Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.
Thorac Cancer. 2023 Jan;14(2):206-209. doi: 10.1111/1759-7714.14751. Epub 2022 Dec 1.
In lung squamous cell carcinoma, KEAP1 mutations frequently coexist with TP53 mutations. A preclinical model showed that mutations leading to the activation of the KEAP1-NRF2 pathway contribute to clinical radioresistance. However, there have been few clinical reports on the association between the presence of KEAP1 and TP53 mutations in patients with lung squamous cell carcinoma. Here, we report the case of a 62-year-old patient with advanced lung squamous cell carcinoma with KEAP1 and TP53 mutations who experienced primary resistance to thoracic radiotherapy. She was administered pembrolizumab in combination with cytotoxic agents as the first-line treatment and the best response was a partial response. However, the mediastinal lymph node metastases regrew 11 months after the chemotherapy. Thus, she received thoracic radiation therapy for localized lesions. However, the lesions within the radiation field had apparently progressed. Although she received subsequent chemotherapy, the lesion rapidly progressed. Treatment strategies including radiotherapy based on genetic stratification, such as KEAP1 and TP53 mutation status, should be implemented for lung squamous cell carcinoma.
在肺鳞状细胞癌中，KEAP1 突变常与 TP53 突变共存。临床前模型表明，导致 KEAP1-NRF2 通路激活的突变可导致临床放射抵抗。然而，关于肺鳞状细胞癌患者中 KEAP1 和 TP53 突变共存的临床报道较少。在此，我们报告了一例 62 岁晚期肺鳞状细胞癌患者，该患者存在 KEAP1 和 TP53 突变，对胸部放疗表现出原发耐药。该患者接受了帕博利珠单抗联合细胞毒药物作为一线治疗，最佳反应为部分缓解。然而，化疗后 11 个月纵隔淋巴结转移复发。因此，她接受了局部病变的胸部放射治疗。然而，放射野内的病变明显进展。尽管她随后接受了化疗，但病变迅速进展。应根据基因分层实施包括放射治疗在内的治疗策略，如 KEAP1 和 TP53 突变状态，用于肺鳞状细胞癌。
