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早期立体定向体部放射治疗可改善表皮生长因子受体(EGFR)突变型肺癌中第一代EGFR酪氨酸激酶抑制剂的无进展生存期:一项观察性队列研究。

Early stereotactic body radiation therapy improves progression-free survival of first-generation EGFR tyrosine kinase inhibitors in EGFR-mutated lung cancer: an observational cohort study.

作者信息

Xu Hailing, Qi Rongbin, Zhou Chao, Yu Yingying, Lin Ling, Wu Xiaomai, Lv Dongqing

机构信息

Department of Pulmonary Medicine, Affiliated Taizhou Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province, China.

Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province, China.

出版信息

Ther Adv Med Oncol. 2024 Nov 4;16:17588359241290133. doi: 10.1177/17588359241290133. eCollection 2024.

DOI:10.1177/17588359241290133
PMID:39502405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536526/
Abstract

BACKGROUND

Stereotactic body radiation therapy (SBRT) in treating non-small-cell lung cancer (NSCLC) exhibits a remarkable therapeutic efficacy. However, its effectiveness in overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced EGFR mutations (EGFRm) NSCLC remains uncertain.

OBJECTIVE

We aimed to analyze the effect of SBRT on patients with first-line EGFR-TKIs.

DESIGN AND METHODS

Eligible patients with advanced NSCLC initially diagnosed with EGFRm were enrolled. Patients in the EGFR-TKIs group received only the first-generation EGFR-TKIs until disease progression or death, while the others in the EGFR-TKIs + SBRT group received EGFR-TKIs and early SBRT (dose of 40-60 Gy/5-8 F) targeting the primary lung tumor at 1 month after EGFR-TKIs. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were treatment-related adverse effects, overall survival (OS), and sites of initial failure.

RESULTS

A total of 184 advanced NSCLC patients with EGFRm were enrolled, including 39 patients in the EGFR-TKIs + SBRT group and 145 patients in the EGFR-TKIs group. The median PFS was 15.50 months in the EGFR-TKIs + SBRT group compared to 9.33 months in the EGFR-TKIs group ( = 0.0020). However, the median OS was 29.10 months in the EGFR-TKIs + SBRT group and 26.33 months in the EGFR-TKIs group, with no significant difference observed ( = 0.22). SBRT is an independent positive prognostic factor for PFS in advanced EGFRm NSCLC. EGFR exon 19 deletion mutation (16.33 vs 11.55 months,  = 0.0087) and fewer metastases (0-5) (31.94 vs 9.59 months,  = 0.0059) were associated with improved PFS in EGFR-TKIs + SBRT versus EGFR-TKIs. Combination therapy increased radiation pneumonitis mainly in Grades 1-2 (89.74% vs 0.0%). The EGFR-TKIs + SBRT group mainly had new site failure (57.10% vs 32.10%) rather than the original site failure.

CONCLUSION

Early SBRT for primary lung tumors may overcome targeted resistance in advanced EGFRm NSCLC patients combined with EGFR-TKIs without serious toxicities, especially for EGFR exon 19-del.

TRIAL REGISTRATION

ChiCTR-OIN-17013920.

摘要

背景

立体定向体部放射治疗(SBRT)在治疗非小细胞肺癌(NSCLC)方面显示出显著的治疗效果。然而,其在克服晚期表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)耐药方面对晚期EGFR突变(EGFRm)NSCLC患者的有效性仍不确定。

目的

我们旨在分析SBRT对一线EGFR-TKIs治疗患者的影响。

设计与方法

纳入最初诊断为EGFRm的晚期NSCLC合格患者。EGFR-TKIs组患者仅接受第一代EGFR-TKIs治疗,直至疾病进展或死亡,而EGFR-TKIs+SBRT组的其他患者在接受EGFR-TKIs治疗1个月后接受EGFR-TKIs和针对原发性肺肿瘤的早期SBRT(剂量为40-60 Gy/5-8次分割)。主要终点是无进展生存期(PFS),次要终点是治疗相关不良反应、总生存期(OS)和初始失败部位。

结果

共纳入184例晚期EGFRm NSCLC患者,其中EGFR-TKIs+SBRT组39例,EGFR-TKIs组145例。EGFR-TKIs+SBRT组的中位PFS为15.50个月,而EGFR-TKIs组为9.33个月(P=0.0020)。然而,EGFR-TKIs+SBRT组的中位OS为29.10个月,EGFR-TKIs组为26.33个月,未观察到显著差异(P=0.22)。SBRT是晚期EGFRm NSCLC患者PFS的独立阳性预后因素。EGFR外显子19缺失突变(16.33 vs 11.55个月,P=0.0087)和转移灶较少(0-5个)(31.94 vs 9.59个月,P=0.0059)与EGFR-TKIs+SBRT组相比EGFR-TKIs组的PFS改善相关。联合治疗主要增加1-2级放射性肺炎(89.74% vs 0.0%)。EGFR-TKIs+SBRT组主要出现新部位失败(57.10% vs 32.10%)而非原部位失败。

结论

对原发性肺肿瘤进行早期SBRT可能克服晚期EGFRm NSCLC患者联合EGFR-TKIs治疗时的靶向耐药,且无严重毒性,尤其是对于EGFR外显子19缺失患者。

试验注册号

ChiCTR-OIN-17013920。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/6183387f9d26/10.1177_17588359241290133-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/98c1f7b445ed/10.1177_17588359241290133-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/c05aba85b4f3/10.1177_17588359241290133-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/e1fe488904cf/10.1177_17588359241290133-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/6183387f9d26/10.1177_17588359241290133-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/98c1f7b445ed/10.1177_17588359241290133-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/c05aba85b4f3/10.1177_17588359241290133-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/e1fe488904cf/10.1177_17588359241290133-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e4d/11536526/6183387f9d26/10.1177_17588359241290133-fig4.jpg

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