Biopsy Tissue Sufficiency for Oncogene Testing: NGS vs. Sequential Panels in NSCLC

Introduction

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The advent of next generation sequencing (NGS) and the identification of a plethora of oncogenes have transformed the landscape of non-small cell lung cancer (NSCLC) diagnostic strategies. Accurately diagnosing and treating NSCLC requires a thorough understanding of the tumor's genetic makeup. This article discusses the challenges of obtaining sufficient tissue from a biopsy to test for all known oncogenes and explores the decision-making process between using sequential single panels and NGS for NSCLC diagnostics.

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Biopsy Tissue Sufficiency for Oncogene Testing

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One of the most critical challenges in NSCLC diagnostics is ensuring that the tissue obtained from a biopsy contains enough DNA to test for all the oncogenes discovered. Traditional methods of identifying specific mutations, such as those targeted by EGFR, ALK, ROS1, BRAF, and PD-L1, rely on the availability of sufficient tissue.

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However, as the number of known mutations continues to grow, the limitations of single-panel testing become more apparent. For instance, testing for EGFR, ALK, ROS1, BRAF, and PD-L1 using separate panels may not be sufficient since there are numerous additional mutations with either approved or near-approval targeted therapies, including NTRK, MET, and RET. Moreover, these mutations are often present in very low levels, necessitating advanced sequencing techniques.

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NGS vs. Sequential Panels in NSCLC Diagnostics

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The shift from single-target panel testing to next generation sequencing (NGS) is driven by the need to identify as many potential targets as possible. NGS allows for comprehensive evaluation of a myriad of mutations, including the ones that may have emerged after initial diagnosis. This capability is critical in ensuring that treatment strategies remain effective and up-to-date with the evolving genetic landscape of NSCLC.

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However, the decision to use NGS or sequential panels in NSCLC diagnostics is complex and requires careful consideration. Below are the key factors that influence this decision:

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Sample Availability and Quality

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The size and quality of the biopsy sample are crucial in determining whether NGS or sequential panels should be used. If the biopsy provides sufficient tissue, sequential panels can be an efficient and cost-effective approach. Conversely, if the sample is limited, NGS might be necessary to comprehensively evaluate the tumor for all relevant mutations.

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Treatment Goals

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The primary goal of the diagnosis and treatment plan often dictates the choice of testing method. For example, if the objective is to identify a variety of potential treatment options, NGS is preferred. If the focus is on specific, well-known mutations, sequential panels may be more appropriate.

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Resource and Financial Considerations

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The availability and cost of sequencing technologies and panels can also play a significant role. While NGS is more comprehensive, it is also more expensive. Universities and research centers often have their own sequencing labs, but commercial labs such as FoundationOne are widely used in the United States.

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Conclusion

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Deciding between sequential single panels and NGS in the context of NSCLC diagnostics is not a one-size-fits-all solution. Factors such as biopsy tissue availability, treatment goals, and financial considerations all play a role. As the field continues to evolve, the importance of accurate and comprehensive genetic testing will only grow, underscoring the need for careful and informed decision-making in the diagnostic process.