The present study was conducted to characterize the clinicopathologic characteristics, immunohistochemical staining results, and immune checkpoint inhibitors (ICIs) efficacy in patients with SMARCA4-deficient/TP53 mutant lung cancer. Patients diagnosed with advanced or metastatic undifferentiated lung cancer harboring SMARCA4-deficient and TP53 mutations, however, without targetable sensitive mutations were retrieved from the electronic medical record system. Descriptive statistics were used to describe the baseline characteristics and clinical features including age, gender, eastern cooperative oncology group performance status, disease stage, smoking status, chief complaint, site of the primary mass, tumor size, gross type, symptoms, local invasion, and metastatic sizes. Immunological markers and potential drive genes were detected by immunohistochemical staining and next generation sequencing. Efficacy and safety profile of ICIs in included patients was evaluated with progression-free survival and overall survival. Between January 2019 and September 2022, there were 4 patients included within the inclusion criteria in the present study. Biomarkers including CK, CK7, and integrase interactor 1 were detected positive, however, other immunological markers including CK20, CD56, P63, P40, NapsinA, TTF-1, CgA, Syn, BRG1, or PD-L1 were detected negative among them. Results of next generation sequencing panel were failed to discover any targetable sensitive mutations. A total of 4 mutation types of TP53, including p.C141Y, p.S240G, p.E339X (terminator acquired), and p.L130F detected for the patients, respectively. Microsatellite stability status, as well as low tumor mutation burden was identified among all the patients. Median progression-free survival for ICIs as first line treatment and median overall survival were 3.25 months (range from 1.3 to 6.8 months), and 6.0 months (range from 2.7 to 9.6 months), respectively. Our results indicated that advanced lung cancer patients harboring co-occurring SMARCA4-deficient/TP53 mutations might respond to ICIs treatment, though within negative programmed cell death-ligand 1 expression or low tumor mutation burden. However, hyperprogressive disease by ICIs may also happen for such patients. The mutation types of TP53 might play a role during the exposure of ICIs, however, need further identification in basic experiments.

中文翻译：

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免疫检查点抑制剂在 SMARCA4 缺陷和 TP53 突变未分化肺癌中的疗效。


本研究旨在表征 SMARCA4 缺陷/TP53 突变肺癌患者的临床病理特征、免疫组织化学染色结果和免疫检查点抑制剂 （ICI） 疗效。诊断为晚期或转移性未分化肺癌且携带 SMARCA4 缺陷和 TP53 突变的患者，然而，从电子病历系统中检索到没有靶向敏感突变的患者。描述性统计用于描述基线特征和临床特征，包括年龄、性别、东部肿瘤合作组表现状态、疾病分期、吸烟状况、主诉、原发肿块部位、肿瘤大小、大体类型、症状、局部浸润和转移大小。免疫组化染色和二代测序检测免疫标志物和潜在驱动基因。通过无进展生存期和总生存期评估 ICIs 在纳入患者中的疗效和安全性。2019 年 1 月至 2022 年 9 月期间，本研究纳入标准包括 4 名患者。包括 CK 、 CK7 和整合酶相互作用子 1 在内的生物标志物检测呈阳性，而其他免疫标志物包括 CK20 、 CD56 、 P63 、 P40 、 NapsinA 、 TTF-1 、 CgA 、 Syn 、 BRG1 或 PD-L1 检测呈阴性。下一代测序组的结果未能发现任何可靶向的敏感突变。共检测到 4 种 TP53 突变类型，分别包括 p.C141Y 、 p.S240G 、 p.E339X （terminator acquired ） 和 p.L130F。在所有患者中确定了微卫星稳定性状态以及低肿瘤突变负荷。 ICIs 作为一线治疗的中位无进展生存期和中位总生存期分别为 3.25 个月 （范围为 1.3 至 6.8 个月） 和 6.0 个月 （范围为 2.7 至 9.6 个月）。我们的结果表明，同时存在 SMARCA4 缺陷/TP53 突变的晚期肺癌患者可能对 ICIs 治疗有反应，尽管程序性细胞死亡配体 1 表达为阴性或肿瘤突变负荷较低。然而，此类患者也可能发生 ICI 引起的急进性疾病。TP53 的突变类型可能在 ICIs 暴露过程中发挥作用，但需要在基础实验中进一步鉴定。