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 anEGFRmutation, seven with aKRASG12C mutation, four with anALKfusion, two with anEGFRfusion 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.
鉴于生物标志物驱动的靶向治疗取得的成功，多数非小细胞肺癌指南均认同：所有非鳞状细胞癌病例均应进行分子反射检测。相比之下，针对鳞状细胞癌的检测建议存在显著差异，特别是在分子检测策略中排除特定年龄或吸烟史患者方面。我们开展了一项回顾性单中心研究，通过分析2019年至2023年间在本学术机构接受DNA与RNA新一代测序检测的316例连续肺鳞癌病例，评估了非选择性队列中分子反射检测的价值。通过电子病历获取临床病理数据，并与测序结果进行关联分析。在316例中有21例（6.6%）检测到已获批准药物对应的成熟分子靶点，包括7例EGFR突变、7例KRAS G12C突变、4例ALK融合、2例EGFR融合及1例MET外显子14跳跃突变。所有携带可靶向基因变异的患者年龄均超过50岁，且多数吸烟史超过15包年，这对限制性分子检测策略提出了质疑。基于真实世界数据，我们提出采用DNA与RNA新一代测序的反射检测流程，该流程应涵盖所有新诊断的非小细胞肺癌病例，且不受组织学类型、年龄或吸烟史的限制。
Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology
肿瘤(癌症)患者之家