Unresectable stage III non-small-cell lung cancer (NSCLC) remains a clinical challenge, due to the need for optimal local and systemic control. The management of unresectable Stage III NSCLC has evolved with advancements in radiation therapy (RT), systemic therapies, and immunotherapy. For patients with locally advanced NSCLC who are not surgical candidates, concurrent chemoradiotherapy (CRT) has modest survival outcomes, due to both local progression and distant metastasis. Efforts to enhance outcomes have led to dose-escalation trials, advances in modern RT techniques such as intensity-modulated RT (IMRT) and proton beam therapy (PBT), and the integration of adaptive RT to optimize target coverage while sparing organs at risk. Concurrent and consolidative immunotherapy, particularly with PD-L1 inhibitors, has shown promise, as evidenced by the PACIFIC trial, which demonstrated improved progression-free survival (PFS) and overall survival (OS) with durvalumab following CRT. Ongoing trials are now investigating novel immunotherapy combinations and targeted therapies in this setting, including dual checkpoint inhibition, DNA repair inhibitors, and molecularly targeted agents like osimertinib for EGFR-mutated NSCLC. Emerging biomarkers, such as circulating tumor DNA and radiomics, offer potential for personalizing treatment and predicting outcomes. Additionally, PBT and MR-guided adaptive RT have shown the potential to reduce toxicities while maintaining efficacy. Integrating these novel approaches may offer opportunities for optimizing treatment responses and minimizing adverse effects in this challenging patient population. Further investigation into patient stratification, biomarker-driven therapy, and refined therapeutic combinations is essential to improve long-term outcomes in unresectable Stage III NSCLC. This narrative review explores the current management strategies for unresectable Stage III NSCLC, from a radiation oncology perspective.
不可切除的III期非小细胞肺癌（NSCLC）因其对局部与全身控制的综合需求，仍是临床治疗中的难题。随着放射治疗（RT）、全身治疗及免疫治疗的进步，不可切除III期NSCLC的治疗策略不断发展。对于无法手术的局部晚期NSCLC患者，同步放化疗（CRT）因局部进展和远处转移问题，其生存获益有限。为改善疗效，临床开展了剂量递增试验，推进了调强放疗（IMRT）和质子束治疗（PBT）等现代放疗技术，并引入自适应放疗以在保护危险器官的同时优化靶区覆盖。同步及巩固免疫治疗，特别是PD-L1抑制剂的应用展现出潜力，PACIFIC试验证实CRT后使用度伐利尤单抗可改善无进展生存期（PFS）和总生存期（OS）。当前研究正探索新型免疫联合疗法及靶向治疗，包括双免疫检查点抑制剂、DNA修复抑制剂以及针对EGFR突变NSCLC的奥希替尼等分子靶向药物。循环肿瘤DNA和影像组学等新兴生物标志物为个体化治疗和预后预测提供了可能。此外，PBT和磁共振引导的自适应放疗在保持疗效的同时显示出降低毒性的潜力。整合这些创新手段有望为这一难治性患者群体优化治疗效果并减少不良反应。未来需进一步研究患者分层、生物标志物导向治疗及精细化联合方案，以改善不可切除III期NSCLC的长期预后。本文从放射肿瘤学视角，系统综述当前不可切除III期NSCLC的治疗策略。
肿瘤(癌症)患者之家