[Timing of Whole Brain Radiotherapy on Survival of Patients with EGFR-mutated Non-small Cell Lung Cancer and Brain Metastases]

Zhongguo Fei Ai Za Zhi. 2016 Aug 20;19(8):501-7. doi: 10.3779/j.issn.1009-3419.2016.08.03.
[Article in Chinese]

Abstract

Background: There is no high-level evidence for the time of whole brain radiotherapy (WBRT) for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) and brain metastases. The aim of this study is to assess the appropriate timing of WBRT for patients with EGFR-mutated NSCLC and brain metastases (BM).

Methods: There were 78 patients diagnosed with EGFR-mutated NSCLC and BM in Beijing Chest Hospital between August 2009 and May 2015. 48 untreated patients who received both WBRT and EGFR-tyrosine kinase inhibitors (TKIs) therapy. Prognostic factors of intracranial progression-free survival (PFS) and overall survival (OS) were identified by Cox proportional hazards modeling.

Results: Intracranial objective response rate was 81.3% and disease control rate was 93.8%. Median intracranial PFS was 10 months. Median OS was 18 months. Multivariate analysis of intracranial PFS revealed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (HR=30.436, 95%CI: 4.721-196.211, P<0.001) and early WBRT (HR=3.663, 95%CI: 1.657-8.098, P=0.001) had a better intracranial PFS. Multivariate analysis of OS revealed that PS 0-1 (HR=57.607, 95%CI: 6.135-540.953, P<0.001), early WBRT (HR=2.757, 95%CI: 1.140-6.669, P=0.024), and stereotactic radiosurgery (HR=5.964, 95%CI: 1.895-18.767, P=0.002) were independent prognostic factors of OS.

Conclusions: Early WBRT combined with EGFR-TKIs can improve outcomes of patients with EGFR-mutated NSCLC and BM, but it needs to be confirmed by large-sample-size and multicenter prospective clinical trials.

背景与目的 全脑放疗(whole brain radiotherapy, WBRT)在表皮生长因子受体(epidermal growth factor receptor, EGFR)突变的非小细胞肺癌(non-small cell lung cancer, NSCLC)脑转移患者治疗中何时应用尚无高级别的循证医学证据。本研究旨在探讨WBRT的参与时间对携有EGFR突变的NSCLC脑转移患者生存的影响。方法 2009年8月-2015年5月在我院确诊的EGFR突变伴脑转移的晚期NSCLC共78例患者,均接受WBRT及EGFR酪氨酸激酶抑制剂(EGFR tyrosine kinase inhibitors, EGFR-TKIs)治疗的48例初治患者进入临床分析,采用Cox比例风险模型分析患者颅内无进展生存期(progression-free survival, PFS)及总生存期(overall survival, OS)的影响因素。结果 全组患者颅内客观缓解率(objective response rate, ORR)为81.3%,颅内疾病控制率(disease control rate, DCR)为93.8%,中位颅内PFS为10个月,中位OS为18个月。颅内PFS的多因素分析显示,美国东部肿瘤协作组评分(Eastern Cooperative Oncology Group performance status, ECOG PS)0分-1分(HR=30.436, 95%CI: 4.721-196.211, P<0.001)及早期WBRT患者(HR=3.663, 95%CI: 1.657-8.098, P=0.001)的颅内PFS更佳。OS的多因素分析显示,ECOG PS 0分-1分(HR=57.607, 95%CI: 6.135-540.953, P<0.001)、早期WBRT(HR=2.757, 95%CI: 1.140-6.669, P=0.024)及立体定向放射外科(stereotaxic radio surgery, SRS)的应用(HR=5.964, 95%CI: 1.895-18.767, P=0.002)是患者OS的独立预后因素。结论 早期WBRT联合TKIs治疗可改善EGFR突变的NSCLC脑转移患者的预后,尚有待大样本的前瞻性临床试验验证。.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cranial Irradiation* / adverse effects
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors