Zacharias Martin, Konjic Selma, Kratochwill Nikolaus, Absenger Gudrun, Terbuch Angelika, Jost Philipp J, Wurm Robert, Lindenmann Jörg, Kashofer Karl, Gollowitsch Franz, Gorkiewicz Gregor, Brcic Luka
Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria.
Division of Oncology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria.
Cancers (Basel). 2024 Feb 23;16(5):903. doi: 10.3390/cancers16050903.
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 mutation, seven with a G12C mutation, four with an fusion, two with an 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.
由于生物标志物驱动的靶向治疗取得了成功，大多数非小细胞肺癌指南一致认为，所有非鳞状细胞癌（非SCC）病例均应进行分子反射检测。相比之下，鳞状细胞癌（SCC）的检测建议差异很大，特别是在将某些年龄或吸烟状况的患者排除在分子检测策略之外方面。我们进行了一项回顾性单中心研究，在2019年至2023年期间，对我们学术机构连续316例肺SCC病例的未选择队列进行了分子反射检测的价值研究，这些病例通过基于DNA和RNA的下一代测序（NGS）进行检测。这些病例的临床病理数据从电子病历中获取，并与测序结果相关联。在21/316（6.6%）例病例中，我们检测到了一种已获批药物的既定分子靶点。其中7例有 突变，7例有G12C突变，4例有 融合，2例有 融合，1例有METex14跳跃事件。所有携带可靶向改变的患者年龄均>50岁，且大多数患者的吸烟史>15包年，这对限制性分子检测策略提出了质疑。基于我们的真实世界数据，我们提出了一种使用基于DNA和RNA的NGS的反射检测工作流程，该流程包括所有新诊断的非小细胞肺癌病例，无论组织学类型如何，也无论年龄或吸烟状况如何。
