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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.

The process of lung carcinogenesis is still not well understood and involves different levels of regulation of several genes. The search for molecular biomarkers, which can be applicable to clinical practice, has been the focus of various studies. XIAP-associated factor 1 (XAF1) was previously shown to be downregulated in many types of tumors, including squamous cell lung cancer. XAF1 is a pro-apoptotic protein and its restoration was found to sensitize cancer cells to apoptotic stimuli; however, the precise mechanism involved in the downregulation of XAF1 in tumors is unknown and promoter hypermethylation or heat-shock transcription factor 1 (HSF1) may be involved. Therefore, the aim of the present study was to evaluate the expression of XAF1 in tumors and adjacent non-tumor specimens from non-small cell lung cancer (NSCLC) patients, and its potential association with various factors including clinicopathological characteristics and other genes involved in NSCLC. Our results indicated that XAF1 expression was markedly altered in NSCLC tumor samples when compared to that found in normal lung tissues. Predominantly, XAF1 was downregulated in the tumors, except in never-smoker patients. In addition, XAF1 may also be important in the whole cell stress mechanism where the p53 status is crucial.

Objective: Pemetrexed plus carboplatin offers survival advantage in first line treatment of advanced lung cancer patients with performance status of 2. We estimated the cost-effectiveness of this combined regimen compared to pemetrexed alone in a Brazilian population., Methods: A cost-effectiveness analysis was conducted based on a randomized phase III trial in patients with advanced non-small cell lung cancer (NSCLC) and ECOG performance status of 2 (PS2), comparing doublet regimen pemetrexed plus carboplatin with pemetrexed alone. The perspective adopted was the public health care sector over a three-year period. Direct medical costs and survival time were calculated from patient-level data and utility values were extracted from the literature. Sensitivity analyses were performed to evaluate uncertainties in the results., Results and Conclusion: The combined regimen pemetrexed plus carboplatin yielded a gain of 0.16 life year (LY) and 0.12 quality-adjusted life year (QALY) compared to pemetrexed alone. The total cost was 17,674.31 USD for the combined regimen and 15,722.39 USD for pemetrexed alone. The incremental cost-effectiveness ratio (ICER) was $12,016.09 per LY gained and $15,732.05 per QALY gained. The factors with the greatest impact on the ICER are pemetrexed price and the time to progression utility value. The cost-effectiveness acceptability curve showed an upper 90% probability of pemetrexed plus carboplatin being cost-effective with a threshold between two and three GDP per capita. Our study suggests superiority of the combined pemetrexed plus carboplatin regimen in terms of efficacy as well as cost-effectiveness in advanced NSCLC patients with a poor performance status of 2., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Non-small cell lung Cancer (NSCLC) is extremely resistant to chemotherapeutic agents, such as cisplatin. High expression of the inflammatory enzyme cyclooxygenase-2 (COX-2) has been shown to inhibit chemotherapy-induced apoptosis, but little is known about COX-2 regulation upon drug treatment. Recent data indicate the tumor suppressor protein p53 as an important regulator of COX-2. Therefore, TP53 status could change tumor sensitivity to chemotherapy through induction of the anti-apoptotic protein COX-2. The main objective of this work was to analyze the effect of chemotherapy on the expression of COX-2, according to TP53 status. We report herein that lung cancer cell lines expressing wild-type p53, when exposed to cisplatin treatment, induced COX-2 (mRNA and protein), with concurrent synthesis of prostaglandins (PGE(2)). In contrast, COX-2 expression was not changed after cisplatin treatment of cells containing an inactive form of p53. Further, after silencing of wild-type p53 expressed in A549 cells by RNA interference, cisplatin was no longer able to induce COX-2 expression. Therefore, we suggest that induction of COX-2 by cisplatin in NSCLC cell lines is dependent on p53. For paclitaxel treatment, an increase in COX-2 mRNA expression was observed in H460 and A549 (wild-type p53 cell lines). Moreover, paclitaxel treatment increased COX-2 expression in ACC-LC-319 cell lines (p53 null), showing a p53-independent effect. These data may have therapeutic implications in the selection of patients and strategy for future COX-2 inhibition trials.