Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature
Background: Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed “driver mutations,” are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well. Next-generation sequencing (NGS) of tumors r...
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doaj-c790132487274402bac545bb77f529252020-11-25T03:02:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-07-01710.3389/fmed.2020.00314465767Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of LiteraturePritam Tayshetye0Katherine Miller1Dulabh Monga2Candice Brem3Jan F. Silverman4Gene Grant Finley5Department of Hematology-Oncology, Allegheny Health Network, Pittsburgh, PA, United StatesDepartment of Internal Medicine, Allegheny Health Network, Pittsburgh, PA, United StatesDepartment of Hematology-Oncology, Allegheny Health Network, Pittsburgh, PA, United StatesDepartment of Pathology and Laboratory Medicine, Allegheny Health Network, Pittsburgh, PA, United StatesDepartment of Pathology and Laboratory Medicine, Allegheny Health Network, Pittsburgh, PA, United StatesDepartment of Hematology-Oncology, Allegheny Health Network, Pittsburgh, PA, United StatesBackground: Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed “driver mutations,” are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well. Next-generation sequencing (NGS) of tumors reveals cancer-related genomic alterations and provides therapeutic recommendations for specific targeted therapy. We analyzed our experience with FoundationOne, a validated NGS genomic profiling test, in a community oncology network.Methods: NGS results from May 2014 to September 2016 from a community oncology network in Western Pennsylvania were analyzed. Medical records were reviewed for primary site, stage, biopsy site, time of testing, prior treatment, FDA-approved therapy in patient's and other tumor types and potential clinical trials based upon mutations detected. Two co-primary endpoints for this study were to determine the percentage of patients having mutations with a FDA-approved targeted agent and the percentage of patients in whom a treatment decision was made based on these NGS results.Results: One Fifty-Seven NGS results were available for analysis. 82% patients had a mutation with a FDA-approved targeted agent available while 18% patients had no FDA-approved targeted agent for the mutation detected. Clinical trials were available for 93% cases. The NGS results were utilized in treatment decisions in 18% patients (n = 28) with, 7% (n = 11) initiating a targeted agent, 6% (n = 9) were on an appropriate targeted agent prior to testing and 5% (n = 8) being unable to start a targeted agent because of insurance denial, clinical deterioration or patient preference. 38% cases were tested early in the disease course (at diagnosis, during or shortly after first-line treatment) and 62% at progression.Conclusions: NGS is a valuable tool to identify molecular targets for personalizing cancer care. From our experience, the actual number of patients starting a targeted agent based on NGS results is low but it provides substantial information in terms of providing additional treatment options, identifying resistance conferring mutations and facilitating clinical trial enrollment. Optimal time of testing, early or late in disease course, financial implications of testing and using targeted therapy and survival benefit of targeted therapy need further studies.https://www.frontiersin.org/article/10.3389/fmed.2020.00314/fulltargeted therapygenomicsdriver mutationsmolecular profilingnext generation sequencingcommunity oncology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pritam Tayshetye Katherine Miller Dulabh Monga Candice Brem Jan F. Silverman Gene Grant Finley |
spellingShingle |
Pritam Tayshetye Katherine Miller Dulabh Monga Candice Brem Jan F. Silverman Gene Grant Finley Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature Frontiers in Medicine targeted therapy genomics driver mutations molecular profiling next generation sequencing community oncology |
author_facet |
Pritam Tayshetye Katherine Miller Dulabh Monga Candice Brem Jan F. Silverman Gene Grant Finley |
author_sort |
Pritam Tayshetye |
title |
Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature |
title_short |
Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature |
title_full |
Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature |
title_fullStr |
Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature |
title_full_unstemmed |
Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature |
title_sort |
molecular profiling of advanced malignancies: a community oncology network experience and review of literature |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2020-07-01 |
description |
Background: Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed “driver mutations,” are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well. Next-generation sequencing (NGS) of tumors reveals cancer-related genomic alterations and provides therapeutic recommendations for specific targeted therapy. We analyzed our experience with FoundationOne, a validated NGS genomic profiling test, in a community oncology network.Methods: NGS results from May 2014 to September 2016 from a community oncology network in Western Pennsylvania were analyzed. Medical records were reviewed for primary site, stage, biopsy site, time of testing, prior treatment, FDA-approved therapy in patient's and other tumor types and potential clinical trials based upon mutations detected. Two co-primary endpoints for this study were to determine the percentage of patients having mutations with a FDA-approved targeted agent and the percentage of patients in whom a treatment decision was made based on these NGS results.Results: One Fifty-Seven NGS results were available for analysis. 82% patients had a mutation with a FDA-approved targeted agent available while 18% patients had no FDA-approved targeted agent for the mutation detected. Clinical trials were available for 93% cases. The NGS results were utilized in treatment decisions in 18% patients (n = 28) with, 7% (n = 11) initiating a targeted agent, 6% (n = 9) were on an appropriate targeted agent prior to testing and 5% (n = 8) being unable to start a targeted agent because of insurance denial, clinical deterioration or patient preference. 38% cases were tested early in the disease course (at diagnosis, during or shortly after first-line treatment) and 62% at progression.Conclusions: NGS is a valuable tool to identify molecular targets for personalizing cancer care. From our experience, the actual number of patients starting a targeted agent based on NGS results is low but it provides substantial information in terms of providing additional treatment options, identifying resistance conferring mutations and facilitating clinical trial enrollment. Optimal time of testing, early or late in disease course, financial implications of testing and using targeted therapy and survival benefit of targeted therapy need further studies. |
topic |
targeted therapy genomics driver mutations molecular profiling next generation sequencing community oncology |
url |
https://www.frontiersin.org/article/10.3389/fmed.2020.00314/full |
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