Background: Several studies in animal models and human with obstructive sleep apnea syndrome (OSAS) demonstrated an increase in cancer aggressiveness and mortality. However, there is a need for further clinical evidence supporting a correlation between OSAS and cancer incidence. Objectives: To reveal whether OSAS presence and severity is correlated with cancer incidence in a large homogenous patients’ cohort. Methods: We analyzed a cohort of over 5,000 concurrently enrolled patients, age > 18, with suspected OSAS, from a tertiary medical academic center. Patients underwent whole night polysomnography, the gold standard diagnostic tool for OSAS, and were classified for severity according to the Apnea Hypopnea Index (AHI). Data on cancer incidence were obtained from the Israel National Cancer Registry. A multivariate Cox proportional-hazards analysis, adjusted for age, gender, and BMI, was performed to estimate the hazard-ratio of new cancer incidence. Results: Among 5,243 subjects with a median follow-up of 5.9 years, 265 were diagnosed with cancer. The most prevalent cancers were prostate (14.7%), hematological (12.8%), urothelial (9.4%), colorectal (9%), and breast (8.3%). In subjects who were diagnosed at age below 45 years (n = 1,533), a high AHI (> 57/h) was significantly associated with cancer (HR 3.7, CI 1.12–12.45, p = 0.008). Conclusions: Patients younger than 45 with severe OSAS have a significantly higher all-type cancer incidence than the general population. These results should encourage clinicians to detect and diagnose young patients with suspected OSAS and to recommend cancer screening methods in this high-risk population.

Background: There are scarce data on venous thromboembolism (VTE) rates among non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICI). The Khorana Score (KS), used to guide thromboprophylaxis in cancer patients, was validated in patients receiving chemotherapy.Objective: To assess VTE rates and KS performance among NSCLC patients treated with ICI or chemotherapy. Methods:We performed a retrospective cohort study of NSCLC patients starting either ICI or platinum-based chemotherapy. The 6-month cumulative incidence of VTE in the ICI and chemotherapy cohorts and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, using death as a competing risk. Subgroup analysis of low (0-1) and high (≥2) KS risk groups was performed. Results:The study included 345 NSCLC patients receiving single agent ICI (n = 176) or chemotherapy (n = 169). The 6-month cumulative incidence of VTE was 7.1% in the chemotherapy cohort and 4.5% in the ICI cohort (HR for chemotherapy = 1.6, 95% CI 0.66-3.9). Among chemotherapy treated patients, the high-risk KS group had a trend toward a higher VTE incidence, compared with patients with a low-risk KS (HR 3.04, 95% CI 0.82-11.22). Among ICI-treated patients, the high-risk KS group had a trend toward a lower VTE incidence compared with the low-risk group (HR 0.17, 95% CI 0.02-1.36). Conclusions: VTE rates were higher among NSCLC patients treated with platinumbased chemotherapy than those treated with ICI alone, though the precision of the relative estimate is low. The KS did not identify high-risk ICI-treated patients, suggesting that an ICI-specific risk model is warranted.

<b><i>Introduction:</i></b> Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. <b><i>Methods:</i></b> All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, <i>t</i> tests, and χ² tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. <b><i>Results:</i></b> Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], <i>p</i> = 0.011, and HR 1.5 [1.08–2.08], <i>p</i> = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], <i>p</i> = 0.79, and HR 1.29 [0.69–2.39], <i>p</i> = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. <b><i>Conclusion:</i></b> Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

Aim: The treatment paradigm of advanced non-small-cell lung cancer has recently changed with the introduction of immune checkpoint inhibitors (ICIs). It is common practice to continue treatment beyond progression (TBP) in selected cases. The aim of this study was to evaluate real life practice and outcomes related to TBP. Materials & methods: We retrospectively evaluated advanced non-small-cell lung cancer patients treated with ICI therapy and identified patients who were treated beyond progression. Results: Of 207 patients included in this analysis, 22% patients received TBP. A total of 36% achieved a clinical benefit. A total of 27% patients had a progression-free interval over 6 months after receiving TBP. Conclusion: A subset of patients who were treated beyond progression with ICI achieved a clinically meaningful response with durable disease control.

Background: Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs). Methods: RCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted. Results: Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72e1.29, p ¼ 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14e0.95, p ¼ 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65e1.43), triple negative (HR 1.4, 95% CI 0.50e3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68 e1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58e1.62) and in visceral disease (HR ¼ 1.02, 95% CI 0.77e1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result. Conclusions: LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.

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Background The treatment paradigm of advanced renal cell carcinoma (RCC) has changed rapidly in recent years. In first‐line treatment of intermediate‐ to poor‐risk patients, the CheckMate 214 study demonstrated a significant survival advantage for nivolumab and ipilimumab versus sunitinib. The high cost of combined immune‐modulating agents warrants an understanding of the combination's value by considering both efficacy and cost. The objective of this study was to estimate the cost‐effectiveness of nivolumab and ipilimumab compared with sunitinib for first‐line treatment of intermediate‐ to poor‐risk advanced RCC from the U.S. payer perspective. Materials and Methods A Markov model was developed to compare the costs and effectiveness of nivolumab and ipilimumab with those of sunitinib in the first‐line treatment of intermediate‐ to poor‐risk advanced RCC. Health outcomes were measured in life‐years and quality‐adjusted life‐years (QALYs). Drug costs were based on Medicare reimbursement rates in 2017. We extrapolated survival beyond the trial closure using Weibull distribution. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Results The total mean cost per‐patient of nivolumab and ipilimumab versus sunitinib was $292,308 and $169,287, respectfully. Nivolumab and ipilimumab generated a gain of 0.978 QALYs over sunitinib. The incremental cost‐effectiveness ratio (ICER) for nivolumab and ipilimumab was $125,739/QALY versus sunitinib. Conclusion Our analysis established that the base case ICER in the model for nivolumab and ipilimumab versus sunitinib is below what some would consider the upper limit of the theoretical willingness‐to‐pay threshold in the U.S. ($150,000/QALY) and is thus estimated to be cost‐effective. Implications for Practice This article assessed the cost‐effectiveness of nivolumab and ipilimumab versus sunitinib for treatment of patients with intermediate‐ to poor‐risk metastatic kidney cancer, from the U.S. payer perspective. It would cost $125,739 to gain 1 quality‐adjusted life‐year with nivolumab and ipilimumab versus sunitinib in these patients.

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