Lim Jeong Uk, Jang Ae Lee, Lee Jayoung, Park Sonya Youngju, An Tai Joon, Sa Young Jo, Kim Hyo Rim, Kim Tae-Jung, Kim Byoung Hyuck, Park Chan Kwon
Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Radiation Oncology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Transl Lung Cancer Res. 2025 May 30;14(5):1848-1861. doi: 10.21037/tlcr-2024-1121. Epub 2025 May 28.
Non-small cell lung cancer (NSCLC) remains one of the primary causes of cancer mortality globally, with an increasing focus on advanced targeted therapies. Despite these advancements, oligometastatic NSCLC, particularly cases with actionable mutations such as those in epidermal growth factor receptor () and anaplastic lymphoma kinase (), presents unique therapeutic challenges and opportunities for improved outcomes. Recent studies indicate that consolidative local ablative therapies (LAT) such as stereotactic body radiation therapy (SBRT) combined with tyrosine kinase inhibitors (TKIs) may enhance progression-free and overall survival for patients with oligometastatic NSCLC harboring these mutations. This narrative review aims to summarize current evidence on the clinical impact of co-mutations in EGFR/ALK-positive oligometastatic NSCLC.
The relevant literature was identified by using PubMed and ClinicalTrials.gov (last search phase November 2024) and was restricted to English language. Peer-reviewed manuscripts but also conference abstracts that did not undergo peer-review were included.
Co-mutations complicate treatment by potentially influencing radiosensitivity and resistance to systemic therapies. This review discusses current findings on co-mutations in /-positive oligometastatic NSCLC, examining their impact on LAT and systemic treatment outcomes, with a particular focus on synchronous and oligoprogressive disease states. Moreover, emerging biomarkers such as circulating tumor DNA may guide therapeutic strategies and optimize personalized treatment plans.
As clinical trials continue to investigate combinative and sequential LAT-TKI strategies, understanding the genomic landscape of co-mutations in oligometastatic NSCLC is important for refining treatment approaches and enhancing long-term survival.
非小细胞肺癌（NSCLC）仍是全球癌症死亡的主要原因之一，人们越来越关注晚期靶向治疗。尽管取得了这些进展，但寡转移NSCLC，特别是具有可靶向治疗突变（如表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）突变）的病例，带来了独特的治疗挑战和改善预后的机会。最近的研究表明，立体定向体部放射治疗（SBRT）等巩固性局部消融治疗（LAT）联合酪氨酸激酶抑制剂（TKIs）可能会提高携带这些突变的寡转移NSCLC患者的无进展生存期和总生存期。本叙述性综述旨在总结关于EGFR/ALK阳性寡转移NSCLC中共突变临床影响的现有证据。
通过使用PubMed和ClinicalTrials.gov（最后检索阶段为2024年11月）确定相关文献，并仅限于英文文献。纳入经过同行评审的手稿以及未经过同行评审的会议摘要。
共突变可能会影响放射敏感性和对全身治疗的耐药性，从而使治疗变得复杂。本综述讨论了EGFR/ALK阳性寡转移NSCLC中共突变的当前研究结果，研究了它们对LAT和全身治疗结果的影响，特别关注同步性和寡进展性疾病状态。此外，循环肿瘤DNA等新兴生物标志物可能会指导治疗策略并优化个性化治疗方案。
随着临床试验继续研究联合和序贯LAT-TKI策略，了解寡转移NSCLC中共突变的基因组格局对于优化治疗方法和提高长期生存率至关重要。
