Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients.

BACKGROUND: The treatment of choice for advanced non-small cell lung cancer is selected according to the presence of specific alterations. Patients should undergo molecular testing for relevant modifications and the mutational status of EGFR and translocation of ALK and ROS1 are commonly tested to offer the best intervention. In addition, the tests costs should also be taken in consideration. Therefore, this work was performed in order to evaluate the cost-effectiveness of a unique exam using NGS (next generation sequencing) versus other routinely used tests which involve RT-PCR and FISH. METHODS: The target population was NSCLC, adenocarcinoma, and candidates to first-line therapy. Two strategies were undertaken, strategy 1 corresponded to sequential tests with EGFR RT-PCR, then FISH for ALK and ROS1. Strategy 2 differed from 1 in that ALK and ROS1 translocation testing were performed simultaneously by FISH. Strategy 3 considered single test next-generation sequencing, a platform that includes EGFR, ALK and ROS1 genes. A decision tree analysis was used to model genetic testing options. From the test results, a microsimulation model was nested to estimate survival outcomes and costs of therapeutic options. RESULTS: The use of NGS added 24% extra true cases as well as extra costs attributed to the molecular testing. The ICER comparing NGS with sequential tests was US$ 3479.11/correct case detected. The NGS improved a slight gain in life years and QALYs. CONCLUSION: Our results indicated that, although precise, the molecular diagnosis by NGS of patients with advanced stage NSCLC adenocarcinoma histology was not cost-effective in terms of quality-adjusted life years from the perspective of the Brazilian supplementary health system.

Subxiphoid uniportal thoracoscopic pulmonary segmentectomy for stage I non-small cell lung cancer: Feasibility, quality of life and financial worthiness.

BACKGROUND: Subxiphoid uniportal video-assisted thoracoscopic surgery (SVATS) is more technically challenging than intercostal uniportal video-assisted thoracoscopic surgery (UVATS), especially in more complex procedures such as segmentectomy. We therefore aimed to investigate the worthiness of undertaking the more demanding subxiphoid approach in patients who had undergone anatomical segmentectomy for stage IA non-small cell lung cancer (NSCLC). METHODS: A total of 491 patients were included in our study who had undergone anatomical segmentectomy for stage IA non-small cell lung cancer from September 2014 to April 2018. They were divided into two groups; 278 patients in the UVATS group and 213 patients in the SVATS group. Different perioperative variables, postoperative pain, quality of life and cost were analyzed and compared between both groups. RESULTS: The SVATS group showed a significantly longer operative time (P = 0.007) and more operative blood loss than the intercostal group (P = 0.004). There was no significant difference between both groups regarding postoperative drainage, duration of chest tube, postoperative hospital stay, operative conversion or postoperative complications. The SVATS group showed a significantly lower pain score postoperatively (P < 0.001). In addition, the SVATS group showed a significantly better postoperative quality of life score along the first postoperative year (P < 0.001). UVATS segmentectomy appeared to be significantly cheaper than SVATS segmentectomy (P < 0.001). CONCLUSIONS: SVATS segmentectomy for stage IA lung cancer is a safe procedure that is worth proceeding with as it is associated with better postoperative pain and better quality of life in the first postoperative year. Further studies are recommended to evaluate the actual cost-effectiveness of SVATS segmentectomy. KEY POINTS: • Significant findings of the study Subxiphoid uniportal approach for pulmonary segmentectomy is safe and feasible approach. It has better postoperative pain and better quality of life than the uniportal intercostal approach; however, it is more expensive. • What this study adds Subxiphoid uniportal approach for pulmonary segmentectomy gives a better quality of life in Chinese patients than the intercostal approach; however, it is more expensive.

Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis.

OBJECTIVES: There is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients. MATERIALS AND METHODS: We identified consecutive patients diagnosed between Jan 2016 to Sep 2017 with residual tissue after standard molecular testing. Tissue samples were tested using a targeted NGS panel for DNA alterations (29 selected genes including BRAF, EGFR, ERBB2 and TP53) and an RNA fusion panel (ALK, ROS1 and RET). PD-L1 immunohistochemistry was also performed. A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted. RESULTS: A total of 174 samples were evaluated: PD-L1 (n = 169), NGS DNA panel (n = 173) and RNA fusion (n = 119) testing. Median age was 68 years, 53 % were male, 58 % were never smokers, 85 % were Chinese, 66 % had stage IV disease and 95 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (56 %), KRAS (14 %), BRAF (2 %) and ERBB2 (1 %) mutations were found. RNA fusion testing revealed fusions in ALK (6 %), RET (3 %) and ROS1 (1 %). Cost-effectiveness analysis demonstrated that compared to sequential testing in EGFR negative patients, upfront NGS testing would result in an additional 1 % of patients with actionable alterations for targeted therapy being identified without significant increases in testing cost or turnaround time. CONCLUSIONS: This study demonstrates that even in an EGFR mutant predominant population, upfront NGS represents a feasible, cost-effective method of diagnostic molecular profiling compared with sequential testing strategies. Our results support the implementation of diagnostic NGS in non-squamous NSCLC in Asia to allow patients access to the most appropriate personalized therapy.

Impact of the American Tax Payer Relief Act on stereotactic radiosurgery utilization in the United States.

INTRODUCTION: Single-fraction stereotactic radiosurgery (SRS) is delivered predominantly via two modalities: Gamma Knife, and linear accelerator (LINAC). Implementation of the American Tax Payer Relief Act (ATRA) in 2013 represented the first time limitations specifically targeting SRS reimbursement were introduced into federal law. The subsequent impact of the ATRA on SRS utilization in the United States (US) has yet to be examined. METHODS: The National Cancer Database from 2010-2016 identified brain metastases patients from non-small cell lung cancer throughout the US having undergone SRS. Utilization between GKRS and LINAC was assessed before (2010-2012), during (2013-2014) and after (2015-2016) ATRA implementation. RESULTS: In 2013, there was a substantial decrease of LINAC SRS in favor of GKRS in non-academic centers. Over the 3-year span immediately preceding ATRA implementation, 39% of all eligible SRS cases received LINAC. There was a modest decrease in LINAC utilization over the 2 years immediately following ATRA implementation (35%), followed by an increase over the next two years (40%). SRS modality showed differences over the three time periods (unadjusted, p = 0.043), primarily in non-academic centers (unadjusted, p = 0.003). CONCLUSIONS: ATRA implementation in 2013 caused an initial spike in Gamma Knife SRS utilization, followed by a decline to rates similar to the years before implementation. These findings indicate that the ATRA provision mandating Medicare reduction of outpatient payment rates for Gamma Knife to be equivalent with those of LINAC SRS had a significant short-term impact on the radiosurgical treatment of metastatic brain disease throughout the US, serving as a reminder of the importance/impact of public policy on treatment modality utilization by physicians and hospitals.

Race, Poverty, and Initial Implementation of Precision Medicine for Lung Cancer.

Data are limited regarding whether the availability of biomarker-directed therapy for lung cancer exacerbates racial and socioeconomic disparities. Patients diagnosed with stage IV lung adenocarcinoma from 2008 to 2013 were identified using Surveillance, Epidemiology, and End Results Program-Medicare. The primary outcome was a Medicare claim for molecular testing within 60 days of diagnosis, analyzed using multivariable logistic regression; the secondary outcome was overall survival, analyzed using multivariable Cox proportional hazards models. All statistical tests were two-sided. Of 5556 patients, 1437 (25.9%) had molecular testing. Testing rates were 14.1% among black, 26.2% among white, and 32.8% among patients of Asian/other descent (adjusted P < .001); 20.6% among patients with Medicaid eligibility vs 28.4% among those without (adjusted P = .01); and 19.9% among patients in the highest census tract-level poverty rate quintile vs 30.7% among patients in the lowest quintile (for all quintiles, adjusted P = .18). Median survival from 60 days was 8.2 months among patients with molecular testing within 60 days of diagnosis and 6.1 months among those without (hazard ratio = 0.92, 95% confidence interval = 0.86 to 0.99; adjusted P = .02). Equitable precision medicine requires concerted implementation efforts.