Weighted metrics are required when evaluating the performance of prediction models in nested case-control studies.

BACKGROUND: Nested case-control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data. METHODS: We proposed how to correctly evaluate prediction models in NCC data, by adjusting performance metrics with sampling weights to account for the NCC sampling. We included in this study the C-index, threshold-based metrics, Observed-to-expected events ratio (O/E ratio), calibration slope, and decision curve analysis. We illustrated the proposed metrics with a validation of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in data from the population-based Rotterdam study. We compared the metrics obtained in the full cohort with those obtained in NCC datasets sampled from the Rotterdam study, with and without a matched design. RESULTS: Performance metrics without weight adjustment were biased: the unweighted C-index in NCC datasets was 0.61 (0.58-0.63) for the unmatched design, while the C-index in the full cohort and the weighted C-index in the NCC datasets were similar: 0.65 (0.62-0.69) and 0.65 (0.61-0.69), respectively. The unweighted O/E ratio was 18.38 (17.67-19.06) in the NCC datasets, while it was 1.69 (1.42-1.93) in the full cohort and its weighted version in the NCC datasets was 1.68 (1.53-1.84). Similarly, weighted adjustments of threshold-based metrics and net benefit for decision curves were unbiased estimates of the corresponding metrics in the full cohort, while the corresponding unweighted metrics were biased. In the matched design, the bias of the unweighted metrics was larger, but it could also be compensated by the weight adjustment. CONCLUSIONS: Nested case-control studies are an efficient solution for evaluating the performance of prediction models that use expensive or difficult-to-obtain biomarkers, especially when the outcome is rare, but the performance metrics need to be adjusted to the sampling procedure.

The majority of observational studies in leading peer-reviewed medicine journals are not registered and do not have a publicly accessible protocol: a scoping review.

OBJECTIVES: Observational studies are not subject to the same requirements as randomized controlled trials, such as registration or publishing a protocol. The aim of this scoping review was to estimate the registration rate of observational studies in leading peer-reviewed medicine journals and to evaluate whether protocols were available in the public domain. STUDY DESIGN AND SETTING: In March 2023, we searched OVID Medline for observational studies published in 2022 in the top five general medicine journals according to impact factor (The Lancet, The British Medical Journal (BMJ), The Journal of the American Medical Association, The New England Journal of Medicine, and Annals of Internal Medicine). We defined an observational study as a cohort study, a case-control study, a cross-sectional study, or a case series. Information on i) the proportion of observational studies that have been registered and ii) the proportion of observational studies that have a protocol available in the public domain was extracted from a random sample of studies. RESULTS: Our search identified 699 studies; 290 studies were selected as full text, and a random sample of 200 studies was included. For half of the studies, the first author worked at a US institution. Most studies were cohort studies (n = 126, 63.0%) and used administrative healthcare records, electronic healthcare records, and registries. Of the 200 observational studies, 20 (10.0%) were registered. Among those, 14 were prospectively registered. Twenty-four studies (12.0%) had a protocol available in the public domain. Studies that were registered or had a protocol, were more frequently published in the BMJ (n = 12/28, 42.9%), had a first author working in the UK (n = 10/28, 35.7%) and used electronic health care records (n = 13/28, 46.4%) compared to studies with no registration and no protocol. CONCLUSION: The rate of prospectively registered observational studies is worryingly low. Prospective registration of observational studies should be encouraged and standardized to ensure transparency in clinical research and reduce research waste.

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study.

BACKGROUND: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. OBJECTIVE: To investigate the cumulative incidence and timing of subsequent cSCCs. METHODS: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. RESULTS: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. LIMITATIONS: Only histopathologically confirmed cSCCs were included. CONCLUSION: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.

Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis.

BACKGROUND: Actinic keratosis (AK) is a common dermatological condition, and among the most common dermatological diagnoses in older populations. Although the prevalence of AK depends on demographic and environmental factors, little is known about the global context of AK. OBJECTIVES: To provide a comprehensive and updated analysis of the global prevalence rate and incidence of AK in the general population through a systematic review and meta-analysis, and - through subgroup analyses - to identify high-risk phenotypes, demographic and lifestyle risk factors and regional variations in disease prevalence. METHODS: A systematic search of Embase, MEDLINE, Web of Science and Google Scholar was performed on 20 May 2022. Two reviewers independently screened and assessed the quality of each study using a validated critical appraisal checklist. Epidemiological measurements (e.g. prevalence) from individual studies performed in the general population were then pooled in a random-effects meta-analysis. Subgroup analyses (i.e. population age, geographical region, occupation, sex and study quality) were conducted. RESULTS: Of the 65 articles that made it through the full-text screening, 60 reported a point prevalence. A meta-analysis of these articles yielded an overall point prevalence of 14% [95% confidence interval (CI) 14-15]. In further analyses, the calculated prevalence rate varied depending on subgroup. The pooled incidence rate from the seven eligible studies analysed was 1928 per 100 000 person-years (PY; 95% CI -439 to 4294). CONCLUSIONS: This comprehensive meta-analysis provides an updated global prevalence rate of AK of 14%, indicating a significant worldwide disease burden. The incidence rate of AK was found to be 1928 per 100 000 PY, emphasizing a growing public health concern. However, high heterogeneity among studies suggests that various factors influence the AK prevalence rate, necessitating further research to understand the observed differences.

Personalised decision making to predict absolute metastatic risk in cutaneous squamous cell carcinoma: development and validation of a clinico-pathological model.

Background: Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, affecting more than 2 million people worldwide yearly and metastasising in 2-5% of patients. However, current clinical staging systems do not provide estimates of absolute metastatic risk, hence missing the opportunity for more personalised treatment advice. We aimed to develop a clinico-pathological model that predicts the probability of metastasis in patients with cSCC. Methods: Nationwide cohorts from (1) all patients with a first primary cSCC in The Netherlands in 2007-2008 and (2) all patients with a cSCC in 2013-2015 in England were used to derive nested case-control cohorts. Pathology records of primary cSCCs that originated a loco-regional or distant metastasis were identified, and these cSCCs were matched to primary cSCCs of controls without metastasis (1:1 ratio). The model was developed on the Dutch cohort (n = 390) using a weighted Cox regression model with backward selection and validated on the English cohort (n = 696). Model performance was assessed using weighted versions of the C-index, calibration metrics, and decision curve analysis; and compared to the Brigham and Women's Hospital (BWH) and the American Joint Committee on Cancer (AJCC) staging systems. Members of the multidisciplinary Skin Cancer Outcomes (SCOUT) consortium were surveyed to interpret metastatic risk cutoffs in a clinical context. Findings: Eight out of eleven clinico-pathological variables were selected. The model showed good discriminative ability, with an optimism-corrected C-index of 0.80 (95% Confidence interval (CI) 0.75-0.85) in the development cohort and a C-index of 0.84 (95% CI 0.81-0.87) in the validation cohort. Model predictions were well-calibrated: the calibration slope was 0.96 (95% CI 0.76-1.16) in the validation cohort. Decision curve analysis showed improved net benefit compared to current staging systems, particularly for thresholds relevant for decisions on follow-up and adjuvant treatment. The model is available as an online web-based calculator (https://emc-dermatology.shinyapps.io/cscc-abs-met-risk/). Interpretation: This validated model assigns personalised metastatic risk predictions to patients with cSCC, using routinely reported histological and patient-specific risk factors. The model can empower clinicians and healthcare systems in identifying patients with high-risk cSCC and offering personalised care/treatment and follow-up. Use of the model for clinical decision-making in different patient populations must be further investigated. Funding: PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.

The association between atopic eczema and lymphopenia: Results from a UK cohort study with replication in US survey data.

BACKGROUND: Lymphocyte skin homing in atopic eczema (AE) may induce lymphopenia. OBJECTIVE: To determine if AE is associated with lymphopenia. METHODS: We used UK primary care electronic health records (Clinical Practice Research Datalink GOLD) for a matched cohort study in adults (18 years+) (1997-2015) with at least one recorded lymphocyte count. We matched people with AE to up to five people without. We used multivariable logistic regression to estimate the association between AE and lymphopenia (two low lymphocyte counts within 3 months) and linear mixed effects regression to estimate the association with absolute lymphocyte counts using all available counts. Cox proportional hazard models were used to investigate the effect of lymphopenia on common infections. We replicated the study using US survey data (National Health and Nutrition Examination Survey [NHANES]). RESULTS: Among 71,731 adults with AE and 126,349 adults without AE, we found an adjusted odds ratio (OR) for lymphopenia of 1.16 (95% CI: 1.09-1.23); the strength of association increased with increasing eczema severity. When comparing all recorded lymphocyte counts from adults with AE (n = 1,497,306) to those of people without AE (n = 4,035,870) we saw a lower mean lymphocyte (adjusted mean difference -0.047 × 109 /L [95% CI: -0.051 to -0.043]) in those with AE. The difference was larger for men, with increasing age, and with increasing AE severity and was present among people with AE not treated with immunosuppressive drugs. In NHANES (n = 22,624), the adjusted OR for lymphopenia in adults with AE was 1.30 (95% CI: 0.80-2.11), and the adjusted mean lymphocyte count difference was -0.03 × 109 /L (95% CI: -0.07 to 0.02). Despite having a lower lymphocyte count, adjusting for time with lymphopenia, did not alter risk estimates of infections. CONCLUSION: Atopic eczema, including increasing AE severity, is associated with a decreased lymphocyte count, regardless of immunosuppressive drug use. Whether the lower lymphocyte count has wider health implications for people with severe eczema warrants further investigation.

Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I-II Melanoma Patients at Risk of Disease Relapse.

Background: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I−II melanoma) is watchful waiting, while >40% of patients with stage IB−IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I−II melanoma at risk of disease relapse. Methods: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (The Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only. Results: In total, 535 patients (stage I−II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4−96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3−84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41−6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a 'low risk' of recurrence (96.8% 5-year RFS (95%CI 91.6−98.8), n = 130), 49% as 'intermediate risk' (88.4% 5-year RFS (95%CI 83.6−91.8), n = 261), and 26% as 'high risk' (61.1% 5-year RFS (95%CI 51.9−69.1), n = 137). Conclusion: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I−II melanoma into two groups differentiated by RFS.

Risk factors for metastatic cutaneous squamous cell carcinoma: Refinement and replication based on 2 nationwide nested case-control studies.

BACKGROUND: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets. OBJECTIVE: To analyze and replicate risk factors for metastatic cSCC. METHODS: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set. RESULTS: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs). LIMITATIONS: Retrospective use of pathology reports in the English data set. CONCLUSION: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.

Limited impact of COVID-19-related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis.

BACKGROUND: The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages. OBJECTIVES: To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods. METHODS: In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre-COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t-test. pT-stage groups were compared using a χ2 -test. Outcomes were corrected for multiple testing using the false discovery rate. RESULTS: In total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii-v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre-COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre-COVID (i) and COVID-affected periods (ii-v) for cSCCs. CONCLUSIONS: To date, the diagnostic delay caused by COVID-19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow-up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term.

Efficacy, cost-minimization, and budget impact of a personalized discharge letter for basal cell carcinoma patients to reduce low-value follow-up care.

BACKGROUND: The incidence of keratinocyte carcinomas is high and rapidly growing. Approximately 80% of keratinocyte carcinomas consist of basal cell carcinomas (BCC) with 50% of these being considered as low-risk tumors. Nevertheless, 83% of the low-risk BCC patients were found to receive more follow-up care than recommended according to the Dutch BCC guideline, which is one visit post-treatment for this group. More efficient management could reduce unnecessary follow-up care and related costs. OBJECTIVES: To study the efficacy, cost-utility, and budget impact of a personalized discharge letter for low-risk BCC patients compared with usual care (no personalized letter). METHODS: In a multi-center intervention study, a personalized discharge letter in addition to usual care was compared to usual care in first-time BCC patients. Model-based cost-utility and budget impact analyses were conducted, using individual patient data gathered via surveys. The outcome measures were number of follow-up visits, costs and quality adjusted life years (QALY) per patient. RESULTS: A total of 473 first-time BCC patients were recruited. The personalized discharge letter decreased the number of follow-up visits by 14.8% in the first year. The incremental costs after five years were -€24.45 per patient. The QALYs were 4.12 after five years and very similar in both groups. The national budget impact was -€2,7 million after five years. CONCLUSIONS: The distribution of a personalized discharge letter decreases the number of unnecessary follow-up visits and implementing the intervention in a large eligible population would results in substantial cost savings, contributing to restraining the growing BCC costs.

Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2-5%). Developments in therapeutic options have highlighted the need to better identify high-risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow-up imaging, while at the same time safely omitting low-risk patients from further follow-up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt. OBJECTIVES: To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women's Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort. METHODS: A nested case-control study using data from the National Disease Registration Service, England, 2013-2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow-up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c-index. RESULTS: We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8-94.3%, PPV (13.2%, 95% CI 10.6-16.2) and c-index (0.84, 95% CI 0.82-0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2-99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging. CONCLUSIONS: We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems.

Cumulative incidence and disease-specific survival of metastatic cutaneous squamous cell carcinoma: A nationwide cancer registry study.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) represents the most serious form of keratinocyte cancers because of its metastatic potential. Studies on nationwide incidence and disease-specific survival rates of metastatic cSCC (mcSCC) are lacking. OBJECTIVE: To investigate the cumulative incidence and disease-specific survival of patients with mcSCC in the Dutch population and assess patient-based risk factors. METHODS: We conducted a nationwide cancer registry study including all patients with the first cSCC in 2007 or 2008, using data from the Netherlands Cancer Registry, the nationwide network and registry of histopathology and cytopathology, and Statistics Netherlands. Cumulative incidence and Kaplan-Meier curves were calculated, and time-dependent Cox proportional hazards regression analyses were used. RESULTS: Of the 11,137 patients, metastases developed in 1.9% (n = 217). The median time to metastasis was 1.5 years (interquartile range 0.6-3.8 years). The risk factors were age (adjusted hazard ratio [aHR] 1.03, 95% CI 1.02-1.05), male sex (aHR 1.7, 95% CI 1.3-2.3), and immunosuppression (aHR [organ transplant recipient] 5.0, 95% CI 2.5-10.0; aHR [hematologic malignancy] 2.7, 95% CI 1.6-4.6). The 5-year disease-specific survival for patients with mcSCC was 79.1%. LIMITATIONS: Only histopathologically confirmed mcSCCs were included. CONCLUSION: About 2% of cSCCs metastasize, with higher risk for men, increasing age, and immunocompromised patients. Disease-specific survival for patients with mcSCC is high.

Practice Variation in Skin Cancer Treatment and Follow-Up Care: A Dutch Claims Database Analysis.

BACKGROUND: Quality indicators are used to benchmark and subsequently improve quality of healthcare. However, defining good quality indicators and applying them to high-volume care such as skin cancer is not always feasible. OBJECTIVES: To determine whether claims data could be used to benchmark high-volume skin cancer care and to assess clinical practice variation. METHODS: All skin cancer care-related claims in dermatology in 2016 were extracted from a nationwide claims database (Vektis) in the Netherlands. RESULTS: For over 220,000 patients, a skin cancer diagnosis-related group was reimbursed in 124 healthcare centres. Conventional excision reflected 75% of treatments for skin cancer but showed large variation between practices. Large practice variation was also found for 5-fluorouracil and imiquimod creams. The practice variation of Mohs micrographic surgery and photodynamic therapy was low under the 75th percentile, but outliers at the 100th percentile were detected, which indicates that few centres performed these therapies far more often than average. On average, patients received 1.8 follow-up visits in 2016. CONCLUSIONS: Claims data demonstrated large practice variation in treatments and follow-up visits of skin cancer and may be a valid and feasible data set to extract quality indicators. The next step is to investigate whether detected practice variation is unwarranted and if a reduction improves quality and efficiency of care.

Melanoma in older patients: declining gap in survival between younger and older patients with melanoma.

Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades.Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 (n = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conductedResults: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89).Conclusion: The gap in melanoma incidence between younger and older people is increasing due to a strong increase in incidence in older adults. Disparities in survival are declining, related to a narrowing gap in Breslow thickness.

Validation of the English Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) Questionnaire.

BACKGROUND: Keratinocyte carcinomas (KC) impact patient quality of life (QoL). There is a need for validated QoL instruments specific to KC. The Basal and Squamous Cell Carcinoma QoL (BaSQoL) questionnaire was developed to comprehensively measure issues of importance to patients with KC. OBJECTIVE: To validate and characterize the BaSQoL questionnaire for QoL measurement after diagnosis and treatment of KC. METHODS: This was a prospective, observational study. Patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) were asked to fill out BaSQoL, Skin Cancer Index (SCI), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Descriptive statistics and classical test theory were used to assess validity. RESULTS: One hundred eighty-seven subjects enrolled in this study: 122 with BCC and 65 with SCC. One hundred seventy-one subjects (91.4%) completed questionnaires at all 3 time points; 16 patients (8.6%) were lost to follow-up. Overall performance using classical test theory was good, with good internal consistency (Cronbach's α 0.63-0.80). BaSQoL subscales were strongly correlated with subscales of the SCI, demonstrating convergent validity, and weakly correlated with HADS, showing divergent validity. CONCLUSION: The English language version of BaSQoL has good face, content, and construct validity. This study validates BaSQoL for use in English-speaking patients with BCC and SCC.

Dermatofibrosarcoma Protuberans Re-excision and Recurrence Rates in the Netherlands Between 1989 and 2016.

Dermatofibrosarcoma protuberans is a rare soft tissue tumour with a very low (p < 0.5%) rate of metastasis. Rates of re-excision and recurrence were determined using data from the Netherlands Cancer Registry between 1989 and 2016. Of the 1,890 instances of dermatofibrosarcoma protuberans included, 87% were treated with excision, 4% with Mohs micrographic surgery, and 9% otherwise or unknown. Linked pathology data were retrieved for 1,677 patients. Half of all excisions (847/1,644) were incomplete and 29% (192/622) of all re-excisions were incomplete. The cumulative incidence of a recurrence was 7% (95% confidence interval (95% CI) 6-8) during a median follow-up of 11 years (interquartile range (IQR) 6-17). After Mohs micrographic surgery (n = 34), there were no recurrences during a median follow-up of 4 years (IQR 3-6). Due to the high rate of incomplete excisions and recurrences after excision, this study supports the European guideline, which recommends treating dermatofibrosarcoma protuberans with Mohs micrographic surgery in order to decrease the rate of recurrence.

Commonly Used Endovenous Laser Ablation (EVLA) Parameters Do Not Influence Efficacy: Results of a Systematic Review and Meta-Analysis.

OBJECTIVES: The objective of this systematic review and meta-analysis was to summarise available randomised controlled trials (RCTs) of EVLA efficacy, and to define the differences in success rate of variations in wavelength, administered energy, outcome definition, and follow up period. METHODS: A literature search was conducted in Embase, Medline (Ovid-SP), Cochrane Central Database, and Web of Science from inception to November 2017. RCTs with follow up of more than three months were included. The studied outcome was the proportion of patients with EVLA treatment success, defined as absence of reflux or occlusion of the great saphenous vein (GSV). Pooled proportions of anatomical success were compared. Subgroup and meta-regression analysis included wavelengths (short [810, 940, and 980 nm], long [1470, 1500, and 1920 nm]), amount of energy (≤50 J/cm, > 50 J/cm), follow up (≤1 year, > 1 year), outcome definition (occlusion, no reflux), and quality of the studies (low risk of bias, unclear/high risk of bias). RESULTS: Twenty-eight RCTs, with a total of 2829 GSVs were included. The overall success rate of EVLA was 92% (95% CI 90-94%, I2 = 68%). In subgroup analysis, no statistically significant differences were found for long or short wavelengths (95% [95% CI 91-97%] vs. 92% [95% CI 89-94%], p = .15), high or low administered energy (93% [95% CI 89-95%] vs. 92% [95% CI 90-94%], p = .99), long or short follow up (89% [95% CI 84-93%] vs. 93% [95% CI 91-95%], p = .13) and outcome definition (occlusion group 94% [95% CI 91-96%] vs. absence of reflux group 91% [95% CI 87-94%], p = .26). Studies with low risk of bias reported a significantly higher success rate than high or unclear risk of bias (93% [95% CI 90-95%] vs. 89% [95% CI 83-93%], p = .04). CONCLUSIONS: The overall success rate of EVLA is high (92%), even with increasing follow up. Commonly used parameters of EVLA (wavelength, administered energy, and outcome definition) have no influence on the treatment success rate.