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The establishment of precision medicine in cancer patients requires the study of several biomarkers. Single-gene testing approaches are limited by sample availability and turnaround time. Next generation sequencing (NGS) provides an alternative for detecting genetic alterations in several genes with low sample requirements. Here we show the impleme...
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Purpose
To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.
Patients and methods
Adult patients with histologically or cytologically...
Citations
... The study was carried out in accordance with the Declaration of Human Rights and the Conference of Helsinki. In January 2021, as a consequence of the accreditation of NGS techniques under the UNE-EN ISO 15189:2022 standard [14], the Lung Cancer Committee of our hospital decided to establish NGS as a routine testing strategy for the molecular profiling of NSCLC. During this period, 128 samples were analyzed using NGS. ...
Next-generation sequencing (NGS) is a molecular approach able to provide a comprehensive molecular profile of non-small cell lung cancer (NSCLC). The broad spectrum of biomarker-guided therapies has positioned molecular diagnostic laboratories as a central component of patient clinical management. Here, we show the results of an UNE-EN ISO 15189:2022 NGS-accredited assay in a cohort of 350 patients. TP53 (51.0%), KRAS (26.6%) and EGFR (12.9%) were the most frequently mutated genes. Furthermore, we detected co-occurring and mutually exclusive alterations, as well as distinct molecular profiles according to sex and smoking habits. Actionable genetic alterations were significantly more frequent in female patients (80.5%, p < 0.001) and in never-smoker patients (87.7%, p < 0.001). When NGS was established as the main molecular testing strategy, 36.4% of patients received at least one line of targeted treatment. Among 200 patients with stage IV NSCLC, first-line treatment with targeted therapies was associated with a longer progression-free survival (PFS) (13.4 months (95% CI, 10.2–16.6) (p = 0.001)). Similarly, the overall survival (OS) of patients receiving at least one targeted drug was significantly longer (26.2 months (95% CI, 11.8–40.5) (p < 0.001)). Our results show that the implementation of NGS in the public healthcare system has provided a broader application of precision medicine.
... The results obtained in our study show that implementing NGS in Spanish reference centers, covering a potential target population of 9,734 patients, would have a clear benefit in terms of LY gained (1,188 Several cost analyses and economic evaluations of NGS have been performed in the past few years, as reported in two systematic reviews of the literature. 37,44,45 The study performed by Weymann et al focused on economic evaluations of NGS published between 2000 and 2016, aiming to characterize the availability and scope of economic evidence. Among the 55 studies identified, only five economic evaluations were performed on lung cancer. ...
... It is worth mentioning that one of the studies identified in the literature review was a cost analysis conducted in Spain and reported that NGS implementation was feasible and could be performed at a reasonable cost because NGS is a multiplexed molecular diagnostic tool able to overcome the limitations of current molecular diagnosis in advanced cancer, allowing an improved and economically sustainable molecular profiling. 44 None of the economic evaluations identified in these literature reviews have used a joint model focused on implementing NGS in reference centers. ...
Purpose:
The aim of this study was to assess the cost-effectiveness of using next-generation sequencing (NGS) versus single-gene testing (SgT) for the detection of genetic molecular subtypes and oncogenic markers in patients with advanced non-small-cell lung cancer (NSCLC) in the setting of Spanish reference centers.
Methods:
A joint model combining decision tree with partitioned survival models was developed. A two-round consensus panel was performed to describe clinical practice of Spanish reference centers, providing data on testing rate, prevalence of alterations, turnaround times, and treatment pathways. Treatment efficacy data and utility values were obtained from the literature. Only direct costs (euros, 2022), obtained from Spanish databases, were included. A lifetime horizon was considered, so a 3% discount rate for future costs and outcomes was considered. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainty.
Results:
A target population of 9,734 patients with advanced NSCLC was estimated. If NGS was used instead of SgT, 1,873 more alterations would be detected and 82 more patients could potentially be enrolled in clinical trials. In the long term, using NGS would provide 1,188 additional quality-adjusted life-years (QALYs) in the target population compared with SgT. On the other hand, the incremental cost of NGS versus SgT in the target population was €21,048,580 euros for a lifetime horizon (€1,333,288 for diagnosis phase only). The obtained incremental cost-utility ratios were €25,895 per QALY gained, below the standard cost-effectiveness thresholds.
Conclusion:
Using NGS in Spanish reference centers for the molecular diagnosis of patients with metastatic NSCLC would be a cost-effective strategy over SgT.
... Therefore, using NGS to identify patients who could benefit from targeted treatments not only improves their overall survival but may also result in healthcare resource savings. Additionally, it has been reported that the introduction of NGS could save between €25 and €1,041 compared to standard diagnostic techniques if a minimum number of patients were tested and that this expenditure reduction increases with the number of mutations analyzed [27][28][29]. In addition, molecular diagnosis with NGS techniques has shown similar or even shorter diagnosis generation times than sequential testing techniques [9,29]. ...
... Additionally, it has been reported that the introduction of NGS could save between €25 and €1,041 compared to standard diagnostic techniques if a minimum number of patients were tested and that this expenditure reduction increases with the number of mutations analyzed [27][28][29]. In addition, molecular diagnosis with NGS techniques has shown similar or even shorter diagnosis generation times than sequential testing techniques [9,29]. However, despite the benefits associated with NGS, cost-effectiveness analyses on the implementation of these techniques for the diagnosis of NSCLC patients have been carried out in a few countries [8,25,30,31], whereas there is no available published evidence for Spain. ...
Background:
To assess the cost-effectiveness of using next-generation sequencing (NGS) compared to sequential single-testing (SST) for molecular diagnostic and treatment of patients with advanced non-small cell lung cancer (NSCLC) from a Spanish single-center perspective, the Hospital Universitario Virgen del Rocio (HUVR).
Research design and methods:
A decision-tree model was developed to assess the detection of alterations and diagnostic cost in patients with advanced NSCLC, comparing NGS versus SST. Model inputs such as testing, positivity rates or treatment allocation, were obtained from the literature and the clinical practice of HUVR experts through consultation. Several sensitivity analyses were performed to test the robustness of the model.
Results:
Using NGS for molecular diagnosis of a 100-patients hypothetical cohort, 30 more alterations could be detected and 3 more patients could be enrolled in clinical trials than using SST. On the other hand, diagnostic costs were increased up to 20,072€ using NGS instead of SST. Using NGS time-to-results would be reduced from 16.7 to 9 days.
Conclusions:
The implementation of NGS at HUVR for the diagnostic of patients with advanced NSCLC provides significant clinical benefits compared to SST in terms of alterations detected, treatment with targeted-therapies and clinical trial enrollment, and could be considered a cost-effective strategy.
... Six studies, two of them USA-based, reported diagnostic outcomes [13][14][15][16][17][18], while nine (five USA-based) reported economic evidence [17,[19][20][21][22][23][24][25][26][27]. Of these, one study conducted in Singapore by Tan et al. reported both diagnostic and economic outcomes [17]. ...
... Among the ten economic studies, six assessed cost-effectiveness [17,19,[23][24][25][26], one reported costs [27], two assessed budget impacts [20,21] and one reported a cost-consequence analysis (Table 2) [22]. ...
... Studies conducted in other regions (e.g., Europe, Asia) were aligned with USA-based studies regarding economic and diagnostic outcomes. In Spain, Simarro et al. reported that NGS implementation was feasible and could be done at reasonable cost [27]. In Singapore, Tan et al. found that routine upfront NGS was cost-effective compared with sequential sequencing [17]. ...
We aimed to assess the diagnostic and economic value of next-generation sequencing (NGS) versus single-gene testing, and of liquid biopsy (LBx) versus tissue biopsy (TBx) in non-small-cell lung cancer biomarker testing through literature review. Embase and MEDLINE were searched to identify relevant studies (n = 43) from 2015 to 2020 in adults with advanced non-small-cell lung cancer. For NGS versus single-gene testing, concordance was 70–99% and sensitivity was 86–100%. For LBx versus TBx, specificity was 43–100% and sensitivity was ≥60%. Turnaround times were longer for NGS versus single-gene testing (but not vs sequential testing) and faster for LBx versus TBx. NGS was cost-effective, and LBx reduced US per-patient costs. NGS versus single-gene testing and LBx versus TBx were concordant. NGS and LBx may be cost-effective for initial screening.
... Although both techniques (NGS and nCounter) require minimum amounts of genetic material, our dropout percentage increased to 15% when considering those samples for which DNA or RNA testing could not be performed. Some groups, which also included combined DNA and RNA in their sequencing workflows, have reported lower invalid test rates of approximately 2%-3% [18,24]. However, these results do not correspond to the total screening failure rates, which should include samples with insufficient material, the major reason for failure in our series. ...
Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, METΔex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69–2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39–0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12–1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care.
... As the cumulative cost of testing three or more genes approaches the cost of multi-gene panel testing using the massively parallel or next-generation sequencing (NGS) technology, there have been calls for the latter being the standard molecular testing platform for lung cancer biomarkers. [6][7][8] This has been further encouraged by early data suggesting that tumor mutation burden could also serve as a predictive biomarker for immune checkpoint inhibitor therapy, additional to or possibly in lieu of programmed death ligand 1 immunohistochemistry (IHC) test. [9][10][11] This begs the question: Is there still a role for IHC in the era of NGS? ...
Background
The molecular diagnostic and therapeutic pathway of Non-Small Cell Lung Cancer (NSCLC) stands as a successful example of precision medicine. The scarcity of material and the increasing number of biomarkers to be tested have prompted the routine application of next-generation-sequencing (NGS) techniques. Despite its undeniable advantages, NGS involves high costs that may impede its broad adoption in laboratories. This study aims to assess the detailed costs linked to the integration of NGS diagnostics in NSCLC to comprehend their financial impact.
Materials and methods
The retrospective analysis encompasses 210 cases of early and advanced stages NSCLC, analyzed with NGS and collected at the IRCCS San Gerardo dei Tintori Foundation (Monza, Italy). Molecular analyses were conducted on FFPE samples, with an hotspot panel capable of detecting DNA and RNA variants in 50 clinically relevant genes. The economic analysis employed a full-cost approach, encompassing direct and indirect costs, overheads, VAT (Value Added Tax).
Results
We estimate a comprehensive cost for each sample of €1048.32. This cost represents a crucial investment in terms of NSCLC patients survival, despite constituting only around 1% of the expenses incurred in their molecular diagnostic and therapeutic pathway.
Conclusions
The cost comparison between NGS test and the notably higher therapeutic costs highlights that the diagnostic phase is not the limiting economic factor. Developing NGS facilities structured in pathology networks may ensure appropriate technical expertise and efficient workflows.
Lung cancer is the leading cause of cancer deaths among both men and women, representing approximately 25% of cancer fatalities each year. The treatment landscape for non-small cell lung cancer (NSCLC) is rapidly evolving due to the progress made in biomarker-driven targeted therapies. While advancements in targeted treatments have improved survival rates for NSCLC patients with actionable biomarkers, long-term survival remains low, with an overall 5-year relative survival rate below 20%. Artificial intelligence/machine learning (AI/ML) algorithms have shown promise in biomarker discovery, yet NSCLC-specific studies capturing the clinical challenges targeted and emerging patterns identified using AI/ML approaches are lacking. Here, we employed a text-mining approach and identified 215 studies that reported potential biomarkers of NSCLC using AI/ML algorithms. We catalogued these studies with respect to BEST (Biomarkers, EndpointS, and other Tools) biomarker sub-types and summarized emerging patterns and trends in AI/ML-driven NSCLC biomarker discovery. We anticipate that our comprehensive review will contribute to the current understanding of AI/ML advances in NSCLC biomarker research and provide an important catalogue that may facilitate clinical adoption of AI/ML-derived biomarkers.
Background: Targeted therapy for cancer is becoming more frequent as the understanding of the molecular pathogenesis increases. Molecular testing must be done to use targeted therapy. Unfortunately, the testing turnaround time can delay the initiation of targeted therapy.
Objective: To investigate the impact of a next-generation sequencing (NGS) machine in the hospital that would allow for in-house NGS testing of metastatic non-small cell lung cancer (mNSCLC) in a US setting.
Methods: The differences between 2 hospital pathways were established with a cohort-level decision tree that feeds into a Markov model. A pathway that used in-house NGS (75%) and the use of external laboratories (so-called send-out NGS) (25%), was compared with the standard of exclusively send-out NGS. The model was from the perspective of a US hospital over a 5-year time horizon. All cost input data were in or inflated to 2021 USD. Scenario analysis was done on key variables.
Results: In a hospital with 500 mNSCLC patients, the implementation of in-house NGS was estimated to increase the testing costs and the revenue of the hospital. The model predicted a $710 060 increase in testing costs, a $1 732 506 increase in revenue, and a $1 022 446 return on investment over 5 years. The payback period was 15 months with in-house NGS. The number of patients on targeted therapy increased by 3.38%, and the average turnaround time decreased by 10 days when in-house NGS was used.
Discussion: Reducing testing turnaround time is a benefit of in-house NGS. It could contribute to fewer mNSCLC patients lost to second opinion and an increased number of patients on targeted therapy. The model outcomes predicted that, over a 5-year period, there would be a positive return on investment for a US hospital. The model reflects a proposed scenario. The heterogeneity of hospital inputs and the cost of send-out NGS means context-specific inputs are needed.
Conclusion: Using in-house NGS testing could reduce the testing turnaround time and increase the number of patients on targeted therapy. Additional benefits for the hospital are that fewer patients will be lost to second opinion and that in-house NGS could generate additional revenue.
