Developing and validating multi-omics prediction models for late patient-reported dysphagia in head and neck radiotherapy.

Background and purpose. To investigate models developed using radiomic and dosiomic (multi-omics) features from planning and treatment imaging for late patient-reported dysphagia in head and neck radiotherapy.Materials and methods. Training (n = 64) and testing (n = 23) cohorts of head and neck cancer patients treated with curative intent chemo-radiotherapy with a follow-up time greater than 12 months were retrospectively examined. Patients completed the MD Anderson Dysphagia Inventory and a composite score ≤60 was interpreted as patient-reported dysphagia. A chart review collected baseline dysphagia and clinical factors. Multi-omic features were extracted from planning and last synthetic CT images using the pharyngeal constrictor muscle contours as a region of interest. Late patient-reported dysphagia models were developed using a random forest backbone, with feature selection and up-sampling methods to account for the imbalanced data. Models were developed and validated for multi-omic feature combinations for both timepoints.Results. A clinical and radiomic feature model developed using the planning CT achieved good performance (validation: sensitivity = 80 ± 27% / balanced accuracy = 71 ± 23%, testing: sensitivity = 80 ± 10% / balanced accuracy = 73 ± 11%). The synthetic CT models did not show improvement over the plan CT multi-omics models, with poor reliability of the radiomic features on these images. Dosiomic features extracted from the synthetic CT showed promise in predicting late patient-reported dysphagia.Conclusion. Multi-omics models can predict late patient-reported dysphagia in head and neck radiotherapy patients. Synthetic CT dosiomic features show promise in developing successful models to account for changes in delivered dose distribution. Multi-center or prospective studies are required prior to clinical implementation of these models.

Dysphagia in Head and Neck Radiotherapy: The Influence of Pharyngeal Constrictor Anatomy and Dosimetry.

The goal of this study was to identify which anatomical and dosimetric changes correlated with late patient-reported dysphagia throughout the course of head and neck chemo-radiotherapy treatment. The patient cohort (n = 64) considered oropharyngeal and nasopharyngeal patients treated with curative intent, exhibiting no baseline dysphagia with a follow-up time greater than one year. Patients completed the MD Anderson Dysphagia Inventory during a follow-up visit. A composite score was measured ranging from 20 to 100, with a low score indicating a high symptom burden; a score ≤60 indicated patient-reported dysphagia. The pharyngeal (PCM) and cricopharyngeal constrictor muscles (CPM) were contoured on a planning CT image and adapted to weekly cone-beam CT anatomy using deformable image registration and dose was accumulated using weighted dose-volume histogram curves. The PCM and CPM were examined for volume, thickness, and dosimetric changes across treatment with the results correlated to symptom group. Anatomical evaluation indicated the PCM thickness increased more during treatment for patients with dysphagia, with base of C2 vertebrae (p = 0.04) and superior-inferior middle PCM (p = 0.01) thicknesses indicating a 1.0-1.5 mm increase. The planned and delivered mean dose and DVH metrics to PCM and CPM were found to be within random error measured for the dose accumulation, indicating delivered and planned dose are equivalent. The PCM and CPM organs were found to lie approximately 5 mm closer to high dose gradients in patients exhibiting dysphagia. The volume, thickness, and high dose gradient metrics may be useful metrics to identify patients at risk of late patient-reported dysphagia.

SpaceOAR© hydrogel rectal dose reduction prediction model: a decision support tool.

Prostate cancer external beam radiation therapy can result in toxicity due to organ at risk (OAR) dose, potentially impairing quality of life. A polyethylene glycol-based spacer, SpaceOAR© hydrogel (SOH), implanted between prostate gland and rectum may significantly reduce dose received by the rectum and hence risk of rectal toxicity. SOH implant is not equally effective in all patients. Determining patients in which the implant will offer most benefit, in terms of rectal dose reduction, allows for effective management of SOH resources. Several factors have been shown to be correlated with reduction in rectal dose including distance between rectum and planning treatment volume (PTV), volume of rectum in the PTV, and change in rectum volume pre- to post-SOH. Several of these factors along with other pre-SOH CT metrics were able to predict reduction in rectal dose associated with SOH implant. Rectal V55Gy metric, was selected as the dose level of interest in the context of 60 Gy in 20 fraction treatment plans. Models were produced to predict change in RV55Gy and pre-SOH hydrogel RV55Gy. These models offered R-squared between 0.81 and 0.88 with statistical significance in each model. Applying an ω 1  = 3% lower limit of pre-SOH RV55 Gy and an ω 2  = 3.5% lower limit on change in RV55 Gy, retained 60% of patients experiencing the largest rectal dose reduction from the hydrogel. This may offer a clinically useful tool in deciding which patients should receive SOH implant given limited resources. Predictive models, nomograms, and a workflow diagram were produced for clinical management of SOH implant.

Maximizing rectal dose sparing with hydrogel: A retrospective planning study.

External beam radiation therapy for prostate cancer can result in urinary, sexual, and rectal side effects, often impairing quality of life. A polyethylene glycol-based product, SpaceOAR© hydrogel (SOH), implanted into the connective tissue between the prostate gland and rectum can significantly reduce the dose received by the rectum and hence risk of rectal toxicity. The optimal way to manage the hydrogel and rectal structures for plan optimization is therefore of interest. In 13 patients, computerized tomography (CT) scans were taken pre- and post-SpaceOAR© implant. A prescription of 60 Gy in 20 fractions was planned on both scans. Six treatment plans were produced per anonymized dataset using either a structure of rectum plus the hydrogel, termed composite rectum wall (CRW), or rectal wall (RW) as an inverse optimization structure and intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) as a treatment technique. Dose-volume histogram metrics were compared between plans to determine which optimization structure and treatment technique offered the maximum rectal dose sparing. RW structures offered a statistically significant decrease in rectal dose over CRW structures, whereas the treatment technique (IMRT vs VMAT) did not significantly affect the rectal dose. There was improvement seen in bladder and penile bulb dose when VMAT was used as a treatment technique. Overall, treatment plans using the RW optimization structure offered the lowest rectal dose while VMAT treatment technique offered the lowest bladder and penile bulb dose.