Consistency of O6-methylguanine-DNA methyltransferase in intracranial and extracranial lesions and the therapeutic effect of temozolomide in patients with advanced lung cancer and brain metastasis.

Abstract

e14001 Background: Targeted drugs have made a major breakthrough except small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) of brain metastasis (BM) patients with negative driving gene. Because of the difficulty to obtain pathology of intracranial metastases lesions and the low acceptance of patients, the heterogeneity of O6-methylguanine-DNA methyltransferase (MGMT) between extracranial lesions and intracranial metastatic lesions worth exploring. Methods: 10 patients were administered TMZ after the progression of radiotherapy and chemotherapy and included in one group; the efficacy and safety of TMZ were assessed. Moreover, 15 patients who underwent resection of the lung and brain without neoadjuvant therapy formed another cohort. The promoter methylation status of MGMT was analyzed and compared in the paired primary and BM lesions. Results: The overall response (OS) rate of TMZ was 50% and the disease control rate was 80% in patients with BM lesions. The median progression-free survival was 13.6 months, and the median overall survival was 18.9 months after a median follow-up of 120 months. No grade 3 or higher side effects were reported, but grade 1 or 2 side effects, such as leucopenia, nausea, or vomiting, occurred. However, in another cohort, MGMT promoter methylation was detected in 2 patients (with primary lesions; unmethylation was detected in BM lesions, and the methylation status of MGMT promoter was consistent in paired primary and BM lesions).Conclusions: TMZ was effective against SCLC and NSCLC combined with BM having negative driving genes. Whether primary lesions can replace the MGMT methylation level of BM lesions, as well as the consistency of the promoter methylation status of MGMT in patients with advanced lung cancer, needs exploration.[Table: see text]