Parotid Gland Volume Research Articles

The Aging Parotid Gland: A Longitudinal Volumetric Study and Implications for Treatment.

The parotid gland accounts for significant soft tissue volume in the face and is therefore of central relevance to facial and neck rejuvenation. The aim of this study was to determine how parotid gland volume is predicted by age and other factors. We conducted a retrospective longitudinal study of patients with multiple computed tomography (CT) scans of the neck performed at least 7 years apart. Parotid gland volumes were measured and multiple linear regression analysis was performed to model the relations between age, body mass index (BMI), and parotid volume. The study cohort comprised 70 patients. The mean [standard deviation] ages at initial and final imaging time points were 47.5 [12.6] and 58.8 [12.2] years, respectively, with an average of 11.3 years elapsed between CT scans. The mean parotid gland volume increased from 28.7 [10.0] to 32.2 [10.7] mL over the average 11.3-year period (P = 0.03). However, the results of the multiple linear regression analysis show that when controlling for BMI and sex, age alone does not predict parotid volume (P = 0.29). BMI was directly correlated with gland volume (P < 0.01). An increase of 1.0 kg/m2 in BMI predicted an increase in parotid volume by 1.1 mL. Male sex was also associated with significantly greater parotid volume. Mean parotid volume increased over time but these gains were driven by increases in BMI and not age alone. These findings are highly relevant to the treatment of the aging face and neck.

Self-channel-and-spatial-attention neural network for automated multi-organ segmentation on head and neck CT images

Accurate segmentation of organs at risk (OARs) is necessary for adaptive head and neck (H&N) cancer treatment planning, but manual delineation is tedious, slow, and inconsistent. A self-channel-and-spatial-attention neural network (SCSA-Net) is developed for H&N OAR segmentation on CT images. To simultaneously ease the training and improve the segmentation performance, the proposed SCSA-Net utilizes the self-attention ability of the network. Spatial and channel-wise attention learning mechanisms are both employed to adaptively force the network to emphasize the meaningful features and weaken the irrelevant features simultaneously. The proposed network was first evaluated on a public dataset, which includes 48 patients, then on a separate serial CT dataset, which contains ten patients who received weekly diagnostic fan-beam CT scans. On the second dataset, the accuracy of using SCSA-Net to track the parotid and submandibular gland volume changes during radiotherapy treatment was quantified. The Dice similarity coefficient (DSC), positive predictive value (PPV), sensitivity (SEN), average surface distance (ASD), and 95% maximum surface distance (95SD) were calculated on the brainstem, optic chiasm, optic nerves, mandible, parotid glands, and submandibular glands to evaluate the proposed SCSA-Net. The proposed SCSA-Net consistently outperforms the state-of-the-art methods on the public dataset. Specifically, compared with Res-Net and SE-Net, which is constructed from squeeze-and-excitation block equipped residual blocks, the DSC of the optic nerves and submandibular glands is improved by 0.06, 0.03 and 0.05, 0.04 by the SCSA-Net. Moreover, the proposed method achieves statistically significant improvements in terms of DSC on all and eight of nine OARs over Res-Net and SE-Net, respectively. The trained network was able to achieve good segmentation results on the serial dataset, but the results were further improved after fine-tuning of the model using the simulation CT images. For the parotids and submandibular glands, the volume changes of individual patients are highly consistent between the automated and manual segmentation (Pearson’s correlation 0.97–0.99). The proposed SCSA-Net is computationally efficient to perform segmentation (sim 2 s/CT).

Botulinum Toxin Injection for Chronic Parotitis: A Multi-Center and Prospective Trial.

When conservative therapy fails for chronic parotitis, sialendoscopic treatment or surgical excision can be considered. However, these are financially costly or invasive. Thus, this study aimed to evaluate the clinical efficacy and safety of botulinum toxin (BTX) injection and to further analyze its effect on parotid gland function and volume using salivary single-photon emission computed tomography (SPECT)-computed tomography (CT). This clinical trial has been registered in the Clinical Research Information Service, Republic of Korea. Fourteen patients with chronic parotitis received BTX injections into the parotid glands. Pain, postprandial pain, swelling, aesthetic discomfort, and salivary flow rate were assessed before injection, at 2 weeks, and at 1, 3, and 6 months. Salivary SPECT-CT was performed before injection and again 3 and 6 months after to assess the volume and uptake changes. All subjective symptoms decreased significantly until 1 month and then increased. However, at 6 months, all subjective symptoms were determined to be better than before injection. The unstimulated and stimulated salivary flow rate did not show a significant difference over time. No significant difference was noted in parotid gland volume or uptake on salivary SPECT-CT over time. BTX injection can be an alternative treatment option for chronic parotitis. 4 Laryngoscope, 131:E1903-E1909, 2021.

A longitudinal study on parotid and submandibular gland changes assessed by magnetic resonance imaging and ultrasonography in post-radiotherapy nasopharyngeal cancer patients.

Objectives:With regard to the intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, this longitudinal study evaluated the radiation-induced changes in the parotid and submandibular glands in terms of gland size, echogenicity and haemodynamic parameters.Methods:21 NPC patients treated by IMRT underwent MRI and ultrasound scans before radiotherapy, and at 6, 12, 18 and 24 months after treatment. Parotid and submandibular gland volumes were measured from the MRI images, whereas the parotid echogenicity and haemodynamic parameters including the resistive index, pulsatility index, peak systolic velocity and end diastolic velocity were evaluated by ultrasonography. Trend lines were plotted to show the pattern of changes. The correlations of gland doses and the post-RT changes were also studied.Results:The volume of the parotid and submandibular glands demonstrated a significant drop from pre-RT to 6 months post-RT. The parotid gland changed from hyperechoic before RT to either isoechoic or hypoechoic after treatment. The resistive index and pulsatility index decreased from pre-RT to 6 month post-RT, then started to increase at 12 month time interval. Both peak systolic velocity and end diastolic velocity increased after 6 months post-RT then followed a decreasing trend up to 24 months post-RT. There was mild correlation between post-RT gland dose and gland volume, but not with haemodynamic changes.Conclusions:Radiation from IMRT caused shrinkage of parotid and submandibular glands in NPC patients. It also changed the echogenicity and vascular condition of the parotid gland. The most significant changes were observed at 6 months after radiotherapy.Advances in knowledge:It is the first paper that reports on the longitudinal changes of salivary gland volume, echogenicity and haemodynamic parameters altogether in NPC patients after radiotherapy. The results are useful for the prediction of glandular changes that is associated with xerostomia, which help to provide timely management of the complication when the patients attend follow-up visits.

Biomechanical modeling of radiation dose-induced volumetric changes of the parotid glands for deformable image registration

Purpose. Early animal studies suggest that parotid gland (PG) toxicity prediction could be improved by an accurate estimation of the radiation dose to sub-regions of the PG. Translation to clinical investigation requires voxel-level dose accumulation in this organ that responds volumetrically throughout treatment. To date, deformable image registration (DIR) has been evaluated for the PG using only surface alignment. We sought to develop and evaluate an advanced DIR technique capable of modeling these complex PG volume changes over the course of radiation therapy. Materials and methods. Planning and mid-treatment magnetic resonance images from 19 patients and computed tomography images from nine patients who underwent radiation therapy for head and neck cancer were retrospectively evaluated. A finite element model (FEM)-based DIR algorithm was applied between the corresponding pairs of images, based on boundary conditions on the PG surfaces only (Morfeus-spatial). To investigate an anticipated improvement in accuracy, we added a population model-based thermal expansion coefficient to simulate the dose distribution effect on the volume change inside the glands (Morfeus-spatialDose). The model accuracy was quantified using target registration error for magnetic resonance images, where corresponding anatomical landmarks could be identified. The potential clinical impact was evaluated using differences in mean dose, median dose, D98, and D50 of the PGs. Results. In the magnetic resonance images, the mean (±standard deviation) target registration error significantly reduced by 0.25 ± 0.38 mm (p = 0.01) when using Morfeus-spatialDose instead of Morfeus-spatial. In the computed tomography images, differences in the mean dose, median dose, D98, and D50 of the PGs reached 2.9 ± 0.8, 3.8, 4.1, and 3.8 Gy, respectively, between Morfeus-spatial and Morfeus-spatialDose. Conclusion. Differences between Morfeus-spatial and Morfeus-spatialDose may be impactful when considering high-dose gradients of radiation in the PGs. The proposed DIR model can allow more accurate PG alignment than the standard model and improve dose estimation and toxicity prediction modeling.

Mid-treatment assessment of dose to parotid gland stem cell region and change in parotid gland volume predicts for long-term patient-reported xerostomia

Mid-treatment assessment of dose to parotid gland stem cell region and change in parotid gland volume predicts for long-term patient-reported xerostomia

Data clustering to select clinically-relevant test cases for algorithm benchmarking and characterization

Algorithm benchmarking and characterization are an important part of algorithm development and validation prior to clinical implementation. However, benchmarking may be limited to a small collection of test cases due to the resource-intensive nature of establishing ‘ground-truth’ references. This study proposes a framework for selecting test cases to assess algorithm and workflow equivalence. Effective test case selection may minimize the number of ground-truth comparisons required to establish robust and clinically relevant benchmarking and characterization results.To demonstrate the proposed framework, we clustered differences between two independent workflows estimating during-treatment dose objective violations for 15 head and neck cancer patients (15 planning CTs, 105 on-unit CBCTs). Each workflow used a different deformable image registration algorithm to estimate inter-fractional anatomy and contour changes. The Hopkins statistic tested whether workflow output was inherently clustered and k-medoid clustering formalized cluster assignment. Further statistical analyses verified the relevance of clusters to algorithm output. Data at cluster centers (‘medoids’) were considered as candidate test cases representative of workflow-relevant algorithm differences.The framework indicated that differences in estimated dose objective violations were naturally grouped (Hopkins = 0.75, providing 90% confidence). K-medoid clustering identified five clusters which stratified workflow differences (MANOVA: p < 0.001) in estimated parotid gland D50%, spinal cord/brainstem Dmax, and high dose CTV coverage dose violations (Kendall’s tau: p < 0.05). Systematic algorithm differences resulting in workflow discrepancies were: parotid gland volumes (ANOVA: p < 0.001), external contour deformations (t-test: p = 0.022), and CTV-to-PTV margins (t-test: 0.009), respectively. Five candidate test cases were verified as representative of the five clusters.The framework successfully clustered workflow outputs and identified five test cases representative of clinically relevant algorithm discrepancies. This approach may improve the allocation of resources during the benchmarking and characterization process and the applicability of results to clinical data.

Examination of parotid gland in diabetics with ultrasound elastography and microvascular imaging.

Diabetes mellitus is a prevalent metabolic disorder that can result in the non-enflamatuar enlargement of the parotid gland. It is recognised as a condition that can impair microvascular perfusion. The parotid glands of 38 individuals with diabetes and 38 healthy controls were examined bilaterally using ultrasound to assess parameters of volume, stiffness and microvascularity. A statistically significant increase in parotid gland volume and a statistically significant decrease in microvascularity were observed in diabetic patients. Furthermore, a statistically significant increase in parotid gland volume was noted in diabetic individuals who were using antidiabetic drugs in comparison to non-users. A significant negative correlation was identified between the duration of exposure to diabetes and microvascularity. Ultrasonographic imaging can be used to assess the dimensions and microvascularity of the parotid gland.

Study of the dose-volume parameters variation in tumor target volumes and organs at risk during nasopharyngeal carcinoma radiotherapy applying deformation registration.

BackgroundDuring intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC), the volume of the target volume and the organs at risk (OARs) will change constantly, which may lead to differences between the actual dose received and the initial planned dose. In this study, the cumulative dose of the two plans was obtained by deformable registration. This study provides an approach to evaluate the dose volume of IMRT for the NPC objective.MethodsFrom July 2014 to May 2018, eighteen NPC patients who accepted simultaneous integrated boost IMRT were enrolled. All patients underwent simulation CT (CT1) and replanning CT (CT2) scans after 20–25 fractions of radiation therapy. The treatment plans were designed on CT1 and CT2 with the name of Plan1 and Plan2, respectively. The Planreg and Plandef were obtained after registering from CT2 to CT1 using rigidity and deformation technology by Velocity. Then the dose-volume indices of the tumor target volumes and OARs at Plan1, Plan2, Planrig and Plandef were compared.ResultsThe gross tumor volume (GTV) and the left and right parotid gland volumes decreased by 20.8% (P<0.001), 36.8% (P<0.001) and 37.5% (P<0.001), respectively, from CT1 to CT2. There was no significant difference in the dose-volume index on the GTV and plan gross tumor volume (PGTV) between Plan1 and Plan2. The V30 of the left and right parotid gland and the Dmax of the brainstem, left and right eyeballs, left and right lens, and left and right optic nerves were all lower in Plan2 than in Plan1 (the average decrease was 17.0% to 60.1%). The differences in some dose-volume parameters (including Dmean, D99 of the GTV and PGTV, Dmean of the parotid glands, Dmax of the lens and optic nerves) between Plandef and Plan1 were less than 5%. The differences in some dose-volume parameters (including Dmean, D95 of the GTV and PGTV, Dmean, D50 and V30 of the parotid glands, Dmax of lens and optic nerves) between Planrig and Plan1 were less than 10%. The Dyce Similarity Coefficient of the target volume and OARs after deformation registration were higher than that after rigid registration.ConclusionsThe volume of the GTV and parotid glands were decreased during the IMRT for NPC. The dose-volume indices of the GTV and the OARs in Plandef were similar to those in Plan1. Therefore, the dose-volume indices of Plan1 can be used to evaluate the efficacy of radiotherapy and to predict radioactive damage.

Acute Toxicity Patterns in Adaptive High Precision Radiotherapy for Head and Neck Cancer - a Randomised Controlled Trial

Adaptive Radiation therapy (ART) aims to take into account the changes in target volume and organs at risk during the course of fractionated radiation therapy & this has possible advantage in terms of improved local control, reduced toxicities and improved the QOL. This study aims to assess the clinical impact of ART in terms of toxicities in primary SCC of HNC undergoing radical/adjuvant concurrent chemo-radiotherapy treatment. The study enrolled 100 patients of histopathologically proven primary head-and-neck cancer and were randomized into ART and non-ART arms. Target/OAR delineation was done after CT simulation following rigid immobilization. All patients were started treatment with VMAT & image guidance. After treatment start, the patients were re-simulated using CT imaging again at 3rd, 5th and 7th week. Predefined adaptive re-contouring workflow using deformable image registration was applied to generate adaptive plan. For patients in ART Arm, the new plan was executed for the remaining fractions. In Non ART Arm treatment was continued as per the original plan. All the patients were observed for total volume of Parotid glands at week 1, 3, 5 and 7. RTOG Criteria was used for documenting acute reactions in form of acute xerostomia, mucositis and dysphagia in both arms at week 3, 5 and 7. Median follow-up was 6mo. The percentage volume change in parotid glands was observed to be 6.25%, 16.37% and 28.39% in adaptive arm and 11.53%, 23.54% and 32.56% at 3, 5 and 7 weeks (P-value 0.009 and 0.0123rd and 5th wk respectively). On clinical examination Grade 2 Xerostomia at 3, 5 and 7 wk was seen in 10%, 36% and 70% patients in adaptive arm whereas in 16%, 46% and 88% in non-adaptive arm (P-value 0.006 at 7th wk). The significant difference in mucosal reactions between both arms was observed throughout the course of study in favour of adaptive arm. None of the patients in adaptive arm had Grade 3 mucosal reactions as compared to 26% in non adaptive arm. The difference in mucosal reaction was most significant at 7th week of treatment (p value 0.004). At week 3 and 5, patients having grade 2 or higher reactions were 14% and 46% in adaptive arm as compared to 26% and 70% in non-adaptive arm. (p values 0.029, 0.023). Dryness of mouth has a significant impact on swallowing. In our study we observed grade 2 or higher dysphagia to be 6%, 38% and 80% in adaptive arm whereas 2%, 48% and 84% in non-adaptive arm at 3, 5 and 7 weeks. Though absolute number of patients having adverse dysphagia reaction was lower in adaptive arm, this difference was not statistically significant (p value 0.15, 0.59, 0.09). Volume changes in parotid glands and gross tumour is observed throughout the course of radiation treatment and ART can aid in better sparing of parotid glands with an advantage over non-ART in terms of reduced acute toxicity reactions. Present study is first RCT reported in literature where an attempt is made to correlate dosimetric and toxicity criteria.

Effective Volume of Parotid Glands for Assessing Radiation Injury during Radiation Therapy for Head and Neck Cancer

Effective Volume of Parotid Glands for Assessing Radiation Injury during Radiation Therapy for Head and Neck Cancer

Biomechanical modeling of neck flexion for deformable alignment of the salivary glands in head and neck cancer images

During head and neck (HN) cancer radiation therapy, analysis of the dose-response relationship for the parotid glands (PG) relies on the ability to accurately align soft tissue organs between longitudinal images. In order to isolate the response of the salivary glands to delivered dose, from deformation due to patient position, it is important to resolve the patient postural changes, mainly due to neck flexion. In this study we evaluate the use of a biomechanical model-based deformable image registration (DIR) algorithm to estimate the displacements and deformations of the salivary glands due to postural changes.A total of 82 pairs of CT images of HN cancer patients with varying angles of neck flexion were retrospectively obtained. The pairs of CTs of each patient were aligned using bone-based rigid registration. The images were then deformed using biomechanical model-based DIR method that focused on the mandible, C1 vertebrae, C3 vertebrae, and external contour. For comparison, an intensity-based DIR was also performed. The accuracy of the biomechanical model-based DIR was assessed using Dice similarity coefficient (DSC) for all images and for the subset of images where the PGs had a volume change within 20%. The accuracy was compared to the intensity-based DIR.The PG mean ± STD DSC were 0.63 ± 0.18, 0.80 ± 0.08, and 0.82 ± 0.15 for the rigid registration, biomechanical model-based DIR, and intensity based DIR, respectively, for patients with a PG volume change up to 20%. For the entire cohort of patients, where the PG volume change was up to 57%, the PG mean ± STD DSC were 0.60 ± 0.18, 0.78 ± 0.09, and 0.81 ± 0.14 for the rigid registration, biomechanical model-based DIR, and intensity based DIR, respectively. The difference in DSC of the intensity and biomechanical model-based DIR methods was not statistically significant when the volume change was less than 20% (two-sided paired t-test, p = 0.12). When all volume changes were considered, there was a significant difference between the two registration approaches, although the magnitude was small.These results demonstrate that the proposed biomechanical model with boundary conditions on the bony anatomy can serve to describe the varying angles of neck flexion appearing in images during radiation treatment and to align the salivary glands for proper analysis of dose-response relationships. It also motivates the need for dose response modeling following neck flexion for cases where parotid gland response is noted.

CD4/CD8 Antibodies Reduce Histopathological Damage in Salivary Glands of Spontaneously Diabetic Mice

Abstract Background and aims: Diabetes affects the metabolism promoting damage in different tissues, including salivary glands. Current treatments, such as insulin, are ineffective to recovery of these tissues. In this aspect, the immunotherapy has been tested, but it can be inefficient as an agent for the control of damage caused by diabetes. The aim of this study to evaluate the association in anti-CD4 and anti-CD8 monoclonal antibody in the recovery of salivary glands of diabetic NOD mice. Material and methods: Fifteen spontaneously diabetic mice (NOD) were divided into three groups with 5 animals each: group I (Balb/C control mice), group II (untreated NOD mice), group III (NOD mice treated with CD4 and CD8 antibodies). The CD4 and CD8 antibodies (IMUNY, Rheabiotech Ltda, Brazil) were administered by intravenously injections (25 ug/days: 0, 7, 14, and 21). After treatment salivary glands samples were analyzed by immunofluorescence, microscopy, light microscopy and stereology. (ethical approval process: 304/11), Analysis of variance (ANOVA) and Kruskal-Wallis nonparametric test were used. Results: Elevated levels of glucose (mg/dl) were observed in untreated animals (group II) (605.25 ± 31.23, p≤0.05), whereas in treated animals (group III), were noted a decrease in these levels (464.77 ± 39.66, p≤0.05). Tissue restructure, characterized by cell volume recovery, also was observed in group III (nuclear volume of parotid glands: (109.91 ± 02.03, p≤0.05) and submandibular glands: (107.52 ± 02, p≤0.05) (cytoplasmic volume of parotid glands: (356.14 ± 26.34, p≤0.05) and submandibular glands: (331.22 ± 32.11, p≤0.05). Intense signaling (+++) of insulin receptors was observed in animals of group I. On the other hand, in group II was noted a reduction of these receptors (+). In treated animals (group III) were observed a recovery of the insulin receptors (+++). Conclusions: This treatment was effective in the recovery of salivary acinar cells, contributed also to homeostasis of body metabolism. Thus, this immunomodulation promoted a beneficial effect on the recovery of these tissues.

Predictive Models to Determine Clinically Relevant Deviations in Delivered Dose for Head and Neck Cancer

PurposeThis study aimed to improve the understanding of deviations between planned and accumulated doses and to establish metrics to predict clinically significant dosimetric deviations midway through treatment to evaluate the potential need to re-plan during fractionated radiation therapy (RT). Methods and materialsA total of 100 patients with head and neck cancer were retrospectively evaluated. Contours were mapped from the planning computed tomography (CT) scan to each fraction cone beam CT via deformable image registration. The dose was calculated on each cone beam CT and evaluated based on the mapped contours. The mean dose at each fraction was averaged to approximate the accumulated dose for structures with mean dose constraints, and the daily maximum dose was summed to approximate the accumulated dose for structures with maximum dose constraints. A threshold deviation value was calculated to predict for patients needing midtreatment re-planning. This predictive model was applied to 52 patients treated at a separate institution. ResultsDose was accumulated on 10 organs over 100 patients. To generate a threshold deviation that predicted the need to re-plan with 100% sensitivity, the submandibular glands required re-planning if the delivered dose was at least 3.5 Gy higher than planned by fraction 15. This model predicts the need to re-plan the submandibular glands with 98.7% specificity. In the independent evaluation cohort, this model predicts the need to re-plan the submandibular glands with 100% sensitivity and 98.0% specificity. The oral cavity, intermediate clinical target volume, left parotid, and inferior constrictor patient groups each had 1 patient who exceeded the threshold deviation by the end of RT. By fraction 15 of 30 to 35 total fractions, the left parotid gland, inferior constrictor, and intermediate clinical target volume had a dose deviation of 3.1 Gy, 5.9 Gy, and 4.8 Gy, respectively. When a deformable image registration failure was observed, the dose deviation exceeded the threshold for at least 1 organ, demonstrating that an automated deformable image registration–based dose assessment process could be developed with user evaluation for cases that result in dose deviations. ConclusionsA midtreatment threshold deviation was determined to predict the need to replan for the submandibular glands by fraction 15 of 30 to 35 total fractions of RT.

A prospective study of weekly intensity modulated radiation therapy plan adaptation for head and neck cancer: improved target coverage and organ at risk sparing.

This prospective study of weekly CT scanning and plan adaption during H&N IMRT reports on the frequency of plan adaptations based on dosimetric differences between original and re-optimised IMRT plans. The volumetric and geometric change occurring in target volumes and salivary glands is also described. Ten H&N cancer patients underwent weekly planning CT imaging and re-optimisation of the IMRT plan if PTV or OAR coverage was unacceptable. Comparisons of PTV and parotid gland dosimetry between the original and adaptive plans were made. Parotid and submandibular gland volume changes and shift were calculated. Eight of ten patients required one or more plan adaptations, with 41% of adaptations occurring by fraction ten. Salivary glands reduced in volume, with a medial shift of the lateral border of the parotid gland and a superior shift of the submandibular gland. Change in PTV coverage did not correlate with weight loss or nutritional score. Inadequate PTV coverage, requiring plan adaptation, occurs early in the course of IMRT. A weekly Adaptive RT (ART) protocol results in significant improvement of PTV coverage. Implementation of a clinical ART protocol should include imaging and dose calculation within the first ten fractions.

Utilization of 18FDG-PET-Based IMRT Planning to Spare the Most Metabolically Active Subvolume of Parotid Glands During Definitive Radiation Therapy for Head and Neck Cancer

To evaluate 18FDG-PET-based IMRT planning to reduce radiation dose to the most metabolically active regions of the parotid glands during radiation therapy for head and neck squamous cell carcinoma (HNSCC) with the goal of reducing xerostomia. A total of 20 patients with HNSCC (19 oropharynx; 1 nasopharynx) underwent 18FDG-PET and contrast-enhanced CT simulation for definitive radiation treatment planning. The original IMRT treatment plan used clinically was generated based on the pretreatment CT with volumetric-based dose constraints for each parotid gland. Prescription was 44 or 50 Gy (low risk PTV) and 70 Gy (high risk PTV) at 2 Gy/fraction. Patients were retrospectively replanned with added metabolically-based constraints for each parotid gland. SUV thresholding was performed in Eclipse to generate a contour encompassing the top one-third most metabolically active region of each parotid gland (SUV-High). SUV-High contours were transferred to the registered CT for the replanning. The original IMRT plans were re-optimized to reduce dose to SUV-High within each parotid while maintaining target coverage and meeting initial dose constraints for all other organs at risk. Median doses (Dmedian) to SUV-High and the entire gland for each parotid were calculated for the original and revised plans. Wilcoxon matched-pairs signed rank test (2-tailed, p<0.05) was performed to compare Dmedian in the initial vs. metabolically-based plan for each structure. SUV-High represented a median of 44% (IQR 38.9 – 52.4%) and 40.7% (IQR 21.7 – 54.8%) of the left and right parotid gland volumes, respectively. Median dose differed significantly between the metabolically-based (replan) and clinical (original) IMRT plans for the entire gland and SUV-High for each parotid (p < 0.0001). The table shows Dmedian from each plan, as well as relative percent change in Dmedian for the metabolically based plan relative to the original plan for each structure.Abstract 207; TableSUV-High, Left ParotidWhole Gland, Left ParotidSUV-High, Right ParotidWhole Gland, Right ParotidOriginal Median Dmedian (IQR), Gy14.3 (11.6, 25.8)16.3 (13.8, 22.3)18.3 (10, 27.6)18.8 (14.8, 22.7)Replan Median Dmedian (IQR), Gy13.7 (10.7, 21.5)15 (13.2, 20.1)15.5 (9.3, 24.4)16.8 (13.9, 19.6)Median % Change (IQR)-8.1% (-12.8, -3.9%)-4.6% (-10.2, 0.1%)-13.7% (-18, -7.1%)-6% (-11.8, -0.2) Open table in a new tab We have demonstrated that it is feasible to utilize 18FDG-PET information in IMRT planning to significantly reduce radiation dose to the most metabolically active sub-volume and whole gland for both parotids. Prospective evaluation is necessary to determine whether this approach can reduce late treatment-related xerostomia for head and neck cancer patients.

Early Changes in Serial CBCT-Measured Parotid Gland Biomarkers Predict Chronic Xerostomia After Head and Neck Radiation Therapy

To determine whether serial cone beam computed tomography (CBCT) images taken during head and neck radiation therapy (HNR) can improve chronic xerostomia prediction. In a retrospective analysis, parotid glands (PGs) were delineated on daily kV CBCT images using deformable image registration for 119 HNR patients (60 or 70Gy in 2Gy fractions over 6 or 7weeks). 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 1year 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. All 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). The 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.

Pattern of geometric changes of parotid gland in conventional and intensity-modulated radiotherapy in nasopharyngeal cancer patients

AbstractIntroductionThis study compared the pattern of radiation induced parotid changes between conventional (ConRT) and intensity modulated radiotherapy (IMRT) in nasopharyngeal carcinoma patients.Methods56 adult NPC patients treated with IMRT (n=28) and conventional radiotherapy (n=28) were recruited. CT scans were acquired before radiotherapy, at 10th, 20th and 30th fractions, and 3 months after treatment. Parotid gland was delineated in the corresponding CT slices and its mean dose was calculated. The volumetric and geometric changes of the parotid gland at various time intervals were compared against the pre-treatment structure set. The pattern of changes was compared between the two techniques.ResultsThe mean parotid dose of IMRT (37.5±9.5 Gy) was significantly lower than ConRT (49.1±7.4 Gy). The parotid gland volume, DICE similarity coefficient and lateral dimension of patient head gradually decreased during the radiotherapy course and partially recovered in 3 months post-treatment. The differences between two groups were not significant until at 3 month after treatment, where IMRT showed significantly better volume recovery.ConclusionSimilar parotid gland size and location changes were observed during the treatment course in both ConRT and IMRT. However IMRT demonstrated better parotid volume recovery after treatment.

Early Prediction of Acute Xerostomia During Radiation Therapy for Head and Neck Cancer Based on Texture Analysis of Daily CT

To investigate radiation-induced changes of computed tomography (CT)textures in parotid glands (PG) to predict acute xerostomia during radiotherapy (RT) for head and neck cancer (HNC). Daily or fraction kilovoltage CTs acquired using diagnostic CT scanners (eg, in-room CTs) during intensity-modulated RT for 59 HNC patients at 3 institutions were analyzed. The PG contours were generated on selected daily/fraction CTs. A series of histogram-based texture features, including the mean CT number (MCTN) in Hounsfield units, volume, standard deviation, skewness, kurtosis, and entropy for PGs were calculated for each fraction. Correlations between the changes of the texture features, radiation dose, and observed acute xerostomia were analyzed. A classifier model and the incurred CT-based xerostomia score (CTXS) were introduced to predict xerostomia based on combined changes of MCTN and volume of PGs. The t test and Spearman and Pearson correlation tests were used in the analyses. Substantial changes in various CT texture features of PGs were observed during RT delivery. The changes of PG MCTN or volume are not strongly correlated with the observed xerostomia grades if they are considered separately. The CTXS showed a significant correlation to the observed xerostomia grades (r=0.71, P<.00001). The CTXS-based classifier can predict the xerostomia severity with a success rate ranging from 79% to 98%. The xerostomia severity at the end of treatment can be predicted based on the CTXS determined at the fifth week with a precision and sensitivity of 100%. Significant changes in the CT histogram features of the parotid glands were observed during RT of HNC. A practical method of using the changes of MCTN and volume of PGs is proposed to predict radiation-induced acute xerostomia, which may be used to help design adaptive treatment.

Xerostomia, salivary characteristics and gland volumes following intensity‐modulated radiotherapy for nasopharyngeal carcinoma: a two‐year follow up

To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients. Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months and 2 years post-radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed. Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2 years post-radiotherapy were 84% and 51% of pre-radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post-radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre-radiotherapy levels. Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation-related oral diseases.