Search

Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs Control subvolumes with an area under curve (AUC) = 0.74 (95% confidence interval (C.I.): 0.61-0.90), significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e. at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN.

ObjectivesTo determine the utility of low-flip angle “black bone” magnetic resonance imaging (MRI) for cortical mandibular bone assessment by comparing interdentium cortical measurements and inter-observer morphometric variability in relation to computed tomography (CT).MethodsQuantification of cortical mandible bone width was performed as per Hamada et al. at 15 cross-sectional interdentium locations on pre-treatment black bone MRI and CT for 15 oropharyngeal cancer patients, with inter-observer analyses on a subset of 3 patients by 11 observers. Bland-Altman limits of agreement and bias estimation, Lin’s concordance correlation (LCC), and Deming orthogonal regression were used to compare CT and MRI measurements. The absolute variance and intraclass correlation coefficient (ICC) were implemented for the inter-observer error quantification.ResultsBoth the Bland Altman and Deming regression analyses showed CT and black bone MRI measurements were comparable within ±0.85 mm limits of agreement, and systematically smaller for MRI. LCC (0.60[0.52;0.67]) showed moderate equivalence between modalities. The average absolute variance between the observers was similar on CT (1.13±0.06 mm) and MRI (1.15 ±0.06 mm). The ICC analyses showed that measurement consistency was significantly higher (pConclusionsBlack bone MR sequence is usable as an alternative to CT for cortical mandible bone measurements, allowing use for early detection of cortical alteration (e.g. osteonecrosis). The cortical bone measurements showed substantive but equivalent inter-observer variation on both CT and black bone MRI. (Semi)automated measurement may mitigate this in future work.

PurposeWe aim to characterize the quantitative DCE-MRI parameters associated with advanced mandibular osteoradionecrosis (ORN) compared to the contralateral normal mandible.Experimental DesignPatients with the diagnosis of advanced ORN after curative-intent radiation treatment of head and neck cancer were prospectively enrolled after institutional-review board approval and study-specific informed consent. Eligibility criteria included; age>18 years, pathological evidence of head and neck malignancy with history of curative-intent external beam radiotherapy; patients with clinically confirmed high-grade ORN requiring surgical intervention; and no contraindications to MRI. The DCE-MRI acquisition consisted of a variable flip angle T1 mapping sequence and a multi-phase 3D FSPGR sequence. Quantitative maps generated with the Tofts and extended Tofts pharmacokinetic model were used for analysis. Motion correction was applied. Manual segmentation of advanced ORN 3-D volume was done using anatomical sequences (T1, T2, and T1+contrast) to create ORN volumes of interest (ORN-VOIs).Subsequently, normal mandibular VOIs were segmented on the contralateral healthy mandible of similar volume and anatomical location (i.e., mirror image) to create self-control VOIs. Finally, anatomical sequences were co-registered to DCE sequences, and contours were propagated to the respective quantitative parameter maps.ResultsThirty patients were included. Median age at diagnosis was 58 years (range 19-78), and 83% were men. The site of tumor origin was in the oropharynx, oral cavity, salivary glands, and nasopharynx in 13, 9, 6, and 2 patients, respectively. The median time to ORN development after completion of IMRT was 38 months (range 6-184). There were statistically significant higher Ktrans and Ve values in ORN-VOIs compared with controls (0.23 vs. 0.07 min−1, and 0.34 vs. 0.15, p trans in ORN-VOIs was 3.2 folds healthy mandibular control VOIs. Moreover, the corresponding rise of Ve in ORN-VOIs was 2.7 folds higher than the controls. Using combined Ktrans and Ve parameters, 27 patients (90%) had at least a 200% increase of either of the studied parameters in the ORN-VOIs compared with their healthy mandible control VOIs.ConclusionOur results confirm there is a quantitatively significant higher degree of leakiness in the mandibular vasculature as measured using DCE-MRI parameters of areas affected with an advanced grade of ORN versus healthy mandible. We were able to measure significant increases in quantitative metrics compared to values from the non-ORN mandibular bone. Further efforts are ongoing to validate these findings to enable the use of these DCE-MRI parameter thresholds for the early detection of subclinical cases of ORN.