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.

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.

Novel imaging classification system of nodal disease in human papillomavirus-mediated oropharyngeal squamous cell carcinoma prognostic of patient outcomes.

BACKGROUND: Matted nodes in human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPC) is an independent predictor of distant metastases and decreased overall survival. We aimed to classify imaging patterns of metastatic lymphadenopathy, analyze our classification system for reproducibility, and assess its prognostic value. METHODS: The metastatic lymphadenopathy was classified based on radiological characteristics for 216 patients with HPV-mediated OPC. Patient outcomes were compared and inter-rater reliability was calculated. RESULTS: The presence of ≥3 abutting lymph nodes with imaging features of surrounding extranodal extension (ENE), one subtype of matted nodes, was associated with worse 5-year overall survival, overall recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival (p ≤ 0.03). Other patterns were not significantly associated with outcome measures. Overall inter-rater agreement was substantial (κ = 0.73). CONCLUSION: One subtype of matted nodes defined by ≥3 abutting lymph nodes with imaging features of surrounding ENE is the radiological marker of worst prognosis.

Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial.

BACKGROUND AND PURPOSE: Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL). MATERIAL AND METHODS: Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474. RESULTS: 152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p < 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up. CONCLUSION: Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT.

Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late outcomes from two prospective clinical trials.

PURPOSE: Optimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials. METHODS: Study1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2. RESULTS: 114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%. CONCLUSIONS: Dose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.

Prospective swallowing outcomes after IMRT for oropharyngeal cancer: Dosimetric correlations in a population-based cohort.

OBJECTIVES: To identify dose constraints to preserve swallowing after head and neck (H&N) radiotherapy using prospectively collected functional outcomes. MATERIALS AND METHODS: Stage III-IV oropharyngeal cancer patients were prospectively evaluated using the Royal Brisbane Hospital Outcome Measure for Swallowing and Performance Status Scale for H&N Cancer Patients at pre-treatment and 3, 6, 12, and 24months after intensity-modulated radiotherapy. Dosimetric parameters were correlated with swallowing function. RESULTS: Ninety-six patients were evaluated with median follow-up of 14.1months (interquartile range 9.9-26.3). Six patients (8.3%) remained feeding tube (FT) dependent at 12months. At 2years, 32.6% tolerated a normal diet without restrictions. Mean doses of 55Gy to supraglottic larynx, 44Gy to glottic larynx, 48Gy to cricopharyngeus, and 44Gy to esophageal inlet were associated with >25% risk of FT dependence at 6months. CONCLUSION: Higher mean doses to the larynx and pharyngo-esophageal junction were associated with longer duration of FT dependence and dietary restrictions.

Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials.

INTRODUCTION: The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340). MATERIAL AND METHODS: Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher's exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL. RESULTS: One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46-60] and 38 months (IQR 32-42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups. CONCLUSION: Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.