Center for Lung Cancer, Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, 27, Inhang-Ro, Jung-Gu, Inchon, 22332, Republic of Korea.
Department of Radiation Oncology, Inha University Hospital, Inha University College of Medicine, Inchon, Republic of Korea.
Sci Rep. 2023 Aug 14;13(1):13173. doi: 10.1038/s41598-023-40235-0.
Current guidelines recommend that cytotoxic chemotherapy be considered first in non-small cell lung cancer (NSCLC) patients with multiple metastases, and whole-brain radiotherapy (WBRT) is not initially recommended even if brain metastases are present. However, cytotoxic chemotherapeutic agents are less effective in brain metastases due to poor blood-brain barrier permeability. We investigated the effect of WBRT in combination with cytotoxic chemotherapy on survival in NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases. From January 2005 to December 2018, histologically confirmed NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases were included in this study. Patients were classified into two groups based on receiving WBRT prior to or concurrently with administration of first-line chemotherapeutic agents or receiving chemotherapy only. We compared intracranial progression-free survival (iPFS) and overall survival (OS). Of the 240 NSCLC patients with brain metastases at diagnosis and an ECOG PS of 2, 67 patients were EGFR, ALK, and PD-L1 negative with multiple metastases including brain metastases. Among those patients, 43 (64.2%) received WBRT prior to or concurrently with platinum-based chemotherapy. Patients who received WBRT prior to or concurrently with chemotherapy had better iPFS (7.7 months [4.8-10.6] vs. 3.5 months [2.1-4.9], p = 0.009) and OS (10.8 months [5.9-15.7] vs. 6.1 months [1.9-10.3], p = 0.038) than those who did not receive WBRT. In multivariate analyses, WBRT was significantly associated with iPFS (HR: 1.94 and 95% CI 1.11-3.40, p = 0.020) and OS (HR: 1.92 and 95% CI 1.08-3.42, p = 0.027). In NSCLC patients who are EGFR, ALK, and PD-L1 negative, have an ECOG PS of 2, and have multiple metastases including brain metastases, WBRT prior to or concurrently with chemotherapy could improve iPFS and OS. Therefore, the combination of WBRT with cytotoxic chemotherapy should be considered in these patients.
目前的指南建议，对于有多发性转移的非小细胞肺癌（NSCLC）患者，应首先考虑细胞毒性化疗，即使存在脑转移也不建议初始使用全脑放疗（WBRT）。然而，由于血脑屏障通透性差，细胞毒性化疗药物在脑转移中的效果较差。我们研究了 WBRT 联合细胞毒性化疗对 EGFR、ALK 和 PD-L1 阴性、ECOG PS 为 2 分且有多发性转移（包括脑转移）的 NSCLC 患者生存的影响。从 2005 年 1 月至 2018 年 12 月，本研究纳入了 EGFR、ALK 和 PD-L1 阴性、ECOG PS 为 2 分且有多发性转移（包括脑转移）的组织学证实的 NSCLC 患者。患者根据是否在一线化疗药物治疗前或同时接受 WBRT 或仅接受化疗分为两组。我们比较了颅内无进展生存期（iPFS）和总生存期（OS）。在初诊时伴有脑转移且 ECOG PS 为 2 分的 240 例 NSCLC 患者中，有 67 例 EGFR、ALK 和 PD-L1 阴性且有多发性转移（包括脑转移）。其中，43 例（64.2%）患者在接受铂类为基础的化疗前或同时接受了 WBRT。与未接受 WBRT 的患者相比，在化疗前或同时接受 WBRT 的患者 iPFS（7.7 个月[4.8-10.6]比 3.5 个月[2.1-4.9]，p=0.009）和 OS（10.8 个月[5.9-15.7]比 6.1 个月[1.9-10.3]，p=0.038）更好。多因素分析显示，WBRT 与 iPFS（HR：1.94，95%CI 1.11-3.40，p=0.020）和 OS（HR：1.92，95%CI 1.08-3.42，p=0.027）显著相关。在 EGFR、ALK 和 PD-L1 阴性、ECOG PS 为 2 分且有多发性转移（包括脑转移）的 NSCLC 患者中，化疗前或同时进行 WBRT 可以提高 iPFS 和 OS。因此，对于这些患者，应考虑将 WBRT 与细胞毒性化疗联合应用。
