Beyond the ratio of tumor reduction: residual volume after induction chemotherapy emerges as the optimal biomarker in advanced nasopharyngeal cancer.

PURPOSE: To investigate and compare the prognostic value of tumor volumetric characteristics during induction chemotherapy (IC) for advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A retrospective cohort of 250 patients with NPC treated with IC followed by radiotherapy or chemoradiotherapy was analyzed. Tumor volumes were measured using MRI at two time points of before-treatment and after-IC. Cohorts with high and low tumor heterogeneity were identified by analyzing the gross tumor volume (GTV) through the gray-level co-occurrence matrix (GLCM). Incorporating the clinical factors, volumetric characteristics (Vpre−IC, Vpost−IC, ΔVabs, and ΔVrel) were evaluated to identify the prognostic value using univariable and multivariable analyses in various cohorts, respectively. Kaplan-Meier survival analyses with median and optimal cutoff values were conducted. Multivariable analysis was repeated on 1 × 105 resampled cohorts with the Bootstrap method to identify the feature importance. Subgroup analyses were performed based on T-category, IC regimens, post-IC treatment protocols, and tumor changes. RESULTS: There is virtually no correlation between Vpost−IC and ΔVrel with ρ = -0.08. Various analyses all suggest Vpost−IC emerged as the most robust biomarker across all endpoints (P < 0.001 ∼ 0.002), followed by ΔVrel and T-category, which were more important than the other features. The predictive value of Vpost−IC surpasses that of ΔVrel especially in the high heterogeneity cohort. Specifically, a Vpost−IC value of 20.6 cm³ could be regarded as a threshold provided optimal risk stratification for progression-free survival (PFS) and overall survival (OS). CONCLUSION: Vpost−IC is a critical biomarker for determining clinical outcomes in advanced NPC. Patients with Vpost−IC measurements above 20.6 cm³ are classified as high-risk, indicating a requirement for escalating radiotherapy and/or chemotherapy.