Xu Xiangyu, Ma Zheng
Department of Thoracic Surgery, Chongqing People's Hospital, Chongqing, China.
Front Immunol. 2025 Jul 4;16:1601125. doi: 10.3389/fimmu.2025.1601125. eCollection 2025.
Brain metastases occur in 40% of advanced NSCLC patients, with poorer prognosis in squamous subtypes. Immune checkpoint inhibitors (ICIs) combined with chemotherapy have revolutionized treatment, yet data on the systematic treatment of stage IV squamous non-small cell lung cancer with surgery remain limited. A 59-year-old male smoker presented with stage cT4N2M1b IVA squamous NSCLC and a solitary brain metastasis. Next-generation sequencing revealed programmed cell death ligand 1 (PD-L1) high expression (TPS=75%) and TMB-High (28.49 Mut/Mb) without driver mutations. After pembrolizumab plus platinum-based chemotherapy induced conversion therapy for 3 cycles, the brain lesion achieved pathological complete response (pCR) following resection, while the primary lung tumor showed major pathological response (MPR) post-surgery. Postoperative adjuvant chemoimmunotherapy and 2-year pembrolizumab maintenance were administered. Serial circulating tumor DNA (ctDNA) monitoring remained negative, with no recurrence observed over 50 months. This is the first reported case of long-term survival (PFS >50 months) in a PD-L1-high/TMB-High squamous NSCLC patient with brain metastasis treated with immunotherapy-based multimodal therapy. Our findings suggest that biomarker-guided strategies integrating systemic therapy, surgery, and MRD monitoring may enable curative potential in select advanced NSCLC patients. Further studies are warranted to validate this "sandwich" approach (drug-surgery-drug) and optimize treatment duration.
40%的晚期非小细胞肺癌（NSCLC）患者会发生脑转移，鳞状细胞亚型患者的预后较差。免疫检查点抑制剂（ICI）联合化疗彻底改变了治疗方式，但关于IV期鳞状非小细胞肺癌手术系统治疗的数据仍然有限。一名59岁男性吸烟者被诊断为cT4N2M1b IVA期鳞状NSCLC并伴有孤立性脑转移。二代测序显示程序性细胞死亡配体1（PD-L1）高表达（TPS=75%）且肿瘤突变负荷高（TMB-High，28.49个突变/Mb），无驱动基因突变。在帕博利珠单抗联合铂类化疗诱导转化治疗3个周期后，脑转移灶在切除后达到病理完全缓解（pCR），而原发性肺肿瘤术后显示主要病理缓解（MPR）。术后给予辅助化疗免疫治疗及2年的帕博利珠单抗维持治疗。连续循环肿瘤DNA（ctDNA）监测一直为阴性，50个月内未观察到复发。这是首例报道的采用基于免疫治疗的多模式治疗的PD-L1高表达/TMB-High鳞状NSCLC脑转移患者长期生存（无进展生存期>50个月）的病例。我们的研究结果表明，整合全身治疗、手术和微小残留病（MRD）监测的生物标志物指导策略可能使部分晚期NSCLC患者具有治愈潜力。有必要进行进一步研究以验证这种“三明治”方法（药物-手术-药物）并优化治疗持续时间。
