Gu Yu, Lai Songtao, Yang Juan, Zhang Junhua, Fan Xingwen, Zheng Qiang
Department of Radiation Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Transl Lung Cancer Res. 2024 Oct 31;13(10):2660-2672. doi: 10.21037/tlcr-24-339. Epub 2024 Oct 28.
The SWItch/Sucrose Nonfermentable (SWI/SNF) complex, a multi-subunit chromatin remodeler, is linked to aggressive tumors when deficient. Accurate identification of SWI/SNF expression status is crucial for tailoring targeted therapies. Previous studies on the efficacy of immunotherapy for SWI/SNF-deficient (SWI/SNF-d) pulmonary tumors primarily focus on non-small cell lung cancer (NSCLC), with limited data on other modalities like radiotherapy. This study aims to analyze the clinicopathological characteristics and prognostic factors of SWI/SNF-d pulmonary neoplasms, including NSCLC and undifferentiated tumors, and to evaluate the effectiveness of radiotherapy and immunotherapy, providing a foundation for improved treatment strategies and prognostic assessments.
Patient data on SWI/SNF-d pulmonary neoplasms were collected from Fudan University Shanghai Cancer Center, assessing ARID1A, SMARCA2, SMARCA4, and SMARCB1 subunit expression via immunohistochemistry, with retrospective analysis of survival and treatment results.
The study analyzed 101 SWI/SNF-d pulmonary neoplasms from 675 SWI/SNF-d cancer patients (January 2017 to August 2023), mostly male smokers, showing high malignancy. Clinicopathologic features were consistent across patients with various SWI/SNF subunit deficiencies. TP53 was the most common co-mutated gene (71%), followed by STK11, CDKN2A, KRAS, APC, and EGFR. Key prognostic factors for overall survival (OS) were distant metastasis, radiotherapy, and immunotherapy. Immunotherapy improved 3-year OS rates from 20.8% to 68.4% (P<0.001). KRAS-mutated patients on immunotherapy showed a lower 1-year survival rate (60.0% . 83.1%, P=0.08). Radiotherapy increased 3-year OS rates to 61.7% from 30.7% (P=0.012). Of 38 patients treated with immunotherapy, 16 benefited from radiotherapy [median OS: 31.4 months . not estimable (NE), P=0.045], with an average 17.2 days between radiotherapy and immunotherapy.
SWI/SNF-d pulmonary neoplasms, whether with multiple or single subunit losses, exhibit similar clinicopathological characteristics. Radiotherapy and immunotherapy are effective treatments for these patients, and the combination of radiotherapy with immunotherapy may offer synergistic effects.
开关/蔗糖非发酵（SWI/SNF）复合物是一种多亚基染色质重塑因子，功能缺陷时与侵袭性肿瘤相关。准确识别SWI/SNF表达状态对于制定靶向治疗方案至关重要。既往关于SWI/SNF缺陷（SWI/SNF-d）型肺肿瘤免疫治疗疗效的研究主要集中于非小细胞肺癌（NSCLC），而关于放疗等其他治疗方式的数据有限。本研究旨在分析SWI/SNF-d型肺肿瘤（包括NSCLC和未分化肿瘤）的临床病理特征和预后因素，并评估放疗和免疫治疗的有效性，为改进治疗策略和预后评估提供依据。
收集复旦大学附属上海肿瘤中心SWI/SNF-d型肺肿瘤患者的数据，通过免疫组化评估ARID1A、SMARCA2、SMARCA4和SMARCB1亚基的表达，并对生存和治疗结果进行回顾性分析。
本研究分析了675例SWI/SNF-d型癌症患者（2017年1月至2023年8月）中的101例SWI/SNF-d型肺肿瘤，患者多为男性吸烟者，显示出高恶性程度。不同SWI/SNF亚基缺陷患者的临床病理特征一致。TP53是最常见的共突变基因（71%），其次是STK11、CDKN2A、KRAS、APC和EGFR。总生存（OS）的关键预后因素为远处转移、放疗和免疫治疗。免疫治疗将3年OS率从20.8%提高至68.4%（P<0.001）。接受免疫治疗的KRAS突变患者1年生存率较低（60.0%对83.1%，P=0.08）。放疗将3年OS率从30.7%提高至61.7%（P=0.012）。在38例接受免疫治疗的患者中，16例从放疗中获益[中位OS：31.4个月对未评估（NE），P=0.045]，放疗与免疫治疗之间的平均间隔为17.2天。
SWI/SNF-d型肺肿瘤，无论存在多个还是单个亚基缺失，均表现出相似的临床病理特征。放疗和免疫治疗对这些患者有效，放疗与免疫治疗联合可能具有协同作用。
