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Open accessJournal ArticleDOI: 10.1007/S41669-020-00249-0

Next-Generation Sequencing in Clinical Practice: Is It a Cost-Saving Alternative to a Single-Gene Testing Approach?

04 Mar 2021-Vol. 5, Iss: 2, pp 285-298
Abstract: This study aimed to compare the costs of a next-generation sequencing-based (NGS-based) panel testing strategy to those of a single-gene testing-based (SGT-based) strategy, considering different scenarios of clinical practice evolution. Three Italian hospitals were analysed, and four different testing pathways (paths 1, 2, 3, and 4) were identified: two for advanced non-small-cell lung cancer (aNSCLC) patients and two for unresectable metastatic colon-rectal cancer (mCRC) patients. For each path, we explored four scenarios considering the current clinical practice and its expected evolution. The 16 testing cases (4 scenarios × 4 paths) were then compared in terms of differential costs between the NGS-based and SGT-based approaches considering personnel, consumables, equipment, and overhead costs. Break-even and sensitivity analyses were performed. Data gathering, aimed at identifying the hospital setup, was performed through a semi-structured questionnaire administered to the professionals involved in testing activities. The NGS-based strategy was found to be a cost-saving alternative to the SGT-based strategy in 15 of the 16 testing cases. The break-even threshold, the minimum number of patients required to make the NGS-based approach less costly than the SGT-based approach, varied across the testing cases depending on molecular alterations tested, techniques adopted, and specific costs. The analysis found the NGS-based approach to be less costly than the SGT-based approach in nine of the 16 testing cases at any volume of tests performed; in six cases, the NGS-based approach was found to be less costly above a threshold (and in one case, it was found to be always more expensive). Savings obtained using an NGS-based approach ranged from €30 to €1249 per patient; in the unique testing case where NGS was more costly, the additional cost per patient was €25. An NGS-based approach may be less costly than an SGT-based approach; also, generated savings increase with the number of patients and different molecular alterations tested.

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Topics: Test strategy (57%)

6 results found

Open accessJournal ArticleDOI: 10.3390/JMP2030022
18 Aug 2021-
Abstract: The development of targeted therapies has improved survival rates for patients with advanced non-small cell lung cancer (NSCLC). However, tissue biopsy is unfeasible or inadequate in many patients, limiting biomarker testing and access to targeted therapies. The increasing numbers of established and emerging biomarkers with available targeted treatments highlights the challenges associated with sequential single-gene testing and limited tissue availability. Multiplex next-generation sequencing (NGS) offers an attractive alternative and represents a logical next step, and in cases where the tumour is inaccessible, tissue biopsy yields insufficient tumour content, or when the patient’s performance status does not allow a tissue biopsy, liquid biopsy can provide valuable material for molecular diagnosis. Here, we explore the role of liquid biopsy (i.e., circulating cell-free DNA analysis) in Europe. Liquid biopsies could be used as a complementary approach to increase rates of molecular diagnosis, with the ultimate aim of improving patient access to appropriate targeted therapies. Expert opinion is also provided on potential future applications of liquid biopsy in NSCLC, including for cancer prevention, detection of early stage and minimum residual disease, monitoring of response to therapy, selection of patients for immunotherapy, and monitoring of tumour evolution to enable optimal adaptation/combination of drug therapies.

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Topics: Liquid biopsy (70%)

1 Citations

Open accessJournal ArticleDOI: 10.1002/ADVS.202102593
Na Zhao1, Jiabao Cao1, Jiayue Xu1, Beibei Liu2  +15 moreInstitutions (4)
23 Oct 2021-Advanced Science
Abstract: Fast and accurate identification of microbial pathogens is critical for the proper treatment of infections. Traditional culture-based diagnosis in clinics is increasingly supplemented by metagenomic next-generation-sequencing (mNGS). Here, RNA/cDNA-targeted sequencing (meta-transcriptomics using NGS (mtNGS)) is established to reduce the host nucleotide percentage in clinic samples and by combining with Oxford Nanopore Technology (ONT) platforms (meta-transcriptomics using third-generation sequencing, mtTGS) to improve the sequencing time. It shows that mtNGS improves the ratio of microbial reads, facilitates bacterial identification using multiple-strategies, and discovers fungi, viruses, and antibiotic resistance genes, and displaying agreement with clinical findings. Furthermore, longer reads in mtTGS lead to additional improvement in pathogen identification and also accelerate the clinical diagnosis. Additionally, primary tests utilizing direct-RNA sequencing and targeted sequencing of ONT show that ONT displays important potential but must be further developed. This study presents the potential of RNA-targeted pathogen identification in clinical samples, especially when combined with the newest developments in ONT.

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Topics: Nanopore sequencing (57%), Metagenomics (55%)

Open accessJournal ArticleDOI: 10.1016/J.CRITREVONC.2021.103525
Pasquale Pisapia1, Francesco Pepe1, Anna Baggi, Massimo Barberis2  +11 moreInstitutions (6)
Abstract: Aims The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. Methods The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. Results For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input parameters and ensuring that results would present a consistent behavior compared to the original ones. Conclusions our project, highlighted that the adoption of NGS allows to save personnel time dedicated to testing activities and to reduce the overall cost of testing per patient.

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Open accessJournal ArticleDOI: 10.3390/CELLS10082157
21 Aug 2021-Cells
Abstract: The recent emergence of novel neoadjuvant and/or adjuvant therapies for early stage (I-IIIA) non-small cell lung carcinoma (NSCLC), mainly tyrosine kinase inhibitors (TKIs) targeting EGFR mutations and immunotherapy or chemo-immunotherapy, has suddenly required the evaluation of biomarkers predictive of the efficacy of different treatments in these patients. Currently, the choice of one or another of these treatments mainly depends on the results of immunohistochemistry for PD-L1 and of the status of EGFR and ALK. This new development has led to the setup of different analyses for clinical and molecular pathology laboratories, which have had to rapidly integrate a number of new challenges into daily practice and to establish new organization for decision making. This review outlines the impact of the management of biological samples in laboratories and discusses perspectives for pathologists within the framework of EGFR TKIs in early stage NSCLC.

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Open accessJournal ArticleDOI: 10.1016/J.CRITREVONC.2021.103561
Abstract: The increasing number of approved drugs along with next generation sequencing (NGS) technologies look out as potential revolution of biomolecular characterization of non-small-cell lung cancer (NSCLC). Nevertheless, several aspects impact on success rate of NGS in clinical practice: a multidisciplinary approach and thorough knowledge of strengths and limits of each technologic diagnostic tool are required. Crucial preliminary step is the selection of the best available sample before testing, aware of clinical condition and setting of disease. Genomic data should be than integrated in the clinical context and matched with available therapeutic options; Molecular Tumor Boards (MTB) are worldwide emerging interdisciplinary groups implemented to transfer the impact of precision medicine in clinical practice. In order to guarantee equity in treatment, these considerations should find their application widely and rapidly. Aim of this review is offering an overview of emerging biomarkers, relative upcoming targeted drugs, and new diagnostic chances with an authors' perspective about a real-life diagnostic-therapeutic algorithm useful for daily clinical practice.

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Topics: Precision medicine (53%)


17 results found

Open accessJournal ArticleDOI: 10.1093/ANNONC/MDY495
01 Jan 2019-Annals of Oncology
Abstract: Background Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required. Materials and methods In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity. Results High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established. Conclusions TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types.

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Topics: Biomarker (medicine) (52%)

654 Citations

Open access
01 Jan 2014-
Abstract: Italy is the sixth largest country in Europe and has the second highest average life expectancy, reaching 79.4 years for men and 84.5 years for women in 2011. There are marked regional differences for both men and women in most health indicators, reflecting the economic and social imbalance between the north and south of the country. The main diseases affecting the population are circulatory diseases, malignant tumours and respiratory diseases. Italy's health care system is a regionally based national health service that provides universal coverage largely free of charge at the point of delivery. The main source of financing is national and regional taxes, supplemented by copayments for pharmaceuticals and outpatient care. In 2012, total health expenditure accounted for 9.2 percent of GDP (slightly below the EU average of 9.6 percent). Public sources made up 78.2 percent of total health care spending. While the central government provides a stewardship role, setting the fundamental principles and goals of the health system and determining the core benefit package of health services available to all citizens, the regions are responsible for organizing and delivering primary, secondary and tertiary health care services as well as preventive and health promotion services. Faced with the current economic constraints of having to contain or even reduce health expenditure, the largest challenge facing the health system is to achieve budgetary goals without reducing the provision of health services to patients. This is related to the other key challenge of ensuring equity across regions, where gaps in service provision and health system performance persist. Other issues include ensuring the quality of professionals managing facilities, promoting group practice and other integrated care organizational models in primary care, and ensuring that the concentration of organizational control by regions of health-care providers does not stifle innovation.

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Topics: Health care (71%), Health care reform (68%), Health policy (67%) ... show more

328 Citations

Journal ArticleDOI: 10.1056/NEJMP1709968
Abstract: In May 2017, the FDA approved pembrolizumab, a programmed death 1 inhibitor, for adult and pediatric patients with unresectable or metastatic, microsatellite-instability–high or mismatch-repair–deficient solid tumors, regardless of tumor site or histology.

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Topics: Pembrolizumab (61%)

310 Citations

Open accessJournal ArticleDOI: 10.1038/GIM.2017.247
Abstract: We conducted a systematic literature review to summarize the current health economic evidence for whole-exome sequencing (WES) and whole-genome sequencing (WGS). Relevant studies were identified in the EMBASE, MEDLINE, Cochrane Library, EconLit and University of York Centre for Reviews and Dissemination databases from January 2005 to July 2016. Publications were included in the review if they were economic evaluations, cost studies, or outcome studies. Thirty-six studies met our inclusion criteria. These publications investigated the use of WES and WGS in a variety of genetic conditions in clinical practice, the most common being neurological or neurodevelopmental disorders. Study sample size varied from a single child to 2,000 patients. Cost estimates for a single test ranged from $555 to $5,169 for WES and from $1,906 to $24,810 for WGS. Few cost analyses presented data transparently and many publications did not state which components were included in cost estimates. The current health economic evidence base to support the more widespread use of WES and WGS in clinical practice is very limited. Studies that carefully evaluate the costs, effectiveness, and cost-effectiveness of these tests are urgently needed to support their translation into clinical practice.

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228 Citations

Journal ArticleDOI: 10.1634/THEONCOLOGIST.13-S1-28
01 Jan 2008-Oncologist
Abstract: For patients with advanced non-small cell lung cancer and a good functional status, platinum-based first-line chemotherapy improves quality of life, reduces diseaserelated symptoms, and improves survival. The addition of bevacizumab to carboplatin and paclitaxel in the first-line setting has been shown to produce a higher response rate and longer progression-free survival and overall survival times than with carboplatin and paclitaxel. Despite these therapies, all patients inevitably experience disease progression. There are currently three agents approved for treating patients who progress after one prior regimen: docetaxel, pemetrexed, and erlotinib. Erlotinib is also indicated for patients who progress after two prior regimens. These agents appear to have similar efficacies in terms of response and overall survival, but have significantly different

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Topics: Erlotinib (58%), Docetaxel (58%), Carboplatin (57%) ... show more

105 Citations

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