Dose-volume Histograms Research Articles

Quantifying Value in an Iterative Disease-Site Specific Peer Review System

To assess the greatest impact of peer review on treatment planning and plan modification in two disease-site specific peer review groups to improve quality assurance workflow. We implemented an iterative peer review checklist tool and treatment planning registry to document recommendations and time spent in breast and thoracic disease-site specific peer review. Plan review included discussion of the clinical scenario, radiation dose/fractionation, prescription, organs at risk and target volumes, planning metrics including dose volume histogram and patient setup. Pre-treatment (Pre-tx) review of volumes and plans occurred prior to treatment start for definitive plans of ≤five fractions or using protons, and cases were re-reviewed in subsequent sessions to complete checklist items as needed. Reviews were graded as follows: discussion (no required changes), minor recommendations (changes recommended at attending discretion) and major recommendations (changes required). Students t-test and chi-squared analysis were used to identify statistical significance. We identified 723 peer reviews over a 3-month period: 275 thoracic reviews of 195 unique patients (32% reviewed ≥twice), and 448 breast reviews of 273 unique patients (48% reviewed ≥twice, most commonly for a boost plan). On average, pre-tx review doubled the amount of time spent per case, (4:47min versus 2:03min, p<0.01) and resulted in significantly more discussion (29.3% vs 9.3%, p<0.01), minor changes recommended (13.2% versus 4.8%, p<0.01) and plan revision (19.2% versus 2.4%, p<0.01). Thoracic pre-tx reviews were twice as long as breast (5:43min versus 3:00min, p<0.01), and had a greater proportion of cases prompting discussion (26.7% vs 13.2%, p<0.01) and minor changes recommended (12.8% vs 6.3%, p<0.01). No time difference was found in regular review (2:19min vs 1:58 min, p = 0.09). The most frequent discussion/recommendation topics also varied by group with planning metrics in thoracic cases (14.9%) and setup imaging including PORT films and electron setup (5.1%) in breast (Table). Iterative plan review with pre-review for selected cases encouraged educational discussion and plan revision, with notable variability by disease site. Thoracic cases required longer review time and had more frequent plan change recommendations likely reflecting differences in case complexity. In contrast, setup imaging in breast cases, which are more commonly 3D or electron-based, more frequently warranted discussion/revision and should be considered within the peer review paradigm.

Quantifying the Dosimetric Impact of Tissue Hounsfield Unit Assignment in Deep Learning-based Synthetic CT Images For MRI-Only Radiation Therapy of The Head and Neck

MRI-only simulation for head and neck (HN) radiotherapy (RT) could allow for single-image modality planning with excellent soft tissue contrast. In the MRI-only simulation workflow, synthetic CTs (sCTs) are generated from MRI to provide electron density information for dose calculation. Bone/air regions produce little MRI signal which could lead to electron density misclassification in sCTs. Establishing the dosimetric impact of this error could inform quality assurance (QA) procedures using MRI-only RT planning. In this study we quantify differences in Hounsfield Unit (HU) values between paired CT/ sCTs of HN cancer patients and investigate the dosimetric impact on clinical treatment plans. Fourteen patients with head and neck cancer undergoing same-day CT and 3T MRI simulation were retrospectively identified. MRIs were deformed to the CT using multimodal deformable image registration. SCTs were generated from T1w DIXON MRI using a commercially available deep learning-based generator (MRIplanner, Spectronics). Tissue voxel assignment was quantified by creating a CT-derived HU threshold contour. CT/sCT HU differences for anatomical/target contours and tissue classification regions including air (<-250HU), adipose tissue (-250HU to -51HU), soft tissue (-50HU to 199HU), spongy (200HU to 499HU) and cortical bone (> 500HU) were quantified. T-test was used to determine if sCT/CT HU differences were significant. The frequency of structures that had a HU difference >70HU (the CT window-width setting for intra-cranial structures) was computed to establish structure classification accuracy. Clinical IMRT treatment plans created on CTs were retrospectively recalculated on sCT images using compared using the gamma metric. The mean ratio of sCT HUs relative to CT for air, adipose tissue, soft tissue, spongy and cortical bone were 1.7±0.3, 1.1±0.1, 1.0±0.1, 0.9±0.1 and 0.8±0.1 (value of 1 indicates perfect agreement). T-tests (significance set at t = 0.05) identified differences in HU values for air, spongy and cortical bone in sCT images compared to CT. The structures with sCT/CT HU differences > 70HU were the L/R cochlea and mandible, occurring in >78% of the tested cohort. These structures contain dense bone/air interfaces. Plans recalculated on sCTs yielded global/local gamma pass rates of 98.7%±1.2% (3mm,3%) and 95.5%±2.5% (1mm,1%). Mean differences in D95, D50, D10 and D2 dose volume histogram (DVH) metrics for organ-at-risk (OAR) and planning tumor volumes (PTV) were 0.8%±1.5% and 2.1% ± 1.2% respectively. In this cohort, HU differences in sCTs were observed but did not translate into a reduction in gamma pass rates and OAR/PTV DVH metrics. The acquisition of additional training data such as ultrashort echo time MRI could improve bone/air contrast and reduce bone/air sCT misclassifications. Further studies will establish the variation in sCT dosimetric accuracy using a larger retrospective cohort to inform QA limits on clinical sCT usage.

Malignant Pleural Mesothelioma and Radiotherapy: Lung Toxicity Results of an Interim Analysis in Prospective Pilot Trial

Malignant Pleural Mesothelioma (MPM) is a rare but aggressive intrathoracic malignancy with an overall poor prognosis. Neoadjuvant chemotherapy, surgery and then radiotherapy is the standard of care in early-stage disease. Our study aim is to evaluate the feasibility and toxicity of the novel adjuvant RT in accelerated hypofractionation. We report the lung toxicity preliminary results of the first patients entreated. Starting in 2017, 29 MPM patients were enrolled in the trial (IRST trial 163). All patients were treated with accelerated hypofractionated radiotherapy using a helical 3-D CRT and IMRT system and intensity-modulated arc therapy. We conducted a prospective mono-institutional clinical trial enrolling cyto-histological proven, MPM patients. The major exclusion criteria were: previous thorax radiotherapy, contralateral mediastinum involvement (N3) and/or M1, interstitial pneumopathy, active pneumonitis, and fissural disease. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. All patients were treated in a 3-D CRT and IMRT system. Patients underwent functional lung study before to start radiotherapy treatment, 2 months and 6 months after the end of the treatment. The organs at risk dose-volume histograms were converted to a 2-Gy equivalent dose, and we closely adhered to the dose constraints of the literature data. We in particular analyzed lung toxicity of the first 20 patients. No G3/G4 lung toxicity was found. We reported 65.0% G1 pneumonitis and 10% G2 as acute lung toxicity. The majority of the G1 patients had only mild symptoms and pneumonitis was described only for radiologic features with no need for medical therapy. Other respiratory toxicities were G1-G2 cough in 50% of the patients; G1 dyspnea occurred in 65% of the patients and G2 in the 15%. The total lung mean dose was 18 Gy (range 13 Gy-23 Gy), and the contralateral lung mean dose was 2 Gy (range 1 Gy-2 Gy). The median value of Forced Expired Volume in one second (FEV1) recorded was 75.5% (range: 46%-137%) before the treatment was started, the median value of Forced Vital Capacity (FVC) at baseline was 74 (range 46-123) with progressive decreasing values through time. DLCO has also been reported with a progressive decrease over time after radiotherapy treatment. No case of respiratory failure was reported after treatment. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. More investigations are mandatory. The protocol is ongoing.

Predicting Prostate VMAT 3D Radiation Doses of Continuously Varying Organ Dose Trade-Offs Using a Conditional Variational Autoencoder

Predicting 3D radiation doses from planning structures is a promising method of knowledge-based treatment planning. However, most models are designed to predict only one 3D dose distribution per patient, based on historical organ dose trade-offs. To allow customizable plan generation, in this study, we aim to show the feasibility of dose prediction in which the degrees of organ dose trade-off could be explicitly specified. Specifically, the bladder vs. rectum dose trade-off in prostate cancer was investigated. In an IRB-approved study, we obtained imaging and structure contours for 167 patients with prostate cancer who received definitive radiotherapy. Training data was generated by automatically creating 3 different plans for each patient: while keeping target dose patterns constant, 1 base plan was generated with optimization objectives directly based on the output of a custom RapidPlan model prediction (S = 0), 1 plan with the goal to significantly lower bladder dose relative to the rectum (S = -1), and 1 plan with the goal to significantly lower rectum dose relative to the bladder (S = 1). This process was achieved by adjusting priority values during optimization. S is a scalar indicating the degree of bladder vs. rectum dose trade-off (higher S = higher dose to the bladder relative to the rectum). A conditional variational autoencoder (cVAE) was constructed as the generative model. Training, validation, and testing sets consist of 124, 10, and 33 patients, respectively. During training, the inputs to the model were 3D structure masks with voxel values modified based on S, and the output was the corresponding 3D dose. For model testing, we selected 7 equispaced values of S in the range [-1, +1] for each of the 33 test patients, generated the 3D doses for each S value (normalized to D2% = 110%), and calculated the differences of key dosimetric parameters (for S levels other than 0) compared to the predicted base plan (S = 0). The mean and standard deviations for these differences were reported. The cVAE model converged after training for 800 epochs. As the value of S increased from -1 to +1, the target coverage remained similar, while the doses to the bladder and rectum increased and decreased, respectively, as expected (Table 1). This pattern was also confirmed by qualitative examination of dose-volume histograms for additional S values. We demonstrated the feasibility of predicting 3D radiation dose distributions for prostate cancer where the degrees of organ dose trade-off could be explicitly specified.

Local Control after Re-Irradiation of Spinal Metastases with Stereotactic Body Radiation Therapy

Determine local control (LC) rate and risk of vertebral compression fractures (VCFs) and radiation myelitis (RM) for patients receiving re-irradiation of spinal metastases (SMs) using stereotactic body radiation therapy (SBRT) from large single-institutional experience with long follow-up. Retrospectively identified patients receiving re-irradiation SBRT (rSBRT, 1, 3, or 5 fractions) to SMs previously treated with radiation therapy (RT) and having follow up imaging to assess local control. 1 fraction patients typically received 20-24 Gy and 16-18 Gy to the high- and low-risk planning target volumes (PTVs), respectively, and 27-39 Gy and 21-24 Gy for the 3 fraction patients, with a single level of 50 Gy for 5 fractions. Patient and treatment characteristics for previous RT (pRT) and rSBRT were collected, including histology and dose-volume histogram statistics (DVH). Kaplan-Meier estimates of overall survival (OS), and cumulative incidence (competing with death) of local failure with death as a competing risk was computed for the whole cohort and stratified by radioresistance of histology, and risk of VCF for RM (for treatments at L1 and above) and 95% confidence intervals. Equivalent dose in 2 Gy fractions (EQD2) for PTV and spinal cord (SC) DVH statistics was computed for each individual course and cumulatively, using a/b = 10 Gy for tumor and 2 Gy for SC. Identified 107 lesions in 91 patients. 48 (45%) had radioresistant histologies. For all patients, at 1 and 2 years, respectively OS was 64% (55-74%) and 43% (34-55%), LC was 88% (81-94%) and 85% (78-91%) with median follow-up of 52 months (Table 1). OS and LC were not significantly different between radiosensitivity groups (p>0.05). Risk of VCF at 1 and 2 years was 7% (3-13%) and 9% (4-16%). RM was identified in 1 patient, who received 30 Gy in 5 fractions to T1, and had 1-fraction rSBRT 21 months later. SC Dmax was 31.5 Gy for pRT and 10.4 Gy, for rSBRT, resulting in total SC EQD2 of 73 Gy. RM was confirmed on MRI 8 months after rSBRT. Cumulative RM risk at 8 months after rSBRT was estimated at 1% (0-4%). Median EQD2 for the minimum dose to the high and low risk PTVs were 17.7 Gy (interquartile range, IQR, 13.0-27.6 Gy) and 13.7 Gy (IQR, 10.8-19.3 Gy) for rSBRT, and maximum EQD to SC for previous RT, rSBRT, and cumulatively was 38 Gy (IQR, 30-41 Gy), 27 Gy (IQR, 22-36 Gy), and 65 Gy (IQR, 54-73 Gy).Re-irradiation of spinal metastasis with SBRT can be delivered safely and provide high rates of local control, including for radioresistant tumors, as demonstrated with the longest reported follow-up in this setting. Re-irradiation of SM with SBRT provides high rates of LC even for radioresistant tumors, and low risk of VCF and RM, based on the longest reported follow-up in this setting.

Comparison of Early Outcomes of Stereotactic Accelerated Partial Breast Irradiation vs. Volumetric Modulated Arc Therapy-Based FAST-FORWARD Whole Breast Irradiation for Breast Cancer

Despite evidence supporting APBI from 8 published prospective randomized trials enrolling over 10,000 women, the uptake of APBI in clinical practice is surprisingly low. This is being exacerbated by a new, convenient, and safe shortened WBI schedule. Here, we report the dosimetric and early outcome analyses of the first >1000 patients treated at our institution since the first adoption of stereotactic APBI and the ultra-hypofractionated WBI regimen. From 2016 to 2022, 801 women with breast cancers in the suitable or cautionary categories according to the ASTRO APBI consensus panel guidelines, received 30 Gy in 5 fractions (92%) either using a robotic stereotactic radiation system (83%) or stereotactic volumetric-based arc therapy (VMAT, 17%). Between 2020 and 2022, 468 women, who were not candidates for APBI and not undergoing any regional irradiation received 26 Gy in 5 fractions using VMAT to the whole breast with the addition of cardiac sparing technique in left-sided breast cancer patients. Tumor bed boosts were delivered in 99% of FF-WBI patients. We evaluated dose-volume histogram parameters for target volumes and organs-at-risk and radiation-related toxicities during RT or within 6 months after the end of RT. Target volume coverage was acceptable in both groups, with mean 96% of the target volumes receiving 95% of the prescribed doses and 0 cm3 within target volumes exceeding 105% of the prescribed doses. S-APBI resulted in small, but statistically significant, reductions in the radiation dose delivered to the ipsilateral breast, contralateral breast, lungs, heart, and coronary artery compared with FF-WBI. Comparing WBI to APBI, the mean contralateral breast dose, ipsilateral lung V20 Gy, mean contralateral lung dose, and mean heart dose, were reduced by 89%, 78%, 73%, and 29%, respectively. With median follow-up periods of 32 months for s-APBI and 19 months for FF-WBI, acute toxicity was assessable in all patients. The risks of any grade acute toxicity were 21% for s-APBI and 25% for FF-WBI (p = .117). Among them, grade 2 rates were 1.3% in both groups and no severe toxicity has been reported. We found s-APBI and VMAT-based FF WBI were associated with favorable dosimetric and acute toxicity profiles. However, considering significantly less irradiated volume in the breast, lungs, and heart, APBI with advanced available technique options should be considered over any WBI-based approach for patients at low risk for local recurrence.

Intrafraction Dosimetric Evaluation of Biology-Guided Radiotherapy to a Target Under Respiratory Motion

To evaluate the reproducibility and variability of biology-guided radiotherapy (BgRT) treatments using a large anthropomorphic phantom modeling the motion amplitude of a lung tumor. RefleXion X1 is equipped with two opposing 90 degrees PET detector arcs to capture the radionuclide emissions and direct the 6MV Linac to treat the lesions in real time. A custom-built phantom filled with a liquid [¹⁸F]Fluorodeoxyglucose (FDG) solution was used. Fillable target and OAR structures were 3D printed and attached to motion stages. The GTV = CTV was matched to the spherical 22 mm diameter target, and the PTV was a 5 mm expansion from the CTV volume. The Biology Tracking Zone (BTZ) was generated after adding 5 mm margin to the motion extent of the CTV. The OAR was a large C-shape annulus (emulating a heart) that was approximately 3 cm from the target. The 3D independent motion trajectory of the target was designed to mimic lung motion: range of +5.8 mm to -4.9 mm in LR, range of +14.4 mm to -11.3 mm in SI, and range of +5.2 mm to -5.1 mm in AP directions. The OAR motion waveform used a 1D sinusoidal pattern with a 5 mm amplitude in SI direction. The target and the OAR were filled with 40 kBq/mL while the background had 5 kBq/mL FDG. A BgRT Modeling (imaging-only) PET acquisition was performed using RefleXion X1 and used to generate a 4-fraction BgRT treatment plan prescribing 10 Gy/fraction to PTV. For each delivery, target, OAR and background were filled with the same FDG concentrations as in the BgRT Modeling PET planning scan. Dosimetry to the target and OAR were both measured using an ion-chamber (Exradin A14SL) and film in the coronal plane through the center of the GTV for all 4 fractions. The mean activity concentration within the (BTZ) was 7.4 ± 0.8 kBq/mL. The calculated signal-to-noise ratio metric (Normalized Target Signal) within the BTZ was 4.0 ± 0.3. Total treatment times were all less than 35 minutes (34.3 ± 0.2). Prescription dose coverage to the CTV for all 4 fractions was 100%. Ion chamber measurements in the CTV were -1.6 ± 1.3% relative to the planned dose over the active area of the ion-chamber. Minimum and maximum doses to the CTV, measured on film, were -7.7 ± 2.2% and 1.3 ± 1.4%, calculated relative to the planned dose distribution, respectively. The OAR maximum point dose measured on film was -8.7 ± 2.9%, calculated relative to the maximum OAR dose predicted on the bounded dose-volume histogram. Based on this initial study, accurate and reproducible dosimetry can be achieved for targets under respiratory motion using biology-guided radiotherapy over the course of a complete course of treatment. Further studies are needed to evaluate the intrafraction dosimetry of BgRT delivery under various motion models and tumor sizes.

Dosimetric and radiobiological comparison between conventional and hypofractionated breast treatment plans using the Halcyon system.

The objective of this research is to compare the efficacy of conventional and hypofractionated radiotherapy treatment plans for breast cancer patients, with a specific focus on the unique features of the Halcyon system. The study collected and analyzed dose volume histogram (DVH) data for two groups of treatment plans implemented using the Halcyon system. The first group consisted of 19 patients who received conventional fractionated (CF) treatment with a total dose of 50 Gy in 25 fractions, while the second group comprised 9 patients who received hypofractionated (HF) treatment with a total dose of 42.56 Gy in 16 fractions. The DVH data was used to calculate various parameters, including tumor control probability (TCP), normal tissue complication probability (NTCP), and equivalent uniform dose (EUD), using radiobiological models. The results indicated that the CF plan resulted in higher TCP but lower NTCP for the lungs compared to the HF plan. The EUD for the HF plan was approximately 49 Gy (114% of its total dose) while that for the CF plan was around 53 Gy (107% of its total dose). The analysis suggests that while the CF plan is better at controlling tumors, it is not as effective as the HF plan in minimizing side effects. Additionally, it is suggested that there may be an optimal configuration for the HF plan that can provide the same or higher EUD than the CF plan.

Dose distribution prediction for head-and-neck cancer radiotherapy using a generative adversarial network: influence of input data.

A three-dimensional deep generative adversarial network (GAN) was used to predict dose distributions for locally advanced head and neck cancer radiotherapy. Given the labor- and time-intensive nature of manual planning target volume (PTV) and organ-at-risk (OAR) segmentation, we investigated whether dose distributions could be predicted without the need for fully segmented datasets. GANs were trained/validated/tested using 320/30/35 previously segmented CT datasets and treatment plans. The following input combinations were used to train and test the models: CT-scan only (C); CT+PTVboost/elective (CP); CT+PTVs+OARs+body structure (CPOB); PTVs+OARs+body structure (POB); PTVs+body structure (PB). Mean absolute errors (MAEs) for the predicted dose distribution and mean doses to individual OARs (individual salivary glands, individual swallowing structures) were analyzed. For the five models listed, MAEs were 7.3 Gy, 3.5 Gy, 3.4 Gy, 3.4 Gy, and 3.5 Gy, respectively, without significant differences among CP-CPOB, CP-POB, CP-PB, among CPOB-POB. Dose volume histograms showed that all four models that included PTV contours predicted dose distributions that had a high level of agreement with clinical treatment plans. The best model CPOB and the worst model PB (except model C) predicted mean dose to within ±3 Gy of the clinical dose, for 82.6%/88.6%/82.9% and 71.4%/67.1%/72.2% of all OARs, parotid glands (PG), and submandibular glands (SMG), respectively. The R2 values (0.17/0.96/0.97/0.95/0.95) of OAR mean doses for each model also indicated that except for model C, the predictions correlated highly with the clinical dose distributions. Interestingly model C could reasonably predict the dose in eight patients, but on average, it performed inadequately. We demonstrated the influence of the CT scan, and PTV and OAR contours on dose prediction. Model CP was not statistically different from model CPOB and represents the minimum data statistically required to adequately predict the clinical dose distribution in a group of patients.

Beam mask and sliding window-facilitated deep learning-based accurate and efficient dose prediction for pencil beam scanning proton therapy.

Accurate and efficient dose calculation is essential for on-line adaptive planning in proton therapy. Deep learning (DL) has shown promising dose prediction results in photon therapy. However, there is a scarcity of DL-based dose prediction methods specifically designed for proton therapy. Successful dose prediction method for proton therapy should account for more challenging dose prediction problems in pencil beam scanning proton therapy (PBSPT) due to its sensitivity to heterogeneities. To develop a DL-based PBSPT dose prediction workflow with high accuracy and balanced complexity to support on-line adaptive proton therapy clinical decision and subsequent replanning. PBSPT plans of 103 prostate cancer patients (93 for training and the other 10 for independent testing) and 83 lung cancer patients (73 for training and the other 10 for independent testing) previously treated at our institution were included in the study, each with computed tomography scans (CTs), structure sets, and plan doses calculated by the in-house developed Monte-Carlo dose engine (considered as the ground truth in the model training and testing). For the ablation study, we designed three experiments corresponding to the following three methods: (1) Experiment 1, the conventional region of interest (ROI) (composed of targets and organs-at-risk [OARs]) method. (2) Experiment 2, the beam mask (generated by raytracing of proton beams) method to improve proton dose prediction. (3) Experiment 3, the sliding window method for the model to focus on local details to further improve proton dose prediction. A fully connected 3D-Unet was adopted as the backbone. Dose volume histogram (DVH) indices, 3D Gamma passing rates with a criterion of 3%/3mm/10%, and dice coefficients for the structures enclosed by the iso-dose lines between the predicted and the ground truth doses were used as the evaluation metrics. The calculation time for each proton dose prediction was recorded to evaluate the method's efficiency. Compared to the conventional ROI method, the beam mask method improved the agreement of DVH indices for both targets and OARs and the sliding window method further improved the agreement of the DVH indices (for lung cancer, CTV D98 absolute deviation: 0.74 ± 0.18 vs. 0.57 ± 0.21 vs. 0.54 ± 0.15 Gy[RBE], ROI vs. beam mask vs. sliding window methods, respectively). For the 3D Gamma passing rates in the target, OARs, and BODY (outside target and OARs), the beam mask method improved the passing rates in these regions and the sliding window method further improved them (for prostate cancer, targets: 96.93% ± 0.53% vs. 98.88% ± 0.49% vs. 99.97% ± 0.07%, BODY: 86.88% ± 0.74% vs. 93.21% ± 0.56% vs. 95.17% ± 0.59%). A similar trend was also observed for the dice coefficients. This trend was especially remarkable for relatively low prescription isodose lines (for lung cancer, 10% isodose line dice: 0.871 ± 0.027 vs. 0.911 ± 0.023 vs. 0.927 ± 0.017). The dose predictions for all the testing cases were completed within 0.25s. An accurate and efficient deep learning-augmented proton dose prediction framework has been developed for PBSPT, which can predict accurate dose distributions not only inside but also outside ROI efficiently. The framework can potentially further reduce the initial planning and adaptive replanning workload in PBSPT.

Characterization of Photon Intensity Modulated Radiation Therapy Robustness in Patients With Prostate Cancer as a Proposed Benchmark for Proton Therapy Robustness Evaluation

Robustness evaluation is increasingly used in particle therapy planning to assess clinical target volume (CTV) coverage in the setting of setup and range uncertainty. However, no clear standard exists as to an acceptable degree of plan robustness. The aim of this study is to quantify x-ray robustness parameters, as this could inform proton planning when held to a similar standard. Consecutive patients with prostate adenocarcinoma treated with definitive x-irradiation to the prostate alone at a single institution in 2019 were retrospectively reviewed. CTV to planned target volume (PTV) margins of 7 mm in all directions, except 4 mm posteriorly, were used in the main cohort. Plans were normalized to PTV V100% ≥ 95%. Patient setup errors were simulated by shifting the isocenter relative to the patient in each of the cardinal directions. The magnitude of each shift equaled the magnitude of the CTV to PTV expansion in that direction. Range uncertainty was set to 0%. A total of 27 patients were evaluated. The mean (SD) nominal plan CTV V100% was 99.6% (1.1%). The mean (SD) worst-case shift CTV V100% was 97.2% (2.8%). The mean (SD) nominal and worst-case CTV V95% were 100% (0%) and 99.7% (0.5%), respectively. A worst-case CTV V100% > 90% and a worst-case CTV V95% > 99% were achieved in over 95% of plans. The mean (SD) nominal and worst-case rectal V70 Gy were 2.37 cc (1.00 cc) and 11.60 cc (3.16 cc), respectively. The mean (SD) nominal and worst-case bladder V60 Gy were 7.8% (4.8%) and 14.5% (9.3%), respectively. Paired 2-tailed t tests comparing the nominal to worst-case dose-volume histograms were significant for each dosimetric parameter (P < .01). X-ray planning uses PTV margins to inherently provide robustness to patient setup errors. Although the prostate remains well covered in various setup uncertainty scenarios, organs at risk routinely exceeded nominal treatment plan institutional constraints in the worst-case scenarios. Robustness metrics obtained from x-ray plans could serve as a benchmark for proton therapy robust optimization and evaluation.

Dosimetric investigation of radiation-induced trigeminal nerve toxicity in parotid tumor patients.

We aimed to describe the association between trigeminal nerve (TN) dose and toxicity and determine a threshold value that leads to TN toxicity in patients with parotid tumors treated with adjuvant conventional fractionated radiation therapy. Eighteen patients who underwent adjuvant radiotherapy (RT) between 2013 and 2018 were included in this retrospective study. TN and its branches were outlined subsequently on the planning CT scans. The doses received by TN were obtained based on the dose-volume histogram. The dose and toxicity relationship was investigated over the total prescribed dose. RT-related toxicity was graded according to Common Terminology Criteria for Adverse Events V4.0 (CTCAEv4.0). The median follow-up was 29.5 months. After RT, 61% of patients had Grade I-II late TN toxicity divided into Grade I in 4 (22%) and Grade II in 7 (39%) patients. TN injury symptoms were as follows: loss of sensation in the chin area in 3, difficulty in jaw movements in 3, and paresthesia in 5 patients. The total RT dose (p = 0.001), Dmax (p = 0.001), PTV-TN Dmax (p = 0.001), D1cc (p = 0.004), D0.5cc (p = 0.001), and D0.1cc (p = 0.01) had a significant effect on TN toxicity. Cut-off values leading to toxicity were determined as 66, 65.5, 65.25, 63.6, and 62.7 Gy for Dmax, PTV-TN Dmax, D0.1cc, D 0.5cc, and D1cc, respectively. Radiation-induced TN injury in head and neck cancer patients may further be investigated in clinically prospective trials by virtue of high toxicity rates with current RT doses in our retrospectively designed dosimetric study in parotid tumors.

Monte Carlo investigation of dose distribution of uniformly and non-uniformly loaded standard and notched eye plaques.

To investigate the effect of using non-uniform loading and notched plaques on dose distribution for eye plaques. Using EGSnrc Monte Carlo (MC) simulations, we investigate eye plaque dose distributions in water and in an anatomically representative eye phantom. Simulations were performed in accordance with TG43 formalism and compared against full MC simulations which account for inter-seed and inhomogeneity effects. For standard plaque configurations, uniformly and non-uniformly loaded plaque dose distributions in water showed virtually no difference between each other. For standard plaque, the MC calculated dose distribution in planes parallel to the plaque is narrower than the TG43 calculation due to attenuation at the periphery of the plaque by the modulay. MC calculated the dose behind the plaque is fully attenuated. Similar results were found for the notched plaque, with asymmetric attenuation along the plane of the notch. Cumulative dose volume histograms showed significant reductions in the calculated MC doses for both tumor and eye structures, compared to TG43 calculations. The effect was most pronounced for the notch plaque where the MC dose to the optic nerve was greatly attenuated by the modulay surrounding the optic nerve compared to the TG43. Thus, a reduction of optic nerve D95% from 14 to 0.2Gy was observed, when comparing the TG43 calculation to the MC result. The tumor D95% reduced from 89.2 to 79.95Gy for TG43 and MC calculations, respectively. TG43 calculations overestimate the absolute dose and the lateral dose distribution of both standard and notched eye plaques, leading to the dose overestimation for the target and organs at risk. The dose matching along the central axis for the non-uniformly loaded plaques to that of uniformly loaded ones was found to be sufficient for providing comparable coverage and can be clinically used in eye-cancer-busy centers.

Correcting for the heterogeneous boron distribution in a tumor for BNCT dose calculation

Most treatment planning systems of boron neutron capture therapy perform dose calculations based on the assumption of a homogeneous boron distribution in tumors, which leads to dose distortion due to the difference between the tumor-to-normal tissue ratio (TNR) range measured in positron emission tomography images (PET) and the target delineation in computed tomography images of the treatment plan. The heterogeneous boron distribution in the target of the treatment plan can be obtained by image fusion. This study provides a way to quantify a heterogeneous boron distribution based on PET images. Theoretically, the same mean TNR for dose calculation by homogeneous or heterogeneous boron distribution should get almost the same mean dose. However, slightly different mean doses are found due to the partial volume effect for a small target volume. The wider the boron distribution is, the higher the impact on the dose-volume histogram distribution is. Dose distribution with homogeneous boron distribution may be overestimated in low boron uptake regions by wrong boron concentration and neutron flux depression. To accurately give the tumor prescription dose and achieve better tumor control, for low dose regions of the tumor should be considered more boron neutron capture therapy treatments or combined with other treatment modalities. The heterogeneous boron distribution must be taken into consideration to have an accurate dose estimation. Therefore, the way how medical physicists and clinicians process the TNR in gross tumor volume should be refined, and the method demonstrated in the work provides a good reference.

Investigation on the physical dose filtered by linear energy transfer for treatment plan evaluation in carbon ion therapy.

Large tumor size has been reported as a predicting factor for inferior clinical outcome in carbon ion radiotherapy (CIRT). Besides the clinical factors accompanied with such tumors, larger tumors receive typically more low linear energy transfer (LET) contributions than small ones which may be the underlying physical cause. Although dose averaged LET is often used as a single parameter descriptor to quantify the beam quality, there is no evidence that this parameter is the optimal clinical predictor for the complex mixed radiation fields in CIRT. Purpose of this study was to investigate on a novel dosimetric quantity, namely high-LET-dose ( , the physical dose filtered based on an LET threshold) as a single parameter estimator to differentiate between carbon ion treatment plans (cTP) with a small and large tumorvolume. Ten cTPs with a planning target volume, (large) and nine with a (small) were selected for this study. To find a reasonable LET threshold ( ) that results in a significant difference in terms of , the voxel based normalized high-LET-dose ( ) distribution in the clinical target volume (CTV) was studied on a subset (12 out of 19 cTPs) for 18 LET thresholds, using standard distribution descriptors (mean, variance and skewness). The classical dose volume histogram concept was used to evaluate the and distributions within the target of all 19 cTPs at the before determined . Statistical significance of the difference between the two groups in terms of mean and volume histogram parameters was evaluated by means of (two-sided) t-test or Mann-Whitney-U-test. In addition, the minimum target coverage at the above determined was compared and validated against three other thresholds to verify its potential in differentiation between small and large volumetumors. An of approximately was found to be a reasonable threshold to classify the two groups. At this threshold, the and were significantly larger ( ) in small CTVs. For the small tumor group, the near-minimum and median (and ) in the CTV were in average (0.31 ± 0.08) and (0.46 ± 0.06), respectively. For the large tumors, these parameters were (0.20 ± 0.01) and (0.28 ± 0.02). The difference between the two groups in terms of mean near-minimum and median ( ) was 2.7 Gy (11%) and 5.0 Gy (18%),respectively. The feasibility of high-LET-dose based evaluation was shown in this study where a lower was found in cTPs with a large tumor size. Further investigation is needed to draw clinical conclusions. The proposed methodology in this work can be utilized for future high-LET-dose basedstudies.

Uncertainty in magnetic resonance imaging-based prostate postimplant dosimetry: Results of a 10-person human observer study, and comparisons with automatic postimplant dosimetry

Uncertainties in postimplant quality assessment (QA) for low-dose-rate prostate brachytherapy (LDRPBT) are introduced at two steps: seed localization and contouring. We quantified how interobserver variability (IoV) introduced in both steps impacts dose-volume-histogram (DVH) parameters for MRI-based LDRPBT, and compared it with automatically derived DVH parameters. Twenty-five patients received MRI-based LDRPBT. Seven clinical observers contoured the prostate and four organs at risk, and 4 dosimetrists performed seed localization, on each MRI. Twenty-eight unique manual postimplant QAs were created for each patient from unique observer pairs. Reference QA and automatic QA were also performed for each patient. IoV of prostate, rectum, and external urinary sphincter (EUS) DVH parameters owing to seed localization and contouring was quantified with coefficients of variation. Automatically derived DVH parameters were compared with those of the reference plans. Coefficients of variation (CoVs) owing to contouring variability (CoVcontours) were significantly higher than those due to seed localization variability (CoVseeds) (median CoVcontours vs. median CoVseeds: prostate D90-15.12% vs. 0.65%, p < 0.001; prostate V100-5.36% vs. 0.37%, p < 0.001; rectum V100-79.23% vs. 8.69%, p < 0.001; EUS V200-107.74% vs. 21.18%, p < 0.001). CoVcontours were lower when the contouring observers were restricted to the 3 radiation oncologists, but were still markedly higher than CoVseeds. Median differences in prostate D90, prostate V100, rectum V100, and EUS V200 between automatically computed and reference dosimetry parameters were 3.16%, 1.63%, -0.00 mL, and -0.00 mL, respectively. Seed localization introduces substantially less variability in postimplant QA than does contouring for MRI-based LDRPBT. While automatic seed localization may potentially help improve workflow efficiency, it has limited potential for improving the consistency and quality of postimplant dosimetry.

Automated evaluation for rapid implementation of knowledge-based radiotherapy planning models.

Knowledge-based planning (KBP) offers the ability to predict dose-volume metrics based on information extracted from previous plans, reducing plan variability and improving plan quality. As clinical integration of KBP is increasing there is a growing need for quantitative evaluation of KBP models. A .NET-based application, RapidCompare, was created for automated plan creation and analysis of Varian RapidPlan models. RapidCompare was designed to read calculation parameters and a list of reference plans. The tool copies the reference plan field geometry and structure set, applies the RapidPlan model, optimizes the KBP plan, and generates data for quantitative evaluation of dose-volume metrics. A cohort of 85 patients, divided into training (50), testing (10), and validation (25) groups, was used to demonstrate the utility of RapidCompare. After training and tuning, the KBP model was paired with three different optimization templates to compare various planning strategies in the validation cohort. All templates used the same set of constraints for the planning target volume (PTV). For organs-at-risk, the optimization template provided constraints using the whole dose-volume histogram (DVH), fixed-dose/volume points, or generalized equivalent uniform dose (gEUD). The resulting plans from each optimization approach were compared using DVH metrics. RapidCompare allowed for the automated generation of 75 total plans for comparison with limited manual intervention. In comparing optimization techniques, the Dose/Volume and Lines optimization templates generated plans with similar DVH metrics, with a slight preference for the Lines technique with reductions in heart V30Gy and spinal cord max dose. The gEUD model produced high target heterogeneity. Automated evaluation allowed for the exploration of multiple optimization templates in a larger validation cohort than would have been feasible using a manual approach. A final KBP model using line optimization objectives produced the highest quality plans without human intervention.

Retrospective Analysis of the Areas Responsible for Light Flash and Odor During Proton Beam Therapy and Photon Therapy.

Background Abnormal sensations were frequently experienced by patients who received irradiation of the brain or head and neck region. We have previously suggested correlations with irradiation of the nasal cavity and retina. Purpose We performed a retrospective dose-volume histogram analysis focused on the brain and head and neck tumor to examine the relationship between these abnormal sensations and the details of irradiation. Methods Multivariate logistic regression models were applied for the presence or absence of light flash and odor. Gender, age, radiotherapy method (proton beam therapy vs. photon radiotherapy), dose of retina, optic nerve, chiasmatic gland, pituitary, nasal cavity, oral cavity, frontal lobe, parietal lobe, occipital lobe, temporal lobe, amygdala, and hippocampus were set as candidates of explanatory variables. Results Light flash and odor during radiotherapy have been suggested to be associated with younger age and retina and nasal cavity irradiation. Multivariate analyses including dose-volume histograms indicated that light flash was related to age, chiasmatic gland irradiation, and pituitary dose, and odor was related to age and nasal cavity irradiation. Conclusion Our results indicate that light flash during radiotherapy is caused by irradiation of the visual pathway and that odor is caused by irradiation of the nasal cavity or olfactory bulb.

Dosimetric Validation for Prospective Clinical Trial of GRID Collimator-Based Spatially Fractionated Radiation Therapy: Dose Metrics Consistency and Heterogeneous Pattern Reproducibility

Dose heterogeneity within a tumor target is likely responsible for the biologic effects and local tumor control from spatially fractionated radiation therapy (SFRT). This study used a commercially available GRID-pattern dose mudulated nonuniform radiation therapy (GRID) collimator to assess the interplan variability of heterogeneity dose metrics in patients with various bulky tumor sizes and depths. The 3-dimensional heterogeneity metrics of 14 bulky tumors, ranging from 155 to 2161 cm3 in volume, 6 to 23 cm in equivalent diameter, and 3 to 13 cm in depth, and treated with GRID collimator-based SFRT were studied. A prescription dose of 15 Gy was given at the tumor center with 6 MV photons. The dose-volume histogram indices, dose heterogeneity parameters, and peak/valley dose ratios were derived; the equivalent uniform doses of cancer cells with various radiosensitivities in each plan were estimated. To account for the spatial fractionation, high dose core number density of the tumor target was defined and calculated. Among 14 plans, the dose-volume histogram indices D5, D10, D50, D90, and D95 (doses covering 5%, 10%, 50%, 90%, and 95% of the target volume) were found within 10% variation. The dose ratio of D10/D90 also showed a moderate consistency (range, 3.9-5.0; mean, 4.4). The equivalent uniform doses were consistent, ranging from 4.3 to 5.5 Gy, mean 4.6 Gy, for radiosensitive cancer cells and from 5.8 to 6.9 Gy, mean 6.2 Gy, for radioresistant cancer cells. The high dose core number density was within 20% among all plans. GRID collimator-based SFRT delivers a consistent heterogeneity dose distribution and high dose core density across bulky tumor plans. The interplan reproducibility and simplicity of GRID therapy may be useful for certain clinical indications and interinstitutional clinical trial design, and its heterogeneity metrics may help guide multileaf-collimator-based SFRT planning to achieve similar or further optimized dose distributions.

An In-House 3D Voxel Dosimetric Tool to Compare Predictive and Post- Treatment Dosimetry in 90Y Radioembolization: A Proof of Concept.

The aim of this study was to implement an in-house dosimetric tool to assess tumour- absorbed doses in pre and post-dosimetry for 90Y radioembolization with resin spheres. To perform dosimetric calculations we set up a dosimetric procedure and developed homemade software to calculate tumour absorbed dose and dose volume histograms (DVHs). The method is based on a simplified voxel dosimetry for an estimated 3D absorbed dose and it can be applied to both 99mTc-MAA SPECT/CT and 90Y PET/CT acquisitions for pre and post-dosimetry. We tested the software performance in a retrospective study using the data of 22 patients with hepatocellular carcinoma who underwent radioembolization with 90Y resin spheres in the period 2016-2021. The software calculates tumour doses (mean, minimum and maximum doses) from voxel counts and dose-volume histograms (DVH_spect, DVH_pet) for both 99mTc-MAA SPECT/CT and 90Y PET/CT imaging. DVH_spect and DVH_pet data were analyzed and compared with the aim to assess an agreement between them. Concordance between dosimetric data were evaluated with the Wilcoxon Signed Ranked test, descriptive statistical analysis and Pearson correlation coefficient. The mean administrated activity was 1313 MBq (range 444 MBq - 2200 MBq). Tumour volumes ranged from 75 mL to 1012 mL. The mean absorbed dose for tumour volume was 161 ± 66 Gy (Dm_spect) and 173 ± 79 Gy (Dm_pet). From Wilcoxon Signed Rank Test the differences between the dosimetric data extrapolated from DVH_spect and DVH_pet results were not significant with α = 0.05 (two-sided test). A good linear correlation was found between 99mTc-MAA and 90Y dosimetric data (Pearson correlation coefficient 0.887 p < 0.001). Generally, DVHs calculated on 99mTc-MAA SPECT/CT and 90Y PET/CT gave comparable results, some discrepancies were observed particularly with those patients where SPECT and PET imaging presented a visual mismatching. A simplified 3D dosimetry methodology was implemented and tested retrospectively on patient data treated with 90Y resin spheres. Even if the clinical feasibility of our approach has to be further validated on an extended patient cohort, the preliminary results of our study highlight the potential of the implemented dosimetric tool for tumour dose assessment.