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中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (04) : 529 -534. doi: 10.3877/cma.j.issn.1674-6902.2024.04.005

论著

SMARCA4缺失的胸部未分化肿瘤临床特征及预后分析
杨攀1, 黄晓寒1, 邓才霞1, 周利航1, 周向东1, 罗虎1,()   
  1. 1. 400038 重庆,陆军(第三)军医大学第一附属医院呼吸与危重症医学科
  • 收稿日期:2024-03-17 出版日期:2024-08-25
  • 通信作者: 罗虎
  • 基金资助:
    陆军军医大学第一附属医院临床研究重点项目资助(2023IITZD02)

Clinical features and prognosis of SMARCA4-deficient thoracic undifferentiated tumors: a single-center, retrospective clinical study

Pan Yang1, Xiaohan Huang1, Caixia Deng1, Lihang Zhou1, Xiangdong Zhou1, Hu Luo1,()   

  1. 1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing 400038, China
  • Received:2024-03-17 Published:2024-08-25
  • Corresponding author: Hu Luo
引用本文:

杨攀, 黄晓寒, 邓才霞, 周利航, 周向东, 罗虎. SMARCA4缺失的胸部未分化肿瘤临床特征及预后分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(04): 529-534.

Pan Yang, Xiaohan Huang, Caixia Deng, Lihang Zhou, Xiangdong Zhou, Hu Luo. Clinical features and prognosis of SMARCA4-deficient thoracic undifferentiated tumors: a single-center, retrospective clinical study[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(04): 529-534.

目的

胸部SMARCA4缺失的未分化肿瘤(SMARCA4-deficient undifferentiated tumors, SMARCA4-UT)是一类高侵袭性预后差的少见恶性肿瘤,对传统化疗反应较差,目前尚无确切针对SMARCA4-UT的治疗指南。回顾性分析SMARCA4-UT的临床特点及预后影响因素。

方法

48例SMARCA4-UT患者,根据治疗方式分为手术治疗组5例,单纯化疗组22例,化疗联合免疫组5例,化疗联合抗肿瘤血管生成组7例,化疗联合抗肿瘤血管生成及免疫治疗组2例,未治疗组7例。通过免疫组化、二代测序分析患者临床病理学及基因特征,观察不同治疗方式疗效,分析临床特征与预后的关系。

结果

化疗联合免疫治疗组的无进展生存期(progression-free survival, PFS)4.5个月及总生存期(overall survival, OS)9.1个月优于单纯化疗组3.6个月,5.2个月及化疗联合抗肿瘤血管生成治疗组4.1个月,9.1个月,其中依托泊苷联合铂类(etopoposide combined with the platinum, EP)方案化疗联合替雷利珠单抗可作为SMARCA4-UT患者治疗的优选治疗方案。肝转移及≥3个转移部位为PFS及OS的影响因素,合并STK11、KEAP1突变患者总体预后较差。截止随访日期,手术治疗组死亡3例(60.00%),单纯化疗组死亡16例(72.73%),化疗联合免疫治疗组死亡3例(60.00%),化疗联合抗肿瘤血管生成治疗组死亡5例(71.43%),化疗联合抗肿瘤血管生成治疗联合免疫治疗组全部存活(0.00%),未接受治疗组7例全部死亡(100.00%)。

结论

晚期SMARCA4-UT患者一线应用免疫检查点抑制剂联合化疗的疗效优于单纯化疗方案,其中EP方案可潜在更优的化疗选择。检测STK11、KEAP1基因突变对SMARCA4-UT患者具有临床意义。

Objective

SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) present a class of rare malignant tumors with high aggressiveness and poor prognosis, which have poor response to traditional chemotherapy. Currently, there are no specific treatment guidelines for SMARCA4-UT, but some patients have been shown to benefit from immunotherapy. This study intends to retrospectively analyze the clinical features and prognostic factors of SMARCA4-UT in the real world.

Methods

The clinical data of 48 patients with SMARCA4-UT treated in the First Affiliated Hospital of Army Military Medical University from March 2021 to June 2023 were retrospectively analyzed, including 40 patients with advanced stage and 8 patients with early and middle stage. 5 cases were treated with surgery, 22 cases with chemotherapy alone, 5 cases with chemotherapy combined with immunization, 7 cases with chemotherapy combined with anti-tumor angiogenesis, 2 cases with chemotherapy combined with anti-tumor angiogenesis and immunotherapy, and 7 cases were untreated. Immunohistochemistry and second-generation sequencing were used to analyze the clinicopathological and genetic characteristics of patients, observe the efficacy of different treatment methods, and analyze the relationship between clinical characteristics and prognosis.

Results

PFS and OS of chemotherapy combined with immunotherapy were superior to chemotherapy alone and chemotherapy combined with anti-tumor angiogenesis therapy, among which EP chemotherapy combined with Tislelizumab could be the preferred treatment for SMARCA4-UT patients. Liver metastasis and ≥3 metastatic sites are both influential factors for PFS and OS. Patients with STK11 and KEAP1 mutations have poor overall prognosis, but immunotherapy can still prolong OS in these patients. End of follow-up date, 3 cases (60.00%) death in surgery group, 16 cases(72.73%) death in chemotherapy group, 3 cases (60.00%)death in chemotherapy combined with immunization, 5 cases (71.43%)death in chemotherapy combined with anti-tumor angiogenesis group, no case (0.00%)death in chemotherapy combined with anti-tumor angiogenesis and immunotherapy group, 7 cases(100.00%) deaths in untreated group.

Conclusion

The efficacy of first-line immunocheckpoint inhibitor combined with chemotherapy in advanced SMARCA4-UT patients may be better than that of chemotherapy alone, among which EP regimen may be a potential better chemotherapy choice. STK11 and KEAP1 gene mutations may be markers of poor prognosis in SMARCA4-UT patients.

图1 影响患者预后的因素(A和B表示有无肝转移的生存曲线;C和D表示不同转移部位数量的生存曲线)
表1 5例SMARCA4-UT手术患者一般情况及预后
表2 2例患者二线予以EP方案联合免疫治疗的结果
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