Cutaneous melanoma in adolescents and young adults.

BACKGROUND: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population. OBJECTIVE: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category. METHODS: This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method. RESULTS: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004). CONCLUSION: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients.

Could the mitotic count improve personalized prognosis in melanoma patients?

A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.

Cutaneous melanoma in older patients.

BACKGROUND: In industrialized countries, the aging population is steadily rising. The incidence of cutaneous malignant melanoma (CMM) is highest in old people. This study focuses on the clinicopathological profile of CMM and indicators of diagnostic-therapeutic performance in older patients. METHODS: This retrospective population-based cohort study included 1,368 incident CMM, as recorded in 2017 by the Regional Veneto Cancer Registry (Northeast Italy). Older subjects were defined as ≥ 80, old as 65-79, and adults as < 65 years of age. The strength of association between pairs of variables was tested by Cramer's-V. Using age groups as the dependent variable, ordered logistic regression was fitted using the clinicopathological CMM profiles as covariates. In each of the three age-groups, the indicators of clinical performance were computed using the Clopper-Pearson exact method. RESULTS: Compared to patients aged younger than 80 years (1,187), CMM in older patients (181; 13.2%) featured different CMM topography, a higher prevalence of ulcers (43.3% versus 12.7%; p < 0.001), a higher Breslow index (p < 0.001), a lower prevalence of tumor-infiltrating lymphocytes (64.4% versus 76.5%, p < 0.01), and a more advanced pTNM stage at clinical presentation (p < 0.001). Elderly patients with a positive sentinel-lymph node less frequently underwent sentinel- lymph node biopsy and lymphadenectomy (60.0% versus 94.2%, and 44.4% versus 85.5%, respectively; p < 0.001). CONCLUSIONS: In older CMM patients, the clinicopathological presentation of CMM shows a distinctive profile. The present results provide critical information to optimize secondary prevention strategies and refine diagnostic-therapeutic procedures tailored to older patients.

Health Economic Consequences Associated With COVID-19-Related Delay in Melanoma Diagnosis in Europe.

Importance: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet. Objective: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe. Design, Setting, and Participants: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous melanomas stages I to IV according to the American Joint Committee on Cancer (AJCC) seventh and eighth editions, including melanomas of unknown primary (T0). Data were collected from January 2017 to December 2021 in Switzerland and from January 2019 to December 2021 in Hungary. Data were used to develop an estimation of melanoma upstaging rates in AJCC stages, which was verified with peripandemic data. Years of life lost (YLL) were calculated and were, together with cost data, used for financial estimations. The total financial burden was assessed through direct and indirect treatment costs. Models were building using data from 50 072 patients aged 18 years and older with invasive primary cutaneous melanomas stages I to IV according to the AJCC seventh and eighth edition, including melanomas of unknown primary (T0) from 2 European tertiary centers. Data from European cancer registries included patient-based direct and indirect cost data, country-level economic indicators, melanoma incidence, and population rates per country. Data were analyzed from July 2021 to September 2022. Exposure: COVID-19 lockdown-related delay of melanoma detection and consecutive public health and economic burden. As lockdown restrictions varied by country, lockdown scenario was defined as elimination of routine medical examinations and severely restricted access to follow-up examinations for at least 4 weeks. Main Outcomes and Measures: Primary outcomes were the total burden of a delay in melanoma diagnosis during COVID-19 lockdown periods, measured using the direct (in US$) and indirect (calculated as YLL plus years lost due to disability [YLD] and disability-adjusted life-years [DALYs]) costs for Europe. Secondary outcomes included estimation of upstaging rate, estimated YLD, YLL, and DALY for each European country, absolute direct and indirect treatment costs per European country, proportion of the relative direct and indirect treatment costs for the countries, and European health expenditure. Results: There were an estimated 111 464 (range, 52 454-295 051) YLL due to pandemic-associated delay in melanoma diagnosis in Europe, and estimated total additional costs were $7.65 (range, $3.60 to $20.25) billion. Indirect treatment costs were the main cost driver, accounting for 94.5% of total costs. Estimates for YLD in Europe resulted in 15 360 years for the 17% upstaging model, ranging from 7228 years (8% upstaging model) to 40 660 years (45% upstaging model). Together, YLL and YLD constitute the overall disease burden, ranging from 59 682 DALYs (8% upstaging model) to 335 711 DALYs (45% upstaging model), with 126 824 DALYs for the real-world 17% scenario. Conclusions and Relevance: This economic analysis emphasizes the importance of continuing secondary skin cancer prevention measures during pandemics. Beyond the personal outcomes of a delayed melanoma diagnosis, the additional economic and public health consequences are underscored, emphasizing the need to include indirect economic costs in future decision-making processes. These estimates on DALYs and the associated financial losses complement previous studies highlighting the cost-effectiveness of screening for melanoma.

Cost items in melanoma patients by clinical characteristics and time from diagnosis.

Background: Costs related to the care of melanoma patients have been rising over the past few years due to increased disease incidence as well as the introduction of innovative treatments. The aim of this study is to analyse CMM cost items based on stage at diagnosis, together with other diagnostic and prognostic characteristics of the melanoma. Methods: Analyses were performed on 2,647 incident cases of invasive CMM that were registered in 2015 and 2017 in the Veneto Cancer Registry (RTV). Direct melanoma-related costs per patient were calculated for each year ranging from 2 years before diagnosis to 4 years after, and were stratified by cost items such as outpatient services, inpatient drug prescriptions, hospital admissions, hospice admissions, and emergency room treatment. Average yearly costs per patient were compared according to available clinical-pathological characteristics. Lastly, log-linear multivariable analysis was performed to investigate potential cost drivers among these clinical-pathological characteristics. Findings: Overall, the average direct costs related to melanoma are highest in the first year after diagnosis (€2,903) and then decrease over time. Hospitalization costs are 8 to 16 times higher in the first year than in subsequent years, while the costs of outpatient services and inpatient drugs decrease gradually over time. When stratified by stage it is observed that the higher expenditure associated with more advanced stages of CMM is mainly due to inpatient drug use. Conclusion: The results of the present study show that grouping patients according to tumour characteristics can improve our understanding of the different cost items associated with cutaneous malignant melanoma. CMM patients experience higher costs in the first year after diagnosis due to higher hospitalization and outpatient services. Policy makers should consider overall and stage-specific annual costs when allocating resources for the management of CMM patients.

Sex Differences in Soft Tissue Sarcoma: Incidence, Clinicopathological Profile, Survival, and Costs.

Background: There are evident sex differences in the incidence of and mortality rates for several tumors. Soft tissue sarcomas (STSs) account for no more than 1% of all malignancies in adults. This study aimed to provide a comprehensive overview of the sex differences in the epidemiology of STSs and the related costs. Methods: This retrospective population-based study draws on epidemiological data regarding cases of STS collected by the cancer registry of the Italian Veneto region for the years 1990-2018. A joinpoint regression analysis was performed to identify significant changes in the trends of the standardized incidence rates in males and females. Bivariate and survival analyses were conducted to assess differences in clinicopathological characteristics and short-term mortality by sex. Direct health care costs incurred over 2 years after a diagnosis of STS were calculated, stratified by sex. Results: The incidence rates of STS at any age were higher for males; only among males the incidence rates showed a tendency to slightly increase. No significant sex differences came to light in short-term mortality or clinicopathological profile, except for the cancer site. Health care costs in the 2 years after a diagnosis of STS were not sex related. Conclusion: The STS incidence was found to be higher for males and showed a rising trend over the last three decades only for males. These findings could result from the occupational exposure to environmental mutagens mainly involving men. Sex did not affect the survival or the clinicopathological STS profile.

Indicators of clinical performance in monitoring soft tissue sarcoma management: a population-based perspective.

Background: Soft tissue sarcomas (STS) are rare malignancies which prognosis varies significantly by primary site, histological subtype, and tumor stage. Their low incidence, and the complexity of their clinico-pathological characteristics demand standardized, cancer-tailored diagnostics and therapies managed at high-volume, multidisciplinary care centers. This study evaluates the quality of STS management in north-east Italy (Veneto Region) through a list of ad hoc defined clinical indicators. Methods: This population-based study concerns all incident cases of STS in 2018 (214 cases) recorded in the adult population censored by the Veneto's regional Cancer Registry. Based on the international literature, a multidisciplinary working group of experts identified a set of indicators for monitoring the quality of diagnostic, therapeutic, and end-of-life clinical interventions. The quality of care was assessed by comparing the reference thresholds with the indicators' values achieved in clinical practice. Results: Diagnostic procedures showed poor adherence to the thresholds, with a low percentage of histological diagnoses validated by a second opinion. The indicators relating to the surgical treatment of superficial, small, low-grade STS, or of medium, high-grade STS of the head-neck, trunk, or limbs were consistent with the thresholds, while for intermediate, high-grade (large-sized, deep) and retroperitoneal STS they fell significantly below the thresholds. Conclusion: A critical evaluation of the clinical indicators allowed to uncover the procedures needing corrective action. Monitoring clinical care indicators improves cancer care, confirms the importance of managing rare cancers at highly specialized, high-volume centers, and promotes the ethical sustainability of the healthcare system.

The Relevant Oral Burden of Patients with Hidradenitis Suppurativa.

INTRODUCTION: Interleukin-17 plays a pivotal role in both hidradenitis suppurativa (HS) and in maintaining oral homeostasis, but their potential link remains unknown. Thus, we aimed to evaluate and quantify the oral burden of patients with HS. METHODS: In this real-life, multicenter, cross-sectional study, patients with HS were clinically evaluated by two board-certified dermatologists and two board-certified dentists. Oral comorbidities were carefully collected with medical history and therapeutic information. RESULTS: A total of 102 patients (44.0 ± 0.9 years, body mass index 27.0 ± 2.2 kg/m2) were enrolled. Remarkably, 48% and 43% did not undergo at least an oral hygiene or a dental visit each year, respectively. Oral disorders were found in 55.9% of patients with HS, in particular 39.2% had caries and 46.7% reported at least one missing tooth. The main oral manifestations in patients with HS were recurrent aphthous stomatitis (N = 19, 19.2%), amalgam tattoo (N = 14, 14.1%), leukoplakia (N = 11, 11.1%), nicotinic stomatitis (N = 9, 9.1%), papilloma (N = 8, 8.1%), and geographic tongue (N = 8, 8.1%). Whilst the main predictor of oral pathological conditions was Hurley staging (P = 0.0276), multivariate regression analysis indicated that gender and International Hidradenitis Suppurativa Severity Score System (IHS4) were the main predictors for the presence of caries and number of missing teeth. CONCLUSION: As a result of the relevant oral burden in patients with HS, dentists should be part of the multidisciplinary team and oral education should be promoted among patients with HS.

Synchronous and metachronous multiple primary cancers in melanoma survivors: a gender perspective.

Background: Long-term survivors of cutaneous malignant melanoma (CMM) risk subsequent malignancies due to both host-related and environmental risk factors. This retrospective population-based study differentially assesses the risk of synchronous and metachronous cancers in a cohort of CMM survivors stratified by sex. Methods: The cohort study (1999-2018) included 9,726 CMM survivors (M = 4,873, F = 4,853) recorded by the cancer registry of all 5,000,000 residents in the Italian Veneto Region. By excluding subsequent CMM and non-CMM skin cancers, the incidence of synchronous and metachronous malignancies was calculated according to sex and tumor site, standardizing for age and calendar year. The Standardized Incidence Ratio (SIR) was calculated as the ratio between the number of subsequent cancers among CMM survivors and the expected number of malignancies among the regional population. Results: Irrespective of the site, the SIR for synchronous cancers increased in both sexes (SIR = 1.90 in males and 1.73 in females). Both sexes also demonstrated an excess risk for synchronous kidney/urinary tract malignancies (SIR = 6.99 in males and 12.11 in females), and women had an increased risk of synchronous breast cancer (SIR = 1.69). CMM male survivors featured a higher risk of metachronous thyroid (SIR = 3.51, 95% CI [1.87, 6.01]), and prostate (SIR = 1.35, 95% CI [1.12, 1.61]) malignancies. Among females, metachronous cancers featured higher SIR values than expected: kidney/urinary tract (SIR = 2.27, 95% CI [1.29, 3.68]), non-Hodgkin's lymphoma (SIR = 2.06, 95% CI [1.24, 3.21]), and breast (SIR = 1.46, 95% CI [1.22, 1.74]). Females had an overall increased risk of metachronous cancers in the first 5 years after CMM diagnosis (SIR = 1.54 at 6-11 months and 1.37 at 1-5 years). Conclusion: Among CMM survivors, the risk of metachronous non-skin cancers is higher than in the general population and differs significantly by sex. These results encourage sex-tailored interventions for metachronous secondary cancer prevention.

Epidemiology, pathological characteristics and survival of retroperitoneal soft­tissue sarcomas compared with non­retroperitoneal soft tissue sarcomas.

Retroperitoneal soft-tissue sarcomas (RPS) are rare forms of mesenchymal tumors that account for ~0.15% of all malignancies. The purpose of the present study was to determine the differences between RPS and non-RPS anatomopathological and clinical features and to analyze whether the hazard ratio for short-term mortality differs between patients with RPS and non-RPS, after adjusting for differences in baseline anatomopathological and clinical features. The Veneto Cancer Registry, a high-resolution population-based dataset spanning the regional population, was used as a data source for the analysis. The current analysis focuses on all incident cases of soft-tissue sarcoma recorded by the Registry from January 1, 2017 to December 31, 2018. A bivariate analysis was carried out to compare demographic and clinical characteristics in RPS and non-RPS. Short-term mortality risk was analyzed by primary tumor site. The significance of variations in survival by site group was determined using Kaplan-Meier curves and the Log-rank test. Finally, Cox regression was used to assess the hazard ratio for survival by sarcoma group. RPS accounted for 22.8% of the total sample (92 out of 404 cases). The mean age at diagnosis was 67.6 years for RPS vs. 63.4 for non-RPS; 41.3% of RPS were >150 mm vs. 5.5% for non-RPS. Stages III and IV were more prevalent in RPS (53.2 vs. 35.6%), despite the fact that, in both groups, advanced stages are the most common onset at diagnosis. Regarding surgical margins, the present study showed that R0 is the most prevalent in non-RPS (48.7%), while R1-R2 is the most frequent in patients with RPS (39.1%). The 3-year mortality rate for retroperitoneum was 42.9 vs. 25.7%. Comparing RPS and non-RPS, the multivariable Cox model showed a hazard ratio of 1.58 after adjusting for all other prognostic factors. RPS clinical and anatomopathological characteristics differ from those of non-RPS. Overall, despite adjusting for other prognostic factors, the retroperitoneum site was an independent prognostic factor associated with a worse overall survival in sarcoma patients compared with other sites.

Improving the Quality of Healthcare Provision Regarding HPV Immunization for Women with CIN2+ Lesions: The Experience of the Veneto Region in Italy.

HPV is the most common cause of sexually-transmitted infections the world over. The aim of this study was to assess the impact of a healthcare quality improvement strategy designed to increase the rate of vaccination against HPV in women diagnosed with cervical lesions graded as CIN2 or higher (CIN2+) during routine screening. The Veneto Regional Health Service developed a 22-item questionnaire to measure the gap between ideal procedure and real practice regarding the offer of vaccination against HPV for women undergoing routine cervical screening. The questionnaire was administered to nine expert doctors, one at each of the region's Local Health Units (LHUs). An additional specific assessment concerned the quality of the related web pages available on the LHU websites. Strategies to close the gap between ideal procedure and real practice were decided collegially, and a checklist to support good practices was developed and shared with operators at the LHUs. Changes in practice were measured using data relating to women diagnosed with CIN2+ lesions extracted from the regional oncological screening database before and after the publication of a Regional Procedure on the topic. The LHUs differed considerably in how they managed each step, in terms of training for healthcare personnel, organization and assessment of the pathway from cervical screening to HPV vaccination, and in dedicated website communication. After implementing the quality improvement strategy, the proportion of women given a first dose of HPV vaccine within 3 months of being diagnosed with CIN2+ lesions at 1st-level screening rose to 50% (compared with 30.85% beforehand), and the median time elapsing between a diagnosis of CIN2+ lesion and a first dose of HPV vaccine dropped from 158 to 90 days. These findings underscore the importance of providing training to promote vaccination for general practitioners and other clinicians. The study also confirms the need for more efforts in communication to ensure that any citizen has the opportunity to access preventive healthcare.

Estimated Direct Costs of Renal Cancer by Stage of Disease at Diagnosis and Phase of Its Management: A Whole-Disease Model.

BACKGROUND: Renal cell carcinoma (RCC) is the seventh most common neoplasm in high-income countries. New clinical pathways have been developed to deal with this tumor, which includes costly drugs that pose an economic threat to the sustainability of healthcare services. This study provides an estimate of the direct costs of care for patients with RCC by stage of disease (early vs. advanced) at diagnosis, and disease management phase along the pathway recommended by local and international guidelines. MATERIALS AND METHODS: Considering the clinical pathway for RCC adopted in the Veneto region (north-east Italy) and the latest guidelines, we developed a very detailed "whole-disease" model that covers the probabilities of all potentially necessary diagnostic and therapeutic actions involved in the management of RCC. Based on the cost of each procedure according to the Veneto Regional Authority's official reimbursement tariffs, we estimated the total and average per-patient costs by stage of disease (early or advanced) and phase of its management. RESULTS: In the first year after diagnosis, the mean expected cost of a patient with RCC is €12,991 if it is localized or locally-advanced and reaches €40,586 if it is advanced. For early disease, the main cost is incurred by surgery, whereas medical therapy (first and second line) and supportive care become increasingly important for metastatic disease. CONCLUSION: It is crucially important to examine the direct costs of care for RCC, and to predict the burden on healthcare services of new oncological therapies and treatments, as the findings could be useful for policy-makers planning the allocation of resources.

Using Failure Mode, Effect and Criticality Analysis to improve safety in the cancer treatment prescription and administration process.

BACKGROUND: Administering cancer drugs is a high-risk process, and mistakes can have fatal consequences. Failure Mode, Effect and Criticality Analysis (FMECA) is a widely recognized method for identifying and preventing potential risks, applied in various settings, including healthcare. The aim of this study was to recognize potential failures in cancer treatment prescription and administration, with a view to enabling the adoption of measures to prevent them. METHODS: This study consists of a FMECA. A team of resident doctors in public health at the University of Padua examined the cancer chemotherapy process with the support of a multidisciplinary team from the Veneto Institute of Oncology (an acknowledged comprehensive cancer center), and two other provincial hospitals. A diagram was drafted to illustrate 9 different phases of chemotherapy, from the adoption of a treatment plan to its administration, and to identify all possible failure modes. Criticality was ascertained by rating severity, frequency and likelihood of a failure being detected, using adapted versions of already published scales. Safety strategies were identified and summarized. RESULTS: Twenty-two failure modes came to light, distributed over the various phases of the cancer treatment process, and seven of them were classified as high risk. All phases of the cancer chemotherapy process were defined as potentially critical and at least one action was identified for a single high-risk failure mode. To reduce the likelihood of the cause, or to improve the chances of a failure mode being detected, a total of 10 recommendations have been identified. CONCLUSIONS: FMECA can be useful for identifying potential failures in a process considered to be at high risk. Safety strategies were devised for each high-risk failure mode identified.

Thirty-two-year trends of cancer incidence by sex and cancer site in the Veneto Region from 1987 to 2019.

Background: This observational study considers the sex-specific incidence of the most incident cancers as recorded in the population-based Veneto Regional Cancer Registry over a period of more than 30 years (1987-2019). Methods: The Veneto Regional Cancer Registry collected data for the time interval 1987-2019. Significant changes in incidence trends calculated on age-standardized incidence rates (Annual Percent Change-APC) were identified by join point regression analysis. Results: Overall, the incidence trend for all cancers decreased in males and remained stable in females. In nine cancer sites, the incidence trends showed consistent differences by sex (oral cavity, esophagus, colon rectum and anus, liver, larynx, lung, cutaneous malignant melanoma, bladder, and thyroid gland). Other malignancies did not show significant sex-related differences (stomach, pancreas, biliary tract, kidney/urinary tract, central nervous system, multiple myeloma, non-Hodgkin lymphoma, and leukemia). Conclusion: In the period 1987-2019, this study revealed sex-related differences in cancer incidence trends. Over time, cancer incidence remained higher in males, with a decreasing epidemiological impact, plausibly resulting from prevention campaigns against environmental cancer risk factors, as tobacco and alcohol. Conversely, a significant decrease was not observed in the incidence trend in females. These findings contribute essential insights for profiling the epidemiological map of cancer in a large Italian population, allowing comparison with other European cancer epidemiology studies and providing updated data supporting sex-related primary and secondary cancer prevention strategies.

Renal cell carcinoma: the population, real world, and cost-of-illness.

BACKGROUND: The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC's cost-of-illness for this tumour's clinical pathway. METHODS: This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis. RESULTS: The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages. CONCLUSIONS: This observational study provides real-world and valuable estimates of RCC's cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs' evaluation.

Per- and polyfluoroalkyl substances (PFAS) exposure in melanoma patients: a retrospective study on prognosis and histological features.

Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals which could be associated with cancer development, such as kidney and testicular cancers, pancreatic and hepatocellular carcinoma and thyroid tumor. Available scientific literature offers no information on the role of PFAS in melanoma development/progression. Since 1965, a massive environmental contamination by PFAS has occurred in northeastern Italy. This study compared histopathology and prognosis between melanoma patients exposed (n = 194) and unexposed (n = 488) to PFAS. All patients were diagnosed and/or treated for melanoma at the Veneto Oncological Institute and the University Hospital of Padua (Italy) in 1998-2014. Patients were categorized in exposed or unexposed groups according to their home address and the geographical classification of municipalities affected by PFAS contamination as provided by Veneto Government in 2018. Presence of mitoses was found in 70.5% of exposed patients and 58.7% of unexposed patients (p = 0.005). Median follow-up was 90 months (IQR 59-136). 5-year overall survival was 83.7% in exposed patients and 88.0% in unexposed patients (p = 0.20); 5-year disease-specific survival was 88.0% in exposed patients and 90.9% in unexposed patients (p = 0.50); 5-year disease-free survival was 83.8% in exposed patients and 87.3% in unexposed patients (p = 0.20). Adjusting for imbalanced characteristics at baseline (presence of mitoses), survival was not statistically different between exposed and unexposed patients (overall survival: HR 1.10, 95% CI 0.77 to 1.58, p = 0.57; disease-specific survival: HR 0.99, 95% CI 0.62 to 1.59, p = 0.99; disease-free survival: HR 1.10, 95% CI 0.74 to 1.64, p = 0.62). Although the magnitude of PFAS exposure was not quantifiable, our findings suggested that exposure to PFAS was associated with higher level of mitosis in melanoma patients, but this did not translate into a survival difference. Further studies are required to investigate this relationship and all effects of PFAS on prognosis.

Cost-effectiveness analysis of the new oncological drug durvalumab in Italian patients with stage III non-small cell lung cancer.

BACKGROUND: The monoclonal antibody durvalumab, an immune-checkpoint inhibitor (ICI) antiprogrammed death ligand 1 (PD-L1), is available for unresectable stage III NSCLC patients as consolidation therapy following induction chemoradiotherapy, with very promising overall survival (OS) and progression-free survial (PFS) results in registration trials. The purpose of this study was to provide policymakers with an estimate of the cost-effectiveness of durvalumab in the treatment of non-small cell lung cancer (NSCLC). METHODS: The study developed a Markov model covering a 5-year period to compare costs and outcomes of treating PD-L1 positive patients with or without durvalumab. We conducted a series of sensitivity analyses (Tornado analysis and Monte Carlo simulation) by varying some parameters to assess the robustness of our model and identify the parameters with the greatest impact on cost-effectiveness. RESULTS: Prior to the release of durvalumab, the management of NSCLC over a 5-year period cost €33 317 per patient, with an average life expectancy of 2.01 years. After the introduction of the drug, this increased to €37 317 per patient, with an average life expectancy of 2.13 years. Treatment with durvalumab led to an incremental cost-effectiveness ratio (ICER) of €35 526 per year. OS is the variable that contributes the most to the variability of the ICER. CONCLUSIONS: The study observed that durvalumab is a cost-effective treatment option for patients with unresectable stage III NSCLC.

Diagnostic-Therapeutic Pathway and Outcomes of Early Stage NSCLC: a Focus on EGFR Testing in the Real-World.

Background: Osimertinib is considered the standard-of-care for previously-untreated EGFR mutant advanced non-small cell lung cancer (NSCLC). Oncogene driver screening in early NSCLC is not standard practice. A real-world study has been designed in order to investigate the optimal testing frequency and timing for EGFR mutations in early NSCLC in clinical practice. Patients and Methods: The present observational, retrospective study evaluated the real-world diagnostic-therapeutic pathway and clinical outcomes of 225 patients with stage I-III NSCLC, with particular reference to the EGFR-mutant subgroup. Results: Prior to surgery, 101 patients had undergone a diagnostic biopsy; EGFR mutational analysis was available in 56 (55%) patients and 12 patients (21%) had a cancer harboring an EGFR mutation. Among surgical specimens, reflex EGFR test was performed in 181 (80%) of 225 and 35 cases (19%) were EGFR mutant. The majority of patients had not received adjuvant chemotherapy (N=174, 77%) or adjuvant radiotherapy (N=201, 89%). Of 49 (22%) patients experiencing disease relapse, 26 (53%) received first-line systemic treatment. All EGFR-mutant relapsed patients (N=6, 12.2%) received an EGFR-TKI. Median overall survival (OS) and relapse-free survival for the entire population were not reached. Multivariate analysis for OS confirmed a significant correlation with age, female gender, EGFR status, necrosis score, perineural invasion, and relapsed disease. EGFR test costs represented 1.6-2.4% of the total costs of management per patient (€34,340). Conclusions: Our results suggest that the frequency of EGFR mutations in early stage (I-III) NSCLC is similar to that of advanced stages. Reflex EGFR testing in all early-stage NSCLC at diagnosis or after surgery appears to be a valid tool to give patients the chance to benefit from targeted adjuvant treatment.

Clinical performance indicators for monitoring the management of cutaneous melanoma: a population-based perspective.

The prognosis of cutaneous malignant melanoma (CMM) is based on disease progression. The highly heterogeneous clinical-pathological characteristics of CMM necessitate standardized diagnostic and therapeutic interventions tailored to cancer's stage. This study utilizes clinical performance indicators to assess the quality of CMM care in Veneto (Northeast Italy). This population-based study focuses on all incidences of CMMs registered by the Veneto Cancer Registry in 2015 (1279 patients) and 2017 (1368 patients). An interdisciplinary panel of experts formulated a set of quality-monitoring indicators for diagnostic, therapeutic, and end-of-life clinical interventions for CMM. The quality of clinical care for patients was assessed by comparing the reference thresholds established by experts to the actual values obtained in clinical practice. The prevalence of stage I-CMM decreased significantly from 2015 to 2017 (from 71.8 to 62.4%; P < 0.001), and almost all the pathology reports mentioned the number of nodes dissected during a lymphadenectomy. More than 90% of advanced CMMs were promptly tested for molecular BRAF status, but the proportion of patients given targeted therapies fell short of the desired threshold (61.1%). The proportion of stage I-IIA CMM patients who inappropriately underwent computerized tomography/MRI/PET dropped from 17.4 to 3.3% ( P < 0.001). Less than 2% of patients received medical or surgical anticancer therapies in the month preceding their death. In the investigated regional context, CMM care exhibited both strengths and weaknesses. The evaluated clinical indicators shed essential insight on the clinical procedures requiring corrective action. It is crucial to monitor clinical care indicators to improve care for cancer patients and promote the sustainability of the healthcare system.

Adolescent gambling behavior: a gender oriented prevention strategy is required?

BACKGROUND: Studies published on gender-related differences in the gambling behavior of adolescents have focused mainly on psychological and social factors. The aim of this study was to develop separate risk factor models for male and female adolescents, considering the environmental, psychological, behavioral and socio-economic factors related to their gambling. METHODS: A survey was conducted through a questionnaire developed on a dedicated web site in 2014 on a representative sample of the Italian 15-19-years-old population, including 34,922 students attending 438 secondary schools. The SOGS-RA questionnaire was used to measure gambling behavior. To verify the risk factors associated with gambling a logistic regression stratified by gender was performed. RESULTS: In our representative sample of Italian adolescents nationwide, the prevalence of each level of gambling was higher in males than in females. The logistic regression stratified by gender found that for both genders, gambling was positively associated with internet surfing, playing sports, getting into a fight, having unprotected sex, pulling stunts, drinking alcohol at least once in the previous month, having not a satisfactory relationship with teachers, receiving pocket money from parents, spending each week much money and having someone in the family (father, sister/brother, other relatives) who gambles. On the other hand, having poor or average school marks, going to ED in the previous year, smoking at least once in the previous month, having dissatisfied with relationships with father and having a lower family income than their friends was only associated with gambling in boys. Having an accident or injury in the previous year and having a mother who gambled was associated only in girls with higher odd of at risk or problem gambling behavior. A low psychological distress is protective only in girls for risk of gambling. CONCLUSIONS: Understanding the gender-related differences, and how they emerge in younger people at the start of their gambling careers, can suggest how best to educate individuals, families and the community on the topic of gambling. Programs to prevent substance use and abuse should be multifaceted, and include efforts to prevent gambling with a gender perspective approach.