Dataset Information

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

ABSTRACT: Importance:Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial. Objective:To assess whether xerostomia is a toxic effect of WBRT. Design, Setting, and Participants:This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated. Main Outcomes and Measures:Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline. Results:Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P?

SUBMITTER: Wang K

PROVIDER: S-EPMC6439567 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

Wang Kyle K Pearlstein Kevin A KA Moon Dominic H DH Mahbooba Zahra M ZM Deal Allison M AM Wang Yue Y Sutton Stephanie R SR Motley Britni B BB Judy Gregory D GD Holmes Jordan A JA Sheets Nathan C NC Kasibhatla Mohit S MS Pacholke Heather D HD Shen Colette J CJ Zagar Timothy M TM Marks Lawrence B LB Chera Bhishamjit S BS

JAMA oncology 20190201 2

<h4>Importance</h4>Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial.<h4>Objective</h4>To assess whether xerostomia is a toxic effect of WBRT.<h4>Design, setting, and participants</h4>This observational cohort study enrolled patients fr ...[more]

PMID: 30489607

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Project description:PurposeTo determine whether serial cone beam computed tomography (CBCT) images taken during head and neck radiation therapy (HNR) can improve chronic xerostomia prediction.Methods and materialsIn a retrospective analysis, parotid glands (PGs) were delineated on daily kV CBCT images using deformable image registration for 119 HNR patients (60 or 70 Gy in 2 Gy fractions over 6 or 7 weeks). Deformable image registration accuracy for a subset of deformed contours was quantified using the Dice similarity coefficient and mean distance to agreement in comparison with manually drawn contours. Average weekly changes in CBCT-measured mean Hounsfield unit intensity and volume were calculated for each PG relative to week 1. Dose-volume histogram statistics were extracted from each plan, and interactions among dose, volume, and intensity were investigated. Univariable analysis and penalized logistic regression were used to analyze association with observer-rated xerostomia at 1 year after HNR. Models including CBCT delta imaging features were compared with clinical and dose-volume histogram-only models using area under the receiver operating characteristic curve (AUC) for grade ≥1 and grade ≥2 xerostomia prediction.ResultsAll patients experienced end-treatment PG volume reduction with mean (range) ipsilateral and contralateral PG shrinkage of 19.6% (0.9%-58.4%) and 17.7% (4.4%-56.3%), respectively. Midtreatment volume change was highly correlated with mean PG dose (r = -0.318, P < 1e-6). Incidence of grade ≥1 and grade ≥2 xerostomia was 65% and 16%, respectively. For grade ≥1 xerostomia prediction, the delta-imaging model had an AUC of 0.719 (95% confidence interval [CI], 0.603-0.830), compared with 0.709 (95% CI, 0.603-0.815) for the dose/clinical model. For grade ≥2 xerostomia prediction, the dose/clinical model had an AUC of 0.692 (95% CI, 0.615-0.770), and the addition of contralateral PG changes modestly improved predictive performance, with an AUC of 0.776 (0.643-0.912).ConclusionsThe rate of CBCT-measured PG image feature changes improves prediction over dose alone for chronic xerostomia prediction. Analysis of CBCT images acquired for treatment positioning may provide an inexpensive monitoring system to support toxicity-reducing adaptive radiation therapy.

Project description:Treatment planning for whole-brain radiation treatment is technically a simple process, but in practice it takes valuable clinical time of repetitive and tedious tasks. This report presents a method that automatically segments the relevant target and normal tissues, and creates a treatment plan in only a few minutes after patient simulation. Segmentation of target and critical structures is performed automatically through morphological operations on the soft tissue and was validated by comparing with manual clinical segmentation using the Dice coefficient and Hausdorff distance. The treatment plan is generated by searching a database of previous cases for patients with similar anatomy. In this search, each database case is ranked in terms of similarity using a customized metric designed for sensitivity by including only geometrical changes that affect the dose distribution. The database case with the best match is automatically modified to replace relevant patient info and isocenter position while maintaining original beam and MLC settings. Fifteen patients with marginally acceptable treatment plans were used to validate the method. In each of these cases the anatomy was accurately segmented, but the beams and MLC settings led to a suboptimal treatment plan by either underdosing the brain or excessively irradiating critical normal tissues. For each case, the anatomy was automatically segmented with the proposed method, and the automated and anual segmentations were then compared. The mean Dice coefficient was 0.97, with a standard deviation of 0.008 for the brain, 0.85 ± 0.009 for the eyes, and 0.67 ± 0.11 for the lens. The mean Euclidian distance was 0.13 ± 0.13 mm for the brain, 0.27± 0.31 for the eye, and 2.34 ± 7.23 for the lens. Each case was then subsequently matched against a database of 70 validated treatment plans and the best matching plan (termed autoplanned), was compared retrospectively with the clinical plans in terms of brain coverage and maximum doses to critical structures. Maximum doses were reduced by a maximum of 8.37 Gy for the left eye (mean 2.08), 11.67 for the right eye (1.90) and, respectively, 25.44 (5.59) for the left lens and 24.40 (4.85) for the right lens. Time to generate the autoplan, including the segmentation, was 3-4min. Automated database- based matching is an alternative to classical treatment planning that improves quality while providing a cost-effective solution to planning through modifying previous validated plans to match a current patient's anatomy.

Project description: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.

Project description:Radiation therapy (RT) plays a vital role in the treatment of brain cancers, but it frequently results in cognitive decline in the patients who receive it. Because the underlying mechanisms for this decline remain poorly understood, the brain is typically treated as a single, uniform volume when evaluating the toxic effects of RT plans. This ignorance represents a significant deficit in the field of radiation oncology, as the technology exists to manipulate dose distributions to spare regions of the brain, but there exists no body of knowledge regarding what is critical to spare. This deficit exists due to the numerous confounding factors that are frequently associated with radiotherapy, including the tumors themselves, other treatments such as surgery and chemotherapy, and dose gradients across the brain. Here, we present a case in which a 57-year-old male patient received a uniform dose of radiation across the whole brain, did not receive concurrent chemotherapy, had minimal surgical intervention and a small tumor burden, and received resting-state functional magnetic resonance imaging (fMRI) scans both before and after RT. To our knowledge, this is the first study on the effects of whole-brain radiotherapy on functional network organization, and this patient's treatment regimen represents a rare and non-replicable opportunity to isolate the effects of radiation on functional connectivity. We observed substantial changes in the subject's behavior and functional network organization over a 12-month timeframe. Interestingly, the homogenous radiation dose to the brain had a heterogeneous effect on cortical networks, and the functional networks most affected correspond with observed cognitive behavioral deficits. This novel study suggests that the cognitive decline that occurs after whole-brain radiation therapy may be network specific and related to the disruption of large-scale distributed functional systems, and it indicates that fMRI is a promising avenue of study for optimizing cognitive outcomes after RT.

Project description:PurposeWhole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits.Methods and materialsNCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy in 10 fractions or 37.5 Gy in 15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher's exact tests.ResultsAmong 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P = .01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P = .66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P = .14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P = .09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P = .18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P = .03).ConclusionsThis post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.

Dataset Information

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

Publications

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

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