Zhang Meng, Wang Qi, Guo Tian-Hui, Gao Wen, Zhang Bi-Yuan, Wang Hai-Ji
Department of Radiation Oncology, the Affiliated Hospital of Qingdao University, Qingdao, China.
J Thorac Dis. 2025 Jun 30;17(6):4287-4301. doi: 10.21037/jtd-2024-1932. Epub 2025 Jun 25.
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), improving survival significantly. However, the integration of TKIs with radiotherapy (RT) for oligometastatic EGFR-mutant NSCLC remains an emerging strategy, with questions surrounding the optimal timing of RT intervention. This review seeks to examine recent insights into the timing of RT in relation to disease progression and to investigate the radiosensitizing effects of TKIs.
A comprehensive literature search was conducted using PubMed, Web of Science and ClinicalTrials.gov, focusing on studies from the three decades published in English. Key terms included "oncogenic-driven NSCLC", "oligometastasis", "radiotherapy", "TKI combination therapy" and "local therapy".
The review assesses studies evaluating two RT intervention timings: after disease progression (oligoprogressive state) and during stable disease (oligoresidual state). Findings indicate that RT timing can influence patient outcomes, with preclinical studies showing that TKIs enhance radiosensitivity through mechanisms that impede deoxyribonucleic acid (DNA) repair, alter cell cycle phases, and inhibit angiogenesis.
The combination of TKIs with RT presents promising survival benefits for oligometastatic EGFR-mutant NSCLC patients, yet timing remains critical to optimizing therapeutic outcomes. This review highlights the need for future research to refine RT protocols, guide clinical practice, and inform policy for advanced NSCLC management, potentially impacting survival and quality of life in this patient population.
酪氨酸激酶抑制剂（TKIs）彻底改变了表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）的治疗方式，显著提高了生存率。然而，将TKIs与放射治疗（RT）联合用于寡转移EGFR突变NSCLC仍是一种新兴策略，关于RT干预的最佳时机仍存在疑问。本综述旨在探讨近期有关RT时机与疾病进展关系的见解，并研究TKIs的放射增敏作用。
使用PubMed、科学网和ClinicalTrials.gov进行了全面的文献检索，重点关注近三十年以英文发表的研究。关键词包括“致癌驱动的NSCLC”、“寡转移”、“放射治疗”、“TKI联合治疗”和“局部治疗”。
本综述评估了两项关于RT干预时机的研究：疾病进展后（寡进展状态）和疾病稳定期（寡残留状态）。研究结果表明，RT时机可影响患者预后，临床前研究显示，TKIs通过阻碍脱氧核糖核酸（DNA）修复、改变细胞周期阶段和抑制血管生成等机制增强放射敏感性。
TKIs与RT联合应用对寡转移EGFR突变NSCLC患者具有显著的生存获益，但时机对于优化治疗效果至关重要。本综述强调，未来研究需要完善RT方案，指导临床实践，并为晚期NSCLC管理提供政策依据，这可能会影响该患者群体的生存和生活质量。
