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Simple Summary: This study aims to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). A total of 177 lung cancer patients, of whom 58 were treated with systemic treatment (either TKIs or pembrolizumab) plus aRT (STRT) and 119 with systemic treatment alone, were selected. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The incremental cost-effectiveness ratio (ICER) value indicated an average cost of €3792 for each month of survival after STRT and confirmed clinical effectiveness but higher healthcare costs. This real-world study suggests that upfront aRT in this setting represents a valid treatment strategy, boosting the efficacy of emerging drug classes with sustainable costs for the health service. Aim: Healthcare administrative databases represent a valuable source for real-life data analysis. The primary aim of this study is to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). Methods: Diagnostic ICD-9-CM codes were used for identifying all patients with a new diagnosis of lung cancer between 2012 and 2019. Among these, patients who had started a first-line systemic treatment with either TKIs or pembrolizumab, alone or in combination with intensity-modulated or stereotactic RT, were selected. Clinical outcomes investigated included overall survival (OS), progression-free survival (PFS), and time-to-treatment failure (TTF). The cost outcome was defined as the average per capita cumulative healthcare direct costs of the treatment, including all inpatient and outpatient costs. Results: The final cohort included 177 patients, of whom 58 were treated with systemic treatment plus aRT (STRT) and 119 with systemic treatment alone. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The ICER (incremental cost-effectiveness ratio) value indicated an average cost of €3792 for each month of survival after STRT treatment and confirmed clinical effectiveness but higher healthcare costs. Conclusions: This real-world study suggests that upfront aRT for NCLSC patients with synchronous BMs represents a valid treatment strategy, boosting the efficacy of novel and emerging drug classes with sustainable costs for the health service. Translational relevance: The present real-world study reports that the use of upfront advanced radiotherapyaRT and new-generation systemic agents, such as TKIs and pembrolizumab, may have higher oncological control and an improved cost-effectiveness profile than the use of new-generation systemic agents alone in NCLSC patients with synchronous brain metastases. Acquired evidence can also be used to inform policymakers that adding advanced radiotherapy results is a sustainable cost for the health service. Since approximately 50% of patients do not meet RCT inclusion criteria, a significant proportion of them is receiving treatment that is not evidence-informed; therefore, these results warrant further studies to identify the best radiotherapy timing and possible dose escalation approaches to improving treatment efficacy in patient subgroups not typically represented in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Germline pathogenic variants (PVs) in oncogenes and tumour suppressor genes are responsible for 5 to 10% of all diagnosed cancers, which are commonly known as hereditary cancer predisposition syndromes (HCPS). A total of 104 individuals at high risk of HCPS were selected by genetic counselling for genetic testing in the past 2 years. Most of them were subjects having a personal and family history of breast cancer (BC) selected according to current established criteria. Genes analysis involved in HCPS was assessed by next-generation sequencing (NGS) using a custom cancer panel with high- and moderate-risk susceptibility genes. Germline PVs were identified in 17 of 104 individuals (16.3%) analysed, while variants of uncertain significance (VUS) were identified in 21/104 (20.2%) cases. Concerning the germline PVs distribution among the 13 BC individuals with positive findings, 8/13 (61.5%) were in the BRCA1/2 genes, whereas 5/13 (38.4%) were in other high- or moderate-risk genes including PALB2, TP53, ATM and CHEK2. NGS genetic testing showed that 6/13 (46.1%) of the PVs observed in BC patients were detected in triple-negative BC. Interestingly, the likelihood of carrying the PVs in the moderate-to-high-risk genes calculated by the cancer risk model BOADICEA was significantly higher in pathogenic variant carriers than in negative subjects. Collectively, this study shows that multigene panel testing can offer an effective diagnostic approach for patients at high risk of hereditary cancers. [ABSTRACT FROM AUTHOR]

No evidence is available on the head-to-head comparison of clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) in a real-world setting. We aimed to compare the effectiveness and cost-effectiveness profile of nivolumab, pembrolizumab and atezolizumab. We used a population-based retrospective cohort study based on the healthcare utilization databases of the Lombardy Region, Italy. The study cohort included all patients with a diagnosis of lung cancer, who started a second-line treatment for advanced NSCLC with nivolumab, pembrolizumab or atezolizumab from 2015 to 30 June 2020. Overall survival and average cumulative healthcare costs were measured from the start of second-line treatment until 31 December 2020. The study cohort included 1607 patients who started a second-line treatment with ICIs, of which there were 1193 with nivolumab, 138 with pembrolizumab and 276 with atezolizumab. No differences were observed between treatment arms in terms of sex, age or comorbidities. Median OS was very similar between groups, being 8.9, 9.4 and 8.7 months, respectively, in patients treated with nivolumab, pembrolizumab and atezolizumab (p = 0.898). The adjusted hazard ratio of death of patients treated with pembrolizumab and atezolizumab, as compared to nivolumab, were 1.01 (95% CI: 0.81 to 1.25) and 1.03 (0.88 to 1.21), respectively. Healthcare cumulative costs measured in the first two years of follow-up were EUR 43,764, 46,233 and 34,116, on average, associated with nivolumab, pembrolizumab and atezolizumab, respectively. In our real-world study, atezolizumab was the ICI associated with the most favorable cost-effectiveness profile. [ABSTRACT FROM AUTHOR]

CKD patients with low-grade proteinuria (LP) are common in nephrology clinics. However, prevalence, characteristics, and the competing risks of ESRD and death as the specific determinants, are still unknown. We analyzed epidemiological features of LP status in a prospective cohort of 2,340 patients with CKD stage III-V referred from ≥6 months in 40 nephrology clinics in Italy. LP status was defined as proteinuria <0.5 g/24h according to current KDIGO guidelines. Patients with higher proteinuria constituted the control group (CON). LP patients were 54.5% of the whole cohort. As compared to CON, LP were older (70.0±12.1 vs 65.4±14.1 y), and less likely to be male (55.8 vs 62.0%) and diabetic (27.6 vs 34.1%), and had hypertension as the most common cause of CKD (39.8%). They had higher eGFR (34.8±13.5 vs 26.8±13.2 mL/min/1.73m2) and hemoglobin (12.7±1.7 vs 12.3±1.7 g/dL), while systolic blood pressure (137±18 vs 140±18 mmHg) and serum phosphorus (3.7±0.8 vs 3.9±0.8 mg/dL) were lower [P<0.001 for all comparisons]. Over a median follow-up of 48 months, an inverse relative risk of ESRD and death was observed in LP (death>>ESRD; P = 0.002) versus CON (ESRD>>death; P<0.0001). Modifiable risk factors were also different in LP, with smoking, lower hemoglobin, and proteinuria being associated with higher mortality risk while lower BMI and higher phosphorus predicting ESRD at multivariable Cox analyses [P<0.05 for all]. Therefore, in nephrology clinics, LP patients are the majority and show distinctive basal features. More important, they are more exposed to death than ESRD and do present specific modifiable determinants of either outcome; indeed, in LP, while smoking plays a role for mortality, lower BMI and higher phosphorus levels -even if in the normal range- are predictors of ESRD. These data support the need to further study the low proteinuric CKD population to guide management. [ABSTRACT FROM AUTHOR]

Aims: It is not known whether heart failure (HF) patients with prolonged QRS who undergo cardiac resynchronization therapy combined with a defibrillator (CRT-D) have a prognostic advantage over HF patients with narrow QRS (therefore without indication for CRT) treated with an implantable cardioverter defibrillator (ICD) only. The aim of this study was to compare the long-term mortality of a group of HF patients with prolonged QRS receiving CRT-D with that of a similar group of patients with narrow QRS receiving ICD only.Methods and Results: A total of 312 patients (mean age 66 ± 13 years; 84% male, mean left ventricular ejection fraction 25 ± 4%, mean New York Heart Association class 2.6 ± 0.5) were included in the analysis. Of these, 138 with a QRS complex duration ≥120 ms received a CRT-D. During follow-up, the time and cause of death were assessed. During a median follow-up of 46 months, CRT-D patients showed significantly lower overall mortality (P = 0.038). Compared with patients receiving ICD only, CRT-D patients showed lower HF mortality (P = 0.003). Coronary mortality, non-cardiac mortality, and sudden mortality were similar in both groups (all P > 0.05). A positive response to CRT was an independent predictor of reduced mortality on multivariate analysis (hazard ratio: 0.27; P = 0.047).Conclusion: In HF patients treated with ICD, the subgroup of patients with prolonged QRS who receive CRT-D displays better long-term survival than narrow QRS ICD recipients, owing to their reduced HF mortality. [ABSTRACT FROM AUTHOR]

On 9 October 1963 a catastrophic landslide suddenly occurred on the southern slope of the Vaiont dam reservoir. A mass of approximately 270 million m3 collapsed into the reservoir generating a wave that overtopped the dam and hit the town of Longarone and other villages nearby. Several investigations and interpretations of the slope collapse have been carried out during the last 45 years, however, a comprehensive explanation of both the triggering and the dynamics of the phenomenon has yet to be provided. In order to re-evaluate the currently existing information on the slide, an electronic bibliographic database and an ESRI-geodatabase have been developed. The chronology of the collected documentation showed that most of the studies for re-evaluating the failure mechanisms were conducted in the last decade, as a consequence of knowledge, methods and techniques recently acquired. The current contents of the geodatabase will improve definition of the structural setting that influenced the slide and led to the the propagation of the displaced rock mass. The objectives, structure and contents of the ebibliography and Geodatabase are indicated, together with a brief description on the possible use of the alphanumeric and spatial contents of the databases. [ABSTRACT FROM AUTHOR]

A randomized clinical trial showed that trastuzumab, added to traditional chemotherapy, significantly improved overall survival in human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic gastric cancer patients. This population-based study aimed at evaluating both the clinical and economic impact of trastuzumab in a real-world setting. By using the healthcare utilization databases of Lombardy, Italy, a cohort of patients newly diagnosed with metastatic gastric cancer during the period 2011–2016 was selected. Among these, patients initially treated with either trastuzumab-based chemotherapy or standard chemotherapy alone were followed up until death, migration in other regions or June 2018. Overall survival and average cumulative costs were estimated and compared between the two treatment arms. Among the 1198 metastatic gastric cancer patients who started therapy within six months after metastasis detection, 87 were initially treated with trastuzumab-based chemotherapy and 1111 with standard chemotherapy. Median overall survival and restricted mean survival were 10.2 and 7.4 months, and 14.9 and 11.4 months, respectively, in the two treatment arms. The adjusted hazard ratio of death was 0.73 (95% CI 0.57–0.93). The average per capita cumulative healthcare costs were, respectively, EUR 39,337 and 26,504, corresponding to an incremental cost-effectiveness ratio of EUR 43,998 for each year of survival gained. Our study shows that adding trastuzumab to conventional chemotherapy is effective and cost-effective. [ABSTRACT FROM AUTHOR]

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan–Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months (p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Evidences show that around 20% of biosimilar or originator erythropoiesis-stimulating agents (ESAs) users are hyporesponsive. Controversial post-marketing data exist on the predictors of ESA hyporesponsiveness. The aim of this study was to identify predictors of ESA hyporesponsiveness in patients with chronic kidney disease (CKD) or cancer in clinical practice.Methods: During the years 2009-2015, a multi-center, population-based, cohort study was conducted using claims databases of Treviso and Caserta Local Health Units (LHUs). All incident ESA users were characterized at baseline and the differences between the baseline hemoglobin (Hb) value, that is the Hb registered within 30 days prior to the first ESA dispensing (index date, ID) and each outcome Hb value (registered between 30 and 180 days after ID) were calculated and defined as delta Hb (ΔHb). Incident ESA users were defined as hyporesponsive if, during follow-up, they registered at least one ΔHb < 0 g/dL. Including all potential predictors of ESA hyporesponsiveness and stratifying by indication for use, univariate and multivariate binary logistic regression models and Receiver Operating Characteristic (ROC) curves were carried out.Results: In general, 1080 incident ESA users (CKD: 57.0%; cancer: 43.0%) were identified. In CKD, predictors of ESA hyporesponsiveness were C-reactive protein (OR = 1.2, 95% CI: 1.0-1.5; P-value = 0.060) and high levels of baseline Hb (OR = 1.7, 95% CI: 1.2-2.2; P-value< 0,001), the latter being also predictor of ESA hyporesponsiveness in cancer (OR = 1.7, 95% CI: 1.1-2.4; P-value = 0.007). Both in CKD and in cancer, the type of ESA, biosimilar or originator, was not a predictor of ESA hyporesponsiveness. In CKD, concomitant use of iron preparations (OR = 0.3, 95% CI: 0.2-0.7; P-value = 0.002) and of high dosage of angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers (OR = 0.5, 95% CI: 0.3-0.9; P-value = 0.022) were protective factors against ESA hyporesponsiveness.Conclusions: The study confirmed traditional potential predictors of hyporesponsiveness to ESA. The use of biosimilar or originator ESA was not a predictor of hyporesponsiveness in an outpatient setting from two large Italian areas. A better knowledge of the predictors of ESA response would allow a better anemia management to improve patients' quality of life. [ABSTRACT FROM AUTHOR]