Thoracic Oncology Unit, National Cancer Institute, México City, México.
Departamento de Radio-Oncología, National Cancer Institute, México City, México.
Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1442-1450. doi: 10.1016/j.ijrobp.2021.02.044. Epub 2021 Feb 25.
To date, studies regarding the use of prophylactic cranial irradiation (PCI) versus standard of care (SoC) for patients with non-small cell lung cancer (NSCLC) have not shown a significant effect in terms of overall survival (OS). Additionally, the effect of PCI among high-risk patients has been scarcely studied. The objective of this randomized phase 2 study was to evaluate the role of PCI in a population of patients at high risk for development of brain metastases (BM).
Eligible patients had histologically confirmed NSCLC without baseline BM, harboring epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels at the time of diagnosis. Participants received systemic therapy according to molecular status, those without progressive disease were then assigned to receive SoC or SoC + PCI (25 Gy in 10 fractions). The primary outcome was cumulative incidence of brain metastases (CBM). The secondary endpoints included progression-free survival and OS. Quality of life and neurocognitive function are discussed in a separate article (Clinicaltrials.gov: NCT01603849).
From May 2012 to December 2017, 84 patients were enrolled in the study, with 41 patients allocated to receive PCI and 43 received SoC. Patients allocated to receive PCI had a CBM at 24 months of 7% versus 38% in those allocated to the SoC arm. PCI was associated with a hazard ratio of 0.12 (95% confidence interval, 0.035-0.42) for developing BM. A benefit in OS was also observed (64.5 vs 19.8 months; hazard ratio: 0.41 (95% confidence interval, 0.22-0.78; P =∙007).
Among a selected population at high risk for developing BM, PCI significantly decreased CBM in addition to increasing progression-free survival and OS. To our knowledge, this is the first study to evaluate PCI in epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels in patients with NSCLC, showing a significant improvement in CBM. This relevant information should be of particular importance in the context of patients without access to third-generation targeted agents. Further studies are warranted to ascertain this effect.
迄今为止，关于预防性颅照射（PCI）与非小细胞肺癌（NSCLC）标准治疗（SoC）相比在总生存（OS）方面的疗效的研究并未显示出显著影响。此外，PCI 在高危患者中的作用研究甚少。本随机 2 期研究的目的是评估 PCI 在发生脑转移（BM）风险较高的患者人群中的作用。
符合条件的患者为组织学证实的 NSCLC，无基线 BM，在诊断时携带表皮生长因子受体突变、间变性淋巴瘤激酶重排或癌胚抗原水平升高。患者根据分子状态接受系统治疗，无疾病进展的患者随后被分配接受 SoC 或 SoC+PCI（25 Gy，10 次分割）。主要结局是脑转移累积发生率（CBM）。次要终点包括无进展生存期和 OS。生活质量和神经认知功能在另一篇文章中讨论（Clinicaltrials.gov：NCT01603849）。
2012 年 5 月至 2017 年 12 月，84 例患者入组研究，41 例患者接受 PCI，43 例患者接受 SoC。接受 PCI 的患者在 24 个月时的 CBM 为 7%，而接受 SoC 治疗的患者为 38%。PCI 与发生 BM 的风险比为 0.12（95%置信区间，0.035-0.42）。OS 也观察到获益（64.5 与 19.8 个月；风险比：0.41（95%置信区间，0.22-0.78；P=0.007）。
在发生 BM 风险较高的选定人群中，PCI 不仅增加了无进展生存期和 OS，而且还显著降低了 CBM。据我们所知，这是第一项在 NSCLC 患者中评估表皮生长因子受体突变、间变性淋巴瘤激酶重排或癌胚抗原水平升高患者 PCI 的研究，显示 CBM 有显著改善。在没有第三代靶向药物的情况下，这一相关信息尤其重要。需要进一步的研究来确定这一效果。
