Abstract

PurposeTo analyze baseline CT/MR-based image features of salivary glands to predict radiation-induced xerostomia 3-months after head-and-neck cancer (HNC) radiotherapy.MethodsA retrospective analysis was performed on 266 HNC patients who were treated using radiotherapy at our institution between 2009 and 2018. CT and T1 post-contrast MR images along with NCI-CTCAE xerostomia grade (3-month follow-up) were prospectively collected at our institution. CT and MR images were registered on which parotid/submandibular glands were contoured. Image features were extracted for ipsilateral/contralateral parotid and submandibular glands relative to the location of the primary tumor. Dose-volume-histogram (DVH) parameters were also acquired. Features were pre-selected based on Spearman correlation before modelling by examining the correlation with xerostomia (p < 0.05). A shrinkage regression analysis of the pre-selected features was performed using LASSO. The internal validity of the variable selection was estimated by repeating the entire variable selection procedure using a leave-one-out-cross-validation. The most frequently selected variables were considered in the final model. A generalized linear regression with repeated ten-fold cross-validation was developed to predict radiation-induced xerostomia at 3-months after radiotherapy. This model was tested in an independent dataset (n = 50) of patients who were treated at the same institution in 2017–2018. We compared the prediction performances under eight conditions (DVH-only, CT-only, MR-only, CT + MR, DVH + CT, DVH + CT + MR, Clinical+CT + MR, and Clinical+DVH + CT + MR) using the area under the receiver operating characteristic curve (ROC-AUC).ResultsAmong extracted features, 7 CT, 5 MR, and 2 DVH features were selected. The internal cohort (n = 216) ROC-AUC values for DVH, CT, MR, and Clinical+DVH + CT + MR features were 0.73 ± 0.01, 0.69 ± 0.01, 0.70 ± 0.01, and 0.79 ± 0.01, respectively. The validation cohort (n = 50) ROC-AUC values for DVH, CT, MR, and Clinical+DVH + CT + MR features were 0.63, 0.57, 0.66, and 0.68, respectively. The DVH-ROC was not significantly different than the CT-ROC (p = 0.8) or MR-ROC (p = 0.4). However, the CT + MR-ROC was significantly different than the CT-ROC (p = 0.03), but not the Clinical+DVH + CT + MR model (p = 0.5).ConclusionOur results suggest that baseline CT and MR image features may reflect baseline salivary gland function and potential risk for radiation injury. The integration of baseline image features into prediction models has the potential to improve xerostomia risk stratification with the ultimate goal of truly personalized HNC radiotherapy.

Highlights

  • Radiation therapy (RT), often with concurrent chemotherapy, is frequently used in the management of head and neck cancer (HNC) as definitive or adjuvant treatment

  • The computed tomography (CT) + MR-ROC was significantly different than the CT-ROC (p = 0.03), but not significantly different than the dose-volume histograms (DVHs)-ROC (p = 0.4) or MR-ROC (p = 0.8)

  • In this study, to better understand the influence of image features in the prediction of RT-induced xerostomia, we investigated the relationships between CT and MR image features with xerostomia scores in HNC patients using machine learning approaches

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Summary

Introduction

Radiation therapy (RT), often with concurrent chemotherapy, is frequently used in the management of head and neck cancer (HNC) as definitive or adjuvant treatment. There is increasing popularity for rapid-learning health systems which use routine clinical data to develop models that can be used to predict patient specific treatment outcomes [5,6,7]. Machine learning algorithms have emerged as popular tools for decision support These algorithms are already being applied to many aspects of radiation therapy including: target delineation [8, 9], treatment planning [10, 11], radiation physics quality assurance [12], and outcome [13] and tumor response modelling [14]. Radiomics derived from computed tomography (CT) have been used to predict xerostomia and survival in HNC patients [18, 21, 22]

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