scholarly journals Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe

2022 ◽  
Vol 12 (1) ◽  
pp. 72
Author(s):  
Denis Horgan ◽  
Giuseppe Curigliano ◽  
Olaf Rieß ◽  
Paul Hofman ◽  
Reinhard Büttner ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Care ◽  
Personalised Medicine ◽  
National Level ◽  
Improve Patient Care ◽  
Patient Access ◽  
Next Generation ◽  
Stakeholder Collaboration ◽  
Multi Stakeholder ◽  
Generation Sequencing

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

Assessing the Value of Next-Generation Sequencing Tests in a Dynamic Environment

2018 ◽  
pp. 139-146 ◽  
Author(s):  
Howard A. Burris ◽  
Leonard B. Saltz ◽  
Peter P. Yu
Keyword(s):  
Next Generation Sequencing ◽  
Cancer Biology ◽  
Health Care Policy ◽  
Clinical Care ◽  
Dynamic Environment ◽  
Investigational Drug ◽  
Next Generation ◽  
Genomic Alterations ◽  
Clinical Annotation ◽  
Generation Sequencing

Next-generation sequencing (NGS)–based technology has lowered the cost of cancer testing for genomic alterations and is now commercially available from a growing number of diagnostic laboratories. However, laboratories vary in the methodologies underlying their tests, the types and numbers of genomic alterations covered by the test, and the clinical annotation of the sequencing findings. Determining the value of NGS tests is dependent on whether it is used to support clinical trials or as a part of routine clinical care at a time when both the investigational drug pipeline and the list of U.S. Food and Drug Administration–approved or Compendium-listed therapeutics is in a high state of flux. Reimbursement policy for NGS testing by the Centers for Medicare & Medicaid is evolving as the value of NGS testing becomes more clearly defined for specific clinical situations. Patient care and clinical decisions-making are dependent on the oncologist’s knowledge of when NGS testing has value. Here, we review principles and practice for NGS testing in this dynamic confluence of technology, cancer biology, and health care policy.

Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 584-584
Author(s):  
Kristin Lynn Koenig ◽  
Jarred Burkart ◽  
Sameh Mikhail ◽  
Christina Sing-Ying Wu ◽  
Anne M. Noonan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Clinical Care ◽  
Comprehensive Cancer Center ◽  
Genomic Profiling ◽  
Next Generation ◽  
Wild Type ◽  
Genomic Alterations ◽  
Generation Sequencing

584 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 265 pts with GI malignancies underwent successful genomic profiling. 1205 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through next generation sequencing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.

scholarly journals Systematic Evaluation of Sanger Validation of Next-Generation Sequencing Variants

2016 ◽  
Vol 62 (4) ◽  
pp. 647-654 ◽  
Author(s):  
Tyler F Beck ◽  
James C Mullikin ◽  
Leslie G Biesecker ◽  
Keyword(s):  
Next Generation Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Best Practice ◽  
Clinical Care ◽  
Systematic Evaluation ◽  
Next Generation ◽  
Current Standard ◽  
Ngs Data ◽  
Generation Sequencing

Abstract BACKGROUND Next-generation sequencing (NGS) data are used for both clinical care and clinical research. DNA sequence variants identified using NGS are often returned to patients/participants as part of clinical or research protocols. The current standard of care is to validate NGS variants using Sanger sequencing, which is costly and time-consuming. METHODS We performed a large-scale, systematic evaluation of Sanger-based validation of NGS variants using data from the ClinSeq® project. We first used NGS data from 19 genes in 5 participants, comparing them to high-throughput Sanger sequencing results on the same samples, and found no discrepancies among 234 NGS variants. We then compared NGS variants in 5 genes from 684 participants against data from Sanger sequencing. RESULTS Of over 5800 NGS-derived variants, 19 were not validated by Sanger data. Using newly designed sequencing primers, Sanger sequencing confirmed 17 of the NGS variants, and the remaining 2 variants had low quality scores from exome sequencing. Overall, we measured a validation rate of 99.965% for NGS variants using Sanger sequencing, which was higher than many existing medical tests that do not necessitate orthogonal validation. CONCLUSIONS A single round of Sanger sequencing is more likely to incorrectly refute a true-positive variant from NGS than to correctly identify a false-positive variant from NGS. Validation of NGS-derived variants using Sanger sequencing has limited utility, and best practice standards should not include routine orthogonal Sanger validation of NGS variants.

scholarly journals Tumor-Agnostic Drug Development

2018 ◽  
pp. 184-187 ◽  
Author(s):  
Michael Offin ◽  
Dazhi Liu ◽  
Alexander Drilon
Keyword(s):  
Next Generation Sequencing ◽  
Drug Development ◽  
Molecular Signatures ◽  
Patient Access ◽  
Next Generation ◽  
Basket Trial ◽  
Key Aspects ◽  
Tumor Types ◽  
Generation Sequencing

Therapies designed to target cancers that harbor specific molecular signatures have reshaped the landscape of oncologic drug development, and advances in next generation sequencing have led to an increase in the identification of these alterations across tumor types. Tumor-agnostic trial designs, such as the “basket trial,” have been developed as an approach to study the efficacy of these treatments and increase patient access, especially for patients whose tumors carry these alterations infrequently. We review key aspects of these genomically enriched trial strategies and their impact on drug development and approval.

scholarly journals Review of Clinical Next-Generation Sequencing

2017 ◽  
Vol 141 (11) ◽  
pp. 1544-1557 ◽  
Author(s):  
Sophia Yohe ◽  
Bharat Thyagarajan
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Care ◽  
Cost Effective ◽  
Next Generation ◽  
Inherited Disorders ◽  
Academic Center ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
Generation Sequencing

Context.— Next-generation sequencing (NGS) is a technology being used by many laboratories to test for inherited disorders and tumor mutations. This technology is new for many practicing pathologists, who may not be familiar with the uses, methodology, and limitations of NGS. Objective.— To familiarize pathologists with several aspects of NGS, including current and expanding uses; methodology including wet bench aspects, bioinformatics, and interpretation; validation and proficiency; limitations; and issues related to the integration of NGS data into patient care. Data Sources.— The review is based on peer-reviewed literature and personal experience using NGS in a clinical setting at a major academic center. Conclusions.— The clinical applications of NGS will increase as the technology, bioinformatics, and resources evolve to address the limitations and improve quality of results. The challenge for clinical laboratories is to ensure testing is clinically relevant, cost-effective, and can be integrated into clinical care.

scholarly journals Comparison of KRAS mutation analysis of colorectal cancer samples by standard testing and next-generation sequencing

2014 ◽  
Vol 67 (9) ◽  
pp. 764-767 ◽  
Author(s):  
Nishi Kothari ◽  
Michael J Schell ◽  
Jamie K Teer ◽  
Timothy Yeatman ◽  
David Shibata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Clinical Laboratory ◽  
Clinical Care ◽  
Next Generation ◽  
Illumina Platform ◽  
Kras Mutations ◽  
Standard Testing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

AimsBased on KRAS testing, the subset of patients with metastatic colorectal cancer (CRC) that could benefit from anti-EGFR therapy can be better delineated. Though KRAS testing has become significantly more prevalent over the last few years, methods for testing remain heterogeneous and discordance has been reported between methods.MethodsIn this study, we examined a CRC patient population and compared KRAS testing done in Clinical Laboratory Improvement Amendments (CLIA) approved laboratories as part of standard clinical care and by next-generation sequencing (NGS) using the Illumina platform. Discordances were further evaluated with manual review of the NGS testing.ResultsOut of 468 CRC patient samples, 77 had KRAS testing done by both CLIA assay and NGS. There were concordant results between testing methodologies in 74 out of 77 patients, or 96% (95% CI 89% to 99%). There were three patient samples that showed discordant results between the two methods of testing. Upon further investigation of the NGS results for the three discordant cases, one sample showed a low level of the mutation seen in the standard testing, one sample showed low tumour fraction and a third did not show any evidence of the mutation that was found with the standard assay. Five patients had KRAS mutations not typically tested with standard testing.ConclusionsOverall there was a high concordance rate between NGS and standard testing for KRAS. However, NGS revealed mutations that are not tested for with standard KRAS assays that might have clinical impact with regards to the role for anti-EGFR therapy.

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