The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

Optimizing the risk stratification of astrocytic tumors by applying the cIMPACT-NOW Update 3 signature: real-word single center experience.

Our work reports implementation of a useful genetic diagnosis for the clinical managment of patients with astrocytic tumors. We investigated 313 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. The cIMPACT-NOW Update 3 (cIMPACT-NOW 3) markers, i.e., alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 96.4% of IDHwt cases. Interestingly, it was also found in 48,5% of IDHmut cases. According to the genomic profile, four genetic subgroups could be distinguished: (1) IDwt/cIMPACT-NOW 3 (n = 270); (2) IDHwt/cIMPACT-NOW 3 negative (= 10); (3) IDHmut/cIMPACT-NOW 3 (n = 16); and 4) IDHmut/cIMPACT-NOW 3 negative (n = 17). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDHwt, HR 2.91 95% CI 1.39-6.06), and validated the prognostic value of the cIMPACT-NOW 3 signature (cIMPACT-NOW 3, HR 2.15 95% CI 1.15-4.03). To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.

BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.

BACKGROUND: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. MATERIALS AND METHODS: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines. RESULTS: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. CONCLUSIONS: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients.

A New Medium (HistoCold) for Surgical Specimens Preserving to Improve the Preanalytic Issues in Histopathological Samples Handling: Morphologic and Antigenic Analysis.

Introduction: The onset of precision medicine has led to the integration of traditional morphologic tissues evaluation with biochemical and molecular data for a more appropriate pathological diagnosis. The preanalytic phase and, particularly, timing of cold ischemia are crucial to guarantee high-quality biorepositories of formalin-fixed paraffin-embedded (FFPE) tissues for patients' needs and scientific research. However, delayed fixation using the gold-standard and carcinogenic fixative neutral-buffered formalin (NBF) can be a significant limitation to diagnosis and biopathological characterization. HistoCold (patented; Bio-Optica Milano S.p.A., Milano, Italy) is a nontoxic, stable, and refrigerated preservative solution for tissue handling. This study examined HistoCold's potential role in improving the preanalytic phase of the pathological diagnostic process. Materials and Methods: Breast, lung, or colorectal cancers (20, 25, and 10 cases, respectively) that were to be surgically resected were recruited between 2019 and 2021. Once specimens were surgically removed, three residual samples for each patient were first promptly immersed into HistoCold for 24, 48, and 72 hours and then FFPE. These were compared with routine specimens regarding morphologic features (hematoxylin and eosin) and tissue antigenicity (immunohistochemical stains). Results: Good concordance regarding both the morphologic characteristics of the neoplasms and their proteins expression between the routine and HistoCold handled tissues were found. The tissue handling with the solution never affected the histopathological diagnosis. Conclusions: The use of HistoCold for samples transporting is easy, allows for improving the management of cold ischemia time, and monitoring the fixation times in NBF, resulting in good quality tissue blocks for biobanking. Moreover, it could be a candidate to eliminate formalin from operating theaters. HistoCold looks very promising for the preanalytic phase of human tissues handling in the era of precision medicine, to provide the best service to patients, and to scientific research.

Nursing students and COVID-19 vaccination. ESitA Study An Observational Study.

BACKGROUND AND AIM: Vaccine hesitancy is an important problem in terms of health policy. This historical moment leads us to wonder if vaccine hesitancy is also present among nursing students who should be particularly sensitive to the subject Methods: Between February 10 to February 17 2021, 1080 students enrolled in the Bachelor of Science in Nursing in the Department of Medicine and Surgery of the University of Perugia, were invited to reply to an online questionnaire sent to their university email accounts. RESULTS AND CONCLUSIONS: A certain amount of vaccination hesitancy was detected among the students in our study. It can be assumed that the issues surrounding the AstraZeneca vaccine, which occurred at the start of the vaccination campaign, may have led to an increase in people's hesitancy. Boosting vaccination campaigns, including appropriate use of social media, may lead to greater acceptance. Also, it would be useful to assess the cultural basis of the recent anti-Vax controversy, particularly for students of nursing or other health professions, who should be able to evaluate, source and recognize the most validated data.

Higher TLR7 Gene Expression Predicts Poor Clinical Outcome in Advanced NSCLC Patients Treated with Immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, their clinical benefit is limited to a minority of patients. To unravel immune-related factors that are predictive of sensitivity or resistance to immunotherapy, we performed a gene expression analysis by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) on a total of 33 advanced NSCLC patients treated with ICI evaluating the expression levels of 365 immune-related genes. We found four genes (CD1C, HLA-DPA1, MMP2, and TLR7) downregulated (p < 0.05) and two genes (IFNB1 and MKI67) upregulated (p < 0.05) in ICI-Responders compared to ICI-Non-Responders. The Bayesian enrichment computational analysis showed a more complex interaction network that involved 10 other genes (IFNA1, TLR4, CD40, TLR2, IL12A, IL12B, TLR9, CD1E, IFNG, and HLA-DPB1) correlated with different functional groups. Five main pathways were identified (FDR < 0.0001). High TLR7 expression levels were significantly associated with a lack of response to immunotherapy (p < 0.0001) and worse outcome in terms of both PFS (p < 0.001) and OS (p = 0.03). The multivariate analysis confirmed TLR7 RNA expression as an independent predictor for both poor PFS (HR = 2.97, 95% CI, 1.16-7.6, p = 0.023) and OS (HR = 2.2, 95% CI, 1-5.08, p = 0.049). In conclusion, a high TLR7 gene expression level was identified as an independent predictor for poor clinical benefits from ICI. These data could have important implications for the development of novel single/combinatorial strategies TLR-mediated for an efficient selection of "individualized" treatments for NSCLC in the era of immunotherapy.

Sensitivity to Immune Checkpoint Blockade in Advanced Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations.

Besides platinum-based chemotherapy, no established treatment option exists for advanced non-small-cell lung cancer (NSCLC) patients with EGFR exon 20 (Ex20ins) insertion mutations. We sought to determine the clinical outcome of patients with this EGFR mutation subtype in the immunotherapy era. Thirty NSCLCs with EGFR Ex20ins mutations were identified, of whom 15 had received immune checkpoint blockade (ICB) treatment as monotherapy (N = 12), in combination with chemotherapy (N = 2) or with another immunotherapeutic agent (N = 1). The response rate was observed in 1 out of 15 patients (6.7%), median progression-free survival (PFS) was 2.0 months and median overall survival (OS) was 5.3 months. A trend towards an inferior outcome in terms of PFS and OS was observed for patients receiving ICB treatment in the first versus second line setting (PFS: 1.6 months versus 2.7 months, respectively, p = 0.16-OS: 2.0 months versus 8.1 months, respectively, p = 0.09). Median OS from the time of diagnosis of advanced disease was shorter for patients treated with ICB versus those who did not receive immunotherapy (12.9 months versus 25.2 months, respectively, p = 0.08), which difference remained associated with a worse survival outcome at multivariate analysis (p = 0.04). Treatment with ICB is poorly effective in NSCLCs with EGFR Ex20ins mutations, especially when given in the first-line setting. This information is crucial in order to select the optimal treatment strategy for patients with this subtype of EGFR mutation.

Evaluation of Lumipulse® G SARS-CoV-2 antigen assay automated test for detecting SARS-CoV-2 nucleocapsid protein (NP) in nasopharyngeal swabs for community and population screening.

OBJECTIVES: To compare the Lumipulse® SARS-CoV-2 antigen test with the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) for diagnosis of SARS-CoV-2 infection and to evaluate its role in screening programs. METHODS: Lumipulse® SARS-CoV-2 antigen assay was compared with the gold standard RT-PCR test in a selected cohort of 226 subjects with suspected SARS-CoV-2 infection, and its accuracy was evaluated. Subsequently, the test was administered to a real-life screening cohort of 1738 cases. ROC analysis was performed to explore test features and cutoffs. All tests were performed in the regional reference laboratory in Umbria, Italy. RESULTS: A 42.0% positive result at RT-PCR was observed in the selected cohort. The Lumipulse® system showed 92.6% sensitivity (95% CI 85.4-97.0%) and 90.8% specificity (95% CI 84.5-95.2%) at 1.24 pg/mL optimal cutoff. In the screening cohort, characterized by 5.2% prevalence of infection, Lumipulse® assay showed 100% sensitivity (95% CI 96.0-100.0%) and 94.8% specificity (95% CI 93.6-95.8%) at 1.645 pg/mL optimal cutoff; the AUC was 97.4%, NPV was 100% (95% CI 99.8-100.0%) and PPV was 51.1% (95% CI 43.5-58.7%). CONCLUSIONS: The Lumipulse® SARS-CoV-2 antigen assay can be safely employed in the screening strategies in small and large communities and in the general population.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

Efficacy of Pembrolizumab Monotherapy in Patients With or Without Brain Metastases From Advanced Non-Small Cell Lung Cancer With a PD-L1 Expression ≥50%.

The authors conducted a multicenter retrospective study on the outcome of programmed death-ligand 1 tumor proportion score≥50% advanced non-small cell lung cancer patients treated with first-line pembrolizumab according to the presence/absence of brain metastases. A total of 282 patients were included, of whom 56 had brain metastases that were treated with upfront local radiation therapy in 80.3% of cases. The overall response rate was 39.2% and 44.4% in patients with and without brain metastases (P=0.48), respectively, while intracranial response rate and intracranial disease control rate were 67.5% and 85.0%, respectively. The median time-to-treatment failure (TTF) and overall survival (OS) were 4.2 and 9.9 months versus 10.8 and 26.5 months for patients with and without brain metastases (P=0.06 and 0.05, respectively). Drug discontinuation rate due to treatment-related adverse events was 10.7% and 10.2% in patients with and without brain metastases, respectively. Multivariate analysis showed that baseline steroids was an independent predictor for a worse OS (P<0.001), while performance status (PS)≥2 was an independent predictor for a poorer TTF (P<0.001) and OS (P<0.001). In patients with brain metastases, only PS ≥2 was predicted for a worse TTF (P=0.02) and OS (P=0.03). Pembrolizumab has activity against brain metastases from non-small cell lung cancers with programmed death-ligand 1≥50%. Presence of brain metastases per se does not appear to be prognostic, and PS ≥2 seems to be the only factor associated with a worse outcome in patients with brain metastases.

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab.

Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1.Methods: Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated.Results: 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI: 0.17-0.57), p < .001). Median PFS was 2.6 months (95% CI: 1.9-5.1) among patients with PS2 and 11.3 months (95% CI: 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI: 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. PS 2 remained predictive of poor outcomes in multivariate analysis.Conclusion: PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.

Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool.

Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage between IDO2 expression and cancer progression is still unclear, in particular in non-small cell lung cancer (NSCLC). Immunohistochemical expression and cellular localization of IDO2 was evaluated on 191 formalin-fixed and paraffin-embedded resected NSCLC. Correlations between IDO2 expression, clinical-pathological data, tumor-infiltrating lymphocytes (TILs), immunosuppressive tumor molecules (IDO1 and programmed cell death ligand-1 - PD-L1 -) and patients' prognosis were evaluated. IDO2 high expression is strictly related to high PD-L1 level among squamous cell carcinomas group (p = 0.012), to either intratumoral or mixed localization of TILs (p < 0.001) and to adenocarcinoma histotype (p < 0.001). Furthermore, a significant correlation between IDO2 high expression and poor non-small cell lung cancer prognosis was detected (p = 0.011). The current study reaches interesting knowledge about IDO2 in non-small cell lung cancer. The close relationship between IDO2 expression, PD-L1 increased levels, TILs localization and NSCLC poor prognosis, assumed IDO2 as a potential prognostic biomarker to be exploited for optimizing innovative combined therapies with immune checkpoint inhibitors.

Significance of Morphine Concentration in Bile, Liver, and Blood: Analysis of 52 Cases of Heroin Overdoses.

Forensic pathologists are requested to select matrices alternative to blood in cases of toxicological interest in which blood is not available for different reasons. We evaluated morphine concentrations in blood, bile, and liver samples in 52 cases of heroin overdoses, relating them to each other, to understand the information that could be derived from their analysis. Gas chromatography/mass spectrometry analysis was performed for all the samples positive on screening for opiates. Shapiro-Wilk test, nonparametric Mann-Whitney test, linear regression analysis, and Bland-Altman test were used for analysis. Linear regression demonstrated that there was not a statistically significant association in morphine concentrations between blood and bile and blood and liver. Mean liver/blood ratio was 2.76, varying from 0.131 to 13.379, and bile/blood ratio was 28.79, varying from 0.28 to 559.16. According to these results, bile analysis is a "screening test"; biliary or hepatic concentration of morphine cannot provide information on hematic concentration at the time of death, having no forensic value taken individually.

Geospatial analysis of the influence of family doctor on colorectal cancer screening adherence.

BACKGROUND: Despite the well-recognised relevance of screening in colorectal cancer (CRC) control, adherence to screening is often suboptimal. Improving adherence represents an important public health strategy. We investigated the influence of family doctors (FDs) as determinant of CRC screening adherence by comparing each FDs practice participation probability to that of the residents in the same geographic areas using the whole population geocoded. METHODS: We used multilevel logistic regression model to investigate factors associated with CRC screening adherence, among 333,843 people at their first screening invitation. Standardized Adherence Rates (SAR) by age, gender, and socioeconomic status were calculated comparing FDs practices to the residents in the same geographic areas using geocoded target population. RESULTS: Screening adherence increased from 41.0% (95% CI, 40.8-41.2) in 2006-2008 to 44.7% (95% CI, 44.5-44.9) in 2011-2012. Males, the most deprived and foreign-born people showed low adherence. FD practices and the percentage of foreign-born people in a practice were significant clustering factors. SAR for 145 (21.4%) FDs practices differed significantly from people living in the same areas. Predicted probabilities of adherence were 31.7% and 49.0% for FDs with low and high adherence, respectively. DISCUSSION: FDs showed a direct and independent effect to the CRC screening adherence of the people living in their practice. FDs with significantly high adherence level could be the key to adherence improvement. IMPACT: Most deprived individuals and foreigners represent relevant targets for interventions in public health aimed to improve CRC screening adherence.

Long-Term Risk of Stroke After Transient Global Amnesia in Two Prospective Cohorts.

Background and Purpose- Transient global amnesia (TGA) is known as a benign syndrome, but recent data from neuroradiological studies support an ischemic cause in some cases, which might suggest an increased susceptibility to cerebrovascular events. We determined the long-term risk of stroke after a first TGA in 2 independent prospective cohorts. Methods- In 2 independent prospective cohorts of patients with TGA (OXVASC [Oxford Vascular Study], population-based; NU (Northern Umbria) cohort, TGA registry), cardiovascular risk factors and long-term outcomes, including stroke and major cardiovascular events, were identified on follow-up. Cardiovascular risk factors were treated according to primary prevention guidelines. In OXVASC, the age-/sex-adjusted risk of stroke during follow-up was compared with that expected from the rate in the underlying study population. Results- Among 525 patients with TGA (425 NU and 100 OXVASC), mean (SD) age was 65.1 (9.5) years and 42.5% male. Hypertension (58.1%), dyslipidemia (40.4%), and smoking (36.4%) were the most frequent cardiovascular risk factors. The risk of stroke was similar in the 2 cohorts, with a pooled annual risk of 0.6% (95% CI, 0.4-0.9) and a 5-year cumulative risk of 2.7% (1.1-4.3). Moreover, the stroke risk in OXVASC cases was no greater than that expected in the underlying study population (adjusted relative risk=0.73; 0.12-4.54; P=0.74). Conclusions- TGA does not carry an increased risk of stroke, at least when cardiovascular risk factors are treated according to primary prevention guidelines.

Stage-related outcome for thymic epithelial tumours.

BACKGROUND: Thymic epithelial tumours (TETs) are characterized by a wide variety of biological behaviors. Radical resection and stage are strong prognostic factors. Aim of this study is to review our Single Center Experience. METHODS: One hundred and seventy-seven patients observed in the period from January 2000 to December 2016 were included in the study. Data regarding clinicopathologic features, treatment, and survival were collected. Stage-related clinical standpoints and therapeutic options were also evaluated. RESULTS: Non-surgical treatment was primarily performed in 15 (8.47%), unresectable disease was intraoperatively found in 12 cases (7.4%). The analysis of 150 patients undergoing curative surgery revealed 70 stage I TET (46.66%), 49 stage II (32.66%), 19 stage III (12.66%), 6 stage IVa (4%) and 6 stage IVb (4%) at the first hospital admission. Histology identified 12 A thymoma (8%), 38 AB (25.33%), 24 B1 (16%), 50 B2 (33.33%), 19 B3 (12.66%) and 7 carcinomas (4.66%). The mean follow up time was 84.14 months (sd = 61.68 months). Disease relapse occurred in 13 patients (8.78%) at a mean period of 78.85 months (sd = 60.87 months) after surgery. Exitus due to thymoma happened in 6 cases (4.05%) after a mean survival of 56.02 months (sd = 25.17 months). The 5-year overall survival rate was 0.94 (95%CI 0.88-0.97) and the 5-year disease-free survival rate was 0.90 (95%CI 0.83-0.94). The 5-year overall survival rates were 96.1% (95% CI, 89.9-98.5%) for the early stages and 87.4% (95% CI, 65.6-95.8%) for the advanced stages (p = 0.670). The 5-year disease-free survival rates resulted being 98.8% (95% CI, 92.3-99.8%) for the early stages and 59.8% (95% CI, 37.8-76.2%) for the advanced stages (p < 0.001). CONCLUSIONS: Advanced stage TETs are characterized by higher mortality and recurrence rates. Although technically demanding, surgery, as part of multimodality therapy, could prolong survival. Iterative surgical treatment of recurrences is a viable option for selected patients. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Perugia and Terni University Hospitals [Code T1003] and was retrospectively registered.

Outcomes from salvage chemotherapy or pembrolizumab beyond progression with or without local ablative therapies for advanced non-small cell lung cancers with PD-L1 ≥50% who progress on first-line immunotherapy: real-world data from a European cohort.

BACKGROUND: In this real-world multicenter study we addressed the activity of post-progression anticancer treatments after first-line pembrolizumab in advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥50%. METHODS: Clinico-pathological data of PD-L1 ≥50% advanced NSCLCs who failed first-line pembrolizumab were collected in 14 Oncologic Centers from different European countries. Types of subsequent anticancer treatment and outcomes on salvage chemotherapy or pembrolizumab beyond progression with or without the addition of local ablative therapies were reported. RESULTS: Out of 173 patients, 100 had progressed on pembrolizumab, of which 60 patients (60%) met eligibility criteria and were treated with either salvage chemotherapy (42/60, 70%) or pembrolizumab beyond progression (18/60, 30%). Overall, median age was 66 years, 63.3% were male, 60.0% had a performance status of 0-1, 88.3% were smokers and 61.7% had adenocarcinoma histology. In patients evaluable for response, objective response rate to salvage chemotherapy was 41.9%, with no significant difference according to the type of regimen (42.9% for platinum-based and 40.0% for single-agent chemotherapy). Median progression-free survival (PFS) to salvage chemotherapy was 4.5 months. Among patients treated with pembrolizumab beyond progression, 13 out of 18 patients (72.2%) had progressive disease in ≤2 organ sites, of whom 9 (69.2%) were managed with the addition of local ablative therapies consisting of radiation at progressive lesion(s). No significant difference was noted in terms of post-progression survival between the salvage chemotherapy and the pembrolizumab beyond progression groups of patients (6.9 versus 8.1 months, respectively, P=0.08). CONCLUSIONS: In PD-L1 ≥50% advanced NSCLCs who progress on first-line pembrolizumab, salvage chemotherapy is associated with a remarkable anticancer activity, while select patients may benefit from continuation of pembrolizumab beyond progression, with the possible addition of local ablative radiotherapy in oligoprogressive cases.

Immigration, screening, and cervical cancer incidence: an application of Age-Period-Cohort analysis.

Cervical cancer (CC) control is based on the implementation of effective screening programs. In the coming years, human papilloma virus vaccination coverage will contribute considerably toward cancer prevention. In Italy, where an organized screening program has been implemented, immigration from low/middle-income countries with a high prevalence of human papilloma virus infections has increased steadily over the last decades. To assess the impact of screening efforts in counteracting background changes, we analyzed the incidence trends of cervical intraepithelial neoplasia grade 3 carcinomas in situ (CIS) and invasive CC from 1994 to 2013 through an Age-Period-Cohort model using data of a regional population-based registry. Moreover, using Joinpoint regression, we compared the incidence of cervical lesions in native women with that observed in foreign-born women, highlighting the differences in age and screening status. The results indicate that the CC incidence trend decreased in Italian women (annual percent change = -2.7*%, 95% confidence interval = -4.3; -1.1), but increased (APC = 12.2*%, 95% confidence interval = 7.6; 17.0) in immigrants. For CIS, incidence rates show a growing trend in both groups, especially in women born abroad. For cancer, no marked changes in period-specific incidence rate ratios were detected until around 2000, when we found a slight decrease, followed by an increase. For CIS, we estimate an important upward trend in cohort-specific risks. The favorable effect of screening in preventing an increase in CC incidence has been counteracted by the progressive increase in immigrants from high-risk countries, where it is of increasing relevance to extend the use of vaccination.

The impact of overdiagnosis on thyroid cancer epidemic in Italy,1998-2012.

AIMS: In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attributable to overdiagnosis. METHODS: Data on TC cases reported to Italian cancer registries during 1998-2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region. RESULTS: In Italy between 1998-2002 and 2008-2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998-2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008-2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders. CONCLUSION(S): Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.