Objective: To investigate the clinicopathological features, treatment-effect assessment and prognosis of SMARCA4-deletion non-small cell lung cancer (NSCLC) that was treated with neoadjuvant therapy. Methods: Eleven consecutive cases of SMARCA4-deletion NSCLC treated with neoadjuvant therapy in Guangdong Provincial People's Hospital, Guangzhou, China from January 2007 to October 2024 were collected. Their clinicopathological features, pathological assessment of treatment effect, and prognosis were retrospectively analyzed. Results: All the 11 patients were male. Their median age at diagnosis was 56 (49,64) years. Nine patients were smokers (9/11). Ten patients received neoadjuvant chemoimmunotherapy, and one received neoadjuvant targeted therapy. Eleven biopsy samples showed SMARCA4 complete loss, including 7 cases of invasive non-mucinous adenocarcinoma, 1 case of invasive mucinous adenocarcinoma, 1 case of non-keratinizing squamous cell carcinoma, and 2 cases of NSCLC, not otherwise specified. The histological response to neoadjuvant therapy in resected specimens varied, including tumor necrosis, foam cell aggregation, cholesterol clefts, immune cell infiltrates, reactive granulomas, and stromal fibrosis. Three cases of the primary lesion achieved major pathological response (MPR), and 2 cases achieved complete pathological response (CPR). The MPR rate of neoadjuvant chemoimmunotherapy was 3/10 while its CPR ratio was 2/10. Of the 9 resected specimens that did not achieve CPR, 5 showed a post-treatment histological type different from the pre-treatment one. Eight tumors showed complete SMARCA4 loss, while 1 showed heterogeneous expression. Of the 11 biopsy specimens examined using next generation sequencing, 9 cases showed class 1 SMARCA4 mutations (including 7 nonsense mutations and 2 acquired nonsense mutations), and 2 cases showed wild-type SMARCA4. Taking immunohistochemistry as the gold standard, the sensitivity of next generation sequencing for the detection of SMARCA4-deletion NSCLC was 9/11. After follow-up of 6.9 to 46.6 months, five patients experienced postoperative recurrence, and 6 patients were disease free. The disease-free survival ranged from 0.7 to 27.5 months (median, 7.6 months). Conclusions: The surgical specimens of SMARCA4-deletion NSCLC with neoadjuvant therapy show varying degrees of treatment response. The tumor components sensitive to chemoimmunotherapy and targeted therapy are mostly adenocarcinoma and squamous cell carcinoma, while large cell carcinoma, spindle cell carcinoma and giant cell carcinoma are relatively less sensitive to treatment. Assessment of MPR and CPR suggests that some NSCLC patients with SMARCA4-deletion can benefit from neoadjuvant therapy.

目的： 探讨SMARCA4缺失性非小细胞肺癌（NSCLC）在新辅助治疗前后的临床病理学特征、疗效评估及预后。方法： 收集2007年1月至2024年10月期间在中国广州广东省人民医院接受新辅助治疗的连续性SMARCA4缺失性非小细胞肺癌病例共11例，回顾性分析其临床病理学特征、疗效评价和预后。结果： 11名患者均为男性。他们的诊断中位年龄为56岁（范围：49至64岁）。其中9名患者是吸烟者（9/11）。10名患者接受了新辅助化免治疗，1名患者接受新辅助靶向治疗。所有11例活检样本均显示SMARCA4完全缺失，包括7例侵袭性非粘液腺癌、1例侵袭性粘液腺癌、1例非角质形成鳞状细胞癌和2例未特指的NSCLC。新辅助治疗后的切除标本表现出不同程度的组织学反应，包括肿瘤坏死、泡沫细胞聚集、胆固醇裂隙、免疫细胞浸润、反应性肉芽肿及间质纤维化。原发灶中3个病例达到主要病理缓解（MPR），2个病例达到完全病理缓解（CPR）。新辅助化免治疗的MPR率为3/10，其CPR比率为2/10。在9例未达到CPR的切除标本中，5例显示治疗前后组织学类型不同。8个肿瘤呈现完全性SMARCA4缺失，一个呈现异质性表达。通过下一代测序方法检测的11例活检样本中有9例显示I类SMARCA4突变（包括7例无义突变和2例获得终止密码子突变），其余2例为野生型SMARCA4。以免疫组化作为金标准，二代测序检测SMARCA4缺失性NSCLC的灵敏度为9/11。随访时间从6.9个月到46.6个月不等，在这期间有5名患者出现术后复发，其余6名患者无病生存。无病生存期范围在0.7至27.5个月之间（中位数为7.6个月）。结论： 接受新辅助治疗的SMARCA4缺失性NSCLC手术标本显示不同程度的疗效反应。化学免疫治疗和靶向治疗对腺癌和鳞状细胞癌成分更敏感，而大细胞癌、梭形细胞癌及巨细胞癌则相对较不敏感。根据MPR与CPR评估结果，部分SMARCA4缺失性NSCLC患者可以从新辅助治疗中获益。