Real-world application of next generation sequencing to guide therapeutic options in lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14645-e14645
Author(s):  
Molly Tokaz ◽  
Anthony Scott ◽  
Maryann Shango ◽  
Sumana Devata ◽  
Shannon Carty ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Real World ◽  
Local Treatment ◽  
Therapeutic Targets ◽  
Therapeutic Options ◽  
Next Generation ◽  
Considerable Uncertainty ◽  
Generation Sequencing

e14645 Background: Despite the increasing availability of targeted and novel therapies, successful treatment of many relapsed/refractory lymphomas remains a challenge. Tumor sequencing is becoming an increasingly available technique to identify potential therapeutic targets; however, there remains considerable uncertainty about the successful application of this data in a “real world” clinical setting. Methods: Herein, we describe 91 lymphoma patients who underwent DNA & RNA sequencing of tumor biopsies via the MIONCOSEQ protocol to identify actionable therapeutic targets. Their charts were reviewed for the clinical use of MIONCOSEQ recommendations. Results: Among the 91 patients were 13 Lymphoma subtypes. Most patients had Stage III/IV disease (68%) at diagnosis, underwent an average of 4 treatments before sequencing (range 0-16) and had approximately 47 distinct molecular alterations (range 2-447). Of the cohort, 60 patients (65%) had actionable targets identified of which 11 ultimately received treatment based on MIONCOSEQ recommendations. The remaining patients did not receive treatment due to multiple reasons: prior CR or on surveillance not requiring treatment (10); death (12); trial ineligibility (4); trial unavailability at the institution (8); patient preference for local treatment (6); and already on alternative treatments (9). Taken as a whole, sequencing late in the disease course and a lack of available clinical trials were identified as barriers for the incorporation of MIONCOSEQ data into clinical practice. Therefore, earlier sequencing and strategies to bolster the availability of targeted therapies may significantly increase the application of genomic data and precision medicine in clinical practice. Conclusions: While next generation sequencing (NGS) is a powerful tool for advancing precision medicine, meaningful clinical application of these results remains a challenge. Our study indicates that early sequencing and improved trial availability could be beneficial in increasing real-world therapeutic options for relapsed/refractory lymphoma. Further research is needed to determine the extent to which a personalized approach, informed by NGS data, improves outcomes.

scholarly journals Molecular and Genomic Profiling of Lung Cancer in the Era of Precision Medicine: A Position Paper from the Italian Association of Thoracic Oncology (AIOT)

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1627
Author(s):  
Nicola Normanno ◽  
Massimo Barberis ◽  
Filippo De Marinis ◽  
Cesare Gridelli ◽  
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Genetic Alterations ◽  
Position Paper ◽  
Genomic Profiling ◽  
Next Generation ◽  
Italian Association ◽  
Generation Sequencing

The identification of the optimal cancer treatment has become progressively more intricate for non-small-cell lung cancer (NSCLC) patients due to the multitude of options available. The testing of biomarkers to predict clinical responses to therapies is pivotal to stratify the patients based on the molecular features of their tumors. The number of actionable genetic alterations to be tested is increasing together with the comprehension of the molecular mechanisms underlying tumor growth and development. The possibility of using next generation sequencing-based approaches enhanced the acquisition of genetic data with potential clinical usefulness, and favored the integration of precision medicine in clinical practice. The availability of targeted sequencing panels that cover genetic alterations in hundreds of genes allows the performance of a comprehensive genomic profiling (CGP) of lung tumors. However, different issues still need to be solved, from the tissue needed for next generation sequencing analysis, to the choice of the test and its interpretation in the clinical context. This position paper from the Italian Association of Thoracic Oncology (AIOT) summarizes the results of a discussion from a Precision Medicine Panel meeting on the challenges to bringing CGP and, therefore, precision medicine into the daily clinical practice.

scholarly journals Next-generation Sequencing-based Test for Resectable Colorectal Cancer in Real-world Clinical Practice

2021 ◽  
Author(s):  
Masayo Ogiri ◽  
Ryo Seishima ◽  
Kohei Nakamura ◽  
Eriko Aimono ◽  
Shimpei Matsui ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Real World ◽  
Gene Panel ◽  
Stage I ◽  
Next Generation ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Ngs Data ◽  
Generation Sequencing

Abstract Purpose: This study aimed to evaluate the significance of Next-generation sequencing (NGS)-based gene panel testing in resectable colorectal cancers (CRC)s by analyzing real-world data collected prospectively from patients. Methods: Patients with CRC who underwent surgery from July 2018 to February 2020 at our institution were included, and correlations between various NGS data and clinicopathological findings were evaluated. Results: Overall, 107 patients were included in this study. The tumor stage was I in 28 cases (26.2%), II in 40 cases (37.4%), III in 32 cases (29.9%), and IV in 7 cases (6.5%). Actionable gene alterations were found in 97.2% of the cases. Co-alteration analysis suggested that either TP53- or APC-related alterations were more frequently found in early-stage tumors (stage I). The copy number alteration count was significantly lower in right side colon tumors than in tumors in other locations (P < 0.05). Homologous recombination deficiency (HRD) was more often identified in stage IV tumors than in stage I or II tumors (P < 0.05). Moreover, high HRD status was suggested to be useful for identifying high-risk stage II tumors (P < 0.05). Conclusion: In this study, real-world NGS data represented the biological features of CRCs. HRD was identified as a useful result of gene panel testing with novel utility in clinical practice.

Novel Next-Generation Sequencing and Networks-Based Therapeutic Targets: Realistic and More Effective Drug Design and Discovery

2014 ◽  
Vol 20 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Dimitrios Roukos ◽  
Giannis Baltogiannis ◽  
Christos Katsouras ◽  
Aris Bechlioulis ◽  
Katerina Naka ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Drug Design ◽  
Therapeutic Targets ◽  
Effective Drug ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Feasibility of next‐generation sequencing test for patients with advanced NSCLC in clinical practice

2020 ◽  
Author(s):  
Ryo Ariyasu ◽  
Ken Uchibori ◽  
Hironori Ninomiya ◽  
Shinsuke Ogusu ◽  
Ryosuke Tsugitomi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Advanced Nsclc ◽  
Next Generation ◽  
Generation Sequencing

The novel approach to distinguish primary multiple lung adenocarcinomas from intrapulmonary metastases by next generation sequencing in Chinese patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20506-e20506
Author(s):  
Lin Li ◽  
Naiquan Mao ◽  
Yingcheng Lyu ◽  
Huayue Lin ◽  
Kefeng Wang ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Chinese Patients ◽  
Comparative Genomic ◽  
Genomic Profiling ◽  
Next Generation ◽  
Architectural Patterns ◽  
Chinese Cohort ◽  
Lung Adenocarcinomas ◽  
Generation Sequencing

e20506 Background: Differentiation of multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM) is critical to determine clinical stage. Although clinicopathological features could provide certain evidences, it’s still challenging to identify the tumor malignancy accurately. In General, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Herein, we propose an integrated molecular algorithm to facilitate MPLCs and IPMs diagnosis in the clinical practice. Methods: 40 Chinese patients with lung adenocarcinomas were enrolled in the study, 84 tumor samples were collected for next-generation sequencing. Somatic alterations with variant allele fraction (VAF) ≥1% were taken into account for molecular algorithm. A genomic database of 2,471 Chinese lung adenocarcinomas (LUAD) was used to calculate odds of coincidental occurrence, prevalence of individual mutation prevalence. Tumor relatedness diagnosed by histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Moreover, the performance of molecular algorithm prediction was evaluated as well. Results: Firstly, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC subtypes in clinical practice. The genomic profiling was described as following: EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Further analysis showed that TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (22.9% vs 51.0%, P<0.05). TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (P<0.05). The classifications based on the three different methodologies mentioned above were compared. Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%), particularly in the prediction of MPLC. Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. For the five undetermined cases, two showed differences in architectural patterns, and remained cases have nodules presented as adenocarcinoma in situ, or minimally invasive adenocarcinoma. Of 28 MPLC cases defined by NGS, 25 cases had unique somatic mutations per pair Based on calculation from the prevalence of EGFR L858R mutation (27%) in large Chinese cohort, the odds of coincidental occurrence of the mutation in two unrelated tumors was 7.3%. Taking together, EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%). Conclusions: Our results support broad panel NGS to assist differential diagnosis to assist approach in clinical practice. It is necessary to conduct large clinical study to establish comprehensive algorithm models to assist diagnosis and predict clinical outcome.

scholarly journals The integration of emerging omics approaches to advance precision medicine: How can regulatory science help?

2018 ◽  
Vol 2 (5) ◽  
pp. 295-300
Author(s):  
Joan E. Adamo ◽  
Robert V. Bienvenu ◽  
F. Owen Fields ◽  
Soma Ghosh ◽  
Christina M. Jones ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Working Group ◽  
Regulatory Science ◽  
Translational Science ◽  
Next Generation ◽  
Clinical Validity ◽  
Knowledge Gaps ◽  
Recent Advances ◽  
Generation Sequencing

Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.

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