Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology.
Martin ZachariasSelma KonjicNikolaus KratochwillGudrun AbsengerAngelika TerbuchPhilipp J JostRobert WurmJoerg LindenmannKarl KashoferFranz GollowitschGregor GorkiewiczLuka BrcicPublished in: Cancers (2024)
Due to the success story of biomarker-driven targeted therapy, most NSCLC guidelines agree that molecular reflex testing should be performed in all cases with non-squamous cell carcinoma (non-SCC). In contrast, testing recommendations for squamous cell carcinoma (SCC) vary considerably, specifically concerning the exclusion of patients of certain age or smoking status from molecular testing strategies. We performed a retrospective single-center study examining the value of molecular reflex testing in an unselected cohort of 316 consecutive lung SCC cases, tested by DNA- and RNA-based next-generation sequencing (NGS) at our academic institution between 2019 and 2023. Clinicopathological data from these cases were obtained from electronic medical records and correlated with sequencing results. In 21/316 (6.6%) cases, we detected an already established molecular target for an approved drug. Among these were seven cases with an EGFR mutation, seven with a KRAS G12C mutation, four with an ALK fusion, two with an EGFR fusion and one with a METex14 skipping event. All patients harboring a targetable alteration were >50 years of age and most of them had >15 pack-years, questioning restrictive molecular testing strategies. Based on our real-world data, we propose a reflex testing workflow using DNA- and RNA-based NGS that includes all newly diagnosed NSCLC cases, irrespective of histology, but also irrespective of age or smoking status.
Keyphrases
- peritoneal dialysis
- end stage renal disease
- squamous cell carcinoma
- small cell lung cancer
- newly diagnosed
- single molecule
- circulating tumor
- ejection fraction
- chronic kidney disease
- tyrosine kinase
- emergency department
- clinical practice
- computed tomography
- big data
- machine learning
- single cell
- cell free
- low grade
- smoking cessation
- radiation therapy
- advanced non small cell lung cancer
- locally advanced
- nucleic acid
- deep learning
- prognostic factors
- dna methylation
- data analysis
- drug induced
- brain metastases
- genome wide