Contralateral Parotid Gland Research Articles

Anatomical and dosimetric variations during volumetric modulated arc therapy in patients with locally advanced nasopharyngeal carcinoma after induction therapy: Implications for adaptive radiation therapy

PurposeTo investigate anatomical and dosimetric changes during volumetric modulated arc therapy (VMAT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) after induction therapy (IT) and explore characteristics of patients with notable variations. Materials and methodsFrom July 2021 to June 2023, 60 LA-NPC patients undergoing VMAT after IT were retrospectively recruited. Adaptive computed tomography (aCT), reconstructed from weekly cone-beam computed tomography(CBCT), facilitates recontouring and planning transplantation. Volume, dice similarity coefficients, and dose to target volumes and organs at risk(OARs) on planning CT(pCT) and aCT were compared to identify changing patterns. Multivariate logistic regression was used to investigate risk factors. ResultsThe volumes of PGTVnasopharynx (PGTVp), PGTVnode (PGTVn), ipsilateral and contralateral parotid glands decreased during VMAT, with reductions of 2.25 %, 6.98 %, 20.09 % and 18.00 %, respectively, at 30 fractions from baseline (P < 0.001). After 25 fractions, D99 and D95 of PGTVn decreased by 7.94 % and 4.18 % from baseline, respectively, while the Dmean of ipsilateral and contralateral parotid glands increased by 7.80 % and 6.50 %, marking the peak rates of dosimetric variations (P < 0.001). The dosimetric fluctuations in PGTVp, the brainstem, and the spinal cord remained within acceptable limits. Furthermore, an initial BMI ≥ 23.5 kg/m2 and not-achieving objective response (OR) after IT were regarded as risk factors for a remarkable PGTVn dose reduction in the later stages of VMAT. ConclusionsReplanning for post-IT LA-NPC patients appears reasonable at 25F during VMAT. Patients with an initial BMI ≥ 23.5 kg/m2 and not-achieving OR after IT should be considered for adaptive radiation therapy to stabilize the delivered dose.

Effect of dose to parotid ducts on Sticky Saliva and Xerostomia in radiotherapy of head and neck squamous cell carcinoma

BackgroundRadiotherapy (RT) in head and neck squamous cell cancer (HNSCC) often leads to sticky saliva and xerostomia (SSX). Dose sparing of salivary glands (SG) reduces occurrence of SSX but few studies investigated the relationship between RT dose to SG substructures and SSX. We therefore investigated this hypothesis, focusing on the parotid duct (PD).MethodsRetrospective data was collected from 99 HNSCC patients treated at our center with (chemo-)radiotherapy (CRT). PD and other organs-at-risk (OAR) were (re-)contoured and DVHs were generated without re-planning. SSX was graded according to CTCAE v.4.03 and evaluated at acute, subacute, and two late timepoints.ResultsMost patients presented with loco-regionally advanced disease. In 47% of patients, up-front neck dissection preceded CRT. Weighted mean dose was 28.6 Gy for bilateral parotid glands (PG), and 32.0 Gy for PD. Acute SSX presented as grades 0 (35.3%), I (41.4%), II (21.2%) and III (2.0%). There was no association of OARs and SSX ≥ grade 2 in univariable logistic regression (LR). Multivariable LR showed statistically significant relationship of acute SSX with: PG weighted mean dose (OR 0.84, p = 0.004), contralateral PG mean dose (OR 1.14, p = 0.02) and contralateral PD planning OAR (PD PRV) mean dose (OR 1.84, p = 0.03).ConclusionsThere was an association of acute SSX with dose exposure of PD PRV in multivariable regression, only. Due to statistical uncertainties and the retrospective nature of this analysis, further studies are required to confirm or reject the hypothesis.

Multicriteria optimization of radiation therapy: Towards empowerment and standardization of reverse planning for head and neck squamous cell carcinoma

PurposeThe purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers. Material and methodsWe performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method. ResultsMedian age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was −2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was −4.6Gy (P<0.001). ConclusionMulticriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.

Dosimetric and NTCP analyses for selecting parotid gland cancer patients for proton therapy.

To perform a dosimetric and a normal tissue complication probability (NTCP) comparison between intensity modulated proton therapy and photon volumetric modulated arc therapy in a cohort of patients with parotid gland cancers in a post-operative or radical setting. From May 2011 to September 2021, 37 parotid gland cancers patients treated at two institutions were eligible. Inclusion criteria were as follows: patients aged ⩾ 18 years, diagnosis of parotid gland cancers candidate for postoperative radiotherapy or definitive radiotherapy, presence of written informed consent for the use of anonymous data for research purposes. Organs at risk (OARs) were retrospectively contoured. Target coverage goal was defined as D95 > 98%. Six NTCP models were selected. NTCP profiles were calculated for each patient using an internally-developed Python script in RayStation TPS. Average differences in NTCP between photon and proton plans were tested for significance with a two-sided Wilcoxon signed-rank test. Seventy-four plans were generated. A lower Dmean to the majority of organs at risk (inner ear, cochlea, oral cavity, pharyngeal constrictor muscles, contralateral parotid and submandibular gland) was obtained with intensity modulated proton therapy vs volumetric modulated arc therapy with statistical significance (p < .05). Ten (27%) patients had a difference in NTCP (photon vs proton plans) greater than 10% for hearing loss and tinnitus: among them, seven qualified for both endpoints, two patients for hearing loss only, and one for tinnitus. In the current study, nearly one-third of patients resulted eligible for proton therapy and they were the most likely to benefit in terms of prevention of hearing loss and tinnitus.

An Observational Dosimetric Study in Definitively Treated Primary Head and Neck Cancers: To Assess the Effect of Weight Loss and Change in Lateral Neck Dimensions on the Difference Between Dose Planned and Received by the Parotid(s) and Correlation with Adaptive Radiation Therapy

The head and neck cancer (HNC) literature is rife with reports of differences in planned versus actual radiation doses to the parotid gland (PG) due to changes in anatomy during the course of radiation therapy. We prospectively studied and quantified changes in planned and delivered doses due to weight loss and changes in lateral neck dimensions. Sixty patients were enrolled in this prospective non-randomized observational study. The inclusion criterion was having a newly diagnosed, histologically proven squamous cell carcinoma of HNC. Weight loss (WL) and change in lateral neck dimensions (LND) were assessed weekly, and new hybrid plans were generated using interval replanning CT scans. Dose variations were monitored and extrapolated for replanning CT scans and correlated with WL and change in LND. The Pearson correlation coefficients for WL and difference in Dmean of ipsilateral and contralateral PG was 0.3292 (P = .0124) and 0.4232 (P = .0010), respectively. There was significantly higher change in the Dmean of bilateral PG (Ipsilateral(I) > contralateral(C)) in patients who experienced WL of >5%. Change in LND correlated with difference in Dmean of ipsilateral PG at 0.4829 (P = .0001) and difference in D50 at 0.4146 (P < .0013). Contralateral PG correlated with difference in Dmean at 0.5952 (P < .0001). The difference in Dmean for ipsilateral PG was 1.8535 Gy for those showing reduction in LND of >1 cm compared with 0.8596 Gy (P = .0091) for those who had ≤1 cm reduction in LND. Either WL of >5% or reduction in LND of >1 cm can be used as an external parameter to help select patients who might benefit most from replanning and adaptive radiation therapy.

Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

Predicting the need for a replan in oropharyngeal cancer: A radiomic, clinical, and dosimetric model.

Patients with oropharyngeal cancer (OPC) treated with chemoradiation can experience weight loss and tumor shrinkage, altering the prescribed treatment. Treatment replanning ensures patients do not receive excessive doses to normal tissue. However, it is a time- and resource-intensive process, as it takes 1 to 2 weeks to acquire a new treatment plan, and during this time, overtreatment of normal tissues could lead to increased toxicities. Currently, there are limited prognostic factors to determine which patients will require a replan. There remains an unmet need for predictive models to assist in identifying patients who could benefit from the knowledge of a replan prior to treatment. We aimed to develop and evaluate a CT-based radiomic model, integrating clinical and dosimetric information, to predict the need for a replan prior to treatment. A dataset of patients (n=315) with OPC treated with chemoradiation was used for this study. The dataset was split into independent training (n=220) and testing (n=95) datasets. Tumor volumes and organs at risk (OARs) were contoured on planning CT images. PyRadiomics was used to compute radiomic image features (n=1218) on the original and filtered images from each of the primary tumor, nodal volumes, and ipsilateral and contralateral parotid glands. Nine clinical features and nine dose features extracted from the OARs were collected and those significantly (p<0.05) associated with the need for a replan in the training dataset were used in a baseline model. Random forest feature selection was applied to select the optimal radiomic features to predict replanning. Logistic regression, Naïve Bayes, support vector machine, and random forest classifiers were built using the non-correlated selected radiomic, clinical, and dose features on the training dataset and performance was assessed in the testing dataset. The area under the curve (AUC) was used to assess the prognostic value. A total of 78 patients (25%) required a replan. Smoking status, nodal stage, base of tongue subsite, and larynx mean dose were found to be significantly associated with the need for a replan in the training dataset and incorporated into the baseline model, as well as into the combined models. Five predictive radiomic features were selected (one nodal volume, one primary tumor, two ipsilateral and one contralateral parotid gland). The baseline model comprised of clinical and dose features alone achieved an AUC of 0.66 [95% CI: 0.51-0.79] in the testing dataset. The random forest classifier was the top-performing radiomics model and achieved an AUC of 0.82 [0.75-0.89] in the training dataset and an AUC of 0.78 [0.68-0.87] in the testing dataset, which significantly outperformed the baseline model (p=0.023, testing dataset). This is the first study to use radiomics from the primary tumor, nodal volumes, and parotid glands for the prediction of replanning for patients with OPC. Radiomic features augmented clinical and dose features for predicting the need for a replan in our testing dataset. Once validated, this model has the potential to assist physicians in identifying patients that may benefit from a replan, allowing for better resource allocation and reduced toxicities.

Dosimetric comparison of postoperative interstitial high-dose-rate brachytherapy and modern external beam radiotherapy modalities in tongue and floor of the mouth tumours in terms of doses to critical organs.

The aim of the study was to dosimetrically compare interstitial high-dose-rate (HDR) brachytherapy (BT) and modern external beam radiotherapy modalities, as volumetric modulated arc therapy (VMAT) and stereotactic radiotherapy with Cyberknife (CK) of tumours of the tongue and floor of the mouth in terms of dose to the critical organs. In National Institute of Oncology, Budapest, between March 2013 and August 2022 twenty patients (11 male/9 female) with stage T1-3N0M0 tongue (n = 14) and floor of mouth (n = 6) tumours received postoperative radiotherapy because of close/positive surgical margin and/or lymphovascular and/or perineural invasion. High-dose-rate interstitial brachytherapy applying flexible plastic catheters with a total dose of 15 × 3 Gy was used for treatment. In addition to BT plans VMAT and stereotactic CK plans were also made in all cases, using the same fractionation scheme and dose prescription. As for the organs at risk, the doses to the mandible, the ipsilateral and the contralateral salivary glands were compared. The mean volume of the planning target volume (PTV) was 12.5 cm3, 26.5 cm3 and 17.5 cm3 in BT, VMAT and CK techniques, respectively, due to different safety margin protocols. The dose to the mandible was the most favourable with BT, as for the salivary glands (parotid and submandibular) the CK technique resulted in the lowest dose. The highest dose to the critical organs was observed with the VMAT technique. The mean values of D2cm3 and D0.1cm3 for the critical organs were as follows for BT, VMAT and CK plans: 47.4% and 73.9%, 92.2% and 101.8%, 68.4% and 92.3% for the mandible, 4.8% and 6.7%, 7.3% and 13.8%, 2.3% and 5.1% for the ipsilateral parotid gland, 3.5% and 4.9%, 6.8% and 10.9%, 1.5% and 3.3% for the contralateral parotid gland, 7.3% and 9.4%, 9.0% and 14.3%, 3.6% and 5.6% for the contralateral submandibular gland. The present results confirm that BT, despite being an invasive technique, is dosimetrically clearly beneficial in the treatment of oral cavity tumours and is a modality worth considering when applying radiotherapy, not only as definitive treatment, but also postoperatively. The use of the CK in the head and neck region requires further investigation.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT

PurposeThis study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6–24 months after radiotherapy for oropharynx cancer. MethodsThe treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. ResultsXerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58–0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. ConclusionsBased on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2–3 the risk for radiation induced xerostomia that is observed at 6–24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6–24 months post-RT by 2.0–2.3 times.

Comparison of Dynamic Trajectory Radiotherapy and Volumetric Modulated Arc Therapy for Loco-Regionally Advanced Oropharyngeal Cancer

Dynamic trajectory radiotherapy (DTRT) extends volumetric modulated arc therapy (VMAT) with dynamic table and collimator rotation. We investigate the potential benefit of DTRT over VMAT with respect to organ-at-risk (OAR) sparing for patients with loco-regionally advanced oropharyngeal cancer (OPC). We created DTRT and VMAT plans for 46 cases with prescribed doses of 50-70 Gy (2 Gy fractions, sequential boost) using 6 MV flattened beam on c-arm Linacs. For DTRT: case-specific collision avoidance maps were created and gantry-table paths were determined based on contoured structures to minimize fractional target/OAR overlap in beam's eye view. Gantry-collimator paths minimized field width in the leaf-travel direction. DTRT paths were imported in a research version of a commercial treatment planning system for intensity modulation optimization using the same optimizer and dose calculation algorithms as for VMAT. Plans at each dose level were normalized with 100% of the prescribed dose to 95% of the planning target volume (PTV). PTV coverage and OAR sparing for DTRT and VMAT were compared using Wilcoxon matched-pair signed rank test (5% significance level). The correlation between the fractional OAR/PTV50Gy volume overlap and difference in OAR Dmean between the two techniques was evaluated using Spearman's correlation coefficient. Plans at each dose level were all acceptable and had D0.03cc<110% prescription dose (difference between DTRT and VMAT were not statistically significant). In the combined plans, PTV50Gy D95% and D98% and PTV70Gy D95% were significantly higher with DTRT compared to VMAT. Differences in PTV66Gy coverage and PTV70Gy D5% were not statistically significant. Mean Dmean to the contralateral (CL) parotid gland was 13.99 / 15.28 Gy for DTRT / VMAT respectively, it was 25.75 / 28.05 Gy for the CL submandibular gland, 44.88 / 45.82 Gy for the pharynx and 30.90 / 33.93 Gy for the oral cavity (all with p<.001). Mean Dmean to the ipsilateral (IL) parotid gland was 29.00 / 29.28 Gy for DTRT / VMAT respectively (p = .77) and 57.71 / 57.91 Gy for the IL submandibular gland (p = .99). Significantly higher doses were observed with DTRT than with VMAT for the optical and auditory OARs and for the brain, but well below the clinical goals. The difference in Dmean (VMAT-DTRT) was negatively correlated to the fractional OAR/PTV50Gy overlap for the CL parotid and submandibular gland and the IL submandibular gland (r = -0.55 to -0.51, p<.001) but not for IL parotid gland (r = -0.17, p = .26), oral cavity (r = -0.13, p = .41) or pharynx (r = -011, p = .47). For at least the same target coverage, DTRT statistically significantly improves sparing for OARs related to salivary and swallowing functions compared to state-of-the-art VMAT. The advantage of DTRT decreases with increasing fractional OAR/PTV50Gy volume overlap for some salivary glands but not for pharynx or oral cavity. DTRT is promising to reduce treatment-related toxicity for patients with OPC.

Online Adaptive Radiotherapy for Pharyngeal Cancer: Dose-Volume Histogram Analysis between Adapted and Scheduled Plan

The present study aimed to evaluate whether online adapted plan with artificial intelligence (AI) driven work flow could be used in clinical settings with variable changes of the targets and organs at risk (OARs) for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy at our institution between January and July 2020 were included for the analysis. All patients had been previously aligned daily with cone-beam computed tomography (CBCT) and treated by O-ring Linac. A simulated treatment was performed on the treatment emulator. Weekly fractions, once in every 4-5 fractions, were simulated in the treatment emulator for each patient using their previous on-treatment CBCTs. The dataset was divided into three groups according to the treatment period (1st-2nd week, 20 CBCTs), middle (3rd-4th week, 20 CBCTs), and late (5th-7th week, 30 CBCTs) period. In the present study, all of reference plan generation in treatment emulator were created on the initial plans of two-step method using 12 equidistant field IMRT. The prescribed dose was 70 Gy in 35 fractions and normalized to the dose of 68.6 Gy (98% dose) to 95% of the planning target volume (PTV). The adaptation process on treatment emulator includes auto-segmentation of daily anatomy, calculation of the dose in scheduled plans using the same monitor units and optimization and calculation of the dose in adapted plan. Dose-volume histogram (DVH) parameters between adapted and scheduled plans in terms of PTV (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brain stem (Dmax), ipsilateral and contralateral parotid glands (Dmedian and Dmean) were evaluated in each period. D98% of PTV of adapted plan was significantly higher than that of scheduled plan in early and middle period (p = 0.02 and <0.01, respectively). D95% of PTV of adapted plan was significantly higher than that of scheduled plan in all periods (p<0.01). D2% of PTV of adapted plan was significantly lower than that of scheduled plan in all periods (p = 0.04, 0.04 and 0.02 in each period, respectively). There was not significant difference in D50% of PTV between adapted and scheduled plan in all periods. In terms of OARs, Dmax of spinal cord of adapted plan was significantly lower than that of scheduled plan in all periods (p<0.01). Similarly, D1cc of spinal cord of adapted plan was lower than that of scheduled plan. Dmean of ipsilateral and contralateral parotid glands of adapted plan were lower than those of scheduled plan in the late period (p<0.01 and 0.03, respectively). The present study revealed that adapted plan with AI driven work flow could create dosimetrically better plans for pharyngeal cancer compared to scheduled plan. It was suggested that online adaptive radiotherapy could be necessary to maintain PTV coverage while reducing the dose to OARs in all periods for pharyngeal cancer.

Use of Explainable AI Algorithm Revealing Longitudinal Changes in Practice Patterns and Toxicity Models

Dosimetric constraints evolve as clinicians implement practice changes, requiring modeling approaches to be dynamic. We applied a semi-automated explainable artificial intelligence (eAI) algorithm and dashboard visualizations to model dysphagia and xerostomia for head and neck cancer patients. We coupled a large, comprehensive, "real-world" database to the eAI for discovery of features with the strongest combined statistical and machine learning based evidence and to identify clinically actionable thresholds. Cohort included 758 patients treated 2017-2021 for HN cancer with conventional fractionation. Features included age, sex, diagnosis, staging, chemotherapy, smoking and alcohol status, BMI, weight loss, re-simulation, DVH curves, PTV and OAR volumes. Patients were scored for toxicity within 2 yrs of RT for dysphagia grade ≥ 3 and xerostomia grade ≥ 2. Bootstrap resampling of thresholds, ROC-AUC, PR-ROC, SN, SP, F1 and diagnostic odds ratio was used to statistically profile strength of evidence for candidate features. XGBoost models with 10-fold cross validation were repeated (n = 20) to identify mean and CIs for statistical measures of predictions. DVH metrics included standard template values and those with highest statistical evidence and low cross correlation with other features. Backward feature selection was used to identify the most relevant feature subset, where the least informative feature is iteratively removed from the model. This workflow was repeated by year and overall. Annual incidence of dysphagia averaged 0.13 ± 0.02 overall years. Xerostomia incidence decreased from 0.32 to 0.12 (2017-2021). Box-whisker plots by year showed consistent reductions in standard practice toxicity linked DVH metric values. Median dose to superior constrictors (PCM), contralateral parotid and contralateral submandibular gland (SMG) declined from 2017 to 2021 by 48 to 33 Gy, 17 to 10 Gy, and 28 to 22 Gy respectively. Statistics of XGBoost models of dysphagia for all years were ROC-AUC = 0.72 ± 0.05. Strongest overall years predictors were Oral Cavity (OC) D50%[Gy] < 32, inferior PCM Max [Gy] < 60, contralateral SMG D10%[Gy] < 53 and use of Paclitaxel. Xerostomia models were less predictive with ROC-AUC = 0.65 ± 0.05. Strongest predictors over each year were ipsilateral parotid D30%[Gy] < 35, contralateral SMG D96%[Gy] < 18.4, and overall staging < II. Predictive features varied substantially by year for both, showing the most consistency for SMG doses. For example, OC D50%[Gy] < 27 and contralateral SMG D96%[Gy] < 18 dominated xerostomia model in 2017 but not in 2021 when practice norms shifted to lower doses. As OAR doses were systematically reduced, statistical and AI models evidence highlighted contralateral SMG dose as important to both dysphagia and xerostomia for clinical practice change. The "real-world" database + eAI + visualization dashboards provided a method for continuous learning as clinical practice changes.

Voxel Based Analysis of Local Dose Patterns on Radiation Induced Xerostomia in Head and Neck Cancer with Machine Learning Methods

Despite the technological advancements, xerostomia caused by the irradiation of parotid and/or submandibular glands significantly impacts a patient's quality of life and remains a clinical challenge. The mean dose within the salivary glands that neglects the local dose effect is an oversimplified predictor thus its efficacy is severely limited. This study aims to uncover the local dose patterns associated with the xerostomia by performing a voxel-based analysis of the spatial parotid dose. A cohort of 143 patients who underwent intensity modulated radiation therapy treatment were retrospectively selected for this study. A binary classification was adopted for predictive modeling: group 1 (102 patients) if grade 0 or 1 and group 2 (41 patients) if grade 2 or 3. The anatomy of the parotid gland from the computed tomography (CT) of these patients were standardized to that of a reference patient with rigid and multistage B-spline deformable registration. The resultant deformation field vectors were subsequently utilized to warp the parotid doses and dose gradients to the reference ones. To facilitate pattern recognition, the bilateral parotid doses and dose gradients were further regrouped into contra- and ipsi-lateral depending on their proximity to the tumor targets. Four supervised machine learning (ML) models including ReliefF, L1 regularized logistic regression (L1LR), ridge regression (RR), and random forest (RF) were employed to determine the feature importance of each voxel and discover the dose patterns within the glands that are correlated with xerostomia. The predictive performance of each model was evaluated with the area under the curves (AUC) of the receiver operating characteristic. The image registration accuracy of an average of 95.6% for the parotid gland standardization on CT images was achieved. The four ML models were assessed with 10-fold cross validation showing comparable performance and the AUC scores were 0.74 ± 0.09, 0.75 ± 0.08, 0.73 ± 0.10, and 0.77 ± 0.09 for ReliefF, L1LR, RR, and RF, respectively. The importance patterns showed that the doses to the superior and medial region of the contralateral parotid gland were more correlated with xerostomia from the ReliefF model but not others. Similar importance patterns were observed from the dose gradient distributions along the left-right and anterior-posterior directions. The voxel-based model, which takes into account the spatial information of dose and dose gradient within the parotid gland, demonstrated an improvement in xerostomia predictive modeling as compared to the mean dose predictor, particularly in the local dose effect on xerostomia. If these findings are validated with more patient data and independent studies, they could be incorporated into treatment planning of head and neck patients to reduce the toxicity occurrence.

Predicting late radiation-induced xerostomia in nasopharyngeal carcinoma based on radiomics features extracted from T2WI images of parotids

ObjectiveTo explore the value of radiomics features extracted from the T2-weighted imaging (T2WI) images of parotids in predicting late radiation-induced xerostomia in nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). MethodsA retrospective analysis was conducted for 123 NPC patients who received RT at the Affiliated Tumour Hospital of Xinjiang Medical University from January 2019 to March 2021. All the patients underwent MRI pre-RT and post-RT. They were randomly divided into a training set and a testing set at a ratio of 4:1 using a random number table, with the former and the latter comprising 98 and 25 cases, respectively. The ipsilateral parotid gland (iPG) and the contralateral parotid gland (cPG) were delineated on T2WI images pre-RT and post-RT as regions of interest (ROIs). A total of 851 radiomics features were extracted from each ROI. Spearman analysis was used to remove redundant features, and the recursive feature elimination (RFE) method was then used to determine useful features. Using radiomics features extracted from images pre-treatment, images post-treatment, and differences between images pre- and post-treatment, this study constructed three radiomic models, namely the pre-treatment radiomics model (preRT), the post-treatment radiomics model (postRT), and the delta-radiomics model (DeltaRT). Then, this study plotted the receiver operating characteristic (ROC) curves based on the late radiation-induced xerostomia grades of patients post-RT. Furthermore, the models’ effectiveness and performance in predicting late radiation-induced xerostomia and advanced radioactive xerostomia was evaluated. In addition, the area under the curve (AUC), sensitivity, specificity, accuracy, precision, and negative predictive value (NPV) were calculated. ResultsAmong the features extracted from bilateral parotid glands (PGs), 20 were determined pre-RT (six from iPG and 14 from cPG), 19 were determined post-RT (six from iPG and 13 from cPG), and 20 were derived from the DeltaRT (20 from cPG). The PGs pre-RT and post-RT in the training set had AUCs of 0.902 (95% CI: 0.895–0.909) and 0.761 (95% CI: 0.744–0.778), respectively, while those in the testing set had AUCs of 0.740 (95% CI: 0.504–0.983) and 0.701 (95% CI: 0.478–0.924), respectively. In contrast, the AUC of the cPG derived from the DeltaRT was 0.867 (95% CI: 0.856–0.878) in the training set and 0.851 (95% CI: 0.697–0.999) in the testing set. ConclusionsThere are significant correlations between radiomics features extracted from MRI T2WI images of parotids and late radiation-induced xerostomia in NPC patients. Among the radiomics features, the changes in cPG features pre-RT and post-RT have higher accuracy in predicting late radiation-induced xerostomia.

Mid-treatment 18F-FDG PET imaging changes in parotid gland correlates to radiation-induced xerostomia

BackgroundThe aim of this study was to measure functional changes in parotid glands using mid-treatment FDG-PET/CT and correlate early imaging changes to subsequent xerostomia in mucosal head and neck squamous cell carcinoma patients undergoing radiotherapy. Materials and Methods56 patients from two prospective imaging biomarker studies underwent FDG-PET/CT at baseline and during radiotherapy (week 3). Both parotid glands were volumetrically delineated at each time point. PET parameter SUVmedian were calculated for ipsilateral and contralateral parotid glands.Absolute and relative change (Δ) in SUVmedian were correlated to moderate-severe xerostomia (CTCAE grade ≥ 2) at 6 months. Four predictive models were subsequently created using multivariate logistic regression using clinical and radiotherapy planning parameters. Model performance was calculated using ROC analysis and compared using Akaike information criterion (AIC) Results29 patients (51.8%) developed grade ≥ 2 xerostomia. Compared to baseline, there was an increase in SUVmedian at week 3 in ipsilateral (8.4%) and contralateral (5.5%) parotid glands. Increase in ipsilateral parotid Δ SUVmedian (p = 0.04) and contralateral mean parotid dose (p = 0.04) were correlated to xerostomia.The reference ‘clinical’ model correlated to xerostomia (AUC 0.667, AIC 70.9). Addition of ipsilateral parotid Δ SUVmedian to the clinical model resulted in the highest correlation to xerostomia (AUC 0.777, AIC 65.4). ConclusionOur study shows functional changes occurring in the parotid gland early during radiotherapy. We demonstrate that integration of baseline and mid-treatment FDG-PET/CT changes in the parotid gland with clinical factors has the potential to improve xerostomia risk prediction which could be utilised for personalised head and neck radiotherapy.

Prediction of Radiation-Induced Parotid Gland-Related Xerostomia in Patients With Head and Neck Cancer: Regeneration-Weighted Dose

Despite improvements to treatment, patients with head and neck cancer (HNC) still experience radiation-induced xerostomia due to salivary gland damage. The stem cells of the parotid gland (PG), concentrated in the gland's main ducts (stem cell rich [SCR] region), play a critical role in the PG's response to radiation. Treatment optimization requires a dose metric that properly accounts for the relative contributions of dose to this SCR region and the PG's remainder (non-SCR region) to the risk of xerostomia in normal tissue complication probability (NTCP) models for xerostomia. Treatment and toxicity data of 1013 prospectively followed patients with HNC treated with definitive radiation therapy (RT) were used. The regeneration-weighted dose, enabling accounting for the hypothesized different effects of dose to the SCR and non-SCR region on the risk of xerostomia, was defined as Dreg PG=Dmean SCR region+r × Dmean non-SCR region, where Dreg is the regeneration-weighted dose, Dmean is the mean dose, and r is the weighting factor. Considering the different volumes of these regions, r > 3.6 in Dreg PG demonstrates an enhanced effect of the SCR region. The most predictive value of r was estimated in 102 patients of a previously published trial testing stem cell sparing RT. For each endpoint, Dreg PG, dose to other organs, and clinical factors were used to develop NTCP models using multivariable logistic regression analysis in 663 patients. The models were validated in 350 patients. Dose to the contralateral PG was associated with daytime, eating-related, and physician-rated grade ≥2 xerostomia. Consequently, r was estimated and found to be smaller than 3.6 for most PG function-related endpoints. Therefore, the contribution of Dmean SCR region to the risk of xerostomia was larger than predicted by Dmean PG. Other frequently selected predictors were pretreatment xerostomia and Dmean oral cavity. The validation showed good discrimination and calibration. Tools for clinical implementation of stem cell sparing RT were developed: regeneration-weighted dose to the parotid gland that accounted for regional differences in radiosensitivity within the gland and NTCP models that included this new dose metric and other prognostic factors.

Validation of the 18F-FDG PET image biomarker model predicting late xerostomia after head and neck cancer radiotherapy

Background and purposePreviously, PET image biomarkers (PET-IBMs) – the 90th percentile standardized uptake value (P90-SUV) and the Mean SUV (Mean-SUV) of the contralateral parotid gland (cPG) – were identified as predictors for late-xerostomia following head and neck cancer (HNC) radiotherapy. The aim of the current study was to assess in an independent validation cohort whether these pre-treatment PET-IBM can improve late-xerostomia prediction compared to the prediction with baseline xerostomia and mean cPG dose alone. Materials and methodsThe prediction endpoint was patient-rated moderate-to-severe xerostomia at 12 months after radiotherapy. The PET-IBMs were extracted from pre-treatment 18 F-FDG PET images. The performance of the model (base model) with baseline xerostomia and mean cPG dose alone and models with additionally P90-SUV or Mean-SUV were tested in the current independent validation cohort. Specifically, model discrimination (area under the curve: AUC) and calibration (calibration plot) were evaluated. ResultsThe current validation cohort consisted of 137 patients of which 40% developed moderate-to-severe xerostomia at 12 months. Both the PET-P90 model (AUC:PET-P90 = 0.71) and the PET-Mean model (AUC: PET-Mean = 0.70) performed well in the current validation cohort. Moreover, their performance were improved compared to the base model (AUC:base model= 0.68). The calibration plots showed a good fit of the prediction to the actual rates for all tested models. ConclusionPET-IBMs showed an improved prediction of late-xerostomia when added to the base model in this validation cohort. This contributed to the published hypothesis that PET-IBMs include individualized information and can serve as a pre-treatment risk factor for late-xerostomia.

Metastatic retinoblastoma at presentation: Clinical presentation, treatment, and outcomes.

The aim of this study was to retrospectively determine clinical features, treatment outcomes, and overall survival in four patients with metastatic retinoblastoma at presentation. The mean age at diagnosis was 63 months (range: 24-108 months). Three patients had overt orbital disease of at least one eye and one patient had microscopic orbital disease with scleral infiltration on histopathology. Metastatic sites included regional lymph nodes (RLN) (n = 4), bone marrow (BM) (n = 2), and cerebrospinal fluid (CSF) (n = 1). The most common sites of RLN were ipsilateral preauricular nodes (two patients) and contralateral parotid gland involvement (one patient). The treatment administered included primary enucleation (n = 1), high-dose intravenous chemotherapy (n = 4), secondary enucleation (n = 2), orbital external beam radiotherapy (n = 3), and intrathecal chemotherapy (n = 1). High-risk features included massive choroidal and microscopic scleral infiltration in the eye that underwent primary enucleation. At a mean follow-up of 33 months (range, 4-68 months), one patient with CSF involvement deceased in 4 months. The remaining three patients were alive and disease-free at the last mean follow-up period of 43 months (range, 18-68 months). The results of our study showed that RLN and BM metastasis respond well to treatment while CSF metastasis is associated with poor prognosis.

Secretory function of the contralateral parotid glands

Background.The study was a reaction to an article about the physiological asymmetry of the salivary glands in right-handed and left-handed people.&#x0D; Aim.To determine the impact of the side of the study on the function of the parotid glands as a possible factor that must be taken into account when evaluating the results of sialometry.&#x0D; Material and methods.In 22patients with xerostomia, controlled dynamic sialometry was performed in two stages. The second stage was a week after the first one. At the first stage, Lashley's capsule was on the right, the catheter was on the left, at the second stage, the catheter was on the right, the capsule was on the left. Sialometry was performed in the morning, 20minutes after taking 8 drops of a 1% aqueous solution of pilocarpine, for 20minutes. The results with the Lashley capsule outside the duct were considered control, the results with the catheter in the duct were controlled. This eliminated the technological measurement error. The significance of differences in sialometry parameters was assessed using statistical analysis with Student's t-test. The results were considered significant at p 0.05.&#x0D; Results.In the sample with use of the Lashley's capsule, higher sialometry values on the right were found in 7 out of 22cases (31.8%), on the left in 13 out of 22cases (59.1%) (p0.05). In the group with the use of a catheter, in 15 out of 22cases (68.2%) and in 5 out of 22cases (22.7%), respectively (t=3.4028; p0.001). In a single sample (capsules and catheter), in 22 out of 44cases (50.0%) and in 18 out of 44cases (40.9%), respectively (p0.05). The results of comparing the average values on the right, obtained in 22cases with a capsule (1.20.6 ml), with those on the left (1.30.7ml) showed no significant difference (t=0.5254). Differences in catheter sialometry (1.00.7ml on the right and 0.80.7ml on the left) were also not significant (p0.05).&#x0D; Conclusion.The secretory function of the contralateral parotid glands under comparable individual conditions is the same. Objectively determined functional symmetry simplifies the analysis of the salivary glands secretory function study results.

Point Shear Wave Elastography in Diagnosis and Follow-Up of Salivary Gland Affection after Head and Neck Cancer Treatment.

Therapies of head and neck squamous cell carcinoma (HNSCC), particularly irradiation and chemotherapy (C/RT), can affect salivary glands to some extent. Recent studies suggest that point shear wave elastography (pSWE) is well suited for the diagnosis and rating of homogenous damage to parenchymatous organs. The purpose of this study was to assess the value of this sonographic modality as a tool for the evaluation both of salivary gland affection after HNSCC therapy and the effect of a salivary replacement therapy based on liposomes. A total of 69 HNSCC patients were included in this study. All patients had finished cancer treatment and attended regular follow-up. pSWE values of ipsi- and contralateral parotid (PG) and submandibular glands (SMG) were obtained in a standardized manner and compared to those of a healthy control (HC) group. After a two months treatment with a liposomal saliva replacement therapy pSWE quantification was performed again. Ipsi- and contralateral salivary glands suffer under standard HNSCC tumor therapy. Here, the ipsilateral parotid gland (PG) is primarily affected. Therefore, a sequence of manifestation (surgery &lt; surgery plus adjuvant C/RT &lt; primary C/RT) is comprehensible, evaluated by pSWE measurements. The examination of all glands and statistical analysis of the values compared to controls resulted in an pSWE cutoff value for affected glandular tissue of &gt;2 m/s. Using a liposomal saliva replacement therapy, pSWE values of the ipsilateral PG can be improved, although the level of HC could not be restored.