Pikelyng8850

Immunotherapy has transformed the treatment of many tumors. Robust data demonstrating improved overall survival and progression-free survival in patients treated with monoclonal antibodies have established immune checkpoint inhibitors as standard of care in stages III and IV non-small cell lung cancer. Nivolumab is effective in previously treated patients with metastatic non-small cell lung cancer. Pembrolizumab and atezolizumab are approved as monotherapy and in combination with other therapies. Ongoing trials investigate the potential role of immunotherapy in earlier disease settings. Identifying predictive biomarkers of response will further amplify the impact of immune checkpoint inhibitors in the treatment of non-small cell lung cancer. Five-year survival rates for patients with early-stage non-small cell lung cancer have room for improvement. Adjuvant chemotherapy results in a small but significant increase in overall survival at 5 years. Efforts to improve outcomes by intensifying adjuvant treatment, utilizing cancer-specific vaccines or tyrosine kinase inhibitors in unselected patients, have been unsuccessful. In addition to research with immune checkpoint inhibitors that are addressed in a separate article, ongoing studies to personalize adjuvant therapy either by selecting only patients with evidence of minimal residual disease or targeting tumor driver mutations are promising. Liquid biopsies for the diagnosis and treatment of lung cancer have developed rapidly, driven primarily by technical advances in sensitivity to detect circulating tumor DNA (ctDNA). Still, technical limitations such as the challenge of detecting low-level ctDNA variants and distinguishing tumor-related variants from clonal hematopoiesis remain. With further technical advancements, new applications for ctDNA analysis are emerging including detection of post-treatment molecular residual disease (MRD), clinical trial selection, and early cancer detection. This chapter reviews the current state of ctDNA testing in NSCLC, the underlying technological advances enabling ctDNA detection, and the potential to expand ctDNA analysis to new applications. Lung cancer is a heterogeneous genomic disease. Smoking remains the primary cause. Genetic susceptibility and environmental exposures are responsible for 10% to 15% of cases. selleckchem Targeted therapies improve survival in patients with tumors with oncogenic drivers. It is critical to expand our understanding of genetic alterations in non-small cell lung cancer to increase the available targeted therapies. Alterations beyond epidermal growth factor receptor (EGFR), ALK, and ROS1 exemplify lung cancer's complexity and the need for investments in precision therapy to extend patient survival and improve outcomes. This article covers genetic targets beyond EGFR, ALK and ROS1, their novel agents, challenges, and future directions. ROS1-rearranged non-small cell lung cancer (NSCLC) makes up approximately 1% to 2% of all NSCLC, is oncogenically driven by a constitutively activated ROS1 kinase paired with certain fusion partners, and can be detected by several different assays. These patients are initially treated with tyrosine kinase inhibitors (TKIs), which target the activated ROS1 kinase. Eventually these tumors develop resistance to initial TKI treatment through secondary kinase mutations that block TKI binding or activation of bypass signaling pathways, which subvert ROS1 as the driver of the malignancy. Investigation of several TKIs that have shown efficacy in secondary resistant patients is underway. The treatment of patients with advanced non-small cell lung cancer with anaplastic lymphoma kinase chromosomal rearrangements has been revolutionized by the development of tyrosine kinase inhibitors (TKIs). Excellent progress has been made over the past decade, with 4 TKIs now approved in the front-line setting. Alectinib is the preferred first-line option based on its efficacy and side-effect profile. The central nervous system (CNS) activity of alectinib and brigatinib has allowed for treatment of CNS metastases with TKI therapy. Once resistance inevitably develops, newer therapies such as lorlatinib can be considered. Up to 20% of lung adenocarcinomas in the United States and Europe and 50% in Asia have activating mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). The identification and subsequent targeting of mutations with EGFR-tyrosine kinase inhibitors (TKIs) led to significant advances in treatment of EGFR-mutant lung cancer. Newer-generation EGFR-TKIs resulted in improvement in outcomes, with less toxic side effects and better tolerability. Resistance to EGFR-TKIs remains a significant barrier, and better understanding of resistance mechanisms is needed. Efforts are ongoing to incorporate targeted therapy into treatment of patients with earlier-stage disease. Almost a half of patients diagnosed with nonesmall-cell lung cancer (NSCLC) present with incurable disease, and a significant number of patients who are treated with curative intent for early-stage disease will eventually recur. Systemic therapy is selected based on tumor histology, squamous versus nonsquamous NSCLC, molecular testing, and PD-L1 score. Depending on PD-L1 score, patients are eligible for immunotherapy alone or in combination with chemotherapy in the first-line setting. Oncogenic driver mutations can be detected in approximately 50% of patients with nonsquamous NSCLC of which several can be targeted therapeutically with small molecular inhibitors. Continued research is needed for more specific agents with less toxicity and better central nervous system penetration, and agents to treat patients who develop resistance against targeted treatments and immunotherapy. OBJECTIVES Development of the ICEpop CAPability measure for Adults (ICECAP-A) was reported in 2012; use of certain capability measures was suggested in the context of social or long-term care soon afterward by decision-making organizations in the United Kingdom and The Netherlands. Despite enthusiasm for the ICECAP-A, this study represents the first attempt to collate evidence on its psychometric properties and its use in economic analysis. METHODS A systematic review of studies published between January 2012 and February 2019 that have either explored the psychometric properties of the ICECAP-A (validity, reliability, and responsiveness) or report its use in economic analysis. RESULTS Twenty-seven studies were identified, 11 undertaking some form of economic analysis (including pilot and feasibility studies) and 16 assessing psychometric properties (7 assessing construct validity). The ICECAP-A has mainly been used in the United Kingdom, but also in other English-speaking countries and in Europe, across a wide range of healthcare contexts. There is promising evidence on content validity, construct validity, and responsiveness. Although there was consistently strong associations between the ICECAP-A and the Assessment of Quality of Life-Eight Dimension, associations with the EuroQol 5-dimension 3-level and EuroQol 5-dimension 5-level were inconsistent. In some cases, it was found that a switch in evaluative space from health to capability well-being would alter resource allocation decisions. CONCLUSION The ICECAP-A is correlated with health-related quality of life but is most appropriately regarded as a complement for and not a substitute to the EuroQol 5-dimension 3-level and EuroQol 5-dimension 5-level in particular. Positive evidence of the measure's content and construct validity is beginning to accumulate, but further conceptual and policy debate is needed regarding the equity implications of switching between evaluative spaces. OBJECTIVES The aims of this study were to formulate a generic reporting checklist for healthcare-related discrete event simulation (DES) studies and to critically appraise the existing studies. METHODS Based on the principles of accessibility and generality, assessment items were derived from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)-Society for Medical Decision Making (SMDM) Task Force reports. The resulting checklist was applied to all 211 DES studies identified in a previous review. The proportion of fulfilled checklist items served as an indicator of reporting quality. A logistic regression was conducted to investigate whether study characteristics (eg, publication before or after the publication of the ISPOR-SMDM reports) increased the likelihood of fulfilling more than the mean number of items fulfilled by the appraised DES studies. RESULTS An 18-item checklist was formulated covering model conceptualization, parameterization and uncertainty assessment, validation, generalizability, and stakeholder involvement. The reporting quality of the DES models fluctuated around the mean of 63.7% (SD 11.0%) over the period studied. A modest nonsignificant improvement in reporting quality was found after the publication of the ISPOR-SMDM reports (64.5% vs 62.9%). Items with the lowest performance were related to predictive validation (2.8% of studies), cross validation (8.5%), face validity assessment (26.5%), and stakeholder involvement (27.5%). Models applied to health economic evaluation (HEE), country under study, and industry sponsorship were significantly associated with the odds of achieving above-average reporting quality. CONCLUSIONS The checklist is applicable across various model-based analyses beyond HEEs. Adherence to the ISPOR-SMDM guidelines should be improved, particularly regarding model validation. OBJECTIVES To measure Australian population preferences for lung cancer screening and to explore whether these preferences are related to respondent characteristics and lung cancer risk. METHODS An online ranking task was administered to a sample of 521 Australians between the ages of 50 and 80 with a history of cigarette smoking. Choice sets contained 2 alternative lungs screens and an opt-out, and respondents were asked to rank the 3 options. Both conditional logit and mixed logit analyses were conducted exploring both the forced choice between the 2 screens and identifying the types of respondent most likely to opt out of any screening. For this, respondent 6-year lung cancer risk was estimated and used as a covariate. RESULTS Respondents valued tests that involved breath or blood tests in addition to computerized tomography (CT), locations that were close to home, receiving results quickly, and minimizing radiation from the CT scan. Willingness to pay differed between relatively higher and lower risk individuals; higher risk individuals placed greater emphasis on convenience, result timeliness, and radiation. Respondent characteristics that predicted opting out of any screening included being male, fewer years of smoking, and not having a previous cancer diagnosis. Lung cancer risk did not influence the likelihood of opting out. CONCLUSIONS Uptake of lung cancer screening is likely to be changeable if different modalities of screening are provided, with effects likely differing across population subgroups. OBJECTIVES The EQ-5D-5L valuation protocol recommends combining time trade-off (TTO) and discrete choice experiments (DCEs). DCEs that include a duration attribute (DCETTO) allow modeling on the quality-adjusted life-year scale. Because the choice sequence in a TTO can be construed as a series of DCETTO, we used data from a single TTO study to investigate the extent to which DCE values match TTO values when based on identical preferences. METHODS In a TTO design in which a fixed set of choices were administered without termination at preference indifference, 202 individuals each valued 10 EQ-5D health states. From identified indifference points, we estimated three sets of TTO values (i) plotting means and (ii) applying censored regressions at -1 and 1. Using all strict preferences, we (iii) estimated DCETTO values with a logit model and a bootstrap procedure. RESULTS Estimated DCETTO and TTO values agreed well at the severe end of the quality-adjusted life-year scale, but with decreasing severity, DCETTO values were higher than TTO-values, with the difference peaking at 0.