Division of Radiation Oncology, Aizawa Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjo, Matsumoto, Nagano Prefecture, 390-0814, Japan.
Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo, Japan.
J Neurooncol. 2019 Oct;145(1):151-157. doi: 10.1007/s11060-019-03282-0. Epub 2019 Sep 5.
Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma.
We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events.
Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0 months, HR 0.60, 95% CI 0.48-0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12-1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups.
Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.
近年来，靶向治疗延长了肺癌患者的总生存期（OS）。然而，表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）对立体定向放射外科（SRS）治疗的脑转移瘤（BM）的影响尚未完全阐明。我们研究了 SRS 后 EGFR-TKI 使用对肺腺癌 BM 患者 SRS 疗效和毒性的影响。
我们使用了日本立体定向放射外科研究会（JLGK）0901 研究的最新数据集，该研究证明了 SRS 在 BM 患者中的疗效。采用倾向评分匹配（PSM）分析来确定 SRS 同时或之后使用 EGFR-TKI 对 OS、神经死亡、颅内疾病复发和 SRS 相关不良事件的影响。
在 JLGK0901 研究中登记的 1194 名患者中，有 608 名符合条件的肺腺癌患者被确定，其中 238 名（39%）患者在 SRS 治疗期间或之后接受了 EGFR-TKI 治疗。PSM 后，有 200 对患者有/无 SRS 后 EGFR-TKI 治疗。EGFR-TKI 治疗与更长的 OS 相关（中位 25.5 个月 vs. 11.0 个月，HR 0.60，95%CI 0.48-0.75，p<0.001），尽管长期 OS 曲线最终交叉。接受 EGFR-TKI 治疗的患者更有可能发生远处颅内复发（HR 1.45，95%CI 1.12-1.89，p=0.005）。两组之间的神经死亡、局部复发和 SRS 相关不良事件发生率没有显著差异。
尽管 SRS 同时或之后接受 EGFR-TKI 治疗的患者 OS 显著延长，但 SRS 的局部治疗效果和毒性在有无 EGFR-TKI 治疗的患者之间没有差异。
