Ye Junru, Ma Yutong, Ou Qiuxiang, Yan Junrong, Ye Bin, Li Yuping
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.
Front Oncol. 2022 May 26;12:883367. doi: 10.3389/fonc.2022.883367. eCollection 2022.
The histological transformation from adenocarcinoma (ADC) to squamous cell carcinoma (SCC) is rare but recurrently occurs post TKI treatment in mutated non-small cell lung cancer patients with a very limited number of clinical cases published. The outcome of patients after SCC onset is poor as no established treatment guidelines were available. Here we report a case who was initially diagnosed with lung ADC with L858R driver mutation and demonstrated a partial response (PR) to gefitinib for 27 months before disease progression. The rapidly progressive lung metastatic lesions were determined as an SCC histology with positive PD-L1 expression. Besides L858R, the metastatic SCC harbored the amplification of and detected by targeted next-generation sequencing (NGS), which encode PD-L1 and PD-L2, respectively. The disease remained stable on the combination therapy of pembrolizumab plus chemotherapy for eight months until the primary ADC lesion progressed. After the failure of progressed primary ADC lesion with radiotherapy and immunotherapy, systemic ADC metastases were developed in multiple locations including kidney, liver, and chest wall with L858R mutation but negative PD-L1 expression. The patient then received the combination therapy of bevacizumab plus chemotherapy and the disease remained stable for five months. Since August 2021, afatinib has been administrated which led to a PR and the disease has remained stable up till present. This study demonstrated a primary lung ADC who developed systemic ADC metastases and local SCC transformation with distinct molecular features. The patient has achieved long-term clinical benefit upon multiple lines of chemotherapy and immunotherapy, which provided valuable insight into the treatment of advanced SCC-transformed lung ADC patients.
腺癌（ADC）向鳞状细胞癌（SCC）的组织学转化较为罕见，但在接受酪氨酸激酶抑制剂（TKI）治疗的非小细胞肺癌突变患者中会反复出现，且仅有非常有限数量的临床病例报道。SCC发生后患者的预后较差，因为尚无既定的治疗指南。在此，我们报告一例患者，最初被诊断为具有L858R驱动突变的肺ADC，在疾病进展前对吉非替尼表现出27个月的部分缓解（PR）。快速进展的肺转移病灶经组织学检查确定为SCC，且PD-L1表达呈阳性。除L858R外，转移性SCC通过靶向二代测序（NGS）检测到 和 的扩增，它们分别编码PD-L1和PD-L2。在帕博利珠单抗联合化疗的治疗方案下，疾病稳定了八个月，直到原发性ADC病灶进展。在原发性ADC病灶放疗和免疫治疗失败后，全身多处出现了ADC转移，包括肾脏、肝脏和胸壁，具有L858R突变但PD-L1表达阴性。患者随后接受了贝伐单抗联合化疗，疾病稳定了五个月。自2021年8月起，患者接受阿法替尼治疗，出现PR，疾病至今保持稳定。本研究展示了一例原发性肺ADC患者发生全身ADC转移和局部SCC转化，且具有不同的分子特征。该患者在接受多线化疗和免疫治疗后获得了长期临床获益，这为晚期SCC转化型肺ADC患者的治疗提供了有价值的见解。
