Molecular updates in lung cancer
Pantai Premier Pathology, Bangsar, Kuala Lumpur
Molecular diagnostics in the care of lung cancer patients continues to develop at a rapid pace. While testing for EGFR mutations, ALK and ROS1 fusion in some countries BRAF mutations are standard practice, other mutations including alterations involving KRAS G12C, NTRK, RET, MET, HER2 and PD-L1 expression is now known to impact on routine clinical practice and improve patients outcome. Molecular biomarkers can be predictive (actionable) or prognostic (indicative of patients survival) independent of treatment received example KRAS G12C mutation (indicator of innate tumour aggressiveness). Prognostic biomarkers include KRAS G12C while predictive biomarkers include ALK rearrangements, BRAFV600E point mutations, sensitizing EGFR mutations, METex14 skipping mutations, NTRK1/2/3 gene fusions, RET rearrangements, ROS1 rearrangements, and PD-L1 expressions. NCCN guidelines recommend molecular testing be performed via a broad, panel-based approach, most typically performed by next-generation sequencing (NGS), so that testing is done for all of the actionable biomarkers at the same time, including the established and emerging biomarkers. This testing technique helps ensure that there is sufficient tissue to test for all of the actionable biomarkers. However, some gene fusions are difficult to detect using DNA-based NGS. For patient who, in broad panel testing, do not have identifiable driver oncogenes (especially never smokers), RNA-based NGS should be considered. Some rarer subtypes of NSCLC such as salivary glands tumours, NUT carcinoma and SMARCA4-deficient undifferentiated tumour is believed to have specific molecular pathological alterations. TMB is now removed as an immune biomarker due to concern about variable TMB measurement and standardization across lab. TMB is also not ideal because some patients with low levels experience a response to immunotherapy and others with high levels do not. The lecture also addressed role of liquid biopsy in lung cancer which includes early screening, diagnosis, and treatment of lung cancer, especially when tissue samples cannot be obtained.