Radiotherapy Department, Hanzhong Central Hospital, Hanzhong, Shanxi, 723000, People's Republic of China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
BMC Cancer. 2024 Oct 23;24(1):1305. doi: 10.1186/s12885-024-13071-2.
There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate.
We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021.
The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69-0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61-0.82; P < 0.001) of the combination therapy were significantly prolonged. Finally, 168 EGFR-mutated BM advanced LAC patients in the real world were verified, and the median iPFS of the combination therapy (n = 88 and EGFR-TKIs alone (n = 80) were 16.0 and 9.0 months, respectively, (P < 0.001). The median OS was 29.0 and 27.0 months, respectively, with no dramatic difference (P = 0.188).
Research on EGFR-mutant LAC brain metastasis has turned towards exploring optimal treatment strategies for this condition. Our meta-analysis and real-world data analysis consistently demonstrate that combination therapy offers a substantial improvement in patient survival compared to EGFR-TKI monotherapy. Notably, among patients undergoing salvage radiotherapy (RT), our subgroup analysis reveals that those initially treated with third-generation TKIs experience more significant benefits than those treated with first- or second-generation TKIs.
对于表皮生长因子受体（EGFR）突变阳性肺腺癌（LAC）患者的脑转移（BM），利用脑放疗（RT）和酪氨酸激酶抑制剂（TKI）联合治疗的方法引起了越来越多的关注。目前，这种治疗策略的现状仍存在争议。
我们通过在 Web of Science 核心合集（WoSCC）的 SCI 扩展数据库中进行全面的文献检索，启动了我们的研究。我们使用 VOSPviewer 软件分析了研究的各个方面，包括发表年份、作者、关键词和国家。随后，我们在流行的在线数据库上进行了广泛而系统的文献检索。我们的主要结局指标是总生存（OS）和颅内无进展生存（iPFS），均通过风险比（HR）进行量化。此外，为了进行数据验证，我们还包括了中山大学肿瘤防治中心和汉中市中心医院放射治疗科于 2012 年 8 月至 2021 年 11 月间接受治疗干预的非小细胞肺癌伴脑转移患者的数据。
文献计量分析显示，过去十年中，关于 RT 和 TKI 联合治疗肺癌脑转移的研究呈上升趋势。然后，我们纳入了 9 项符合研究方向的研究进行荟萃分析。荟萃分析显示，联合治疗的 OS（HR=0.81，95%置信区间：0.69-0.94；P=0.007）和 iPFS（HR=0.71，95%置信区间：0.61-0.82；P<0.001）显著延长。最后，我们验证了 168 名真实世界的 EGFR 突变型 BM 晚期 LAC 患者，联合治疗（n=88）和 EGFR-TKIs 单药治疗（n=80）的中位 iPFS 分别为 16.0 和 9.0 个月（P<0.001）。中位 OS 分别为 29.0 和 27.0 个月，无显著差异（P=0.188）。
针对 EGFR 突变型 LAC 脑转移的研究已经转向探索这种疾病的最佳治疗策略。我们的荟萃分析和真实世界数据分析一致表明，与 EGFR-TKI 单药治疗相比，联合治疗可显著提高患者的生存。值得注意的是，在接受挽救性放疗（RT）的患者中，我们的亚组分析表明，与接受第一代或第二代 TKI 治疗的患者相比，初始接受第三代 TKI 治疗的患者获益更为显著。
