Ipsilateral Parotid Research Articles

HN-SIB-BPI: A single click, sub-site specific, dosimetric scorecard tuned RapidPlan model created from a foundation model for treating head and neck with bilateral neck

To develop a Knowledge Based Planning (KBP) model for creating quantifiably high quality VMAT treatment plans in a single click for head and neck cases treated Simultaneous Integrated Boost (SIB) with bilateral parotid involvement (BPI) where both parotids are near, abutting or partially overlapping target volume. Eclipse RapidPlan and the publicly available PlanScorecard tool were used to assess existing Head and Neck RapidPlan models on two representative cases. The best performer was used as a foundation model to assist in creating new initial training set doses from previously treated cases. Those initial 27 cases were first replanned using only the selected foundation model, then further improved based on manual replanning, informed by dosimetric scorecard assessment. A new, initial model was trained from those 27 foundation model created cases that had been manually improved. Then, that initial model was used to replan those cases again, resulting in higher scores. Additional cases were also replanned using the initial model along with some manual changes to the optimization objectives to increase the score. This resulted in a total of 66 cases from which the final, released, HN-SIB-BPI was trained. A 27 case subset of the full training set was replanned and rescored at each phase of the process with a 260 total point 3-target scorecard. The average score increased: 210.5 foundation model; 226.96 manually improved plans; 230.1 initial model; 231.7 HN-SIB-BPI. On the same 27 case subset, mean ipsilateral and contralateral parotid dose decreased by 1.05Gy and 1.58Gy respectively from the foundation model to HN-SIB-BP. Eight external cases were created from HN-SIB-BPI with dosimetric scorecard validation on Halcyon (3-PTV:221.38/260; 2-PTV:196.1/228.5) and TrueBeam (3-PTV:222.01/260; 2-PTV:202.24/228.5). A specific clinical intent (ie: max parotid sparing) can be articulated in a comprehensive and precise manner by creating a dosimetric scorecard with individual metrics points assigned to each OAR and target metric reflecting their relative importance. This process improved the KBP model (HN-SIB-BPI) in several quantifiable ways including further sparing of parotid dose. All results and tools in this work are shared publicly.

Clinical features and prognosis of parotid metastasis of breast cancer: retrospective analysis of 57 cases.

Parotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate. A comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators. The primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy. Parotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.

Synchronous ipsilateral parotid tumors containing amylase crystalloids with cytologic and histologic correlation

Synchronous ipsilateral parotid tumors containing amylase crystalloids with cytologic and histologic correlation

Volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy for locally advanced oropharyngeal cancers.

This study aimed to evaluate the volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy (IGRT) for locally advanced oropharyngeal cancers. Twenty patients receiving radiotherapy using IGRT at a dose of 70 Gy/35 fractions/7 weeks for locally advanced oropharyngeal cancers were accrued. Radiotherapy planning computed tomography (CT) scans were performed at pre-radiotherapy (RT), 20, 40, and 60 Gy for each patient. Volume changes in target and parotids along with shifts of parotids were assessed with respect to pre-RT scan after co-registration. In study scans, GTVp and GTVn were recontoured as per particular CT. CTV and PTV were copied from planning CT to study CT. CTV was edited from anatomical barriers, and PTV was edited only from the skin in the study CT. The parotids were recontoured on each study scan. The center of mass (COM) of C2 vertebral body was considered as the reference to evaluate its shifts. There was a statistically significant percentage regression of ipsilateral and contralateral parotid mean volumes at the rate of 0.85%/0.207 cc and 0.98%/0.26 cc per day, respectively. We observed the mean medial shift of center of mass of ipsilateral parotid of 2.23 mm (p = 0.011) and contralateral parotid of 2.67 mm (p = 0.069) at the end of 60 Gy. GTVp (mean) reduced from 41.87 cc at 0 Gy to 31.13 cc (25.65%) at 60 Gy (p = 0.003), while GTVn (mean) reduced from 19.98 cc at 0 Gy to 10.79 cc (45.99%) at 60 Gy (p = 0.003). There was a statistically significant reduction in CTV and PTV volumes at 60 Gy. Statistically significant volumetric and geometric changes occurred during intensity-modulated radiation (IMRT), which were most prominent after 40 Gy and were maximum at 60 Gy. There was a medial shift of parotid glands toward the high-dose region. This study can be useful to devise an adaptive radiotherapy strategy.

Clinical Implementation of an Automated IMRT/VMAT Treatment Planning Tool

To create an in-house automated treatment planning tool for IMRT/VMAT treatments and evaluate the dosimetric plan quality against manually generated plans. A scripting application programming interface is employed to interact with a commercial treatment planning system (TPS) to implement automatic plan evaluation and update optimization parameters by mimicking the human planning process. The automated planning performs in an iterative fashion until reaching an acceptable tradeoff among target coverage/dose homogeneity and sparing of critical organs at risk. In each iteration, the dose constraints, priorities, and optimization structures for are automatically updated based on the results of the current iteration. Twenty previously treated plans (10 prostate and 10 head and neck), were preliminarily used to evaluate the performance of the automated planning tool. The differences in target and organ-at-risk metrics from the manually generated clinical plans were analyzed using paired t-test to evaluate clinical acceptability of tour automated planning tool. The current in-house-developed automated planning solution is able to create plans for different disease sites, including head & neck, prostate, pelvis, and lung. So far, the VMAT plans for more than 150 different cases have been generated with the tool. The results for these were also evaluated. Compared to the manually generated clinical head and neck plans, all auto plans achieved PTV D95% coverage and critical organs at risk sparing without statistically significant change in average global Dmax (107.4% for manual vs 107.3% for automated plans). The auto-planning solution provided reduced maximum doses to brainstem and spinal cord (average reductions with standard deviations of 5.1 ± 2.6 Gy and 2.9 ± 1.4 Gy, respectively, all p <0.03), reduced average mean doses to contralateral parotid, ipsilateral parotid, contralateral submandibular gland, pharynx, esophagus, cochleae (reductions of 2.2 ± 2.9 Gy, 4.8 ± 4.7 Gy, 3.6 ± 5.2 Gy, 2.0 ± 7.1 Gy, 3.9 ± 2.6 Gy, 3.8 ± 5.0 Gy, respectively, all p < 0.045). Similar results were observed for the prostate plans. With the same PTV coverage and without statistically significant change in average global Dmax (106.5% for manual vs 106.8% for automated plans), the automated solution provided superior sparing for both bladder and rectum. Bladder V75, V70, V65 were reduced by 0.6% ± 2.1%, 0.8% ± 2.5%, and 0.9% ± 2.9% (all p <0.04), respectively. Rectum V75, V70, V65, V60 were reduced by 1.0% ± 2.3%, 1.2% ± 2.8%, 1.3% ± 3.2%, 1.6% ± 3.6% (all p < 0.01), respectively. Our automated treatment planning solution is capable of efficiently generating VMAT plans for different disease sites with superior dosimetric indices compared to manually generated plans. Our tool is integrated within a commercial TPS platform, so it has the advantage of seamless adoption into the standard workflow to improve plan quality and treatment planning efficiency in our clinic.

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.

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.

Treatment replanning in head and neck cancer radiotherapy: an investigation based on clinical dosimetry

Radiotherapy is a medical specialty based on controlled use of ionizing radiation for therapeutic purposes. Patients submitted to external beam radiation therapy of head and neck may suffer anatomical changes during the course of treatment. Frequent causes of such variations are the reduction of tumor volume, the progression of the disease during the course of radiotherapy, the loss of weight, and other causes. The conventional treatments are made of 33 to 35 fractions. Thus, the interval of time between the treatment planning computed tomography (CT) and the conclusion of the treatment surpasses two months. Monitoring significant anatomical variations and making adjustments to the plans of radiotherapy during the course of radiotherapy could be a relevant strategy to achieve the objectives proposed for the treatments. The objective of this study was to analyze how the variations in volume of interest, both target structures and healthy tissues could affect the dose distribution in the patient in radiation therapy treatment of head and neck cancer. This analysis will be made through investigation of metrics dose-volume, volumetric variations of target structures, as well as the parotid glands, patient thickness in the cervical region, image fusion, and isodose surfaces plotted on the CTs. The timing to Replan head and neck cancer appears to be around the 15th fraction of treatment, however a study with a larger number of patients is necessary. In case of adaptive radiotherapy, reduction of mean dose in the ipsilateral parotid was observed in 100% of patients, while in the contralateral parotid reduction was observed in 80% of patients. The decision to replan head and neck cancer has benefit in the spinal cord and brainstem since this study showed reduction in the maximum dose in 70% of patients in case of treatment replan. Decrease of dose including 95% of volume and minimum dose in the PTV (mean percentage decrease observed was 7.71%) was observed in case of no treatment replan. Increase in the maximum dose in the PTV was observed, for which the mean percentage increase observed was 2.42%. Adaptive radiotherapy improves the coverage of target volumes as well as the doses in OARs.

Automated tracking of morphologic changes in weekly magnetic resonance imaging during head and neck radiotherapy.

Anatomic changes during head and neck radiotherapy can impact dose delivery, necessitate adaptive replanning, and indicate patient-specific response to treatment. We have developed an automated system to track these changes through longitudinal MRI scans to aid identification and clinical intervention. The purpose of this article is to describe this tracking system and present results from an initial cohort of patients. The Automated Watchdog in Adaptive Radiotherapy Environment (AWARE) was developed to process longitudinal MRI data for radiotherapy patients. AWARE automatically identifies and collects weekly scans, propagates radiotherapy planning structures, computes structure changes over time, and reports important trends to the clinical team. AWARE also incorporates manual structure review and revision from clinical experts and dynamically updates tracking statistics when necessary. AWARE was applied to patients receiving weekly T2-weighted MRI scans during head and neck radiotherapy. Changes in nodal gross tumor volume (GTV) and parotid gland delineations were tracked over time to assess changes during treatment and identify early indicators of treatment response. N=91 patients were tracked and analyzed in this study. Nodal GTVs and parotids both shrunk considerably throughout treatment (-9.7±7.7% and -3.7±3.3% per week, respectively). Ipsilateral parotids shrunk significantly faster than contralateral (-4.3±3.1%vs. -2.9±3.3% per week, p=0.005) and increased in distance from GTVs over time (+2.7±7.2% per week, p<1×10-5 ). Automatic structure propagations agreed well with manual revisions (Dice=0.88±0.09 for parotids and 0.80±0.15 for GTVs), but for GTVs the agreement degraded 4-5weeks after the start of treatment. Changes in GTV volume observed by AWARE as early as one week into treatment were predictive of large changes later in the course (AUC=0.79). AWARE automatically identified longitudinal changes in GTV and parotid volumes during radiotherapy. Results suggest that this system may be useful for identifying rapidly responding patients as early as one week into treatment.

Early Experience of Online Adaptive Radiation Therapy for Definitive Radiation of Patients With Head and Neck Cancer

The advent of cone beam computed tomography-based online adaptive radiation therapy (oART) has dramatically reduced the barriers of adaptation. We present the first prospective oART experience data in radiation of head and neck cancers (HNC). Patients with HNC receiving definitive standard fractionation (chemo)radiation who underwent at least 1 oART session were enrolled in a prospective registry study. The frequency of adaptations was at the discretion of the treating physician. Physicians were given the option of delivering 1 of 2 plans during adaptation: the original radiation plan transposed onto the cone beam computed tomography with adapted contours (scheduled), and a new adapted plan generated from the updated contours (adapted). A paired t test was used to compare the mean doses between scheduled and adapted plans. Twenty-one patients (15 oropharynx, 4 larynx/hypopharynx, 2 other) underwent 43 adaptation sessions (median, 2). The median ART process time was 23 minutes, median physician time at the console was 27 minutes, and median patient time in the vault was 43.5 minutes. The adapted plan was chosen 93% of the time. The mean volume in each planned target volume (PTV) receiving 100% of the prescription dose for the scheduled versus adapted plan for high-risk PTVs was 87.8% versus 95% (P < .01), intermediate-risk PTVs was 87.3% versus 97.9% (P < .01), and low-risk PTVs was 94% versus 97.8% (P < .01), respectively. The mean hotspot was also lower with adaptation: 108.8% versus 106.4% (P < .01). All but 1 organ at risk (11/12) saw a decrease in their dose with the adapted plans, with the mean ipsilateral parotid (P=.013), mean larynx (P < .01), maximum point spinal cord (P < .01), and maximum point brain stem (P=.035) reaching statistical significance. Online ART is feasible for HNC, with significant improvement in target coverage and homogeneity and a modest decrease in doses to several organs at risk.

Equine conjunctival haemangiosarcoma: Clinical presentation, management, and outcome of seven cases in the United Kingdom.

Only 27 cases of equine conjunctival haemangiosarcoma have been reported in the literature over the past 37 years. Out of these, 22% of cases were lost to follow-up, 52% were euthanized, and 26% survived. A scarcity of cases and information is available for this rarely seen conjunctival tumour. To describe the clinical features, management, and outcome of conjunctival hemangiosarcoma in seven horses in the UK. Optivet medical records were reviewed for equine cases seen or advised on with a histopathological diagnosis of conjunctival haemangiosarcoma between January 2013 and March 2023. Medical records were accessed for details of signalment, history, management, and follow-up. Histopathology was used to confirm the diagnosis of haemangiosarcoma and assess the surgical margins. Immunohistochemistry was performed in a minority of cases with poorly differentiated solid tumours to support vascular lineage. Seven eyes from seven horses (five geldings and two mares) with a mean age of 16 years and median of 18 years (range 10-21 years) met the criteria. Serosanguinous discharge was seen in six eyes. All eyes were managed surgically; 4 by exenteration and 3 by conjunctivectomy/keratectomy. Adjunctive cryotherapy was performed in two eyes. Metastatic disease in the ipsilateral parotid salivary gland, confirmed with histopathology, was seen in one horse. Surgical margins were clear in all but one eye. Solar elastosis was noted in five eyes. All horses were healthy at the last follow-up (0.2-5 years, mean 2.9 years, and median 2 years). Equine conjunctival haemangiosarcoma is rare. Serosanguinous ocular discharge is a common clinical sign. Early surgical excision is highly effective. Solar elastosis is a common histopathological feature, suggesting a role for UV-light in the pathogenesis.

Can Superficial Parotid Sparing Alone Reduce Xerostomia? A Retrospective Study Correlating Type of Tobacco Use, Chronic Xerostomia and Parotid Sparing

<h3>Purpose/Objective(s)</h3> Head and neck cancer is one of the most common cancers in India. Tobacco chewing is the most widespread form of tobacco consumption. Majority of the patients present in locally advanced stage and achieving parotid sparing with IMRT in these patients can be challenging. We aimed to correlate the incidence of chronic xerostomia with the type of tobacco use and parotid volumes. <h3>Materials/Methods</h3> Patients with squamous carcinomas of head and neck region treated with conventionally fractionated curative-intent radiotherapy (bilateral neck) to a dose of 60-70 Gy between June 2017 and March 2020 were included in the study. The superficial and deep lobes of parotid were contoured retrospectively and the dosimetric data along with physician-assessed Radiation Therapy Oncology Group (RTOG) xerostomia toxicity grades at one year were retrieved. The individual, superficial and deep lobe parotids were considered spared if the mean dose was less than 26Gy. Patients were divided into five groups: Group 1 constituted bilateral parotid-spared, Group 2 of contralateral parotid-spared, Group 3 of contralateral superficial parotid-spared, Group 4 of bilateral superficial parotid-spared, and Group 5 where no sparing could be achieved. The groups were compared using chi-square test. <h3>Results</h3> 174 patients were included in the study. The median age was 59 years (IRQ 20 - 89). Chewing (40%), followed by smoking (35%) were the most frequent forms of tobacco consumption. The most common subsite was oropharynx (30.5%) followed by hypopharynx (26.4%), and about 83% had locally advanced disease. The mean bilateral parotid volume was 55.9 cc (18-130 cc). Tobacco chewers had significantly smaller mean parotid (53cc vs 60cc, p=0.02) and submandibular gland volumes (6cc vs 14cc, p<0.001) as compared to smokers. Bilateral or contralateral parotid sparing was achieved in 62.7%, bilateral or contralateral superficial lobe in 27.6%, and no sparing in 9.8% of patients. At one year, grade 0/I xerostomia was reported by 89.5%, and ≥grade II xerostomia in 11.5%. The grade of xerostomia was similar in smokers and chewers (p=0.95). The ipsilateral (26.5 Gy vs 37.8 Gy, p <0.001) and contralateral (23.3 Gy vs 34.1 Gy, p <0.001) superficial parotid mean dose in patients with grade 0/I and ≥grade II xerostomia was significantly different. Patients with bilateral or contralateral superficial lobe sparing had lower rates of grade II/III xerostomia compared to no sparing group (p<0.001). <h3>Conclusion</h3> Tobacco chewers have smaller parotid and submandibular glands compared to smokers. This did not impact the sparing of glands or the severity of xerostomia. Contralateral or bilateral superficial parotid sparing translated into superior salivary gland function at 1 year.

Dosimetric Impact of Simulated Daily Adaptive Radiotherapy with Significantly Reduced Setup Margins in the Definitive Treatment of Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Even when treating head and neck cancer (HNC) with daily image-guided radiation therapy, setup margins of 3-5 mm are required to ensure adequate coverage of disease due to setup error. These margins lead to additional normal tissue dose that may compromise acute and long-term quality-of-life. The use of daily adaptive radiotherapy (ART) using an online adaptive system significantly reduces the need for a PTV margin, since the targets and organs-at-risk (OAR) are recontoured each fraction. In this study, we hypothesized using daily ART (simulated) with 1 mm margins based on our involved nodal radiotherapy (INRT) paradigm would improve coverage and reduce OAR dose. <h3>Materials/Methods</h3> Ten patients with HNC treated on our institutional phase II INRT trial were selected for this study. Cone-beam CT scans were uploaded to the ETHOS emulator for daily adaptive replanning which was simulated using fractions 5, 10, 15, 20, 25, 30, and 35. Two plans were generated with a 1 mm (reduced) and a 5 mm (conventional) PTV expansion. The dose grid from the delivered, conventional margin plan was transposed onto the CBCT and adapted contours. Separately, a reduced target margin plan optimized on the online adaptive system was created. PTV coverage (70 Gy-gross/primary disease, 66.5 Gy-suspicious nodes, 63 Gy-extended volume surrounding the primary disease) and D1 were calculated for target structures along with the dose to OARs. Comparisons performed via paired two tailed t-test. <h3>Results</h3> Six patients with oropharynx cancer and four patients with larynx cancer were included. Median V100% coverage for 70 Gy (96% vs 95.6%), 66.5 Gy (98.5% vs 76.5%), and 63 Gy (98.9% vs 74.9%) were improved with the adaptive planning (all p-values<0.03). Plan homogeneity was improved in the ART plan (e.g., PTV70 median D1% 72.8 Gy vs 74.8 Gy, all p-values<0.02). The total median dose reduction was 10.8 Gy (interquartile range, IQR 8.0-12.6 Gy) for the ipsilateral submandibular gland (SMG), 12.2 Gy (IQR 7.3-23.5 Gy) for the contralateral SMG, 8.3 Gy (IQR 3.8-12.6 Gy) for the ipsilateral parotid, 8.1 Gy (IQR 4.4-11.0 Gy) for the contralateral parotid, 7.0 Gy (IQR 4.5-9.1 Gy) for larynx, 6.6 Gy (IQR 2.7-8.4 Gy) for oral cavity, and 8.6 Gy (IQR 5.9-12.1 Gy) for constrictors. <h3>Conclusion</h3> Simulated daily ART using a 1 mm PTV margin provided significant improvement over conventional PTV margins in coverage and critical OAR dosimetry. This small proof-of-concept study suggests this approach may lead to improved quality-of-life while preserving or improving tumor coverage. Further evaluation is needed to assess the resources needed to implement daily adaptations. A phase II randomized trial of daily ART is underway to determine if dosimetric improvements lead to similar gains in patient-reported outcomes.

Dosimetric evaluation of three-phase adaptive radiation therapy in head and neck cancer

The aim of this prospective study was to evaluate the dosimetric benefits of the 3-phase adaptive radiation therapy (ART) technique for head and neck cancer (HNC). In addition, it was aimed to examine the changes in skin dose due to the anatomical changes that occurred in the patients during radiation therapy with Thermoluminescent dosimeters (TLDs). Fifteen patients with head and neck cancer were included in this prospective study. TLDs were placed on the patient's neck at 5 different points determined during computed tomography (CT). A new CT was recommended for patients with a skin dose increase of more than 10% and a weight loss of more than 5% during treatment. Control CTs CT14 and CT24 were obtained in the patient due to weight loss and increase in skin dose. Offline adaptive replans were generated after fractions 14 and 24 and used for further processing (Aplan 1 and Aplan 2, respectively). All patients received 3-stage ART. Accordingly, iPlan Aplan1 and Aplan2 were applied between 0–14, 15–24 and 25–33 fractions, respectively. Dose-volume histograms (DVHs) were compared for adaptive (ART: iPlan + Aplan1+Aplan2) and non-adaptive (non-ART) plans. Lateral neck diameter (LND) change was statistically significant, with a decrease of 7.35% (p < 0.001) and 5.44% (p < 0.001) for CT14 and CT24, respectively. The mean weight loss for CT14 compared to CT0 was 7.80%. Weight loss in CT24 compared to CT14 was 5.65%. As a result of the measurements made with TLDs on different days between 0–15 fractions during the application of iPlan, a 15.25% increase in skin dose was measured. During Aplan 1 and Aplan 2 applications, the increase in skin dose was measured as 10.56% and 2.83%, respectively. For ART, the ipsilateral parotid and contralateral parotid Dmean doses were decreased by 1.62 Gy (p < 0.001) and 2.25 Gy (p < 0.001), respectively. During treatment, an increase in skin dose of more than 10% and a weight loss of more than 5% should be considered as a trigger point for initiation of ART. Repeat CT scanning and replanning after fractions 15 and 25 is recommended during intensity modulated radiotherapy (IMRT) in patients with HNC. In conclusion, the 3-phase ART approach provides dosimetric benefits to patients with HNC.

Impact of Dose-Volume Parameters of Parotid Glands on Xerostomia in Patients Irradiated for Head-and-Neck Cancer.

Optimal planning of radiotherapy for head-and-neck cancers should consider the risk of xerostomia. This study investigated the prognostic value of dosevolume parameters of the parotid glands. Dose-volume parameters were evaluated for xerostomia in 145 patients including D40 (minimum dose to 40% of corresponding parotid volume), D60 (minimum dose to 60%), D80 (minimum dose to 80%), and mean dose of ipsilateral, contralateral, and bilateral parotid glands. Grade ≥2 xerostomia was significantly associated with D40 of ipsilateral and all parameters of bilateral glands; trends were found for all other parameters. Grade ≥3 xerostomia was significantly associated with D80 of bilateral glands; trends were found for other parameters of ipsilateral and bilateral glands. Since grade ≥2 xerostomia was associated with all parameters, D40, D60, and D80 did not provide additional information to mean doses. D80 of bilateral glands is a new factor and more predictive than mean dose regarding grade ≥3 xerostomia.

Adaptive Radiotherapy in Head and Neck Cancer Using Volumetric Modulated Arc Therapy

A dosimetric study was performed to show the importance of adaptive radiotherapy (ART) for head and neck cancer (HNC) patients using volumetric modulated arc therapy (VMAT). A total of 13 patients with HNC who required replanning during radiotherapy were included in this study. All plans succeeded to achieve the set objectives regarding target volume coverage and organ sparing. All target volumes presented a significant decrease with an average of 76.44 cm3 (p = 0.007) for PTVlow risk, 102.81 cm3 (p = 0.021) for PTVintermediate risk, and 47.10 cm3 (p = 0.003) for PTVhigh risk. Additionally, a positive correlation was found between PTV shrinkage and the number of fractions completed before replanning. Significant volume decrease was also observed for the parotid glands. The ipsilateral parotid decreased in volume by a mean of 3.75 cm3 (14.43%) (p = 0.067), while the contralateral decreased by 4.23 cm3 (13.23%) (p = 0.033). For all analyzed organs, a reduction in the final dose received after replanning was found. Our study showed that ART via rescanning, recontouring, and replanning using VMAT is essential whenever anatomical and positional variations occur. Furthermore, comparison with the literature has confirmed that ART using VMAT offers similar results to ART with intensity modulated radiotherapy.

Novel VMAT Planning Technique Improves Dosimetry for Head and Neck Cancer Patients Undergoing Definitive Chemoradiotherapy

<h3>Purpose/Objective(s)</h3> Intensity modulated radiotherapy (IMRT) allows for substantial sparing of organs-at-risk (OARs) without compromising delivery of curative-intent doses in patients with head and neck cancers. Volumetric modulated arc therapy (VMAT) allows for rapid treatment delivery and minimizes fractional treatment time. Given the intrinsic complexity of VMAT planning, standard two-arc techniques often fail to achieve planning objectives. We hypothesize that a simple, institutional approach improves OAR dosimetry compared to a standard two-arc technique. <h3>Materials/Methods</h3> Head and neck cancer patients who received definitive chemoradiotherapy were included in this single institution study. VMAT plans were generated per institutional protocol using 6 MV photon beams. Briefly, three single arcs were employed with assigned collimator angles of (C) 0°, (C) 90°, and (C) 90°. The maximum jaw extension of the (C) 0° field encompassed the entirety of the treatment volume. The inferior jaw on the first collimated arc was set with a maximum extension of 1 cm beyond the isocenter, while the superior jaw of the second collimated arc was set with a maximum extension of 1 cm beyond the isocenter. Comparison plans were generated for each patient using the manufacturer's recommended beam arrangement, comprising two collimated arcs - (C) 30° and a reciprocal (C) 330° - with jaw tracking enabled. Mean differences in target volume and OAR dosimetry between planning approaches were calculated. A two-tailed, paired Student's t-test was employed to determine statistically significant differences in dosimetry between standard and institutional plans. <h3>Results</h3> Ten patients were planned using institutional and standard two-arc protocols. Statistically significant mean improvements were observed in ipsilateral parotid mean dose (∆314.7 cGy, p = 0.007) and V30Gy (∆6.62%, p = 0.004), contralateral parotid mean dose (∆292.6 cGy, p = 0.006) and V30Gy (∆5.36%, p = 0.004), parotid volume receiving less than 20 Gy (∆7.36 cc, p = 0.010), pharyngeal constrictor mean dose (∆269.3 cGy, p = 0.003), ipsilateral brachial plexus maximum dose (∆96.0 cGy, p = 0.036), and global maximum dose (∆1.73%, p = 0.047) with the three-arc technique. No significant differences in PTV, spinal cord, mandible, cricopharyngeus, cochlear, or contralateral brachial plexus dosimetry were identified. Subjectively, dosimetrists reported shorter planning time and easier achievement of objectives with the three-arc approach. <h3>Conclusion</h3> Our institutional approach to head and neck VMAT conveys significant dosimetric improvements compared to a standard VMAT beam arrangement. This approach represents a simple and reproducible solution to planning for head and neck cancer patients which may reduce planning time. Additional research is warranted to further optimize this technique and quantify reductions in planning time.

Clinical Use of A Priori Knowledge of Organ-At-Risk Sparing During Radiation Therapy Treatment for Oropharyngeal Cancer: Dosimetric and Patient Reported Outcome Improvements

PurposeThis study aimed to prospectively assess dosimetric and clinical effects of treatment planners having a priori knowledge of the maximum achievable dose sparing for organs at risk (OARs) for patients with oropharynx cancer receiving intensity modulated radiation therapy (RT). Methods and MaterialsWe examined patients with oropharynx cancer who were treated in prospective clinical trials between February 2012 and April 2019 at our institution. A tool generating estimates of maximum achievable dose sparing for OARs (feasibility dose-volume histogram [FDVH]) was used clinically starting July 2016. Patients were divided into 2 cohorts: Before (ie, baseline) and after (ie, FDVH-guided) FDVH. Doses received by various OARs were compared with those estimated to be achievable per FDVH, and that difference was defined as the excess of feasible dose (EFD). Patient-reported outcome (PRO) questionnaires were completed at 3, 6, and 12 months after treatment. The baseline and FDVH-guided cohorts were compared in terms of EFD, plan quality metrics, and post-RT PRO assessments. ResultsA total of 139 patients were included in the analysis (60 in the baseline cohort, 79 in the FDVH-guided cohort). The FDVH-guided cohort had lower EFD to the contralateral parotid by 4.1 Gy, the ipsilateral parotid by 10.6 Gy, the larynx by 4.3 Gy, the oral cavity by 1.5 Gy, and the contralateral submandibular gland by 0.4 Gy. Plan quality metrics were similar between the cohorts. Less variation of EFD was seen in the FDVH-guided cohort for the parotid glands and contralateral submandibular gland (P < .05). The average post-RT PROs were better in the FVHD cohort versus baseline (particularly at the 6-month timepoint for dry mouth frequency, sticky saliva, meal enjoyment, severity of pain, and Eating Assessment Tool 10 composite [swallowing]; P < .05). ConclusionsUse of FDVH was associated with improved and less variable OAR sparing for clinically delivered plans. FDVH-guided patients had improved PROs compared with baseline with a variety of outcomes significantly improved at 6 months after treatment.

A Priori Knowledge of Maximum Achievable Organ at Risk Sparing: Impact on Organ Doses and Patient Reported Outcomes

IMRT planning is challenging, at least in part, due to the essentially-infinite number of possibilities, and since the planner is never sure that they have gotten "the best", or at least "nearly the best" achievable plan. We prospectively assessed the impact of providing IMRT planners with a priori knowledge of the maximum achievable dose sparing for organs at risk (OARs) for patients on both dosimetric and clinical endpoints. We hypothesized that a priori knowledge of maximum achievable sparing would improve dosimetric and clinical (i.e., patient reported outcome) measures.We examined patients receiving IMRT for oropharynx cancer on prospective clinical trials from 2012-2019 at our institution. A tool that generates estimates of maximum achievable dose sparing for organs at risk was used starting July 2016. Patients treated pre-implementation (i.e., baseline) and post-implementation (i.e., experimental) were compared for the endpoints: (1) Doses received by various OARs MINUS doses achievable (per the tool), termed the 'excess of feasible dose'; (2) Plan quality metrics (e.g., target homogeneity and conformity), and (3) Patient reported outcomes (PRO) per questionnaires completed at 3-, 6- and 12-months post-treatment.139 patients were analyzed (60-baseline cohort, 79-experimental). (1) The excess of feasible dose was lower in the experimental (vs baseline) cohort, for the contralateral parotid (9.6 vs 5.5 Gy; P < 0.001), the ipsilateral parotid (17.6 vs 6.8 Gy; P < 0.001), larynx (12.5 vs 8.2 Gy; P = < 0.001), oral cavity by (15.8 vs 14.3 Gy; P = 0.002), and contralateral submandibular gland (17.4 vs 17 Gy; P = 0.40). Lesser variation of excess of feasible dose (i.e., more consistent sparing) was seen in the experimental (vs. baseline) cohort for the parotid and contralateral submandibular glands (P < 0.05). (2) Some small differences in target homogeneity and conformity were observed but not felt to be clinically significant. (3) The average post-RT PROs were significantly better in the experimental cohort vs baseline at 6 months post-RT. Dry mouth severity, sticky saliva, meal enjoyment, severity of pain, and EAT10 composite (swallowing) were all significantly improved; P < 0.05).Clinical plans aided by an a priori estimate of maximum achievable dose sparing for OARs was associated with improved (and more consistent) OAR sparing and better clinical outcomes (i.e., better post-RT PROs). Clinical implementation of this tool can yield quantifiable dosimetric and patient benefits.

Feasibility of DW-MRI analysis of salivary glands during head and neck radiotherapy.

With no effective treatment for xerostomia, there remains an unmet need to reduce radiation induced toxicity. Measuring physiological changes during RT in salivary glands using DW-MRI may predict which patients are most at risk of severe toxicity. This study evaluated the feasibility of measuring apparent diffusion coefficient (ADC) in the major salivary glands and describes the observed changes in volume and ADC during RT. Scans were acquired at baseline (MR_base) and after 10 fractions (MR_rpt). Sequences included T1 post contrast fat saturated (T1PCFS) and DW-MRI (5b values, 0-1000s/mm2). Ipsilateral and contralateral parotid (iPG/cPG), submandibular (iSMG/cSMG) and sublingual glands (iSLG/cSLG) were delineated on T1PCFS, modified on b0 and copied to the ADC map. 31 patients with intermediate/high risk squamous cell carcinoma (SCC) of the oropharynx were evaluated. On 124 scans, SMG and SLG delineations were successful on all; parotids were fully contoured in 90.7%. Baseline mean ADC were significantly different between each gland type (p<0.0001). IPG and cPG volume decreased during treatment by 6.7% and 11.2%. ISMG, cSMG, iSLG and cSLG volume increased by 6.9, 0.9, 60.8 and 60.3% respectively. All structures showed an increase in mean_ADC values. For each gland the increase in ADC was statistically significant p<0.0001. A smaller mean percentage increase in ADC was observed in the group experiencing a higher grade (2 or>) of toxicity. It is feasible to measure volume and ADC of the salivary glands prior to and during RT for HNC. Early data suggests a lower rise in ADC during treatment is associated with more severe late xerostomia.