Hung Joseph Shang-En, Su Yan-Hua, Chen Ching-Jen, Chiang Chi-Lu, Shen Chia-I, Yang Huai-Che, Shiau Cheng-Ying, Luo Yung-Hung, Wu Hsiu-Mei, Hu Yong-Sin, Lin Chung-Jung, Liu Kang-Du, Chung Wen-Yuh, Guo Wan-Yuo, Lee Cheng-Chia
Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Neurological Surgery, The University of Texas Health Science Center at Houston, Houston, TX, USA.
J Neurooncol. 2023 Sep;164(2):413-422. doi: 10.1007/s11060-023-04425-0. Epub 2023 Sep 1.
Given the availability of TKIs with high central nervous system efficacy, the question arises as to whether upfront SRS provides additional clinical benefits. The goal of this study was to characterize the clinical outcomes of SRS as salvage therapy for TKI-uncontrolled BMs.
This retrospective study included EGFR-mutant NSCLC patients presenting BMs at the time of primary tumor diagnosis. BMs were categorized into three subgroups, referred to as "Nature of TKI-treated BMs", "TKI-controlled brain metastases ± SRS", and "SRS salvage therapy". The first subgroup analysis characterized the effects of TKIs on tumor behavior. In the second subgroup, we compared outcomes of TKI-controlled BMs treated with TKI alone versus those treated with combined TKI-SRS therapy. The third subgroup characterized the outcomes of TKI-uncontrolled BMs treated with SRS as salvage therapy Clinical outcomes include local and distant tumor control.
This study included 106 patients with a total of 683 BMs. TKI treatment achieved control in 63% of local tumors at 24 months. Among the TKI-controlled BMs, local tumor control was significantly higher in the combined TKI-SRS group (93%) than in the TKI-alone group (65%) at 24 months (p < 0.001). No differences were observed between the two groups in terms of distant tumor control (p = 0.832). In dealing with TKI-uncontrolled BMs, salvage SRS achieved local tumor control in 58% of BMs at 24 months.
While upfront TKI alone proved highly effective in BM control, this study also demonstrated the outcomes of SRS when implemented concurrently with TKI or as salvage therapy for TKI-uncontrolled BMs. This study also presents a strategy of the precise timing and targeting of SRS to lesions in progression.
鉴于已有中枢神经系统疗效高的酪氨酸激酶抑制剂(TKIs),对于 upfront 立体定向放射治疗(SRS)是否能带来额外临床获益的问题随之出现。本研究的目的是明确 SRS 作为 TKI 难治性脑转移瘤(BMs)挽救治疗的临床结局。
这项回顾性研究纳入了在原发性肿瘤诊断时出现 BMs 的表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者。BMs 被分为三个亚组,分别称为“TKI 治疗的 BMs 的性质”、“TKI 控制的脑转移瘤±SRS”和“SRS 挽救治疗”。第一个亚组分析描述了 TKIs 对肿瘤行为的影响。在第二个亚组中,我们比较了单独使用 TKI 治疗与 TKI-SRS 联合治疗的 TKI 控制的 BMs 的结局。第三个亚组描述了将 SRS 作为挽救治疗的 TKI 难治性 BMs 的结局。临床结局包括局部和远处肿瘤控制。
本研究纳入了 106 例患者,共 683 个 BMs。TKI 治疗在 24 个月时使 63%的局部肿瘤得到控制。在 TKI 控制的 BMs 中,联合 TKI-SRS 组在 24 个月时的局部肿瘤控制率(93%)显著高于单独使用 TKI 组(65%)(p<0.001)。两组在远处肿瘤控制方面未观察到差异(p = 0.832)。在处理 TKI 难治性 BMs 时,挽救性 SRS 在 24 个月时使 58%的 BMs 实现了局部肿瘤控制。
虽然单独 upfront TKI 在 BM 控制方面被证明非常有效,但本研究也展示了与 TKI 同时实施或作为 TKI 难治性 BMs 的挽救治疗时 SRS 的结局。本研究还提出了针对进展性病变精确安排 SRS 时间和靶向的策略。