The combination of stereotactic ablative radiotherapy (SABR) with immune checkpoint inhibitors, known as iSABR, marks a significant evolution in treating early-stage, inoperable non-small cell lung cancer (NSCLC). Managing these cases requires a multidisciplinary approach involving radiation and medical oncologists. Clinical evidence from a meta-analysis of seven studies, including 462 patients, indicates that iSABR may offer better outcomes than SABR alone. The analysis showed significantly improved progression-free survival (PFS) rates at 1-, 2-, and 3-year follow-ups for iSABR compared to SABR. There was also a trend toward better overall survival (OS) with iSABR. Subgroup analyses highlighted enhanced 3-year PFS with programmed death-1 (PD-1) inhibitors and doses per fraction ≥ 12.5 Gy. While iSABR slightly increased the risk of grade ≥ 3 adverse events like pneumonitis, fatigue, and skin reactions, these risks are generally manageable within a multidisciplinary treatment framework. In conclusion, iSABR demonstrates potential benefits and manageable risks in phase I/II trials for early-stage, inoperable NSCLC, with improved PFS and acceptable toxicity. These findings warrant further investigation in a larger phase III prospective randomized controlled trial to validate efficacy, optimize protocols, and establish long-term safety.
