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Introduction: The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program. Methods: PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability. Results: Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate. Conclusion: The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to assess the costs and healthcare resource utilization (HCRU) of metastatic non-small cell lung cancer (NSCLC) by biomarker status in the pre- and post-approval of the immuno-oncology agent. The analysis examined healthcare costs and HCRU before and after the local regulatory approval of pembrolizumab as a first-line (1L) treatment. Patients were stratified into mutation-positive and negative/unknown groups according to mutational status. The negative/unknown group was further sub-grouped based on the availability of pembrolizumab at the time of starting 1L treatment. Costs and HCRU were analyzed separately for the 1L treatment and overall disease follow-up across lines of therapy and by groups. The study found that introducing 1L immunotherapy has improved overall survival, but healthcare spending has increased concurrently. Decision-makers may find our results useful in deciding how best to allocate resources for treating metastatic NSCLC in terms of the health–economic model and policy. This study evaluated the economic burden of metastatic non-small cell lung cancer patients before and after the availability of an immuno-oncology (IO) regimen as a first-line (1L) treatment. Patients from 2014 to 2020 were categorized according to mutational status into mutation-positive and negative/unknown groups, which were further divided into pre-1L IO and post-1L IO sub-groups depending on the availability of pembrolizumab monotherapy in 1L. Healthcare costs and HCRU for a 1L treatment and overall follow-up were reported as the mean total and per-month cost per patient by groups. Of 644 patients, 125were mutation-positive and 519 negative/unknown (229 and 290 in pre- and post-1L IO, respectively). The mean total per-patient cost in 1L was lower in pre- (EUR 7804) and post-1L IO (EUR 19,301) than the mutation-positive group (EUR 45,247), persisting throughout overall disease follow-up. However, this difference was less when analyzing monthly costs. Therapy costs were the primary driver in 1L, while hospitalization costs rose during follow-up. In both mutation-positive and post-IO 1L groups, the 1L costs represented a significant portion (70.1% and 66.3%, respectively) of the total costs in the overall follow-up. Pembrolizumab introduction increased expenses but improved survival. Higher hospitalisation and emergency room occupation rates during follow-up reflected worsening clinical conditions of the negative/unknown group than the mutation-positive population. [ABSTRACT FROM AUTHOR]

BACKGROUND After the introduction of a mammography screening program, the incidence of late-stage breast cancer is expected to decrease. The objective of the current study was to evaluate variations in the total incidence of breast cancer and in the incidence of breast cancers with a pathologic tumor (pT) classification of pT2 through pT4 after the introduction of mammography screening in 6 Italian administrative regions. METHODS The study area included 700 municipalities, with a total population of 692,824 women ages 55 to 74 years, that were targeted by organized mammography screening between 1991 and 2005. The year screening started at the municipal level (year 1) was identified. The years of screening were numbered from 1 to 8. The ratio of the observed 2-year, age-standardized (Europe) incidence rate to the expected rate (the incidence rate ratio [IRR]) was calculated. Expected rates were estimated assuming that the incidence of breast cancer was stable and was equivalent to that in the last 3 years before year 1. RESULTS The study was based on a total of 14,447 incident breast cancers, including 4036 pT2 through pT4 breast cancers. The total IRR was 1.35 (95% confidence interval, 1.03-1.41) in years 1 and 2, 1.16 (95% confidence interval, 1.10-1.21) in years 3 and 4, 1.14 (95% confidence interval, 1.08-1.20) in years 5 and 6, and 1.14 (95% confidence interval, 1.08-1.21) in years 7 and 8. The IRR for pT2 through pT4 breast cancers was 0.97 (95% confidence interval, 0.90-1.04) in years 1 and 2, 0.81 (95% confidence interval, 0.75-0.88) in years 3 and 4, 0.79 (95% confidence interval, 0.73-0.87) in years 5 and 6, and 0.71 (95% confidence interval, 0.64-0.79) in years 7 and 8. CONCLUSIONS A significant and stable decrease in the incidence of late-stage breast cancer was observed from the third year of screening onward, when the IRR varied between 0.81 and 0.71. Cancer 2013;119:2022-2028. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Although poorly described in the literature, the practice of early (short-interval) rescreen after a negative screening mammogram is controversial due to its financial and psychological burden and because it is of no proven benefit. Methods: The present study targeted an Italian 2-yearly screening programme (Emilia-Romagna Region, 1997- 2002). An electronic dataset of 647,876 eligible negative mammography records from 376,257 women aged 50-69 years was record-linked with the regional breast cancer registry. The statistical analysis addressed the following research questions: (1) the prevalence of recommendation for early (<24 months) rescreen (RES) among negative mammography reports; (2) factors associated with the likelihood of a women receiving RES; and (3) whether women receiving RES and women receiving standard negative reports differed in terms of proportional incidence of interval breast cancer, recall rate at the next rescreen, detection rate of breast cancer at the next rescreen and the odds of having late-stage breast cancer during the interscreening interval and at the next rescreen. Results: RES was used in eight out of 13 screening centres, where it was found in 4171 out of 313,320 negative reports (average rate 1.33%; range 0.05%-4.33%). Reports with RES were more likely for women aged 50-59 years versus older women (odds ratio (OR) 1.33; 95% CI 1.25-1.42), for the first versus subsequent screening rounds (OR 1.91; 95% CI 1.79-2.04) and with a centre-specific recall rate below the average of 6.2% (OR 1.41; 95% CI 1.32-1.50). RES predicted a 3.51-fold (95% CI 0.94-9.29) greater proportional incidence of first-year interval cancers, a 1.90-fold (95% CI 1.62-2.22) greater recall rate at the next screen, a 1.72-fold (95% CI 1.01-2.74) greater detection rate of cancer at the next screen and a non-significantly decreased risk of late disease stage (OR 0.59; 95% CI 0.23-1.53). Conclusion: The prevalence of RES was in line with the maximum standard level established by the Italian national guidelines. RES identified a subset of women with greater incidence of interval cancers and greater prevalence of cancers detected at the next screen. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the total proportional incidence of interval breast cancers in a two-yearly mammography screening programme, and to perform subgroup analyses by woman's age, screening centre-specific recall rate and screening round. Methods: Using unconverted electronic data-sets from the 13 screening centres in the Emilia-Romagna Region of northern Italy (540,450 women aged 50–69 years), a database of 919,538 mammography records was created. Of these, 655,175 eligible single-mammography records (1997–2002) from 379,318 women were record-linked with the regional Breast Cancer Registry. In the two-year inter-screening interval, a total of 1,022,694.3 woman-years at risk were accumulated, with 695 interval cancers observed and 2428.3 expected. The observed number of interval cancers was divided by the expected number to obtain the proportional incidence. Results: The total proportional incidence of first- and second-year interval cancers was 0.18 (95% CI 0.15–0.20) and 0.43 (0.39–0.47), respectively. Woman's age was inversely associated with proportional incidence in both interval years, with a cut-off point at age 60. A screening centre-specific recall rate greater than the regional average of 5% was associated with a proportional incidence of 0.14 (0.11–0.17) versus 0.20 (0.17–0.24) in the first interval year, and of 0.36 (0.31–0.41) versus 0.50 (0.44–0.56) in the second. The proportional incidence remained unchanged between the first and subsequent screening rounds. Conclusions: The results were in line with the previous Italian data and with the recommended European standards. The inverse effect of woman's age and of recall rate was expected. [ABSTRACT FROM AUTHOR]

Purpose: Cost evaluation is becoming mandatory to support healthcare sustainability and optimize the decision-making process. This topic is a challenge, especially for complex and rapidly evolving treatment modalities such as radiotherapy (RT). The aim of the present study was to investigate the cost of RT in the last month of life of patients in an Italian cancer center., Methods: This was a retrospective study on a cancer population (N= 160) who underwent RT or only an RT planning simulation in an end of life (EOL) setting. The cost of RT procedures performed on patients was collected according to treatment status, care setting, and RT technique used. Costs were valued according to the sum of reimbursements relating to all procedures performed and assessed from the perspective of the National Health System., Results: The total cost of RT in the last month of life was €244,774, with an average cost per patient of €1530. Around 7.7% and 30.3% of the total cost was associated with patients who never started RT or who discontinued RT, respectively, while the remaining 62.0% referred to patients who completed treatment. Costs associated with outpatient and inpatient settings represented 54.3% and 38.6% of the total cost, respectively. The higher average cost per patient for the never-started and discontinued groups was correlated with patients who had a poor ECOG Performance Status., Conclusion: Improved prognostic accuracy and a better integration between radiotherapy and palliative care units could be a key to a better use of resources and to a reduction in the cost of EOL RT.

Bone metastases (BM) are still the main cause of morbidity in cancer patients because of skeletal-related events (SREs) that reduce quality of life. They have also led to increased social and healthcare costs. At present, data available on BM are insufficient. This was a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 months' follow-up. Information on patients at the first diagnosis of BM, including demographics and characteristics of the primary tumor and BM. Data were periodically updated by participating centres and reviewed by the coordinator centre. From October 2014 to July 2019, 618 patients with BM from solid tumors were enrolled and 220 were eligible for the present study. Median age was 62 years (range 26-86). Median follow-up was 34 months (range 6-149). At the time of enrolment, 109 (50%) had only BM (BOM) and 109 (50%) had concomitant visceral lesions and BM (BVM). Median time-to-first BM was 47 months (range 0-312) in BOM and 78.6 months in BVM patients. Disease-free interval differed on the basis of BC molecular subtype and stage. Ninety-eight BM patients had at least on SRE. Zoledronate was used in 69.1% of cases and denosumab in 28.3%. First-line treatment was hormone-based (50.7%), chemotherapy-based (38.7%) or chemotherapy- + hormone therapy-based (9.7%). Median progression-free and overall survival were 15.1 months (95% CI 12.6-18.4) and 66.8 months (95% CI 52.1-79.2), respectively. Our prospective study could substantially help to better understand the natural history of BM from BC.

Introduction: Patients with metastatic or locally advanced, non-resectable, grade 3 poorly differentiated gastroenteropancreatic (GEP) and lung neuroendocrine carcinomas (NECs) are usually treated with in first-line platinum compounds. There is no standard second-line treatment on progression. Accurate biomarkers are needed to facilitate diagnosis and prognostic assessment of patients with NEC., Methods and Analysis: The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. Secondary aims are to correlate the serum miRNA profile and primary mutational status of MEN1, DAXX, ATRX and RB-1 with prognosis and outcome and to investigate the prognostic and predictive role of the Ki-67 score and 18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) or 68 Ga-PET/CT. The main eligibility criteria are age ≥18 years; metastatic or locally advanced, non-resectable, grade 3 lung or GEP-NECs; progression to first-line platinum-based chemotherapy. A Bryant and Day design taking into account treatment activity and toxicity was used to estimate the sample size. All analyses will be performed separately for each treatment group in the intention-to-treat population. A total of 112 patients (56/arm) will be randomly assigned (1:1) to receive FOLFIRI every 14 days or CAPTEM every 28 days until disease progression or unacceptable toxicity or for a maximum of 6 months. Patients undergo testing for specific biomarkers in primary tumour tissue and for miRNA in blood samples. MiRNA profiling will be performed in the first 20 patients who agree to participate in the biological substudy., Ethics and Dissemination: The SENECA trial, supported by Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), was authorised by the locals Ethics Committee and the Italian Medicines Agency (AIFA). Results will be widely disseminated via peer-reviewed manuscripts, conference presentations and reports to relevant authorities.The study is currently open in Italy., Trail Registration Number: NCT03387592; Pre-results. EudraCT-2016-000767-17., Protocol Version: Clinical Study Protocol Version 1, 7 November 2016., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims and Background: Few studies show what happens outside of randomized clinical trials. The purpose of the study was to describe the clinical management of metastatic gastric cancer patients resident in the Forlì area from 2000 to 2009., Methods and Study Design: A total of 270 metastatic gastric cancer patients at diagnosis or relapse were considered. Data from medical records were analysed, and survival probabilities were calculated using the Kaplan-Meier method., Results: A total of 115 patients received best supportive care, 155 at least one line of chemotherapy, 71 (45.8%) underwent second-line therapy, and 49 (31.6%) required a drug dose reduction during the first cycle of first-line therapy. Twelve (7.7%) patients died within 15 days of finishing the last chemotherapy. Median overall survival with best supportive care or chemotherapy was 3 months (95% CI, 2-4) and 11 months (95% CI, 9-12) (P <0.0001), respectively., Conclusions: Drug dose reductions and delivery of second-line therapy were common. Chemotherapy given towards the end of life was similar to other experiences. Median overall survival was similar to randomized clinical trials.

Objective: to estimate the standard performance measures of prostate-specific antigen (PSA) screening as implemented in the existing health care system and to compare the observed results with those fom the European Randomized Screening for Prostate Cancer (ERSPC) trial., Design: in a consecutive series of men living in two Italian health districts, aged > or = 30 years, with at least one total PSA test between 2000 and 2003, those subjects putatively tested for screening purposes were identified using record linkage with multiple local health databases. This was also used to determine the outcomes of follow-up of subjects with positive test result (PSA > or = 4 ng/ml) at 12 and 24 months of observation., Setting: clinical chemistry laboratories, outpatient urology clinics, pathology departments, and mortality registries of the health districts of Ravenna and Forlì, and the Romagna Cancer Registry., Participants: 52,513 total subjects, 42,398 of whom putatively tested for screening purposes., Main Outcome Measures: the most common performance measures of cancer screening., Results: the 2-year screening rate increased until 80 years of age. In the age range 55-69 years, i.e. the target age of the ERSPC trial, the screening rate was 38.1%, and the rate of positive test results (9.1%) was within the expected range. The PSA level, but not the subjects age, was strongly associated with follow-up procedures. After 24 months of observation, 24.4% PSA-positive patients received no further evaluation, 54.8% underwent repeat testing as the initial follow-up action, and 44.0% were referred for urologic assessment. The biopsy rate was 25.3%, the positive predictive value of PSA testing 10.1%, the detection rate of prostate cancer 9.4 per thousand, and the detected/expected ratio 8.4., Conclusion: compared with methods and results of the ERSPC trial, the management of PSA-positive subjects was much more conservative, and the yield of disease much smaller.