Prognostic generalization of multi-level CT-dose fusion dosiomics from primary tumor and lymph node in nasopharyngeal carcinoma.

Abstract

To investigate the prognostic performance of multi-level computed tomography (CT)-dose fusion dosiomics at the image-, matrix-, and feature-levels from the gross tumor volume (GTV) at nasopharynx and the involved lymph node for nasopharyngeal carcinoma (NPC) patients. Two hundred and nineteen NPC patients (175 vs. 44 for training vs. internal validation) were used to train prediction model, and 32 NPC patients were used for external validation. We first extracted CT and dose information from intratumoral nasopharynx (GTV_nx) and lymph node (GTV_nd) regions. Then, the corresponding peritumoral regions (RING_3mm and RING_5mm) were also considered. Thus, the individual and combination of intratumoral and peritumoral regions were as follows: GTV_nx, GTV_nd, RING_3mm_nx, RING_3mm_nd, RING_5mm_nx, RING_5mm_nd, GTV_nxnd, RING_3mm_nxnd, RING_5mm_nxnd, GTV+RING_3mm_nxnd, and GTV+RING_5mm_nxnd. For each region, 11 models were built by combining five clinical parameters and 127 features from: (1) dose images alone; (2-7) fused dose and CT images via wavelet-based fusion using CT weights of 0.2, 0.4, 0.6, and 0.8, gradient transfer fusion, and guided-filtering-based fusion (GFF); (8) fused matrices (sumMat); (9-10) fused features derived via feature averaging (avgFea) and feature concatenation (conFea); and finally, (11) CT images alone. The concordance index (C-index) and Kaplan-Meier curves with log-rank test were used to assess model performance. The fusion models' performance was better than single CT/dose model on both internal and external validation. Models that combined the information from both GTV_nx and GTV_nd regions outperformed the single region model. For internal validation, GTV+RING_3mm_nxnd GFF model achieved the highest C-index both in recurrence-free survival (RFS) and metastasis-free survival (MFS) predictions (RFS: 0.822; MFS: 0.786). The highest C-index in external validation set was achieved by RING_3mm_nxnd model (RFS: 0.762; MFS: 0.719). The GTV+RING_3mm_nxnd GFF model is able to significantly separate patients into high-risk and low-risk groups compared to dose-only or CT-only models. Fusion dosiomics model combining the primary tumor, the involved lymph node, and 3mm peritumoral information outperformed single-modality models for different outcome predictions, which is helpful for clinical decision-making and the development of personalized treatment.