Advances in Radiation Therapy for Unresectable Locally Advanced Non-Small Cell Lung Cancer: From Technical Advances to Immunotherapy Integration.

The management of unresectable locally advanced non-small cell lung cancer (NSCLC) has undergone significant transformation over the past three decades. This review summarizes the evolution of radiation therapy for unresectable locally advanced NSCLC, from radiation therapy alone to concurrent chemoradiotherapy, and the subsequent integration of immunotherapy or targeted therapy against driver mutations as consolidation treatment. Technical advances in radiation delivery, including the progression from two-dimensional radiotherapy to three-dimensional conformal radiotherapy (3D-CRT), followed by intensity- modulated radiotherapy (IMRT), have improved therapeutic outcomes while reducing toxicity. The PACIFIC trial established durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, consolidation as the standard of care following concurrent chemoradiotherapy, resulting in significant improvements in survival. More recently, the LAURA trial demonstrated the efficacy of Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), consolidation in EGFR-mutated NSCLC. However, radiation pneumonitis remains a potentially fatal radiation-induced toxicity that can prevent patients from receiving optimal treatment. Careful attention to dose-volume parameters, particularly lung V20Gy and mean lung dose, is essential for safe treatment delivery. Risk prediction models have been developed to identify high-risk patients, particularly those with pre-existing interstitial pneumonia. The successful transition to consolidation immunotherapy requires meticulous radiation pneumonitis management to maximize clinical benefit. This review summarizes current evidence and provides guidance for optimizing treatment approaches in this challenging patient population.