Estimating Individualized Survival Benefit of Consolidative Metastasis-Directed Radiotherapy Following Chemoimmunotherapy in Nasopharyngeal Carcinoma With Exclusive Distant Metastasis.

Optimal patient selection for consolidative metastasis-directed radiotherapy (MDRT) after chemoimmunotherapy (CIT) remains uncertain in nasopharyngeal carcinoma (NPC) with exclusive distant metastasis, defined as distant metastasis without synchronous locoregional recurrence. This study was aimed at estimating the survival benefit of MDRT and identifying patients most likely to benefit. A total of 1083 patients from two independent centers were analyzed using a target trial emulation with cloning, artificial censoring, and inverse probability of censoring weighting. The emulation estimated a 4.2-month gain in 3-year progression-free survival (PFS) restricted mean survival time with the MDRT strategy (95% CI: 2.4-5.9; bootstrap p < 0.001). Eight survival machine-learning algorithms were developed and compared, among which the gradient boosting machine achieved 3-year PFS AUROCs of 0.875 in internal validation and 0.877 in geographical external validation. Heterogeneous treatment effects were further estimated using a T-learner framework across risk groups defined by recursive partitioning analysis. In the external cohort, model-estimated 3-year absolute risk reductions with MDRT were 21.6%, 14.7%, and 5.7% in intermediate-, low-, and high-risk groups, respectively. The framework was subsequently implemented as a web-based clinical decision-support system. These findings support individualized selection of consolidative MDRT after CIT and provide a practical framework for multidisciplinary decision-making.