| Autor: |
Zacharias M; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Konjic S; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Kratochwill N; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Absenger G; Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria., Terbuch A; Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria., Jost PJ; Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria., Wurm R; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria., Lindenmann J; Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, 8010 Graz, Austria., Kashofer K; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Gollowitsch F; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Gorkiewicz G; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Brcic L; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria. |
| Abstrakt: |
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. |
