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Title: Cranial Irradiation for Patients with Epidermal Growth Factor Receptor (EGFR) Mutant Lung Cancer Who Have Brain Metastases in the Era of a New Generation of EGFR Inhibitors.
Author: Lee JH, Chen HY, Hsu FM, Chen JS, Liao WY, Shih JY, Yu CJ, Chen KY, Tsai TH, Yang JC.
Journal: Oncologist; 2019 Dec; 24(12):e1417-e1425. PubMed ID: 31127020.
Abstract:
BACKGROUND: Immediate whole brain radiation (WBRT) has been the standard for patients with lung cancer with brain metastases. The study aims to evaluate the effect of immediate cranial irradiation in patients with epidermal growth factor receptor (EGFR) mutant lung cancer in the era of a new generation of EGFR inhibitors. MATERIALS AND METHODS: Medical records of 198 patients with EGFR mutant non-small cell lung cancer and brain metastases at initial metastatic diagnosis were reviewed. Patients were categorized into four groups: immediate WBRT, immediate cranial stereotactic radiosurgery (SRS), delayed radiation upon progression of cranial lesions (DRT), and never cranial irradiation (NRT). Overall survival (OS) and progression-free survival related to EGFR inhibitors were analyzed. RESULTS: The SRS group had the fewest brain metastases and fewest extracranial lesions, and the DRT and NRT groups had the smallest brain metastases. Median survival were 18.5, 55.7, 21.1, and 18.2 months for the WBRT, SRS, DRT, and NRT groups, respectively. Patients who had received EGFR T790M inhibitors survived longer (41.1 vs. 19.8 months). In multivariate analysis, the OS of patients in the SRS group was longer than that in the NRT group (adjusted hazard ratio [aHR]: 0.315). Patients who had fewer extracranial lesions and who had received EGFR T790M inhibitor treatments also survived longer (aHR: 0.442 and 0.357, respectively). CONCLUSION: Immediate stereotactic radiosurgery but not whole brain radiation was associated with longer survival. Because of patient heterogeneity and the introduction of EGFR T790M inhibitors, the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted for selected patients. IMPLICATIONS FOR PRACTICE: Immediate whole brain radiation has been the standard for patients with lung cancer with brain metastases. In this study, it was observed that, for patients with epidermal growth factor receptor (EGFR) mutant advanced lung cancer who had brain metastases, there was no difference in survival between patients who never received cranial irradiation and those who received whole brain radiation immediately. Patients who received immediate stereotactic radiosurgery or who had ever received EGFR T790M inhibitors survived longer. Patients who received immediate stereotactic radiosurgery have fewer brain metastases. These findings suggest that the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted in selected patients. 摘要背景。及时全脑放疗 (WBRT) 已成为发生脑转移的肺癌患者的标准疗法。在新一代表皮生长因子受体(EGFR)抑制剂问世的时代，本研究旨在评估及时全脑照射对EGFR突变型肺癌患者的疗效。 材料和方法。对 198 例EGFR突变型非小细胞肺癌和脑转移患者最初确诊发生转移的病历进行了回顾性分析。将患者分为四组:及时WBRT组、及时全脑立体定向放射外科治疗 (SRS) 组、对颅脑病灶进展实施延迟放射治疗 (DRT) 组及不实施全脑照射 (NRT) 组。我们对总生存期 (OS) 和无进展生存期与EGFR抑制剂的相关性进行了分析。结果。SRS 组的脑转移和颅外病灶病例最少，DRT 和 NRT 组的脑转移病灶最小。WBRT、SRS、DRT 和 NRT 组的中位生存期分别为 18.5、55.7、21.1 及 18.2 个月。接受 EGFR T790M 抑制剂治疗的患者存活期较长(41.1 个月与 19.8 个月)。在多变量分析中，SRS 组患者的OS要长于 NRT 组 [校正风险比(aHR):0.315]。颅外病灶较少和接受 EGFR T790M 抑制剂治疗的患者生存期也较长(aHR:分别为 0.442 和 0.357)。 结论。及时立体定向放射外科治疗可延长生存期，而全脑放疗无法实现这一点。由于患者的异质性和 EGFR T790M 抑制剂的问世，全脑照射的时机和方式应因人而异，对于经选患者可无需接受全脑照射。 实践意义:及时全脑放疗已成为发生脑转移的肺癌患者的标准疗法。在本研究中发现，在发生脑转移的表皮生长因子 (EGFR) 突变型晚期肺癌患者中，从未接受全脑照射者与及时接受全脑放疗者在生存期方面无差异。接受及时立体定向放射外科治疗或曾接受 EGFR T790M 抑制剂治疗的患者生存期较长。接受及时立体定向放射外科治疗的患者脑转移的病灶较少。这些结果表明，全脑照射的时机和方式应因人而异，对于经选患者可无需接受全脑照射。

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