Chen Lijin, Su Chunyang, Yao Jiadi, Li Xiaofeng, Lin Xiaoyan
Oncology Department, Fujian Medical University Union Hospital, Fuzhou, China.
Oncology Department, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.
Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251345377. doi: 10.1177/15330338251345377. Epub 2025 May 22.
IntroductionThoracic SMARCA4-deficient tumors, which are rare and aggressive malignancies found in the lung or thoracic cavity, present a challenge in treatment standardization. This challenge arises from their resistance to chemotherapy and the absence of targeted therapy options.MethodsThoracic SMARCA4-deficient tumors were identified retrospectively using pathology databases. The clinicopathological characteristics of these tumors are outlined, and the clinical outcomes of advanced patients treated with immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy alone are reviewed.ResultsThirty-nine patients had thoracic SMARCA4-deficient tumors, with a median age of 62 years. The cohort consisted of 92.3% males, and 89.7% had a history of smoking. Within this group, 94.9% had stage III/IV disease at diagnosis. SMARCA4-deficient non-small cell lung cancer (SMARCA4-DNSCLC) and SMARCA4-deficient undifferentiated tumors (SMARCA4-DUT) display distinct histological and immunohistochemical features. Thirty-five patients underwent systemic therapy, achieving an ORR of 51.4%, a DCR of 82.9%, and a median OS of 20.9 months. Patients were categorized into chemotherapy (28.6%) and ICIs plus chemotherapy (71.4%) groups. The ICIs plus chemotherapy group exhibited an ORR of 64.0% and a DCR of 96.0%, while the chemotherapy group had an ORR of 20.0% and 50.0%, respectively ( < .0001 for ORR and DCR). The median OS for ICIs plus chemotherapy and chemotherapy groups were 20.9 months and 6.5 months, and median PFS were 9.6 months and 3.5 months, respectively, all statistically significant ( < .05). Multivariate COX regression analysis indicated that treatment was an independent prognostic factor for OS.ConclusionThoracic SMARCA4-deficient tumors exhibit a lack of SMARCA4 expression, displaying high malignancy and aggressiveness while exhibiting poor response to standard chemotherapy. The combination of ICIs with chemotherapy could potentially serve as an effective treatment approach for thoracic SMARCA4-deficient tumors.
引言
胸段SMARCA4缺陷型肿瘤是在肺部或胸腔发现的罕见侵袭性恶性肿瘤，在治疗标准化方面面临挑战。这一挑战源于它们对化疗的耐药性以及缺乏靶向治疗选择。
方法
通过病理数据库对胸段SMARCA4缺陷型肿瘤进行回顾性鉴定。概述了这些肿瘤的临床病理特征，并回顾了晚期患者接受免疫检查点抑制剂（ICI）联合化疗及单纯化疗的临床结局。
结果
39例患者患有胸段SMARCA4缺陷型肿瘤，中位年龄62岁。该队列中男性占92.3%，89.7%有吸烟史。在这个组中，94.9%在诊断时为III/IV期疾病。SMARCA4缺陷型非小细胞肺癌（SMARCA4-DNSCLC）和SMARCA4缺陷型未分化肿瘤（SMARCA4-DUT）表现出不同的组织学和免疫组化特征。35例患者接受了全身治疗，客观缓解率（ORR）为51.4%，疾病控制率（DCR）为82.9%，中位总生存期（OS）为20.9个月。患者被分为化疗组（28.6%）和ICI联合化疗组（71.4%）。ICI联合化疗组的ORR为64.0%，DCR为96.0%，而化疗组的ORR分别为20.0%和50.0%（ORR和DCR的P均<0.0001）。ICI联合化疗组和化疗组的中位OS分别为20.9个月和6.5个月，中位无进展生存期（PFS）分别为9.6个月和3.5个月，均具有统计学意义（P<0.05）。多因素COX回归分析表明治疗是OS的独立预后因素。
结论
胸段SMARCA4缺陷型肿瘤表现出SMARCA4表达缺失，具有高恶性和侵袭性，同时对标准化疗反应不佳。ICI与化疗联合可能是胸段SMARCA4缺陷型肿瘤的一种有效治疗方法。
