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Tumor mutational burden in non-small cell lung cancer-the pathologist's point of view
Frédérique Penault-Llorca1, Nina Radosevic-Robin1
1Department of pathology, Centre Jean Perrin, Clermont-Ferrand, France.
Abstract:
In non-small cell lung cancer (NSCLC), the pathologist has contributed to the development of personalized medicine from the determination of the right histological type to EGFR and ALK/ROS1 molecular screening for targeted therapies. With the development of immunotherapies, pathologists intervene forefront with programmed death-ligand 1 (PD-L1) immunohistochemical testing, companion test for pembrolizumab monotherapy, first line and complementary test to the other programmed cell death-1 (PD-1) PD-L1 inhibitors. Recently, tumor mutational burden has emerged as a promising tool to evaluate sensitivity to immunotherapy (IO). The pathologist has a crucial role in the setting of tumor mutational burden (TMB) testing for the selection and the preparation of the sample for high throughput molecular analysis, and in the first steps of the next-generation sequencing (NGS) workflow.
Insights
Pathologists play a vital role in non-small cell lung cancer (NSCLC) personalized medicine, from histological typing to molecular screening for targeted therapies and immunotherapy. They are crucial for tumor mutational burden (TMB) testing and next-generation sequencing (NGS).
Area of Science:
- Oncology
- Pathology
- Molecular Diagnostics
Background:
- Pathologists are integral to personalized medicine in non-small cell lung cancer (NSCLC).
- Their role has evolved from histological classification and molecular screening (EGFR, ALK/ROS1) to include immunotherapy companion diagnostics.
- Emerging biomarkers like tumor mutational burden (TMB) further expand the pathologist's contribution.
Purpose of the Study:
- To highlight the evolving and critical role of pathologists in advancing NSCLC personalized medicine.
- To emphasize the pathologist's involvement in molecular testing for targeted therapies and immunotherapies.
- To underscore the pathologist's essential function in emerging diagnostic fields like TMB and next-generation sequencing (NGS).
Main Methods:
- Review of the pathologist's contributions to NSCLC diagnostics and personalized medicine.
- Analysis of immunohistochemical testing for programmed death-ligand 1 (PD-L1) in relation to immunotherapy.
- Examination of the pathologist's role in tumor mutational burden (TMB) assessment and next-generation sequencing (NGS) workflows.
Main Results:
- Pathologists determine NSCLC histological type and screen for EGFR, ALK/ROS1 mutations for targeted therapies.
- Pathologists perform PD-L1 testing, a companion diagnostic for immunotherapy (e.g., pembrolizumab).
- Pathologists are key in TMB testing and NGS sample preparation for immunotherapy sensitivity evaluation.
Conclusions:
- The pathologist's expertise is indispensable for NSCLC personalized medicine, spanning targeted therapies to immunotherapies.
- Pathologists are central to implementing novel biomarkers and advanced molecular techniques like TMB and NGS.
- Continued pathologist involvement is crucial for optimizing patient selection and treatment strategies in NSCLC.