The Role of Patient- and Treatment-Related Factors and Early Functional Imaging in Late Radiation-Induced Xerostomia in Oropharyngeal Cancer Patients

SIMPLE SUMMARY: In the present prospective study, we assessed the role of various Magnetic Resonance Imaging biomarkers combined with self-assessed xerostomia questionnaires and patient- and treatment-related factors, in predicting xerostomia at 12 months after chemoradiotherapy for oropharyngeal squamous cell carcinoma. We hypothesized that the integration of pre-treatment imaging biomarkers, which addresses the tissue heterogeneity and individual variations among patients, could improve the accuracy of conventional prediction models that are based only on dose information, ultimately providing a better understanding of the pathophysiological mechanisms underlying radiation induced salivary dysfunction. The implementation of multifactorial models, driven by machine learning algorithms, may improve prediction accuracy of radiation-induced toxicity and tailor individual treatment options for patients. ABSTRACT: The advent of quantitative imaging in personalized radiotherapy (RT) has offered the opportunity for a better understanding of individual variations in intrinsic radiosensitivity. We aimed to assess the role of magnetic resonance imaging (MRI) biomarkers, patient-related factors, and treatment-related factors in predicting xerostomia 12 months after RT (XER(12)) in patients affected by oropharyngeal squamous cell carcinoma (OSCC). Patients with locally advanced OSCC underwent diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline; DWI was repeated at the 10th fraction of RT. The Radiation Therapy Oncology Group (RTOG) toxicity scale was used to evaluate salivary gland toxicity. Xerostomia-related questionnaires (XQs) were administered weekly during and after RT. RTOG toxicity ≥ grade 2 at XER(12) was considered as endpoint to build prediction models. A Decision Tree classification learner was applied to build the prediction models following a five-fold cross-validation. Of the 89 patients enrolled, 63 were eligible for analysis. Thirty-six (57.1%) and 21 (33.3%) patients developed grade 1 and grade 2 XER(12), respectively. Including only baseline variables, the model based on DCE-MRI and V65 (%) (volume of both glands receiving doses ≥ 65 Gy) had a fair accuracy (77%, 95% CI: 66.5–85.4%). The model based on V65 (%) and XQ-Int(mid) (integral of acute XQ scores from the start to the middle of RT) reached the best accuracy (81%, 95% CI: 71–88.7%). In conclusion, non-invasive biomarkers from DCE-MRI, in combination with dosimetric variables and self-assessed acute XQ scores during treatment may help predict grade 2 XER(12) with a fair to good accuracy.