Delta-Radiomics Guides Adaptive De-Intensification after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma in the IMRT Era

Abstract

In the setting of intensity-modulated radiotherapy (IMRT) and induction chemotherapy (IC), the benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma (LANPC). This study aimed to construct a delta-radiomics model for benefit prediction and patient selection for omitting concurrent chemotherapy. Between December 2009 and December 2015, a total of 718 patients with LANPC treated with IC+IMRT or IC+concurrent chemoradiotherapy (CCRT) were retrospectively enrolled and randomly assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from magnetic resonance images of pre-IC and post-IC. Interclass correlation coefficients and Pearson correlation coefficients were calculated to select robust radiomic features. After univariate Cox analysis, a delta-radiomics signature was built using the LASSO-Cox regression. A nomogram incorporating the delta-radiomics signature and clinical prognostic factors was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated by Kaplan-Meier methods. The primary outcome was overall survival (OS). The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. It yielded an area under the receiver operating characteristic curve (AUC) of 0.77 (95% confidence interval [CI] 0.71 to 0.82) for the training set and 0.71 (95% CI 0.61 to 0.81) for the validation set. The nomogram composed of the delta-radiomic signature, age, T category, N category, pre-treatment Epstein-Barr virus DNA, and treatment showed great calibration and discrimination performance with an AUC of 0.80 (95% CI 0.75 to 0.85) for the training set and 0.75 (95% CI 0.64 to 0.85) for the validation set. Risk stratification by the nomogram excluding the treatment variable resulted in two risk groups with distinct OS. Significant better outcomes were observed in the high-risk patients with IC+CCRT compared to those with IC+IMRT (5-year OS: 73.8% vs. 61.4% in the training set and 85.8% vs. 65.6% in the validation set; all log-rank p < 0.05), while comparable outcomes between IC+CCRT and IC+IMRT were shown for the low-risk patients (95.8% vs. 95.8% in the training set and 92.2% vs. 88.3% in the validation set; all log-rank p > 0.05). The delta-radiomics signature was identified as an independent indicator of LANPC. Integrating clinical predictors with the delta-radiomics signature, the radiomics-based nomogram could predict individual's survival outcomes and benefits from concurrent chemotherapy after IC for LANPC. Low-risk patients with LANPC determined by the nomogram may be potential candidates for omission of concurrent chemotherapy following IC in the IMRT era.