Intentional internal high-dose policy in VMAT for stage III NSCLC with consolidation durvalumab - a retrospective...

Concurrent chemoradiotherapy followed by durvalumab is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). However, uniform radiation dose escalation has failed to improve outcomes due to increased toxicity. The intentional internal high dose policy (IIHDP) selectively escalates radiation dose within the tumor while sparing organs at risk (OARs). This study assesses the feasibility and clinical outcomes of IIHDP using volumetric modulated arc therapy (VMAT).

We retrospectively analyzed 280 patients treated with definitive VMAT from 2017 to 2024, divided into IIHDP (n = 112) and homogeneous dose distribution policy (HDDP; n = 168) groups. The primary endpoint was local recurrence control (LRC); secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity. Receiver operating characteristic (ROC) analysis was used to evaluate planning target volume (PTV) volume as a predictor of LRC.

Median follow-up was 20.5 months. The 2-year LRC was 75% (IIHDP) and 72% (HDDP) (p = 0.296). In patients with large PTVs (≥ 373 cc), IIHDP showed a trend toward improved LRC, though not statistically significant. The 2-year OS was 75% in both groups. Durvalumab ≥ 6 months was a strong independent predictor of OS [p < 0.001; hazard ratio (HR) = 0.274]. Rates of grade ≥ 3 pneumonitis (2.7% vs. 3.6%, p = 0.490) and esophagitis (0% vs. 1.2%, p = 0.212) were similar across groups.

IIHDP with VMAT appears feasible and safe in selected patients with stage III NSCLC, achieving favorable tumor control without added toxicity or interruption of durvalumab. Further prospective studies are warranted to validate its benefit and define optimal patient selection.