Parotid Dose 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.

Dosimetry of lutetium-177 PSMA-targeted radiopharmaceutical therapies for prostate cancer patients: A comparative systematic review and meta-analysis.

e17033 Background: Novel theranostic approaches using radiopharmaceuticals targeting PSMA have emerged for treating metastatic castrate resistant prostate cancer (mCRPC). The physical properties and commercial availability of Lutetium-177 (Lu177) makes it one of the most used radionuclides for radiopharmaceutical therapy (RPT). In this review we aimed at comparing the dosimetry of the most used Lu177-PSMA RPT compounds. Methods: This is a systematic review and meta-analysis of Lu177-PSMA RPT (617, I&T, and J591) dosimetry for prostate cancer. Absorbed doses in Gy/GBq for each organ (kidney, parotid and submandibular glands, bone marrow, liver, lacrimal glands) and for tumor lesions (bone and non- bone lesions) were extracted. These were used to estimate the pooled average absorbed dose of each RPT, and normalize each to the respective injected activity (Gy/cycle) as determined by the dose per cycles used in VISION (7.4 GBq), SPLASH (6.8 GBq), and PROSTACT Trials (5.8 GBq). Results: 29 published manuscripts comprising 535 patients were included in the meta-analysis. The pooled dose was calculated for kidney based on (28 studies, 485 patients), parotid (20, 309), submandibular (7, 100) and lacrimal glands (9, 174), bone marrow (18, 293), and liver (14, 245) were 4.04 and 4.70, 5.85 and 2.62, 5.15 and 4.35, 11.03 and 19.23, 0.24 and 0.19 and 1.11 and 0.56 Gy respectively for Lu177-PSMA-617 and Lu177-PSMA-I&T. Lu177-PSMA-J591 reported absorbed doses to the kidney, bone marrow and liver were 3.95, 0.90, and 5.88 Gy respectively. There was no significant difference between Lu177-PSMA-I&T and Lu177-PSMA-617 for the dose to kidneys (p=0.10), submandibular glands (p=0.56), bone marrow (p=0.31), lacrimal glands (p=0.20), or tumors (p=0.16). However, parotid dose from Lu177-PSMA-617 was higher than that of Lu177-PSMA-I&T (p=<0.01). Average tumor doses tended to be higher for Lu177-PSMA-617 than for Lu177-PSMA-I&T, (27.94 vs. 21.31 Gy); p=0.16. Lu177-PSMA-J591 exposed the bone marrow and liver, to a significantly higher dose while resulting in a lower dose to the kidney than either of the two small molecule compounds. Absorbed doses to the salivary glands, lacrimal glands, and tumors after the treatment with Lu177-PSMA-J591 have not been published yet. Conclusions: The clinical impact of higher tumor to kidney dose ratio for Lu177-PSMA-617 than Lu177-PSMA-I&T has yet to be determined. Data for Lu177-PSMA-J591 are thus far too limited to draw firm conclusions.

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas

BackgroundThe utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. Methods and AnalysisReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy.The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DiscussionThe ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Clinical Experience With an Offline Adaptive Radiation Therapy Head and Neck Program: Dosimetric Benefits and Opportunities for Patient Selection

PurposeTo develop a LINAC-based adaptive radiotherapy (ART) workflow for head and neck that is informed by automated image tracking to identify major anatomic changes warranting adaptation. In this study we report our initial clinical experience with the program and an investigation into potential trigger signals for ART. Methods and MaterialsOffline ART was systematically performed on patients receiving radiotherapy for head and neck cancer on C-arm LINACs. Adaptations were performed at a single timepoint during treatment with resimulation approximately 3 weeks into treatment. Throughout treatment, all patients were tracked using an automated image tracking system called the IN_HOUSE_SOFTWARE*. IN_HOUSE_SOFTWARE measures volumetric changes in gross tumor volumes (GTV) and selected normal tissues via cone-beam computed tomography (CBCT) scans and deformable registration. The benefit of ART was determined by comparing adaptive plan dosimetry and normal tissue complication probabilities (NTCP) against the initial plans recalculated on resimulation CT scans. Dosimetric differences were then correlated with IN_HOUSE_SOFTWARE-measured volume changes to identify patient-specific triggers for ART. Candidate trigger variables were evaluated using receiver operator characteristic (ROC) analysis. ResultsN=46 patients received ART in this study. Amongst these patients, we observed a significant decrease in dose to the submandibular glands (mean ± standard deviation: -219.2±291.2cGy, p-value<10−5), parotids (-68.2±197.7cGy, p-value=0.001) and oral cavity (-238.7±206.7cGy, p-value<10−5) with the adaptive plan. NTCPs for xerostomia computed from mean parotid doses also decreased significantly with the adaptive plans (p-value=0.008). We also observed systematic intra-treatment volume reductions (ΔV) for GTVs and normal tissues. Candidate triggers were identified which did predict significant improvement with ART including parotid ΔV=7%, neck ΔV=2%, and nodal GTV ΔV=29%. ConclusionsSystematic offline head and neck ART was successfully deployed on conventional LINACs and reduced doses to critical salivary structures and oral cavity. Automated CBCT tracking provided information regarding anatomic changes that may aid patient-specific triggering for ART. (*Anonymized for review)

Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy

ObjectivesWe sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). Materials and MethodsPatients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. ResultsMedian follow-up was 12.9 months (1.3 – 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was −3.8 kg (-14.1 – 5.1) for VMAT and −3 kg (-16.8 – 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. ConclusionsCutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

Predicting Parotid Dose Changes in Head-and-Neck Radiotherapy Using Machine Learning: Leveraging Anatomical Variations

Predicting Parotid Dose Changes in Head-and-Neck Radiotherapy Using Machine Learning: Leveraging Anatomical Variations

Comparative Analysis of Parotid Doses in Tomotherapy Versus Volumetric Modulated Arc Therapy for Head and Neck Cancer Patients Undergoing Bilateral Neck Irradiation: A Non-randomized, Prospective, Dosimetric and Clinical Study

Background and Objectives: Xerostomia, a common side effect of head and neck radiation therapy, significantly impacts subjective well-being and quality of life. Its severity depends on the radiation dosage received by the parotids. Advanced techniques like Volumetric Modulated Arc Therapy (VMAT) and Tomotherapy offer improved parotid sparing. This prospective, non-randomized, double arm, dosimetric, and clinical study aims to compare parotid dosages between Tomotherapy and VMAT (Rapid Arc) in head and neck cancer patients undergoing bilateral neck irradiation. Methods: Fifty-two eligible patients were included, with 26 treated by Tomotherapy and 26 by VMAT. Plans were cross planned between the two techniques while maintaining similar Planning Target Volume (PTV) coverage. Bilateral parotid dosages were evaluated, and clinical xerostomia assessment utilized the Xerostomia Questionnaire (XQ) and Radiation Therapy Oncology Group (RTOG) scoring criteria. Statistical analysis employed the paired t-test. Results: Both right and left parotids received significantly lower mean doses on Tomotherapy (21.23Gy ± 4.429) compared to VMAT (23.26Gy ± 4.531) (p &lt; 0.001). XQ scores and RTOG scores did not show statistically significant differences between the two arms at both follow-ups. Tomotherapy demonstrated better parotid sparing, translating into reduced acute salivary gland morbidities. Conclusion: This study highlights Tomotherapy's superiority in parotid sparing over Rapid Arc (VMAT), leading to clinically relevant reductions in xerostomia. Notably, oral cavity cancer patients exhibited higher xerostomia scores, emphasizing the importance of minor salivary glands. Long-term follow-up, extending to at least 2 years post-radiotherapy, is crucial for a comprehensive assessment of the technique's advantage in reducing xerostomia and improving quality of life.

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.

Results of a Multi-institutional Randomized Phase 3 Trial of Parotid-Sparing Whole Brain Radiotherapy

Observational studies have reported that xerostomia is common after conventional whole brain radiotherapy (WBRT) and associated with parotid dose. In this multi-institutional, single-blind randomized controlled trial, we hypothesized that patient-reported xerostomia is reduced in patients randomized to parotid-sparing vs. standard WBRT fields. Between 2018 and 2021, patients receiving conventional WBRT (30-35 Gy in 10-15 fractions) for any diagnosis were enrolled at 3 academic institutions. Patients were randomized between standard WBRT fields covering the C1 vertebra with no prospective parotid delineation (control) vs. parotid-sparing fields without C1 coverage (experimental). Patients completed the University of Michigan Xerostomia Questionnaire (Scored 0-100, higher is worse) at baseline, EndRT, 2 weeks, 1 month, 3 months, and 6 months. Patients were excluded from toxicity analyses if baseline xerostomia score was >50 or if they did not complete any post-baseline questionnaires. The primary endpoint was proportion of patients with ≥15 point absolute increase in xerostomia score from baseline to 1 month; 108 patients were needed for an 80% power to detect a 22% absolute difference (1-sided significance of 0.05). The secondary endpoint was the rate of marginal failures. The study closed early after 56 patients were randomized. Median survival was 4.6 months. 46 patients (23 in each arm) were eligible for analysis. Mean parotid dose was 17 vs. 10 Gy in the standard vs. parotid-sparing arms, respectively. The table below shows mean xerostomia score and proportion of patients with ≥15 increase in xerostomia score at each time point. There was no difference in the proportion of patients experiencing ≥15 increase in xerostomia score at 1 month, though there was a trend toward lower xerostomia score at 1 month in patients randomized to parotid-sparing fields (p = 0.07, Table). Xerostomia rates were also significantly improved in the parotid-sparing arm at EndRT (p = 0.03), but no longer-term difference was observed with greater attrition at 3 and 6 months. On linear regression, there was a trend toward association between mean parotid dose and xerostomia score at 1 month (p = 0.06). There were no reported marginal failures in either arm. Parotid-sparing without coverage of the C1 vertebra appears safe and may meaningfully reduce acute xerostomia in patients with limited life expectancy who are candidates for conventional WBRT, although the study was underpowered to detect a significant difference at 1 month.

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.

Radiomics and dosiomics-based prediction of radiotherapy-induced xerostomia in head and neck cancer patients

Background and aim Dose-response modeling for radiotherapy-induced xerostomia in head and neck cancer (HN) patients is a promising frontier for personalized therapy. Feature extraction from diagnostic and therapeutic images (radiomics and dosiomics features) can be used for data-driven response modeling. The aim of this study is to develop xerostomia predictive models based on radiomics-dosiomics features. Methods Data from the cancer imaging archive (TCIA) for 31 HN cancer patients were employed. For all patients, parotid CT radiomics features were extracted, utilizing Lasso regression for feature selection and multivariate modeling. The models were developed by selected features from pretreatment (CT1), mid-treatment (CT2), post-treatment (CT3), and delta features (ΔCT2-1, ΔCT3-1, ΔCT3-2). We also considered dosiomics features extracted from the parotid dose distribution images (Dose model). Thus, combination models of radio-dosiomics (CT + dose & ΔCT + dose) were developed. Moreover, clinical, and dose-volume histogram (DVH) models were built. Nested 10-fold cross-validation was used to assess the predictive classification of patients into those with and without xerostomia, and the area under the receiver operative characteristic curve (AUC) was used to compare the predictive power of the models. The sensitivity and accuracy of models also were obtained. Results In total, 59 parotids were assessed, and 13 models were developed. Our results showed three models with AUC of 0.89 as most predictive, namely ΔCT2-1 + Dose (Sensitivity 0.99, Accuracy 0.94 & Specificity 0.86), CT3 model (Sensitivity 0.96, Accuracy 0.94 & Specificity 0.86) and DVH (Sensitivity 0.93, Accuracy 0.89 & Specificity 0.84). These models were followed by Clinical (AUC 0.89, Sensitivity 0.81, Accuracy 0.97 & Specificity 0.89) and CT2 & Dose (AUC 0.86, Sensitivity 0.97, Accuracy 0.87 & Specificity 0.82). The Dose model (developed by dosiomics features only) had AUC, Sensitivity, Specificity, and Accuracy of 0.72, 0.98, 0.33, and 0.79 respectively. Conclusion Quantitative features extracted from diagnostic imaging during and after radiotherapy alone or in combination with dosiomics markers obtained from dose distribution images can be used for radiotherapy response modeling, opening up prospects for personalization of therapies toward improved therapeutic outcomes.

A Prospective Cohort Study Analyzing Radiation-Induced Xerostomia and Quality of Life of Head and Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy Techniques at a Tertiary Cancer Center in Eastern India.

Introduction Cancer of the head and neck is one of the most common cancers in India. Radiotherapy (RT) plays a vital role in the management of head and neck cancer both as a curative and adjuvant modality. Xerostomia is the most common acute and late toxicity. Therefore, this study aimed to analyzeradiation-induced xerostomia and the quality of life of patients treated with intensity-modulated radiotherapy (IMRT) and three-dimensional (3D) conformal radiotherapy (3DCRT). Objectives We aimto evaluate radiation-induced acute xerostomia both subjectively and objectively at three-monthand one-year post-radiotherapy follow-up period in patients who received radiotherapy in conformal technique (IMRT) to the head and neck region and compare it with those who received the 3DCRT technique. We also aim to assess the recovery of salivary flowin the third month post-radiotherapy by measuring the parotid scintigraphy excretion fraction. Materials and methods Forty patients with head and neck squamous cell carcinoma (SCC) were randomly assigned to the IMRT and 3DCRT arms. Xerostomia during radiation and at three-monthand one-year post-radiotherapy follow-up was assessed subjectively using the xerostomia-related quality of life (XeQOL)questionnaire and objectively by measuring the salivary flow rate and parotid scintigraphy. Results The result is analyzed using an independent t-test, Mann-Whitney U test, and Fisher's exact test. The analysis showed that patients treated with radiation by IMRT showed better XeQOL scores (43.40±2.326 in IMRT and 52.10±2.573 in 3DCRT, p<0.001) and Eating Assessment Tool-10 (EAT-10) score (27.65±2.796 in IMRT and 33.80±1.936 in 3DCRT, p<0.001) compared to those treated with 3DCRT. Analysis of the excretion fraction (EF%) of parotid scintigraphy depicted improvement in EF% for both right and left parotids in the IMRT arm with statisticalsignificance (for right parotid, 25.22±12.98 in IMRT and 19.60±10.17 in 3DCRT, p=0.136, and for left parotid, 28.03±12.51 in IMRT and 15.35±11.49 in 3DCRT, p=0.0019). The mean rate of flow (ROF) of saliva showed a declining trend during the end of radiotherapy treatment compared to baseline, but the mean ROF of saliva was better in IMRT compared to 3DCRT, and the difference was statistically significant. The ROF of saliva starts improving during the one-year post-radiotherapy follow-up period. Pearson's chi-square test was used to analyzethe correlation between mean parotid dose with EF% of parotid scintigraphy,and it showed a negative correlation, which is statistically significant for both 3DCRT and IMRT arms. Conclusion Xerostomia can be reduced by precision radiotherapies such as the parotid-sparing IMRT technique in head and neck cancer patients, hence improving the quality of life.

Development of prediction model for mean parotid dose of HNC undergoing radiotherapy - A single institutional study

Development of prediction model for mean parotid dose of HNC undergoing radiotherapy - A single institutional study

Dosimetric Analysis of Online Adaptive Radiation Therapy in the Adjuvant Setting for Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Online adaptive radiotherapy (OnART) system designed to deliver re-optimized plans in real time using on-board cone beam CT and artificial intelligence has enabled frequent adaptation. Given the paucity of data on the role of adaptive radiotherapy (RT) and its frequency in the treatment of post-operative patients with head and neck squamous cell carcinoma (HNSCC), a dosimetric study was performed to assess the potential benefits of a single vs weekly OnART in this setting. <h3>Materials/Methods</h3> Twelve patients receiving conventionally fractionated RT (CFRT) over 6 weeks and 12 patients receiving hypofractionated RT (HFRT) over 3 weeks on a clinical trial between 2020 and 2021 were analyzed. The OnART plan was generated to meet the same quality as the original clinical plan and the OnART emulator was used to virtually conduct adaptive RT based on the patient's cone beam CT. The PTV coverage, dose heterogeneity, and cumulative dose to the organs-at-risk of a single mid-treatment OnART (at week 4 for CFRT and week 2 for HFRT) and weekly OnART were compared to the non-adapted plan. <h3>Results</h3> In total, 13, 8, and 3 patients had oral cavity, oropharynx, and larynx primaries, respectively, with 11 of the 24 patients receiving ipsilateral RT only. The average absolute and % weight loss during treatment were 5.7 lb and 3.1%, respectively. In the CFRT cohort, weekly OnART led to a significant improvement in high risk PTV (PTVHR) and standard risk PTV (PTVSR) V100 coverage (9.9% and 3.4% absolute) as well as hot spot (-1.3 Gy), max cord dose (-3.4 Gy), and mean oral cavity dose (-1.3 Gy), while the mean contralateral parotid dose increased modestly (0.76 Gy) (Table). When adapted once, only PTVHR coverage was improved (3.3%). For the HFRT cohort, weekly OnART resulted in a significant improvement in PTVHR/PTVSR coverage (3.7%/2.0%), hot spot (-0.82 Gy), and max cord dose (-2.5 Gy) (Table). When adapted once, mean oral cavity dose decreased (-1.4 Gy) and mean contralateral parotid dose increased (1.1 Gy). <h3>Conclusion</h3> There was a limited benefit of one-time OnART, but weekly adaptations improved the dosimetry, predominantly in PTV coverage and dose heterogeneity for patients receiving adjuvant RT for HNSCC. A prospective study is ongoing to determine the potential benefit in clinical and patient-reported outcomes of OnART in this setting.

Changes in Organs at Risk Dose Estimates Due to Anatomic Changes and Registration Method During Head and Neck Radiotherapy and its Relationship to Percent Weight Loss

<h3>Purpose/Objective(s)</h3> Weight loss and anatomic changes are common during radiation therapy for head and neck cancers. The best method for assessing the impact of anatomic changes on dose distribution is unknown. We compared planned doses to organs at risk (OARs) to delivered dose estimates using a cone beam computed tomography (CBCT) from the final week of treatment. <h3>Materials/Methods</h3> Ten patients who underwent bilateral neck radiation and had weekly extended CBCT's available to capture critical OARs were identified. CBCT from the final week was reconstructed to 2mm slices to match the resolution of the CT simulation (CTsim). The CBCT's were registered to the sim using both rigid and deformable registration techniques. The parotid glands, spinal cord, and skin (defined as 3mm from body contour) were contoured on the CBCT's. Mean dose to the parotids, and maximum dose (D0.035cc) to the spinal cord and skin were extracted from the treatment plan based on CTsim, rigid CBCT and deformed CBCT respectively. Independent t-tests were used to determine and compare mean percent (%) dose changes in OAR's from initially planned to delivered dose estimates using the rigid and deformed CBCT's. Linear regression was then performed to identify which set of OAR doses were the best predictors of the variation in % mean weight change during the treatment course. Statistical software was used for the statistical analyses. <h3>Results</h3> Among the 10 patients analyzed, mean % change in mean right parotid dose was -6.99% between planned and rigid CBCT estimated dose and +12.02% between planned and deformed CBCT estimated dose, for a mean total difference of 19.01% (SE 5.61%, p=0.004). These differences were statistically significant. A similar trend was observed for the left parotid gland, with mean % changes of -1.67%, +6% and 7.67% respectively (SE 5.62%, p=0.19). No differences were observed for cord (mean difference 0.19%, SE 1.27%, p = 0.89) or skin (mean difference 0.26%, SE 2.83%, p = 0.92). On regression analysis the delivered dose estimates from the rigid CBCT model were a better predictor of % weight change (R²=0.543) compared to the deformed CBCT (R²=0.463) or CT sim planned doses (R²=0.460) <h3>Conclusion</h3> The data shows a significant difference in estimating dose delivered to the right parotid gland using final week CBCT between using rigid and deformable registration techniques. Change in dose to left parotid gland also trended towards significance and may prove to be meaningful with a larger sample size. There were no significant differences in cord or skin % dose changes. We found that doses collected from the Rigid CBCT were the best predictors of % weight change during the whole course of treatment on regression analysis. Future work will focus on mid treatment dose estimates using a larger sample size, and correlation with clinical outcomes.

Dosimetric Comparison of Intensity Modulated Radiotherapy (IMRT) and Intensity Modulated Proton Therapy (IMPT) for Novel Oral Tongue Avoidance Concept in Low-Risk Squamous Cell Carcinoma of the Oral Tongue

<h3>Purpose/Objective(s)</h3> A subset of favorable oral tongue squamous cell carcinoma patients who undergo adequate surgical resection are at low risk of local recurrence to the primary site. Since irradiation of the primary site is the major cause of treatment morbidity during adjuvant radiotherapy, avoidance of this target while still treating the at-risk lymph nodes including the intervening lymphatics between the tongue and neck is an attractive potential treatment strategy. Prior to initiation of an investigator-initiated trial, we sought to quantify the dosimetric advantage of this strategy, hypothesizing intensity modulated proton therapy (IMPT) may further reduce dose to organs at risk (OAR) when avoiding the oral tongue compared to intensity modulated radiation therapy (IMRT). <h3>Materials/Methods</h3> Five consecutive patients with oral tongue cancer treated with postoperative radiation therapy from 8/2020 to 9/2021 were retrospectively reviewed. Novel Clinical Target Volume (CTV) contours were generated that excluded the oral tongue while maintaining coverage of at-risk lymph nodes. Comparison IMRT (X) and IMPT (PBT) plans were generated using both standard treatment volumes (Control) and oral tongue avoidance volumes (Study) (n=4 plans per patient). Dosimetric variables for critical OARs were compared using the paired t-test. <h3>Results</h3> Patients had T1-2 and N0-N2b disease with complete margin-negative partial or hemiglossectomy and bilateral neck dissections. The prescribed dose was 60 Gy in 30 fractions. D95% CTV coverage was similar between X and PBT plans for both Control and Study target volumes. Comparing Control to Study plans, both X (58.9 Gy vs. 38.3 Gy, p=0.007) and PBT (60.2 Gy vs. 26.1 Gy, p<0.001) decreased the mean dose to the oral cavity (OC). Similar results were demonstrated for mean pharyngeal constrictor dose with X (47.7 Gy vs. 44.6 Gy, p=0.003) and PBT (45.0 Gy vs. 34.9 Gy, p=0.001). There was no difference between Control and Study plans for larynx (p>0.19) or parotid (p>0.11) mean dose, or mandible max dose (p>0.59). Comparing the Study plans alone, PBT resulted in a significant reduction in mean OC dose (38.3 Gy vs. 26.1 Gy, p=0.007) and reduction in mean parotid dose (23.3 Gy vs.19.3 Gy, p=0.03) compared to X. For Control plans, there was no difference in OC dose using PBT compared to X but an improvement in mean parotid dose (26.6 Gy vs 19.7 Gy, p=0.02). <h3>Conclusion</h3> This study quantifies the dosimetric advantage of avoiding the oral tongue while still treating the at-risk intervening lymphatics and the bilateral necks during adjuvant radiotherapy for oral tongue cancer. The dosimetric difference between PBT and X was most prominent with an oral tongue avoidance strategy. Prospective studies are warranted to evaluate the clinical efficacy of oral tongue avoidance for favorable oral tongue cancer patients with indications for elective nodal irradiation.

Serum MicroRNAs as Xerostomia Biomarkers in Patients With Oropharyngeal Cancer Undergoing Radiation Therapy

Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. This prospective study enrolled patients with oropharyngeal cancer treated between 2016 and 2018 in 3 centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the European Organisation for Research and Treatment of Cancer H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before radiation therapy, after receiving 20 Gy, and within 24 hours after treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both the exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiation therapy had an area under the curve of 0.96 (95% confidence interval, 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (area under the curve 0.90; 95% confidence interval, 0.75-1.00). These results were confirmed in the validation group. In the validation group, preradiation therapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same 2 miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6% sensitivity and 55.2% specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0% sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0% sensitivity and 58.6% specificity. Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiation therapy or during therapy (after 20 Gy) had significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from that related to the dosimetric data.

Salivary and Dental Complications in Childhood Cancer Survivors Treated With Radiation Therapy to the Head and Neck: A PENTEC Comprehensive Review

Radiation therapy (RT) to the head and neck (H&N) region is critical in the management of various pediatric malignancies; however, it may result in late toxicity. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on salivary dysfunction and dental abnormalities in survivors who received RT to the H&N region as children. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Of the 2,164 articles identified through a literature search, 40 were included in a qualitative synthesis and 3 were included in a quantitative synthesis. The dose-toxicity data regarding salivary function demonstrate that a mean parotid dose of 35 to 40 Gy is associated with a risk of acute and chronic grade ≥2 xerostomia of approximately 32% and 13% to 32%, respectively, in patients treated with chemo-radiation therapy. This risk increases with parotid dose; however, rates of xerostomia after lower dose exposure have not been reported. Dental developmental abnormalities are common after RT to the oral cavity. Risk factors include higher radiation dose to the developing teeth and younger age at RT. This PENTEC task force considers adoption of salivary gland dose constraints from the adult experience to be a reasonable strategy until more data specific to children become available; thus, we recommend limiting the parotid mean dose to ≤26 Gy. The minimum toxic dose for dental developmental abnormalities is unknown, suggesting that the dose to the teeth should be kept as low as possible particularly in younger patients, with special effort to keep doses <20 Gy in patients <4 years old.

Parotid sparing adaptive radiotherapy in head and neck cancer patients: A study evaluating resource intensiveness and impact on quality of life.

e24037 Background: Anatomical changes during the course of parotid sparing IMRT for head and neck cancer can lead to an increase in the actual dose absorbed by the parotid glands, which may be controlled with the use of interval adaptive replanning. In this prospective assessment of adaptive replanning for parotid dose changes, we explored the feasibility of carrying out adaptive replanning based on predefined objective dosimetric criteria at specified time points. We sought to assess the impact of this measure using a clinically meaningful endpoint of patient reported quality of life outcomes. Methods: 90 patients with head and neck radiotherapy indicated for definitive management or adjuvant therapy who had at least one parotid gland receiving a mean dose (MD) of between 25-30Gy were accrued in the study. The index parotid was delineated on the images acquired on 14th and 19th day and the MD was determined by overlaying the verification image on the planned CT. If the MD had increased by 2% of the initial intended dose, an adaptive plan was attempted with an aim to reduce MD by 2% without compromising PTV coverage; this plan was then used to deliver the remaining treatment. Patients were invited to complete QoL questionnaires: EORTC-QLQC30 with HN35 module, and XeQoL score at baseline, at 3 and 9 months after completion of treatment. Results: 46 out of 90 patients met the threshold for adaptive replanning and were switched to the new plan during treatment. Adaptive replanning was triggered at D14 for 31 patients and D19 for the remaining 15. Need for adaptive replanning was associated with receipt of concurrent chemotherapy and weight loss in the first two weeks of RT. QoL was evaluable for 50 patients at 3 months post treatment. In patients who required adaptive replanning per protocol, Mean XeQoL scores at 3 months showed significantly worse scores for overall scores (1.1 vs 2.3, p 0.001) and for the component individual physical, pain, psychological, and social domains. EORTC QLQ-C30 and HN35 questionnaires at 3 months also demonstrated significantly worse mean symptom scores of the relevant domains of mouth dryness (39 vs 60), stickiness (32 vs 54) and swallowing (39 vs 60) in patients who required adaptive replanning versus those who did not. No significant QoL trends were observable in the 31 patients who were evaluable at 9 months post treatment. The average time required for each step in the planning process was comparable for both the initial planning workflow and adaptive replanning process. Conclusions: The trigger criteria for replanning identified a population of patients who have significantly worsened quality of life due to radiation induced xerostomia. The benefits of adaptive replanning strategies based on weekly evaluation, binary thresholds and standard planning procedures is doubtful Clinical trial information: CTRI/2017/11/010683.

Significance of site-specific radiation dose and technique for success of implant-based prosthetic rehabilitation in irradiated head and neck cancer patients-A cohort study.

Radiotherapy aggravates implant-based prosthetic rehabilitation in patients with head and neck cancer. To evaluate the impact of radiation dose at implant and parotid gland site for prosthetic rehabilitation. The retrospective study includes 121 irradiated head and neck cancer patients with 751 inserted implants. Radiation doses on implant bed and parotid gland site were recorded by 3-dimensional modulated radiation plans. Implant success was clinically and radiographically evaluated according to modified Albrektsson criteria and compared to treatment- and patient-specific data. Implant overall survival after 5 years was 92.4% with an implant success rate of 74.9%. Main reasons for implant failure were marginal bone resorption (20.9%), implant not in situ or unloaded (9.6%) and peri-implantitis (7.5%). A mean radiation dose of 62.6Gy was applied with a mean parotid dose of 35 Gy. Modulating radiation techniques went along with lower grades of xerostomia (p < 0.001). At implant site mean doses of 57.5, 42.0, and 32.3Gy were recorded for oral, oropharyngeal, and hypopharyngeal/laryngeal carcinoma, respectively. Implant success inversely correlated to radiation dose at implant site. Strong predictors for implant failure in uni- and multivariate analysis were implant-specific dose >50 Gy (HR 7.9), parotid dose >30 Gy (HR 2.3), bone (HR 14.5) and soft tissue (HR 4.5) transplants, bad oral hygiene (HR 3.8), nonmodulated radiation treatment planning (HR 14.5), and nontelescopic prosthetics (HR 5.2). Radiotherapy impedes implant success in a dose-dependent manner at implant site. Modern radiation techniques effectively reduce xerostomia favoring implant-based prosthetic rehabilitation. Implantation in bone grafts is more critical and telescopic-retained overdentures should be preferred.