Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer-A Cost-Efficient Strategy in a Public Healthcare System.
Ontology highlight
ABSTRACT:
SUBMITTER: Makarem M
PROVIDER: S-EPMC8395515 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:AimsTo compare fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative real-time reverse transcription-PCR (qRT-PCR) assays for detection of ROS1 fusion in a large number of ROS1-positive lung adenocatcinoma (ADC) patients.MethodsUsing IHC analysis, sixty lung ADCs including 16 cases with ROS1 protein expression and 44 cases without ROS1 expression were selected for this study. The ROS1 fusion status was examined by FISH and qRT-PCR assay.ResultsAmong 60 cases, 16 (26.7%), 13 (21.7%) and 20 (33.3%) cases were ROS1 positive revealed by IHC, FISH and qRT-PCR, respectively. Using FISH as a standard method for ROS1 fusion detection, the sensitivity and specificity of IHC were 100% and 93.6%, respectively. Three IHC-positive cases, which showed FISH negative, were demonstrated with ROS1 fusion by qRT-PCR analysis. The sensitivity and specificity of qRT-PCR for detection for ROS1 fusion were 100% and 85.1%, respectively. The total concordance rate between IHC and qRT-PCR were 93.3%.ConclusionIHC is a reliable and rapid screening tool in routine pathologic laboratories for the identification of suitable candidates for ROS1-targeted therapy. Some ROS1 IHC-positive but FISH-negative cases did harbor the translocation events and may benefit from crizotinib.
| S-EPMC4351102 | biostudies-literature
Project description:ObjectiveTo detect ROS1 rearrangement using three different assays, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR), and to analyze the clinicopathologic features of ROS1 rearrangement in patients with lung adenocarcinoma.MethodsOne hundred eighty-three consecutive patients with lung adenocarcinoma with operation and follow-up data were analyzed for ROS1 rearrangement by IHC, FISH, and RT-PCR. PCR products of the RT-PCR-positive samples were sequenced for confirmation of the specific fusion partners.ResultsThree of the 183 (1.64%) cases were identified to be positive for ROS1 rearrangement through all three methods. The fusion patterns were CD74 e6-ROS1 e32, CD74 e6-ROS1 e34, and TPM3 e8-ROS1 e35, respectively. FISH-positive cases showed two types of signals, single 3' signals (green) and split red and green signals. Using FISH as a standard method, the sensitivity and specificity of ROS1 IHC with 1+ staining or more were 100% and 96.67%, respectively. The sensitivity and specificity of RT-PCR were both 100%. Univariate analysis identified female sex (P=0.044), Stage I disease (P<0.001), and ROS1-negative status (P=0.022) to be significantly associated with longer overall survival.ConclusionIHC, FISH, and RT-PCR are all effective methods for the detection of ROS1 rearrangement. IHC would be a useful screening method in routine pathologic laboratories. RT-PCR can detect exact fusion patterns. ROS1 rearrangement may be a worse prognostic factor. The exact correlation of ROS1 rearrangement with prognosis and whether different fusion types are correlated with different responses to targeted therapy need to be further investigated.
| S-EPMC4706119 | biostudies-literature
Project description:BackgroundGovernment spending on provision of secondary healthcare has increased four-fold (in real terms) over the last decade in India. The evidence on the cost of secondary care to the health system is limited. The present study estimates the total and unit cost of services at community health centres (CHCs) and district hospitals (DHs) across India.MethodsThe present study was undertaken in 19 CHCs and ten DHs across the four Indian states of Himachal Pradesh, Tamil Nadu, Kerala and Odisha to assess the economic cost of health services using a bottom-up methodology. Data on annual consumption of both capital and recurrent resources, spent in the provision of health services during the financial year of 2014-2015, were collected. Capital expenditure was annualised and shared resources were allocated to each of the shared activities using appropriate statistics.ResultsThe mean annual costs of providing services at the CHC and DH level were 17 million Indian rupees (₹) ($US0.27 million) and ₹147 million ($US2.3 million), respectively. More than half of this annual cost was attributed to salaries (57% and 62% for CHC and DH level, respectively) and curative care (60% and 65%, respectively). At CHCs, the unit cost ranged from ₹134 (95% confidence interval [CI] 104-160) for an outpatient consultation to ₹3833 (95% CI 2668-5839) for institutional delivery. Similarly, at DH level, the unit cost varied from ₹183 (95% CI 124-248) for an outpatient consultation in an orthopaedics department to ₹4764 (95% CI 3268-6960) for an operation.ConclusionThe estimates from the present study may help generate benchmarks to aid in setting up provider payment rates and be used in future economic evaluations.
| S-EPMC7248147 | biostudies-literature
Project description:BackgroundDetection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain.MethodsA joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty.ResultsA target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis.ConclusionsOur study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.
| S-EPMC8933896 | biostudies-literature
Project description:Although cost-effectiveness analysis has a long tradition of supporting healthcare decision-making in Sweden, there are no clear criteria for when an intervention is considered too expensive. In particular, the opportunity cost of healthcare resource use in terms of health forgone has not been investigated empirically. In this work, we therefore seek to estimate the marginal cost of a life year in Sweden's public healthcare sector using time series and panel data at the national and regional levels, respectively. We find that estimation using time series is unfeasible due to reversed causality. However, through panel instrumental variable estimation we are able to derive a marginal cost per life year of about SEK 370,000 (EUR 39,000). Although this estimate is in line with emerging evidence from other healthcare systems, it is associated with uncertainty, primarily due to the inherent difficulties of causal inference using aggregate observational data. The implications of these difficulties and related methodological issues are discussed.
| S-EPMC6602994 | biostudies-literature
Project description:Isobaric stable isotope labeling using, for example, tandem mass tags (TMTs) is increasingly being applied for large-scale proteomic studies. Experiments focusing on proteoform analysis in drug time course or perturbation studies or in large patient cohorts greatly benefit from the reproducible quantification of single peptides across samples. However, such studies often require labeling of hundreds of micrograms of peptides such that the cost for labeling reagents represents a major contribution to the overall cost of an experiment. Here, we describe and evaluate a robust and cost-effective protocol for TMT labeling that reduces the quantity of required labeling reagent by a factor of eight and achieves complete labeling. Under- and over-labeling of peptides derived from complex digests of tissues and cell lines were systematically evaluated using peptide quantities of between 12.5 and 800�?g and TMT-to-peptide ratios (wt/wt) ranging from 8:1 to 1:2 at different TMT and peptide concentrations. When reaction volumes were reduced to maintain TMT and peptide concentrations of at least 10�mM and 2�g/L, respectively, TMT-to-peptide ratios as low as 1:1 (wt/wt) resulted in labeling efficiencies of >�99�% and excellent intra- and inter-laboratory reproducibility. The utility of the optimized protocol was further demonstrated in a deep-scale proteome and phosphoproteome analysis of patient-derived xenograft tumor tissue benchmarked against the labeling procedure recommended by the TMT vendor. Finally, we discuss the impact of labeling reaction parameters for N-hydroxysuccinimide ester-based chemistry and provide guidance on adopting efficient labeling protocols for different peptide quantities.
2020-01-14 | PXD012703 | Pride
Project description:IntroductionALK and ROS1 rearrangements are molecular targets of several tyrosine kinase inhibitors. RNA-sequencing approaches are regarded as the new standard for fusion gene detection, representing an alternative to standard immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques.Patients and methodsWe aimed to compare two recent amplicon-based RNA-sequencing techniques: FusionPlex® Alk Ret Ros1 v2 Kit (Archer® ) with FHS-003Z-12-Human Lung Cancer Panel (Qiagen® ) and assessed the accuracy of the data for therapy management. Thirty-seven formalin-fixed paraffin-embedded non-small cell carcinoma (NSCC) lesions initially explored by IHC and FISH were selected for RNA-sequencing analysis.ResultsQiagen® and Archer® kits produced similar results and correctly identified 85.1% (23/27) and 81.5% (22/27) of IHC/FISH ALK- and ROS1-positive samples, respectively, and 100% (6/6) of the negative samples. With regard to the ambiguous IHC-positive/FISH-negative cases, RNA-sequencing confirmed 75% (3/4) of the FISH conclusion. Although not statistically significant, patients with common EML4-ALK variants presented shorter overall survival and progression-free survival compared with patients harboring rare variants.ConclusionOur findings assessed the implementation of RNA-sequencing approaches to explore ALK and ROS1 rearrangements from formalin-fixed paraffin-embedded samples. We highlighted the similarities between Qiagen® and Archer® kits in terms of handling time, cost, and outcomes. We confirmed the feasibility of molecular testing in routine organization and its possible use not only as an alternative for standard IHC and FISH techniques, but as a supplementary technique helping to classify discrepant cases.
| S-EPMC6912030 | biostudies-literature
Project description:Our research explored the incidence and appropriateness of the much-maligned confirmatory approach to testing scientific hypotheses. Psychological scientists completed a survey about their research goals and strategies. The most frequently reported goal is to test the non-absolute hypothesis that a particular relation exists in some conditions. As expected, few scientists reported testing universal hypotheses. Most indicated an inclination to use a confirmation strategy to test the non-absolute hypotheses that a particular relation sometimes occurs or sometimes does not occur, and a disconfirmation strategy to test the absolute hypotheses that a particular relation always occurs or never occurs. The confirmatory search that dominates the field was found to be associated with the testing of non-absolute hypotheses. Our analysis indicates that a confirmatory approach is the normatively correct test of the non-absolute hypotheses that are the starting point of most studies. It also suggests that the strategy of falsification that was once proposed by Popper is generally incorrect given the infrequency of tests of universal hypotheses.
| S-EPMC4575142 | biostudies-literature
Project description:ObjectivesTo present a comprehensive real-world micro-costing analysis of bariatric surgery.MethodsPatients were included if they underwent primary bariatric surgery (gastric banding [GB], gastric bypass [GBP] and sleeve gastrectomy [SG]) between 2013 and 2019. Costs were disaggregated into cost items and average-per-patient costs from the Australian healthcare systems perspective were expressed in constant 2019 Australian dollars for the entire cohort and subgroup analysis. Annual population-based costs were calculated to capture longitudinal trends. A generalized linear model (GLM) predicted the overall bariatric-related costs.ResultsN = 240 publicly funded patients were included, with the waitlist times of ≤ 10.7 years. The mean direct costs were $11,269. The operating theatre constituted the largest component of bariatric-related costs, followed by medical supplies, salaries, critical care use, and labour on-costs. Average cost for SG ($12,632) and GBP ($15,041) was higher than that for GB ($10,049). Operating theatre accounted for the largest component for SG/GBP costs, whilst medical supplies were the largest for GB. We observed an increase in SG and a decrease in GB procedures over time. Correspondingly, the main cost driver changed from medical supplies in 2014-2015 for GB procedures to operating theatre for SG thereafter. GLM model estimates of bariatric average cost ranged from $7,580 to $36,633.ConclusionsWe presented the first detailed characterization of the scale, disaggregated profile and determinants of bariatric-related costs, and examined the evolution of resource utilization patterns and costs, reflecting the shift in the Australian bariatric landscape over time. Understanding these patterns and forecasting of future changes are critical for efficient resource allocation.
| S-EPMC8586836 | biostudies-literature
Project description:AimTo quantify the healthcare costs associated with opioid use disorder among members in a public healthcare system and compare them with healthcare costs in the general population.DesignRetrospective cohort study.SettingInpatient and outpatient care settings of Israel's largest public healthcare provider (that covers 4.7 million members).ParticipantsParticipants included 1173 members who had a diagnosis of opioid use disorder in the years between 2013 and 2018. Each patient was matched with 10 controls based on age and sex.MeasurementsThe main outcome was monthly healthcare costs.FindingsThe mean monthly healthcare cost of members with opioid use disorder was $1102 compared with $211 among controls (5.2-fold difference; 95% CI, 4.6-6.0). After excluding members with heroin related diagnoses before the index date (to focus on prescription opioids), this healthcare cost ratio did not substantially change (4.6-fold; 95% CI, 3.9-5.4). Members with opioid use disorder under the age of 65 years had a cost difference of 6.1-fold (95% CI, 5.2-7.1), whereas those 65 years and older experienced cost difference of 3.4-fold (95% CI, 2.6-4.5), compared with controls. The category with the highest cost for members with opioid use disorder was inpatient services, which was 8.7-fold (95%CI, 7.2-10.4) greater than among controls.ConclusionsHealthcare costs among individuals with opioid use disorder in Israel's public health system are substantially higher than among controls, at least partially attributable to prescription opioid use disorder. Differences are greater among individuals under 65 years.
| S-EPMC9796021 | biostudies-literature