due to the relatively high dosing in a cohort of underweight patients. Conclusions These data identify rigosertib as a promising drug therapy for patients with RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumours arise on a background of a unique fibrotic and inflammatory environment characterized by germline mutations in COL7A1 that promote the development of homogenous primary tumours with aberrant PLK1 activity. An author video to accompany this article is available online. 3c:T7f4,Several widely used drugs have photosensitizing properties, and much research has been conducted to find associations between their use and the risk of developing cutaneous malignant melanoma (cM), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC), often with conflicting results. To assess whether the use of commonly prescribed photosensitizing drugs increases skin cancer risk. Analyses were performed using a large cohort of women, with prospectively collected information on phenotypic traits and sun exposure. Comprehensive information on pharmaceutical treatments and skin cancer occurrence was obtained through national registries. Drugs with photosensitizing properties were grouped according to the Anatomical Therapeutic Chemical system in nine groups, and associations between the use of such drugs were investigated using multivariable Cox regression analysis. The number of retrieved daily doses was analyzed to test the dose-response relationship. Hormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11-1.39), cSCC (HR 1.23; 95% CI: 1.03-1.47) and cM (HR 1.31; 95% CI: 1.01-1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3-2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09-1.44) and cM (HR 1.41; 95% CI: 1.03-1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC. Estrogen treatment increased the risk of all investigated skin cancers. Among those using diuretics, loop diuretics increased the risk of cSCC, and thiazide use increased the risk of BCC. We suggest that physicians should advise female patients prescribed estrogen, thiazides, or loop diuretics to limit their sun exposure.3d:T986,ABSTRACTBackgroundSeveral widely used drugs have photosensitizing properties, and much research has been conducted to find associations between their use and the risk of developing cutaneous malignant melanoma (cM), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC), often with conflicting results.ObjectiveTo assess whether the use of commonly prescribed photosensitizing drugs increases skin cancer risk.MethodsAnalyses were performed using a large cohort of women, with prospectively collected information on phenotypic traits and sun exposure. Comprehensive information on pharmaceutical treatments and skin cancer occurrence was obtained through national registries. Drugs with photosensitizing properties were grouped according to the Anatomical Therapeutic Chemical system in nine groups, and associations between the use of such drugs were investigated using multivariable Cox regression analysis. The number of retrieved daily doses was analyzed to test the dose–response relationship.ResultsHormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11–1.39), cSCC (HR 1.23; 95% CI: 1.03–1.47) and cM (HR 1.31; 95% CI: 1.01–1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3–2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09–1.44) and cM (HR 1.41; 95% CI: 1.03–1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC.ConclusionsEstrogen treatment increased the risk of all investigated skin cancers. Among those using diuretics, loop diuretics increased the risk of cSCC, and thiazide use increased the risk of BCC. We suggest that physicians should advise female patients prescribed estrogen, thiazides, or loop diuretics to limit their sun exposure.3e:T71d,The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65 years old. This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP. Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models). The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.3f:T4cd,Ashley Wysong and Anna Bar receive research funding from CBI. Christie Regula, Ally-Khan Somani, and Sherrif Ibrahim are speakers and principal investigators for CBI. Aaron Farberg is consultant for CBI and has funding from Regeneron, Replimune, Enspectra Health, Gerson Lehrman Group. Alison Fitzgerald, Jennifer Siegel, Anesh Prasai, and Matthew Goldberg are employees, stock and options holders for CBI. Shlomo Koyfman is a consultant for CBI, Merck, BMS, Regeneron and Galera therapeutics; has research support from Merk, BMS and Regeron and honoraria from UpToDate and Varian. Sarah Arron is a paid consultant for Enspectra Health, CBI, and WorldCare Clinical; paid speaker bureaus for Regeneron and CBI; paid expert testimony from Forensis, Inc, and Muro & Lampe; travel expenses paid by CBI; paid participation on a data safety monitoring board for Replimune; paid advisory board participation for Regeneron, Dermatology Times/Multimedia Medical, and Matrix Medical; leadership in the International Transplant Skin Cancer Collaborative; stock holding in Rakuten Medical and Enspectra Health, with stock held by spouse in Genentech and 23andMe. All remaining authors participated as investigators for CBI during this study.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Cutaneous Squamous Cell Carcinoma: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Cutaneous Squamous Cell Carcinoma (condition). Clinician-written summaries and actionable practice insights. 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Results for non-BCC cancers should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2025-0274","tag_type":"warning","value":"The study cannot fully exclude reverse causation or detection bias, though the authors argue surveillance was comparable between cases and controls.","value_numeric":null}],"summaries":{"what_studied":"This nested case-control study evaluated whether cumulative narrow-band TL-01 UVB phototherapy exposure increases skin cancer risk in a Finnish cohort of 4,815 patients (treated 1999–2019) with psoriasis or atopic dermatitis who received TL-01 monotherapy. Cases included 38 BCC, 13 cutaneous melanoma (CM), and 9 cutaneous squamous cell carcinoma (cSCC), each matched to up to 4 controls by sex, skin disease, and birth year.","key_result":"Higher TL-01 session count was associated with increased BCC risk (OR per 20 sessions: 1.36, 95% CI 1.08–1.72); patients receiving ≥60 sessions had a >4-fold BCC risk vs. those with 1–29 sessions (OR 4.16, 95% CI 1.49–11.6). No significant association was found for CM or cSCC. Occupational outdoor UV exposure did not confound results.","limitations":"- Small case numbers (especially cSCC n=9, CM n=13) limit power for reliable conclusions on those cancer types.\n- Lag period for cancer induction could not be formally modeled; per-session dose data were often unavailable.\n- Registry-based design lacked data on sunbathing habits, skin phototype, sunscreen use, and systemic immunosuppressants.","practice_takeaway":"Clinicians should track cumulative TL-01 session counts and consider heightened BCC surveillance in patients approaching or exceeding 60 sessions. This signal does not yet apply to melanoma or cSCC, but larger studies with longer follow-up are needed before firm safety conclusions can be drawn."}},{"doi":"10.1001/jamadermatol.2026.3297","pmid":"42684729","title":"Comparison of Pleomorphic Dermal Sarcoma to Advanced Cutaneous Squamous Cell Carcinoma and Soft-Tissue Sarcoma","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2026-09-02T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13539441/","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-11T06:19:58.683Z","updated_at":"2026-09-11T06:19:58.683Z","tags":[{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"condition","value":"Pleomorphic Dermal Sarcoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"condition","value":"Soft-Tissue Sarcoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"modality","value":"Tumor Genomic Profiling","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"sample_size","value":"n=49","value_numeric":49},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"warning","value":"Full text is under embargo until September 2, 2027; summary is based solely on the abstract and results section provided. Additional methods, patient characteristics, and supplementary data could not be reviewed.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"warning","value":"Sample sizes are very small (9 PDS, 15 CSCC, 25 STS), which substantially limits the reliability of subgroup comparisons and machine learning clustering results.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3297","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the conceptual shift in treatment paradigm suggested by the authors, but should be interpreted cautiously given the small, single-center, retrospective design.","value_numeric":null}],"summaries":{"what_studied":"This single-center retrospective cohort study compared tumor mutational burden (TMB), UV mutational signature, and single-nucleotide and pathway-level mutational profiles of pleomorphic dermal sarcoma (PDS) to metastatic cutaneous squamous cell carcinoma (CSCC) and soft-tissue sarcoma (STS) using a 447-gene sequencing panel at Dana-Farber/Brigham and Women's Hospital (January 2015–October 2025).","key_result":"PDS and CSCC shared nearly identical genetic profiles: mean TMB was 44.6 (95% CI, 37.5–51.8) for PDS vs. 54.1 (95% CI, 40.4–67.8) for CSCC (no significant difference), both far above STS at 4.2 (95% CI, 3.2–5.2). All PDSs and CSCCs carried UV signature mutations; no STSs did. Principal component analysis showed completely overlapping PDS/CSCC clusters, distinct from a narrow, separate STS cluster.","limitations":"Very small sample sizes (9 PDS, 15 CSCC, 25 STS) limit statistical power and generalizability. Single-center design may introduce selection bias. Full text is under embargo, so additional methodological detail could not be reviewed.","practice_takeaway":"PDS appears genetically far closer to cutaneous squamous cell carcinoma than to other soft-tissue sarcomas — clinicians should consider whether cutaneous cancer treatment protocols (including immunotherapy strategies targeting high TMB and UV-driven tumors) may be more appropriate than standard sarcoma regimens for PDS."}},{"doi":"10.1016/j.jaad.2026.08.075","pmid":"42637048","title":"Validation of the integrated 40-gene expression profile (i40-GEP) which provides prognostic and adjuvant radiation benefit for high-risk cutaneous squamous cell carcinoma","journal_title":"Journal of the American Academy of Dermatology","journal_issn":"0190-9622","published_at":"2026-08-24T00:00:00.000Z","url":"https://doi.org/10.1016/j.jaad.2026.08.075","source_score":43,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-11T06:20:04.937Z","updated_at":"2026-09-11T06:20:04.937Z","tags":[{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"modality","value":"Gene Expression Profiling","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"modality","value":"Radiation Therapy","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"sample_size","value":"n=572","value_numeric":572},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"warning","value":"ART benefit in Class 2B is derived from a retrospective, non-randomized comparison — confounding by indication cannot be excluded.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"warning","value":"Level of evidence assigned as 3 (retrospective cohort); no control arm or randomization present.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"warning","value":"Sex distribution of the cohort is not explicitly reported in the abstract; the 'mixed' sex tag is inferred from typical HRcSCC population studies.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.075","tag_type":"warning","value":"The paper is published in August 2026; data were not available for independent replication review at time of extraction.","value_numeric":null}],"summaries":{"limitations":"Retrospective study design limits causal inference; no randomization for ART assignment; generalizability may be limited to settings where 40-GEP testing is accessible.","practice_takeaway":"i40-GEP Class 2B results can help identify HRcSCC patients most likely to benefit from adjuvant radiation — roughly 1 in 8 patients. Class 1A results (>95% NPV) may help avoid overtreatment in lower-risk patients.","key_result":"i40-GEP significantly stratified metastatic and local recurrence risk (p<0.001); Class 1A had >95% NPV across NCCN subsets; Class 2B patients (12.9% of cohort) had the lowest 3-year metastasis-free survival (66.2%) and demonstrated benefit from ART; multivariable analysis showed i40-GEP outperformed individual clinicopathologic factors.","what_studied":"A validation study of the integrated 40-gene expression profile (i40-GEP) — which combines 40-GEP tumor biology with five clinicopathologic features (immunosuppression, location, differentiation, tumor diameter, and perineural invasion) — for risk stratification and adjuvant radiation treatment (ART) benefit in high-risk cutaneous squamous cell carcinoma (HRcSCC); validation cohort n=572."}},{"doi":"10.1093/bjd/ljag315","pmid":"42508807","title":"Trends in keratinocyte cancers in England, 2013–2022: basal cell carcinoma incidence, cutaneous squamous cell carcinoma incidence, and non-melanoma skin cancer mortality","journal_title":"British Journal of Dermatology","journal_issn":"0007-0963","published_at":"2026-07-28T00:00:00.000Z","url":"https://doi.org/10.1093/bjd/ljag315","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-01T13:21:56.739Z","updated_at":"2026-08-01T13:21:56.739Z","tags":[{"paper_doi":"10.1093/bjd/ljag315","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"condition","value":"Basal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"condition","value":"Non-Melanoma Skin Cancer","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"study_design","value":"Population-Based Cohort Study","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"warning","value":"Mortality data cover 'NMSC' broadly and may not be fully disaggregated into BCC vs. CSCC, so mortality trends may reflect both tumour types combined.","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"warning","value":"No total sample size (N) was reported in the abstract or results; a sample_size tag could not be assigned.","value_numeric":null},{"paper_doi":"10.1093/bjd/ljag315","tag_type":"warning","value":"The study period ends in 2022; COVID-19-related disruptions to diagnosis and registration (2020–2021) may have affected incidence trends but are not explicitly addressed in the provided text.","value_numeric":null}],"summaries":{"what_studied":"This population-based study described incidence and mortality trends for basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) in England from 2013 to 2022, using per patient per annum (PPPA) counting methodology and data from the National Disease Registration Service.","key_result":"By 2022, age-standardised incidence rates were 295/100,000 PYs for BCC and 102/100,000 PYs for CSCC. BCC rates stabilised after 2015 (APC −0.2%), while CSCC rose sharply 2013–2015 (APC +6.1%) and continued rising through 2019 (APC +2.3%). NMSC mortality increased significantly across the decade (APC +4.0%), rising roughly twice as fast in males (APC +4.4%) vs. females (APC +2.2%). The PPPA method captured 67% more BCCs and 42% more CSCCs than first-registration-only counting.","limitations":"- Study covers England only, limiting generalisability to other regions or countries.\n- KCs are acknowledged to be substantially underreported, meaning even PPPA counts likely underestimate true burden.\n- No individual-level risk factor data (e.g., UV exposure, immunosuppression) were available to explain observed trends.","practice_takeaway":"CSCC incidence and NMSC mortality are rising — especially in males and at the age extremes (<60 and ≥80 years) — signalling a need for stronger UV prevention messaging and earlier diagnosis pathways. Clinicians should be aware that standard registry counts likely undercount keratinocyte cancers substantially; the PPPA method offers a more accurate picture for service planning."}},{"doi":"10.1111/jdv.70624","pmid":"42482600","title":"Half of metastatic\n CSCC\n arises from low‐stage primaries: A nationwide analysis","journal_title":"Journal of the European Academy of Dermatology and Venereology","journal_issn":"0926-9959","published_at":"2026-07-22T00:00:00.000Z","url":"https://doi.org/10.1111/jdv.70624","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-01T13:22:01.776Z","updated_at":"2026-08-01T13:22:01.776Z","tags":[{"paper_doi":"10.1111/jdv.70624","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"condition","value":"Metastatic Skin Cancer","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"warning","value":"Sex breakdown and sample size are unknown from available information and have been omitted from tags.","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"warning","value":"Study design inferred as a nationwide retrospective registry/cohort analysis based on the described 'nationwide analysis'; this has not been confirmed from the full text.","value_numeric":null},{"paper_doi":"10.1111/jdv.70624","tag_type":"warning","value":"The full text was not available — summary is based solely on the title and journal metadata. Key details such as exact sample size, staging system used (e.g., AJCC 8th edition, BWH), country of origin, follow-up duration, and specific outcome definitions could not be verified.","value_numeric":null}],"summaries":{"what_studied":"A nationwide analysis examining the tumor stage distribution of primary cutaneous squamous cell carcinomas (CSCC) that gave rise to metastatic disease, to determine what proportion of metastatic CSCC originates from low-stage primaries.","key_result":"Approximately half (50%) of metastatic CSCC cases arose from low-stage primary tumors, suggesting that high-stage classification of the primary is not a prerequisite for metastatic spread.","limitations":"As a nationwide registry/database analysis, it may be subject to staging inconsistencies, coding inaccuracies, and incomplete data capture across institutions. Causality and granular clinical details (e.g., immunosuppression status, specific histologic features) cannot be fully assessed.","practice_takeaway":"Clinicians should not reserve metastatic surveillance only for high-stage CSCC primaries — low-stage tumors carry a meaningful risk of metastasis and may warrant closer follow-up than current guidelines suggest."}},{"doi":"10.2340/actadv.v106.adv-2026-0385","pmid":"42423360","title":"The Role of RCM and LC-OCT in Genodermatoses Associated with Skin Cancer: A Narrative Review","journal_title":"Acta Dermato-Venereologica","journal_issn":"1651-2057","published_at":"2026-07-09T00:00:00.000Z","url":"https://doi.org/10.2340/actadv.v106.adv-2026-0385","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-17T13:24:20.738Z","updated_at":"2026-07-17T13:24:20.738Z","tags":[{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Basal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Familial Atypical Multiple Mole and Melanoma Syndrome","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Ichthyosis with Confetti","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Nevoid Basal Cell Carcinoma Syndrome","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Recessive Dystrophic Epidermolysis Bullosa","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"condition","value":"Xeroderma Pigmentosum","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"modality","value":"Dermoscopy","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"modality","value":"Line-Field Confocal Optical Coherence Tomography","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"modality","value":"Reflectance Confocal Microscopy","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"sample_size","value":"n=5","value_numeric":5},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"study_design","value":"Narrative Review with Illustrative Case Series","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"warning","value":"Performance statistics cited (e.g., RCM sensitivity/specificity for BCC, 43.3% reduction in excisions) are drawn from referenced external studies conducted in general populations—not in genodermatosis patients specifically.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"warning","value":"Study design label 'Narrative Review with Illustrative Case Series' is assigned based on the authors' own description; the case series component is retrospective and non-systematic.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"warning","value":"The AI-assisted LC-OCT BCC probability tool demonstrated a critical failure in the IWC case (99% BCC prediction for a confirmed pT1a melanoma), underscoring that rare-disease patients are likely absent from AI training datasets.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.adv-2026-0385","tag_type":"warning","value":"The sample size of 5 cases is very small and selected from 2 specialized tertiary centres; findings may not generalise to community practice settings.","value_numeric":null}],"summaries":{"what_studied":"This narrative review with illustrative case series (5 cases from 2 tertiary referral centres in Italy and Spain) evaluated the role of reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT) in managing suspicious skin lesions in patients with genodermatoses associated with high skin cancer risk: NBCCS, RDEB, FAMMM, xeroderma pigmentosum, and ichthyosis with confetti.","key_result":"Adding RCM to dermoscopy raised BCC diagnosis sensitivity from 93.2% to 97.8% and specificity from 51.7% to 86.8% (cited multicentric study, n=1,005 lesions); LC-OCT raised BCC specificity from 37% to 90% vs. dermoscopy alone. In a pivotal RCT of >3,000 patients, RCM reduced unnecessary melanocytic excisions by 43.3%. In the IWC case, the LC-OCT AI misclassified a pT1a melanoma (0.7 mm Breslow) as BCC with 99% probability, highlighting AI limitations in rare, underrepresented populations.","limitations":"- Only 5 illustrative cases are presented; no prospective data in genodermatosis cohorts for RCM/LC-OCT specifically.\n- Performance data cited are from general or transplant populations, not validated in these rare syndromes.\n- AI tools were trained on common lesion datasets and may systematically misclassify lesions in rare genodermatoses (demonstrated by the IWC melanoma/BCC misclassification).","practice_takeaway":"For patients with skin cancer–prone genodermatoses, add RCM (preferred for melanocytic lesions) or LC-OCT (preferred for keratinocyte carcinomas and hyperkeratotic/deeper lesions) as a second-level tool after dermoscopy to cut unnecessary biopsies while catching true malignancies earlier. Do not rely on AI-assisted LC-OCT outputs as independent decision-makers in rare genodermatosis patients, as these populations are likely underrepresented in AI training data."}},{"doi":"10.2340/actadv.v106.46508","pmid":"42423362","title":"Corrigendum: Does Teledermatology Enable Earlier Diagnosis of Cutaneous Squamous Cell Carcinoma Than Face-to-face Consultation?","journal_title":"Acta Dermato-Venereologica","journal_issn":"1651-2057","published_at":"2026-07-09T00:00:00.000Z","url":"https://doi.org/10.2340/actadv.v106.46508","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-16T13:37:23.759Z","updated_at":"2026-07-16T13:37:23.759Z","tags":[{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"modality","value":"Teledermatology","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"sample_size","value":"n=224","value_numeric":224},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"study_design","value":"Corrigendum","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"warning","value":"Sample size of n=224 is derived from corrected group totals (n=101 + n=123); the original paper had reported n=219.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"warning","value":"Study design labeled 'Corrigendum' as there is no standard level-of-evidence hierarchy entry for corrections; level of evidence tag omitted accordingly.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"warning","value":"The impact_flag 'safety_signal' is used loosely here to flag that a previously reported borderline significant finding (tumour surface area, p=0.051) is now non-significant (p=0.4479) after correction — clinicians relying on the original should update their interpretation.","value_numeric":null},{"paper_doi":"10.2340/actadv.v106.46508","tag_type":"warning","value":"This is a corrigendum, not the original study — the structured data reflects corrections to the parent article (DOI: 10.2340/actadv.v105.44362), not a new independent study.","value_numeric":null}],"summaries":{"what_studied":"This is a corrigendum to a study comparing teledermatology vs. face-to-face consultation for earlier diagnosis of cutaneous squamous cell carcinoma (cSCC), correcting several statistical values reported in the original 2025 publication (DOI: 10.2340/actadv.v105.44362).","key_result":"Key corrections include: revised group sizes (face-to-face n=101, teledermatology n=123, not 112/107); corrected minor tumour diameter SDs (0.56 ± 0.96 cm vs 1.09 ± 0.63 cm); and tumour surface area bivariate analysis now shows **no significant difference** between groups (p=0.4479), reversing the originally reported borderline difference (p=0.051). The multivariate predictor for minor diameter is now reported as an estimate (–4.31751; p<0.001) rather than an OR. Referral delay corrected to 55.8 days (from 55 days).","limitations":"The corrigendum itself does not discuss study-level limitations, but the principal conclusions of the original study are stated to be unchanged except for the tumour surface area finding, which now shows no significant between-group difference.","practice_takeaway":"The core finding that teledermatology significantly reduced referral delay (55.8 days → 3 days) and that minor tumour diameter predicts teledermatology-based diagnosis remains valid after correction. Clinicians should note that tumour surface area is **not** significantly different between care pathways."}},{"doi":"10.1001/jamadermatol.2026.2163","pmid":"42418212","title":"Consensus Guidelines for Staging and Surveillance Imaging in Cutaneous Squamous Cell Carcinoma","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1001/jamadermatol.2026.2163","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-12T13:19:34.247Z","updated_at":"2026-07-12T13:19:34.247Z","tags":[{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"modality","value":"Computed Tomography","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"sample_size","value":"n=45","value_numeric":45},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"study_design","value":"Delphi Consensus Study","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"warning","value":"Delphi panels reflect expert opinion (Level 5 evidence); these recommendations should not be treated as equivalent to guideline recommendations backed by clinical trial data.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"warning","value":"The 15% metastasis risk threshold used to trigger imaging is a consensus-derived benchmark, not validated in prospective studies — apply with clinical judgment.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2163","tag_type":"warning","value":"The panel was predominantly White and academic — applicability to diverse or community practice settings may be limited.","value_numeric":null}],"summaries":{"what_studied":"A multidisciplinary Delphi consensus panel (n=45) evaluated when and how to use staging and surveillance imaging for localized cutaneous squamous cell carcinoma (CSCC), across 3 iterative survey rounds (January–June 2025).","key_result":"Consensus (≥80% agreement) was reached to recommend imaging for CSCCs with ≥15% metastasis risk — including tumors ≥4 cm, bone invasion, invasion beyond subcutaneous fat, or large-caliber nerve invasion. CT was the preferred modality for both nodal staging (84%) and surveillance (78%). Consensus supported imaging surveillance for at least 2 years; near-consensus (70–79%) supported at least 3 years.","limitations":"Expert opinion-based Delphi design without prospective clinical validation; panel was predominantly White (67%) and academic, which may limit generalizability; thresholds (e.g., 15% metastasis risk) are consensus-derived, not empirically tested.","practice_takeaway":"For CSCC with high-risk features — diameter ≥4 cm, bone or deep soft tissue invasion, large-caliber perineural invasion, or poorly differentiated histology combined with ≥2 cm size or lymphovascular invasion — obtain CT imaging for nodal staging and plan surveillance imaging for at least 2–3 years. Use this framework to standardize practice while awaiting prospective guideline data."}},{"doi":"10.1053/j.ajkd.2026.01.011","pmid":"42167833","title":"Malignancy and Kidney Transplant: Core Curriculum 2026","journal_title":"American Journal of Kidney Diseases","journal_issn":"0272-6386","published_at":"2026-05-20T00:00:00.000Z","url":"https://doi.org/10.1053/j.ajkd.2026.01.011","source_score":24,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:31.911Z","updated_at":"2026-06-03T13:44:31.911Z","tags":[{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"brand","value":"Opdivo","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"AL Amyloidosis","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Kidney Transplantation","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Merkel Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Plasma Cell Dyscrasia","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Posttransplant Lymphoproliferative Disorder","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Renal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"acitretin","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"azathioprine","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"belzutifan","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"cemiplimab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"ipilimumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"mycophenolate mofetil","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"nivolumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"sirolimus","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"tacrolimus","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Calcineurin Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"mTOR Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Oncolytic Virus Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"study_design","value":"Review Article / Core Curriculum","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"Emerging therapies (oncolytic virus, EBV-VST, CAR-T in transplant) are discussed based on early-phase or limited case data and should not be considered standard of care.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"ICI rejection risk figures (25–42%) are pooled from retrospective cohorts with heterogeneous IS reduction practices, limiting direct applicability.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"Sample size tag omitted as no single study population is defined across this multi-topic review.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"This is a narrative Core Curriculum review, not a primary research study; evidence grades vary widely by topic and most recommendations are expert consensus or based on observational data.","value_numeric":null}],"summaries":{"what_studied":"This Core Curriculum reviews cancer risk, screening, and management in kidney transplant candidates and recipients (KTRs), covering skin cancers, PTLD, plasma cell dyscrasias, and solid tumors, with emphasis on immunosuppression (IS) management and emerging therapies including immune checkpoint inhibitors (ICIs) and CAR-T cells.","key_result":"KTRs face 2–4× higher overall cancer risk vs. the general population; skin cancer SIRs reach 65–250 (cSCC) and 13–24 (Merkel cell); DLBCL is 8× more common; kidney cancer is 7× more common. ICI use carries ~25–42% acute rejection risk; patients on corticosteroids + mTOR inhibitors had lower rejection (HR 0.30). Median overall survival after transplant was 8.4 years for myeloma and 8.6 years for AL amyloidosis KTRs.","limitations":"Most recommendations are based on expert consensus, observational data, and case series rather than RCTs; ICI safety/efficacy data in KTRs come largely from retrospective analyses; screening benefit on long-term mortality in KTRs remains unproven.","practice_takeaway":"Convert azathioprine to mycophenolate or switch to an mTOR inhibitor for KTRs with recurrent non-melanoma skin cancers; minimize IS (remove antimetabolites first) when initiating ICI, and treat ICI-associated rejection with pulse steroids rather than antithymocyte globulin to preserve antitumor response. Cervical cancer screening should be more frequent (every 6–12 months) after transplant, and IMiDs should be stopped ≥4 weeks before kidney transplant in myeloma patients."}},{"doi":"10.1001/jamadermatol.2026.0964","pmid":"42126833","title":"Global Skin Cancer Burden From 1990 to 2023 and Projection to 2050","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2026-05-13T00:00:00.000Z","url":"https://doi.org/10.1001/jamadermatol.2026.0964","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:19.319Z","updated_at":"2026-05-18T13:25:19.319Z","tags":[{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"condition","value":"Basal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"condition","value":"Malignant Melanoma","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"condition","value":"Skin Cancer","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"warning","value":"BCC regional projections were withheld due to numerical instability in long-term extrapolation — global BCC projections only.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"warning","value":"No sample size tag applied — this is a secondary analysis of the GBD 2023 database covering global population-level estimates, not a discrete patient cohort. Level of evidence set to 3 (cross-sectional/ecological analysis); some may rate GBD-based projection studies differently.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.0964","tag_type":"warning","value":"The paper is a Research Letter, so methodology and subgroup data are abbreviated; full statistical detail is in unpublished supplements.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study used GBD 2023 data (1990–2023) to analyze global prevalence and DALYs for malignant melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC) by sex, age, and Sociodemographic Index (SDI) level, with Bayesian age-period-cohort projections to 2050.","key_result":"By 2050, melanoma DALYs are projected to rise from ~2 million (2025) to >3.3 million, cSCC from 1.2 million to 4.0 million, and BCC to ~5.0 million. Low- and middle-SDI regions drive the steepest growth. Melanoma DALYs fell in high-SDI regions (e.g., −36.1% in North America, 1990–2023), while cSCC DALYs rose 93.2% in low-SDI settings.","limitations":"GBD estimates likely undercount burden in low-SDI settings due to incomplete reporting and limited health infrastructure. BCC projections excluded a 2005–2009 surveillance-artifact period, and regional BCC projections were omitted due to numerical instability. Future projections may not account for policy or screening changes.","practice_takeaway":"Clinicians and public health planners should expect sharply rising skin cancer burden—especially cSCC and BCC—in low- and middle-income settings through 2050, where screening infrastructure is limited. Prioritizing early detection programs and sun-protection campaigns in these regions is increasingly urgent."}},{"doi":"10.1038/s42255-026-01514-y","pmid":"42045479","title":"Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion","journal_title":"Nature Metabolism","journal_issn":"2522-5812","published_at":"2026-04-28T00:00:00.000Z","url":"https://doi.org/10.1038/s42255-026-01514-y","source_score":30,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-30","doi":"10.1038/s42255-026-01514-y","days":"14","issn":"2522-5812","rank":"7","field":"Clinical Medicine","score":"30","category":"Endocrinology & Metabolism","categories":["Endocrinology & Metabolism"],"_categories":["Endocrinology & Metabolism"]},"pubmed":{"doi":"10.1038/s42255-026-01514-y","title":"Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion.","journal":"Nature 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invasion"],"author":[{"given":"Timothy","family":"Budden","sequence":"first","affiliation":[]},{"given":"Noah","family":"Palombo","sequence":"additional","affiliation":[]},{"given":"Shilpa","family":"Gurung","sequence":"additional","affiliation":[]},{"given":"Martha","family":"Gutteridge","sequence":"additional","affiliation":[]},{"given":"Charlotte","family":"Russell","sequence":"additional","affiliation":[]},{"given":"Jair","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Alex","family":"von Kriegsheim","sequence":"additional","affiliation":[]},{"given":"Lyutong","family":"An","sequence":"additional","affiliation":[]},{"given":"Catherine","family":"Harwood","sequence":"additional","affiliation":[]},{"given":"Luisa","family":"Motta","sequence":"additional","affiliation":[]},{"given":"Claus","family":"Jorgensen","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"López-Garcîa","sequence":"additional","affiliation":[]},{"given":"Caroline","family":"Gaudy-Marqueste","sequence":"additional","affiliation":[]},{"given":"Kevin","family":"Harrington","sequence":"additional","affiliation":[]},{"given":"Malin","family":"Pedersen","sequence":"additional","affiliation":[]},{"given":"Ben","family":"O’Leary","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"Rullan","sequence":"additional","affiliation":[]},{"given":"Amaya","family":"Virós","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/501100000289","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100000289","name":"Cancer 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Patients received cosibelimab 800 mg IV every 2 weeks (both cohorts) or 1200 mg every 3 weeks (mCSCC); primary endpoint was objective response rate, with duration of response and safety as secondary endpoints.","key_result":"In mCSCC (n=78), ORR was 50.0% with 12.8% complete responses; median DOR was not reached and the estimated 24‑month DOR was 72.1%. In laCSCC (n=31), ORR was 54.8% with 25.8% complete responses; median DOR was not reached and the estimated 24‑month DOR was 80.2%. 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Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79).","abstract":"$35","keywords":[],"pubmed_id":"40991277","conclusions":"","publication_date":"2025-09-24T00:00:00"},"crossref":{"DOI":"10.1001/jamadermatol.2025.3473","URL":"https://doi.org/10.1001/jamadermatol.2025.3473","ISSN":["2168-6068"],"link":[{"URL":"https://jamanetwork.com/journals/jamadermatology/articlepdf/2839012/jamadermatology_weber_2025_oi_250047_1762976591.27629.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1148","type":"journal-article","issue":"11","score":1,"title":["Sunburn and Cutaneous Squamous Cell Carcinoma"],"author":[{"given":"Isaac","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston"}]},{"given":"Kaiping","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston"}]},{"given":"Tran","family":"Dang","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Baltimore, Maryland"}]},{"given":"Malay","family":"Shah","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas"}]},{"given":"Mackenzie R.","family":"Wehner","sequence":"additional","affiliation":[{"name":"Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston"},{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston"}]}],"issued":{"date-parts":[[2025,11,1]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":"161","created":{"date-time":"2025-09-24T15:31:19Z","timestamp":1758727879000,"date-parts":[[2025,9,24]]},"indexed":{"date-time":"2025-11-19T17:20:39Z","timestamp":1763572839073,"date-parts":[[2025,11,19]]},"subject":[],"abstract":"$36","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamadermatology/fullarticle/2839012"}},"subtitle":["A Meta-Analysis"],"deposited":{"date-time":"2025-11-19T16:00:55Z","timestamp":1763568055000,"date-parts":[[2025,11,19]]},"issn-type":[{"type":"print","value":"2168-6068"}],"published":{"date-parts":[[2025,11,1]]},"publisher":"American Medical Association (AMA)","reference":[{"DOI":"10.3389/fonc.2025.1523169","key":"doi250047r1","year":"2025","issue":null,"author":"Liu","volume":"15","first-page":null,"unstructured":null,"article-title":"Global, regional, national prevalence, mortality, and disability-adjusted life-years of cutaneous squamous cell carcinoma and trend analysis from 1990 to 2021 and prediction to 2045.","journal-title":"Front Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1111/ijd.16164","key":"doi250047r2","year":"2023","issue":"4","author":"Caudill","volume":"62","first-page":"483","unstructured":null,"article-title":"The risk of metastases from squamous cell carcinoma of the skin.","journal-title":"Int J Dermatol","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ejca.2023.01.017","key":"doi250047r3","year":"2023","issue":null,"author":"Keim","volume":"183","first-page":"60","unstructured":null,"article-title":"Incidence, mortality and trends of cutaneous squamous cell carcinoma in Germany, the Netherlands, and Scotland.","journal-title":"Eur J Cancer","doi-asserted-by":"publisher"},{"DOI":"10.1001/jama.2015.8045","key":"doi250047r4","year":"2015","issue":"6","author":"Thompson","volume":"314","first-page":"638","unstructured":null,"article-title":"JAMA patient page: suntan and sunburn.","journal-title":"JAMA","doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ejca.2004.10.016","key":"doi250047r5","year":"2005","issue":"1","author":"Gandini","volume":"41","first-page":"45","unstructured":null,"article-title":"Meta-analysis of risk factors for cutaneous melanoma: II. 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Within the matched dataset there were 10,994 basal cell carcinomas and 12,551 cutaneous squamous cell carcinomas; the risk reduction was seen for both (greatest for cSCC). Among transplant recipients, no overall significant reduction was observed, though early use was linked to lower cSCC incidence.","limitations":"Observational EHR-based design from a predominantly older, White, male veteran population (about 2% women) limits generalizability and leaves room for residual confounding despite matching. The abstract does not report absolute rates, hazard ratios, or confidence intervals, and event attribution across exposure groups is not fully clear.","practice_takeaway":"In this large VA cohort, nicotinamide 500 mg twice daily was associated with lower risk of subsequent skin cancers, especially when initiated after the first skin cancer, with the largest effect in cSCC. 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studies were pooled and used oral or IV dosing, which may affect generalizability.","value_numeric":null}],"summaries":{"what_studied":"Two investigator-initiated, open-label, single-arm phase 2 studies in Europe and the US evaluated rigosertib (oral or intravenous) for anti-tumor activity and safety in five patients with RDEB-associated locally advanced and/or metastatic cutaneous SCC who had failed standard care, with 12 months of monitoring.","key_result":"Of five treated patients, two achieved complete responses within six months. Treatment showed anti-tumor activity with acceptable toxicity, quality of life was not negatively affected, and drug absorption exceeded prior populations.","limitations":"Extremely small sample (n=5) and uncontrolled, open-label design without a comparator. Heterogeneous administration (oral vs IV), and pharmacokinetics were assessed in only four patients.","practice_takeaway":"Rigosertib produced signals of efficacy with tolerable safety in RDEB-associated advanced/metastatic cutaneous SCC after standard care failure, including two complete responses by six months. Given the tiny, uncontrolled dataset, this remains investigational and needs confirmation in larger controlled studies."}},{"doi":"10.1111/phpp.70013","pmid":"40102189","title":"Photosensitizing Drugs and Risk of Skin Cancer in Women—A Prospective Population‐Based Study","journal_title":"Photodermatology, Photoimmunology & Photomedicine","journal_issn":"0905-4383","published_at":"2025-03-19T00:00:00.000Z","url":"https://doi.org/10.1111/phpp.70013","source_score":64,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-04-07","doi":"10.1111/phpp.70013","days":"30","issn":"0905-4383","rank":"5","field":"Clinical Medicine","score":"64","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1111/phpp.70013","title":"Photosensitizing Drugs and Risk of Skin Cancer in Women-A Prospective Population-Based Study.","journal":"Photodermatology, photoimmunology & photomedicine","methods":"","results":"Hormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11-1.39), cSCC (HR 1.23; 95% CI: 1.03-1.47) and cM (HR 1.31; 95% CI: 1.01-1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3-2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09-1.44) and cM (HR 1.41; 95% CI: 1.03-1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC.","abstract":"$3c","keywords":["basal cell carcinoma","melanoma","photosensitizing drugs","prospective","squamous cell carcinoma"],"pubmed_id":"40102189","conclusions":"","publication_date":"2025-03-19T00:00:00"},"crossref":{"DOI":"10.1111/phpp.70013","URL":"https://doi.org/10.1111/phpp.70013","ISSN":["0905-4383","1600-0781"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/phpp.70013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"2","score":1,"title":["Photosensitizing Drugs and Risk of Skin Cancer in Women—A Prospective Population‐Based Study"],"author":[{"given":"Gustav Boelsgaard","family":"Christensen","sequence":"first","affiliation":[{"name":"Department of Dermatology Skåne University Hospital Lund Sweden"},{"name":"Lund University Skin Cancer Research Group, Dermatology, Department of Clinical 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Among diuretic users, loop diuretics increased cSCC risk (HR 1.6; 95% CI 1.3-2.0) with a dose relation, thiazides increased BCC (HR 1.25; 95% CI 1.09-1.44) and melanoma (HR 1.41; 95% CI 1.03-1.93), and NSAIDs showed a possible curvilinear association with BCC and cSCC.","practice_takeaway":"Counsel women prescribed estrogen therapy, thiazides, or loop diuretics to limit sun exposure and practice photoprotection, given observed increases in skin cancer risk."}},{"doi":"10.1007/s13555-024-01111-5","pmid":"38424384","title":"Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients","journal_title":"Dermatology and Therapy","journal_issn":"2193-8210","published_at":"2024-03-01T00:00:00.000Z","url":"https://doi.org/10.1007/s13555-024-01111-5","source_score":99,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2024-03-09","doi":"10.1007/s13555-024-01111-5","days":"30","issn":"2193-8210","rank":"2","field":"Clinical Medicine","score":"99","category":"Dermatology","categories":["Dermatology"],"_categories":["Dermatology"]},"pubmed":{"doi":"10.1007/s13555-024-01111-5","title":"Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients.","journal":"Dermatology and therapy","methods":"","results":"Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models).","abstract":"$3e","keywords":["40-GEP","Cutaneous squamous cell carcinoma","Metastasis","Prognostic","Risk assessment"],"pubmed_id":"38424384","conclusions":"The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. 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The cohort included 897 patients; Kaplan–Meier and nested Cox models compared clinicopathologic systems alone versus with 40‑GEP added.","key_result":"Metastatic risk differed across 40‑GEP Classes 1, 2A, and 2B (p<0.0001), and adding 40‑GEP to clinicopathologic factors or staging systems (BWH, AJCC8, NCCN) improved prediction accuracy for metastasis (ANOVA p<0.0001 for all models).","practice_takeaway":"In high‑risk cSCC, integrating 40‑GEP results with BWH/AJCC8/NCCN staging improves metastatic risk stratification, supporting more risk‑aligned management decisions."}}],"initialOffset":20,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Cutaneous Squamous Cell Carcinoma"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Cutaneous Squamous Cell Carcinoma"}}}]]

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