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The screening of persons at risk for lung cancer may reduce lung-cancer mortality by 20%. Although cost-effectiveness estimates vary widely depending on assumptions, a careful analysis indicates that the cost is $81,000 per quality-adjusted life-year. Lung cancer is the leading cause of cancer-related deaths in the United States 1 ; however, until recently, no method of screening had been shown to reduce mortality from lung cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) of the chest in patients at high risk for lung cancer was associated with a 20% reduction in lung-cancer mortality. 2 Several major medical societies have since recommended screening with low-dose CT for patients with a similarly high risk of lung cancer. 3 The U.S. Preventive Services Task Force has released a grade B recommendation for low-dose . . .

We evaluate public health and climate impacts of low-sulphur fuels in global shipping. Using high-resolution emissions inventories, integrated atmospheric models, and health risk functions, we assess ship-related PM 2.5 pollution impacts in 2020 with and without the use of low-sulphur fuels. Cleaner marine fuels will reduce ship-related premature mortality and morbidity by 34 and 54%, respectively, representing a ~ 2.6% global reduction in PM 2.5 cardiovascular and lung cancer deaths and a ~3.6% global reduction in childhood asthma. Despite these reductions, low-sulphur marine fuels will still account for ~250k deaths and ~6.4 M childhood asthma cases annually, and more stringent standards beyond 2020 may provide additional health benefits. Lower sulphur fuels also reduce radiative cooling from ship aerosols by ~80%, equating to a ~3% increase in current estimates of total anthropogenic forcing. Therefore, stronger international shipping policies may need to achieve climate and health targets by jointly reducing greenhouse gases and air pollution. Aerosol pollution from shipping contributes to cooling but also leads to premature mortality and morbidity. Here the authors combine emission inventories, atmospheric models and health risk functions to show how cleaner marine fuels will reduce premature deaths and childhood asthma but results in larger warming.

Abstract Introduction The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) patients. Methods Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib. Results Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost–effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient. Conclusions This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation. This article reports updated survival data, post-progression diagnostic-therapeutic pathway, cost-effectiveness, and budget impact of osimertinib in patients treated with first-line osimertinib and included in the FLOWER study.

BackgroundGrowing evidence indicates that prolonged sedentary behaviour increases the risk of several chronic health conditions and all-cause mortality. Sedentary behaviour is prevalent among adults in the UK. Quantifying the costs associated with sedentary behaviour is an important step in the development of public health policy.MethodsNational Health Service (NHS) costs associated with prolonged sedentary behaviour (≥6 hours/day) were estimated over a 1-year period in 2016–2017 costs. We calculated a population attributable fraction (PAF) for five health outcomes (type 2 diabetes, cardiovascular disease [CVD], colon cancer, endometrial cancer and lung cancer). Adjustments were made for potential double-counting due to comorbidities. We also calculated the avoidable deaths due to prolonged sedentary behaviour using the PAF for all-cause mortality.ResultsThe total NHS costs attributable to prolonged sedentary behaviour in the UK in 2016–2017 were £0.8 billion, which included expenditure on CVD (£424 million), type 2 diabetes (£281 million), colon cancer (£30 million), lung cancer (£19 million) and endometrial cancer (£7 million). After adjustment for potential double-counting, the estimated total was £0.7 billion. If prolonged sedentary behaviour was eliminated, 69 276 UK deaths might have been avoided in 2016.ConclusionsIn this conservative estimate of direct healthcare costs, prolonged sedentary behaviour causes a considerable burden to the NHS in the UK. This estimate may be used by decision makers when prioritising healthcare resources and investing in preventative public health programmes.

Brain metastases (BM) significantly impact prognosis and healthcare utilization but remain underrepresented in economic evaluations. The IMpower133 trial demonstrated the efficacy of atezolizumab plus chemotherapy (carboplatin and etoposide), particularly among patients without baseline BM, leading to its approval for extensive-stage small-cell lung cancer (EX-SCLC) in several countries. As previous studies did not incorporate BM status, we addressed this gap by including BM in the cost-effectiveness analysis of atezolizumab for EX-SCLC. A four-state Markov model was constructed with the following health states: progression-free, progressive disease (PD) without brain metastases, PD with brain metastases, and death, over a 15-year time horizon. Time-varying efficacy and utility were derived from IMpower133; direct medical costs were estimated using population-based databases. Both deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in input parameters. Adding atezolizumab to chemotherapy increased QALYs by 0.721 at an incremental cost of NT$2,111,359, yielding an incremental net monetary benefit of NT$68,264, and a 53.22% probability of cost-effectiveness. Key sources of uncertainty include efficacy, cost of atezolizumab, time horizon, and utility. In conclusion, adding atezolizumab to chemotherapy is cost-effective for patients with EX-SCLC without baseline BM. Incorporating BM status into CEA could support more nuanced policy recommendations.

This study aims to conduct a cost-effectiveness analysis of tislelizumab in combination with platinum and etoposide compared to the standard treatment of etoposide and platinum as first-line therapy for extensive-stage small cell lung cancer(ES-SCLC) from the Chinese medical system perspective. A partitioned survival model was developed utilizing data from the RATIONALE-312 trial to accurately simulate the clinical and economic outcomes of both treatment arms. This model incorporates three distinct health states, namely progression-free survival, disease progression, and death. These states are exclusive of each other, and patients can transition between them as their disease progresses.The model accounted for various cost components such as drug therapy, management of adverse events, disease progression, and overall survival. To evaluate the cost-effectiveness of the interventions, quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) were chosen as the metrics. The analysis employed a willingness to pay (WTP) threshold of $39,855.79 per QALY. Additionally, sensitivity analyses were conducted to assess the robustness and reliability of the model. The tislelizumab group had a total cost of $52,749.69, whereas the chemotherapy group's total expenses amounted to $8,811.62. Additionally, the tislelizumab group experienced a gain of 2.21 QALY compared to the chemotherapy group, albeit incurring an additional cost of $43,938.07. Consequently, this led to an ICER of $19,881.48, which falls below the Chinese WTP threshold of $39,855.79. Sensitivity analyses confirmed the robustness of the findings across a range of scenarios. This cost-effectiveness analysis based on the RATIONALE-312 trial demonstrates that tislelizumab plus platinum and etoposide is a cost-effective treatment option for ES-SCLC compared to the standard chemotherapy from the Chinese medical system perspective.

Objectives Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. Methods We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years. Parametric models were fitted to Kaplan–Meier estimates of time on treatment, progression-free survival and overall survival from the KEYNOTE-024 randomized clinical trial (patients aged ≥18 years with stage IV NSCLC, TPS ≥50%, without epidermal growth factor receptor ( EGFR )-activating mutations or anaplastic lymphoma kinase ( ALK ) translocations who received no prior systemic chemotherapy) and validated with long-term registry data. Quality-adjusted life-years (QALYs) were calculated based on EuroQoL-5 Dimensions (EQ-5D) utility data collected in the trial. Costs ($US, year 2016 values) for drug acquisition/administration, adverse events and clinical management were included. Costs and outcomes were discounted at 3% per year. A series of deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. Results In the base-case scenario, pembrolizumab resulted in an expected gain of 1.31 life-years (LYs) and 1.05 QALYs and an incremental cost of $US102,439 compared with SoC. The incremental cost per QALY gain was $US97,621/QALY and the incremental cost per LY gain was $US78,344/LY. Conclusions Pembrolizumab is projected to be a cost-effective option compared with SoC platinum-based chemotherapy as first-line treatment in adults with metastatic NSCLC expressing high levels of PD-L1.

Right detection of anaplastic lymphoma kinase (ALK) gene rearrangement is pivotal to selection of patients with lung adenocarcinoma for ALK-targeted therapy. We explored the potential of combination of immunohistochemistry (IHC) screening and fluorescence in situ hybridization (FISH) as an affordable practice. We analyzed 410 unselected lung adenocarcinomas by ALK IHC (D5F3 clone) and FISH. Some equivocal cases were further analyzed by RT-PCR. The EGFR mutation was detected by pyrosequencing assay. In total 368 cases which got all IHC, FISH, EGFR mutation results were eligible for analysis. Cases were evaluated as IHC score 3+ (n = 26), score 2+ (n = 9), score 1+ (n = 51), and score 0 (n = 282), respectively. 23 of 26 IHC 3+ and 5 of 9 IHC 2+ cases were FISH positive, whereas 3 of 26 IHC 3+, 4 of 9 IHC 2+ and all 333 IHC 1+/0 cases were FISH negative. If considering FISH as the standard, the sensitivity and specificity of ALK IHC 3+/2+ as ALK positive were 100% and 97.9%, respectively. Three IHC 3+ cases reported as FISH \"negative\" were actually ALK positive confirmed by ALK RT-PCR or re-detected. Based on the final classify, ALK IHC 3+/2+ was 100% sensitive and 98.8% specific. However, FISH was 90.3% sensitive and 100% specific. IHC 2+ was regarded as equivocal and need to be confirmed by FISH or RT-PCR. In the 368 cases, 8.4% cases had ALK positive, 52.2% cases had EGFR mutation, and only one case had a coexisting. Manually semiquantitative ALK IHC (primary antibody D5F3 coupled with secondary DAKO Envision system) used as the initial screening combined with auxiliary FISH confirmation is a reliable, economical approach to identify ALK positive lung adenocarcinoma. The IHC can find some ALK positive cases which would be missed by FISH only.

•A Markov model evaluated the cost-effectiveness of perioperative nivolumab in stage III NSCLC.•Nivolumab plus chemotherapy improved QALYs and remained cost-effective under a $150,000/QALY threshold.•Sensitivity analysis confirmed robustness; postoperative nivolumab cost had the greatest ICER impact.•Subgroup analysis showed cost-effectiveness in non-squamous and PD-L1–positive patients, but not in others.•Findings support stratified reimbursement policies and equitable access to immunotherapy in real-world settings. The NADIM II trial demonstrated that combining perioperative nivolumab, an immune checkpoint inhibitor, with intensified chemotherapy significantly enhanced pathological complete response rates and overall survival in patients with surgically resectable stage III non–small-cell lung cancer (NSCLC) compared to those receiving chemotherapy alone. However, concerns persist regarding the substantial cost of immunotherapy. Our study aims to evaluate the cost-effectiveness of neoadjuvant treatment combining nivolumab with chemotherapy versus standard neoadjuvant chemotherapy alone in resectable stage III NSCLC patients within the U.S. healthcare system. Using data from the NADIM II trial, we developed a Markov model with 3 distinct health states to accurately simulate the overall health outcomes of NSCLC patients following different treatment strategies. This model not only computed essential economic metrics such as life years (LY), quality-adjusted life years (QALY), incremental cost-effectiveness ratio (ICER), and total costs but also ensured robustness through sensitivity and subgroup analyses. The group receiving nivolumab plus chemotherapy achieved 7.89 QALYs (9.75 LYs) at a total cost of $428,701.08, whereas the chemotherapy-alone group attained 6.80 QALYs (8.53 LYs) with total costs amounting to $318,550.20. This resulted in an incremental cost of $110,150.88. Considering a willingness-to-pay (WTP) threshold of $150,000/QALY in the United States, the ICER was determined to be $100,879.21/QALY ($90,193.76/LY). Based on these findings, in the United States, the perioperative use of nivolumab combined with chemotherapy appears to be cost-effective compared to chemotherapy alone for patients with stage III NSCLC, given a WTP threshold of $150,000/QALY.