Clinicopathological characteristics and treatment outcomes of advanced SMARCA4‐deficient thoracic tumors

Abstract

PurposeSMARCA4‐deficient thoracic tumors, characterized by distinct clinicopathological, morphological, immunohistochemical, and genetic features, differ significantly from conventional non‐small‐cell lung carcinomas (NSCLCs). This group encompasses both SMARCA4‐deficient NSCLCs (SMARCA4‐NSCLCs) and SMARCA4‐deficient undifferentiated tumors (SMARCA4‐UTs). The efficacy of PD‐1 inhibitors in treating SMARCA4‐deficient thoracic tumors remains uncertain.MethodsMedical records of 36 patients diagnosed with stage IIIB, IIIC, or IV SMARCA4‐deficient thoracic tumors were analyzed. We assessed the clinical, pathological, and genetic features of these patients through immunohistochemistry (IHC) and a 68‐gene panel next‐generation sequencing (NGS). We compared the differences between SMARCA4‐NSCLCs and SMARCA4‐UTs, and evaluated the impact of chemotherapy and immunotherapy on patient outcomes.ResultsThe majority of patients with SMARCA4‐deficient thoracic tumors were heavy‐smoking males, averaging 64.6 years in age. IHC predominantly showed weak or negative staining for markers such as TTF‐1, CK5/6, p40, synaptophysin, chromogranin A, and CD56, which are often associated with adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors. The most common genetic mutations identified via NGS included TP53, CDKN2A, KRAS, STK11, NF1, and PTEN. No significant overall survival (OS) difference was observed between SMARCA4‐NSCLCs and SMARCA4‐UTs (p = 0.366). The median OS for patients treated with chemotherapy (n = 9) was 447 days, while the median OS for patients undergoing PD‐1‐inhibitor‐based therapy (n = 16) was not reached (p = 0.105).ConclusionSMARCA4‐deficient thoracic tumors exhibit distinct characteristics from conventional NSCLCs, and PD‐1 inhibitors show promise in treating advanced SMARCA4‐deficient thoracic tumors.

Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go

“…Recently, Wang et al characterized SMARCA4-UT patients using 68-panel next-generation sequencing (NGS), confirming TP53 as the most frequent co-mutation (81%), followed by CDKN2A (26%), KRAS (15%), STK11 (15%), NF1 (15%), and PTEN (11%) [ 65 ].…”