Dose-volume Histogram Parameters Research Articles

Minimizing normal tissue low dose bath for left breast Volumetric Modulated Arc Therapy (VMAT) using jaw offset.

With proper beam setup and optimization constraints in the treatment planning system, volumetric modulated arc therapy (VMAT) can improve target dose coverage and conformity while reducing doses to adjacent structures for whole breast radiation therapy. However, the low-dose bath effect on critical structures, especially the heart and the ipsilateral lung, remains a concern. In this study, we present a VMAT technique with the jaw offset VMAT (JO-VMAT) to reduce the leakage and scatter doses to critical structures for whole breast radiation therapy. The data of 10 left breast cancer patients were retrospectively used for this study. CT images were acquired on a CT scanner (GE, Discovery) with the deep-inspiration breath hold (DIBH) technique. The planning target volumes (PTVs) and the normal structures (the lungs, the heart, and the contralateral breast) were contoured on the DIBH scan. A 3D field-in-field plan (3D-FiF), a tangential VMAT (tVMAT) plan, and a JO-VMAT plan were created with the Eclipse treatment planning system. An arc treatment field with the x-jaw closed across the central axis creates a donut-shaped high-dose distribution and a cylinder-shaped low-dose volume along the central axis of gantry rotation. Applying this setup with proper multi-leaf collimator (MLC) modulation, the optimized plan potentially can provide sufficient target coverage and reduce unnecessary irradiation to critical structures. The JO-VMAT plans involve 5-6 tangential arcs (3 clockwise arcs and 2-3 counterclockwise arcs) with jaw offsets. The plans were optimized with objective functions specified to achieve PTV dose coverage and homogeneity; For organs at risk (OARs), objective functions were specified individually for each patient to accomplish the best achievable treatment plan. For tVMAT plans, optimization constraints were kept the same except that the jaw offset was removed from the initial beam setup. The dose volume histogram (DVH) parameters were generated for dosimetric evaluation of PTV and OARs. The D95% to the PTV was greater than the prescription dose of 42.56Gy for all the plans. With both VMAT techniques, the PTV conformity index (CI) was statistically improved from 0.62 (3D-FiF) to 0.83 for tVMAT and 0.84 for JO-VMAT plans. The difference in the homogeneity index (HI) was not significant. The Dmax to the heart was reduced from 12.15Gy for 3D-FiF to 8.26Gy for tVMAT and 7.20Gy for JO-VMAT plans. However, a low-dose bath effect was observed with tVMAT plans to all the critical structures including the lungs, the heart, and the contralateral breast. With JO-VMAT, the V5Gy and V2Gy of the heart were reduced by 32.7% and 15.4% compared to 3D-FiF plans. Significantly, the ipsilateral lung showed a reduction in mean dose (4.65-3.44Gy) and low dose parameters (23.4% reduction for V5Gy and 10.7% reduction for V2Gy) for JO-VMAT plans compared to the 3D-FiF plans. The V2Gy dose to the contralateral lung and breast was minimal with JO-VMAT techniques. A JO-VMAT technique was evaluated in this study and compared with 3D-FiF and tVMAT techniques. Our results showed that the JO-VMAT technique can achieve clinically comparable coverage and homogeneity and significantly improve dose conformity within PTV. Additionally, JO-VMAT eliminated the low-dose bath effect at all OARs evaluation metrics including the ipsilateral/contralateral lung, the heart, and the contralateral breast compared to 3D-FiF and tVMAT. This technique is feasible for the whole breast radiation therapy of left breast cancers.

Dosimetric analysis of different optimization algorithms for three-dimensional brachytherapy for gynecologic tumors

To investigate the dosimetric difference between manual and inverse optimization in 3-dimensional (3D) brachytherapy for gynecologic tumors. This retrospective study was conducted among a total of 110 patients with gynecologic tumors undergoing intracavitary combined with interstitial brachytherapy or interstitial brachytherapy. Based on the original images, the brachytherapy plans were optimized for each patient using Gro, IPSA1, IPSA2 (with increased volumetric dose limits on the basis of IPSA1) and HIPO algorithms. The dose-volume histogram (DVH) parameters of the clinical target volume (CTV) including V200, V150, V100, D90, D98 and CI, and the dosimetric parameters D2cc, D1cc, and D0.1cc for the bladder, rectum, and sigmoid colon were compared among the 4 plans. Among the 4 plans, Gro optimization took the longest time, followed by HIPO, IPSA2 and IPSA1 optimization. The mean D90, D98, and V100 of HIPO plans were significantly higher than those of Gro and IPSA plans, and D90 and V100 of IPSA1, IPSA2 and HIPO plans were higher than those of Gro plans (P < 0.05), but the CI of the 4 plans were similar (P > 0.05). For the organs at risk (OARs), the HIPO plan had the lowest D2cc of the bladder and rectum; the bladder absorbed dose of Gro plans were significantly greater than those of IPSA1 and HIPO (P < 0.05). The D2cc and D1cc of the rectum in IPSA1, IPSA2 and HIPO plans were better than Gro (P < 0.05). The D2cc and D1cc of the sigmoid colon did not differ significantly among the 4 plans. Among the 4 algorithms, the HIPO algorithm can better improve dose coverage of the target and lower the radiation dose of the OARs, and is thus recommended for the initial plan optimization. Clinically, the combination of manual optimization can achieve more individualized dose distribution of the plan.

Impact of Radiation on Dysphagia-Related Structures: A Dosimetric and Clinical Comparative Analysis of Three-Dimensional Conformal Radiotherapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) Techniques in Patients With Head and Neck Cancer.

Introduction Head and neck squamous cell carcinoma (HNSCC)is a significant health concern in India, with around one million new cases annually. The prevalence of HNSCC is notably high in Asia, especially in India, due to habitslike tobacco chewing, betel nut usage, and alcohol consumption. Treatment typically involves a combination of surgery, radiation, chemotherapy, and biological therapy, aiming for tumor control while preserving function and quality of life. However, survivors often face long-term side effectslike difficulty swallowing, leading to complicationssuch as aspiration pneumonia. Intensity-modulated radiotherapy (IMRT) has shown promise in improving outcomes by sparing critical swallowing structures. Efforts to minimize radiation-related dysphagia are crucial for enhancing patients' quality of life post-treatment. Our study focuses on examining dosimetric parameters associated with dysphagia aspiration, alongside evaluating dysphagia grades in both treatment groups using the RTOGscale. Material and methods Patients with histologically confirmed non-metastatic head and neck carcinomas were included in our study in November 2018-April 2020. A total of 56 patients were taken into our study with 28 in each arm. They underwent radical radiotherapy (RT) with a total dose of 66-70 Gy, with or without concurrent chemotherapy, meeting specific inclusion criteria and excluding those receiving reirradiation or with distant metastasis. Patients were divided into two groups: Group I received three-dimensional conformal radiotherapy (3D-CRT), and Group II received IMRT. Treatment planning involved immobilization, CT imaging, delineation of target volumes and organs at risk, and contouring of swallowing structures. Dose-volume histogram parameters (mean dose, maximum dose, V30, V70, V80, D50, and D80) were used to assess mean dose to swallowing structures outside the planning target volume (PTV), with a mean dose constraint of 50 Gy. Dysphagia was evaluated using the RTOGcriteria at baseline, during treatment, and six months post-treatment. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In our study, the mean age at presentation differed slightly between the IMRT and 3D-CRT arms: 58 years versus 55 years, respectively. A higher proportion of patients in both arms experienced symptoms for three to six months, with 53.6% in 3D-CRT and 42.9% in IMRT. Stage distribution varied, with IV being most common in 3D-CRT and stage II in IMRT. Approximately 56% of patients in both groups had a history of smoking. Significant differences were observed in spinal cord dose between 3DCRT and IMRT techniques (p < 0.001). Similarly, a significant difference was found in the mean dose received by dysphagia aspiration-related structures (DARSs) between the 3D-CRT and IMRT arms (p = 0.04). Patients in the IMRT arm exhibited superior dysphagia grades compared to those in the 3D-CRT arm, with statistical significance observed in the third month (p = 0.008) and sixth month (p = 0.048). Conclusion Our study found a notable decrease in the mean DARS dose and reduced dysphagia severity at three and six months in the IMRT group compared to the 3D-CRT group. However, due to the diverse study population, establishing a definitive correlation between the DARS dose and dysphagia severity was challenging. Future large-scale studies are needed to validate these findings for improved preservation of DARS structures.

Minimum imaging dose for deep learning-based pelvic synthetic computed tomography generation from cone beam images

Background and purposeDaily cone-beam computed tomography (CBCT) in image-guided radiotherapy administers radiation exposure and subjects patients to secondary cancer risk. Reducing imaging dose remains challenging as image quality deteriorates. We investigated three imaging dose levels by reducing projections and correcting images using two deep learning algorithms, aiming at identifying the lowest achievable imaging dose. Materials and methodsCBCTs were reconstructed with 100%, 25%, 15% and 10% projections. Models were trained (30), validated (3) and tested (8) with prostate cancer patient datasets. We optimized and compared the performance of 1) a cycle generative adversarial network (cycleGAN) with residual connection and 2) a contrastive unpaired translation network (CUT) to generate synthetic computed tomography (sCT) from reduced imaging dose CBCTs. Volumetric modulated arc therapy plans were optimized on a reference intensity-corrected full dose CBCTcor and recalculated on sCTs. Hounsfield unit (HU) and positioning accuracy were evaluated. Bladder and rectum were manually delineated to determine anatomical fidelity. ResultsAll sCTs achieved average mean absolute mean absolute error/structural similarity index measure/peak signal-to-noise ratio of ⩽59HU/⩾0.94/⩾33 dB. All dose-volume histogram parameter differences were within 2 Gy or 2%. Positioning differences were ⩽0.30 mm or 0.30°. cycleGAN with Dice similarity coefficients (DSC) for bladder/rectum of ⩾0.85/⩾0.81 performed better than CUT (⩾0.83/⩾0.76). A significantly lower DSC accuracy was observed for 15% and 10% sCTs. cycleGAN performed better than CUT for contouring, however both yielded comparable outcomes in other evaluations. ConclusionsCTs based on different CBCT doses using cycleGAN and CUT were investigated. Based on segmentation accuracy, 25% is the minimum imaging dose.

IMRT Planning Using 5, 7 and 9 Radiation Field Directions for Nasopharyngeal Cancer Cases

Nasopharyngeal carcinoma (NPC) is one of the deadliest cancers in the world. In treating NPC, Intensity Modulated Radiation Therapy (IMRT) uses radiation fields from several directions to kill cancer cells and shrink tumours. IMRT requires accurate planning using the Treatment Planning System (TPS) to avoid organs at risk (OARs) around the nasopharyngeal cavity. The purpose of this study is to analyse the results of different number of radiation field directions in treatment planning for nasopharyngeal cancer using IMRT. The study focuses on the distribution of dose in the target tumour and organs at risk around the target. The treatment planning parameters are Dose Volume Histogram (DVH), Conformity Index (CI), Homogeneity Index (HI), dose at organs at risk (OARs) and beam on time (BOT). This study used TPS Monaco with the Monte Carlo algorithm and the inverse planning method. Based on DVH, CI, HI and BOT parameters, the results of this study indicate that the most optimal number of radiation field directions to give prescribed doses was 9 radiation field directions. There was no significant difference in the average dose received by OARs in planning with 7 and 9 radiation field directions. In the planning using 5 field directions, some of the OARs received doses above the tolerance limit. While in the planning using 7 and 9 field directions, most of the OARs received doses below the tolerated doses which met the permitted treatment requirements.

Development of patient and catheter specific error thresholds for high dose rate prostate brachytherapy.

In-vivo source tracking has been an active topic of research in the field of high-dose rate brachytherapy in recent years to verify accuracy in treatment delivery. Although detection systems for source tracking are being developed, the allowable threshold of treatment error is still unknown and is likely patient-specific due to anatomy and planning variation. The purpose of this study was to determine patient and catheter-specific shift error thresholds for in-vivo source tracking during high-dose-rate prostate brachytherapy (HDRPBT). A module was developed in the previously described graphical processor unit multi-criteria optimization (gMCO) algorithm. The module generates systematic catheter shift errors retrospectively into HDRPBT treatment plans, performed on 50 patients. The catheter shift model iterates through the number of catheters shifted in the plan (from 1 to all catheters), the direction of shift (superior, inferior, medial, lateral, cranial, and caudal), and the magnitude of catheter shift (1-6mm). For each combination of these parameters, 200 error plans were generated, randomly selecting the catheters in the plan to shift. After shifts were applied, dose volume histogram (DVH) parameters were re-calculated. Catheter shift thresholds were then derived based on plans where DVH parameters were clinically unacceptable (prostate V100<95%, urethra D0.1cc>118%, and rectum Dmax>80%). Catheter thresholds were also Pearson correlated to catheter robustness values. Patient-specific thresholds varied between 1 to 6mm for all organs, in all shift directions. Overall, patient-specific thresholds typically decrease with an increasing number of catheters shifted. Anterior and inferior directions were less sensitive than other directions. Pearson's correlation test showed a strong correlation between catheter robustness and catheter thresholds for the rectum and urethra, with correlation values of -0.81 and -0.74, respectively (p<0.01), but no correlation was found for the prostate. It was possible to determine thresholds for each patient, with thresholds showing dependence on shift direction, and number of catheters shifted. Not every catheter combination is explorable, however, this study shows the feasibility to determine patient-specific thresholds for clinical application. The correlation of patient-specific thresholds with the equivalent robustness value indicated the need for robustness consideration during plan optimization and treatment planning.

Evaluation of robustness of optimization methods in breast intensity-modulated radiation therapy using TomoTherapy.

Intensity-modulated radiation therapy (IMRT) has become a popular choice for breast cancer treatment. We aimed to evaluate and compare the robustness of each optimization method used for breast IMRT using TomoTherapy. A retrospective analysis was performed on 10 patients with left breast cancer. For each optimization method (clipping, virtual bolus, and skin flash), a corresponding 50Gy/25 fr plan was created in the helical and direct TomoTherapy modes. The dose-volume histogram parameters were compared after shifting the patients anteriorly and posteriorly. In the helical mode, when the patient was not shifted, the median D1cc (minimum dose delivered to 1cc of the organ volume) of the breast skin for the clipping and virtual bolus plans was 52.2 (interquartile range: 51.9-52.6) and 50.4 (50.1-50.8) Gy, respectively. After an anterior shift, D1cc of the breast skin for the clipping and virtual bolus plans was 56.0 (55.6-56.8) and 50.9 (50.5-51.3) Gy, respectively. When the direct mode was used without shifting the patient, D1cc of the breast skin for the clipping, virtual bolus, and skin flash plans was 52.6 (51.9-53.1), 53.4 (52.6-53.9), and 52.3 (51.7-53.0) Gy, respectively. After shifting anteriorly, D1cc of the breast skin for the clipping, virtual bolus, and skin flash plans was 55.6 (54.1-56.4), 52.4 (52.0-53.0), and 53.6 (52.6-54.6) Gy, respectively. The clipping method is not sufficient for breast IMRT. The virtual bolus and skin flash methods were more robust optimization methods according to our analyses.

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

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

Potential dosimetric error in the adaptive workflow of a 1.5 T MR-Linac from patient movement relative to immobilisation systems.

In magnetic resonance- (MR-) based adaptive workflows for an MR-linac, the treatment plan is optimized and recalculated online using the daily MR images. The Unity MR-linac is supplied with a patient positioning device (ppd) using pelvic and abdomen thermoplastic masks attached to a board with high-density components. This study highlights the dosimetric effect of using this in such workflows when there are relative patient-ppd displacements, as these are not visualized on MR imaging and the treatment planning system assumes the patient is fixed relative to the ppd. The online adapted plans of two example rectum cancer patients treated at a Unity MR-linac were perturbed by introducing relative patient-ppd displacements, and the effect was evaluated on plan dosimetry. Forty-eight perturbed clinical adapted plans were recalculated, based on online MR-based synthetic computed tomography, and compared with the original plans, using dose-volume histogram parameters and gamma analysis. The target volume covered by the prescribed dose ( ) and by at least 107% of varied up to - 1.87% and + 3.67%, respectively for 0.5cm displacements, and to- 3.18% and + 4.96% for 2cm displacements; whilst 2%-2mm gamma analysis showed a median value of 92.9%. The use of a patient positioning system with high-density components in a Unity MR-based online adaptive treatment workflow can introduce unrecognized errors in plan dosimetry and it is recommended not to use such a device for such treatments, without modifying the device and the workflow, followed by careful clinical evaluation, or alternatively to use other immobilization methods.

Knowledge-based versus deep learning based treatment planning for breast radiotherapy

Background and PurposeTo improve radiotherapy (RT) planning efficiency and plan quality, knowledge-based planning (KBP) and deep learning (DL) solutions have been developed. We aimed to make a direct comparison of these models for breast cancer planning using the same training, validation, and testing sets. Materials and MethodsTwo KBP models were trained and validated with 90 RT plans for left-sided breast cancer with 15 fractions of 2.6 Gy. The versions either used the full dataset (non-clean model) or a cleaned dataset (clean model), thus eliminating geometric and dosimetric outliers. Results were compared with a DL U-net model (previously trained and validated with the same 90 RT plans) and manually produced RT plans, for the same independent dataset of 15 patients. Clinically relevant dose volume histogram parameters were evaluated according to established consensus criteria. ResultsBoth KBP models underestimated the mean heart and lung dose equally 0.4 Gy (0.3–1.1 Gy) and 1.4 Gy (1.1–2.8 Gy) compared to the clinical plans 0.8 Gy (0.5–1.8 Gy) and 1.7 Gy (1.3–3.2 Gy) while in the final calculations the mean lung dose was higher 1.9–2.0 Gy (1.5–3.5 Gy) for both KPB models. The U-Net model resulted in a mean planning target volume dose of 40.7 Gy (40.4–41.3 Gy), slightly higher than the clinical plans 40.5 Gy (40.1–41.0 Gy). ConclusionsOnly small differences were observed between the estimated and final dose calculation and the clinical results for both KPB models and the DL model. With a good set of breast plans, the data cleaning module is not needed and both KPB and DL models lead to clinically acceptable results.

Validation of a deep-learning segmentation model for adult and pediatric head and neck radiotherapy in different patient positions

Background and purposeAutocontouring for radiotherapy has the potential to significantly save time and reduce interobserver variability. We aimed to assess the performance of a commercial autocontouring model for head and neck (H&N) patients in eight orientations relevant to particle therapy with fixed beam lines, focusing on validation and implementation for routine clinical use. Materials and methodsAutocontouring was performed on sixteen organs at risk (OARs) for 98 adult and pediatric patients with 137 H&N CT scans in eight orientations. A geometric comparison of the autocontours and manual segmentations was performed using the Hausdorff Distance 95th percentile, Dice Similarity Coefficient (DSC) and surface DSC and compared to interobserver variability where available. Additional qualitative scoring and dose-volume-histogram (DVH) parameters analyses were performed for twenty patients in two positions, consisting of scoring on a 0–3 scale based on clinical usability and comparing the mean (Dmean) and near-maximum (D2%) dose, respectively. ResultsFor the geometric analysis, the model performance in head-first-supine straight and hyperextended orientations was in the same range as the interobserver variability. HD95, DSC and surface DSC was heterogeneous in other orientations. No significant geometric differences were found between pediatric and adult autocontours. The qualitative scoring yielded a median score of ≥ 2 for 13/16 OARs while 7/32 DVH parameters were significantly different. ConclusionsFor head-first-supine straight and hyperextended scans, we found that 13/16 OAR autocontours were suited for use in daily clinical practice and subsequently implemented. Further development is needed for other patient orientations before implementation.

Continuous time-resolved estimated synthetic 4D-CTs for dose reconstruction of lung tumor treatments at a 0.35 T MR-linac

Objective. To experimentally validate a method to create continuous time-resolved estimated synthetic 4D-computed tomography datasets (tresCTs) based on orthogonal cine MRI data for lung cancer treatments at a magnetic resonance imaging (MRI) guided linear accelerator (MR-linac). Approach. A breathing porcine lung phantom was scanned at a CT scanner and 0.35 T MR-linac. Orthogonal cine MRI series (sagittal/coronal orientation) at 7.3 Hz, intersecting tumor-mimicking gelatin nodules, were deformably registered to mid-exhale 3D-CT and 3D-MRI datasets. The time-resolved deformation vector fields were extrapolated to 3D and applied to a reference synthetic 3D-CT image (sCTref), while accounting for breathing phase-dependent lung density variations, to create 82 s long tresCTs at 3.65 Hz. Ten tresCTs were created for ten tracked nodules with different motion patterns in two lungs. For each dataset, a treatment plan was created on the mid-exhale phase of a measured ground truth (GT) respiratory-correlated 4D-CT dataset with the tracked nodule as gross tumor volume (GTV). Each plan was recalculated on the GT 4D-CT, randomly sampled tresCT, and static sCTref images. Dose distributions for corresponding breathing phases were compared in gamma (2%/2 mm) and dose–volume histogram (DVH) parameter analyses. Main results. The mean gamma pass rate between all tresCT and GT 4D-CT dose distributions was 98.6%. The mean absolute relative deviations of the tresCT with respect to GT DVH parameters were 1.9%, 1.0%, and 1.4% for the GTV D 98%, D 50%, and D 2%, respectively, 1.0% for the remaining nodules D 50%, and 1.5% for the lung V 20Gy. The gamma pass rate for the tresCTs was significantly larger (p < 0.01), and the GTV D 50% deviations with respect to the GT were significantly smaller (p < 0.01) than for the sCTref. Significance. The results suggest that tresCTs could be valuable for time-resolved reconstruction and intrafractional accumulation of the dose to the GTV for lung cancer patients treated at MR-linacs in the future.

Prediction of radiation pneumonitis using the effective α/β of lungs and heart in NSCLC patients treated with proton beam therapy

PurposeRadiation pneumonitis (RP) remains a major complication in non-small cell lung cancer (NSCLC) patients undergoing radiochemotherapy (RCHT). Traditionally, the mean lung dose (MLD) and the volume of the total lung receiving at least 20 Gy (V20Gy) are used to predict RP in patients treated with normo-fractionated photon therapy.However, other models, including the actual dose-distribution in the lungs using the effective α/β model or a combination of radiation doses to the lungs and heart, have been proposed for predicting RP. Moreover, the models established for photons may not hold for patients treated with passively-scattered proton therapy (PSPT). Therefore, we here tested and validated novel predictive parameters for RP in NSCLC patient treated with PSPT. MethodsData on the occurrence of RP, structure files and dose-volume histogram parameters for lungs and heart of 96 NSCLC patients, treated with PSPT and concurrent chemotherapy, was retrospectively retrieved from prospective clinical studies of two international centers. Data was randomly split into a training set (64 patients) and a validation set (32 patients). Statistical analyses were performed using binomial logistic regression. ResultsThe biologically effective dose (BED) of the’lungs - GTV’ significantly predicted RP ≥ grade 2 in the training-set using both a univariate model (p = 0.019, AUCtrain = 0.72) and a multivariate model in combination with the effective α/β parameter of the heart (pBED = 0.006, pα/βeff = 0.043, AUCtrain = 0.74). However, these results did not hold in the validation-set (AUCval = 0.52 andAUCval = 0.50, respectively). Moreover, these models were found to neither outperform a model built with the MLD (p = 0.015, AUCtrain = 0.73, AUCval = 0.51), nor a multivariate model additionally including the V20Gy of the heart (pMLD = 0.039, pV20Gy,heart = 0.58, AUCtrain = 0.74, AUCval = 0.53). ConclusionUsing the effective α/β parameter of the lungs and heart we achieved similar performance to commonly used models built for photon therapy, such as MLD, in predicting RP ≥ grade 2. Therefore, prediction models developed for photon RCHT still hold for patients treated with PSPT.

Rectum and Bladder Toxicity in Postoperative Prostate Bed Irradiation: Dose-Volume Parameters Analysis.

Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs) and the prognostic value of dose-volume histogram (DVH) parameters for the occurrence of treatment toxicity in patients treated with post-prostatectomy prostate bed radiotherapy (RT). The AEs were scored according to the CTCAE v.5.0. The rectum and bladder were contoured according to the RTOG Guidelines. The DVH parameters were assessed using data exported from the ECLIPSE treatment-planning system. Genitourinary (GU) and gastrointestinal (GI) toxicity were analysed using consecutive dose thresholds for the percentage of an organ at risk (OAR) receiving a given dose and the QUANTEC dose constraints. A total of 213 patients were included in the final analysis. Acute grade 2 or higher (≥G2) GU AEs occurred in 18.7% and late in 21.3% of patients. Acute ≥G2 GI toxicity occurred in 11.7% and late ≥G2 in 11.2% of the patients. Five patients experienced grade 4 AEs. The most common adverse effects were diarrhoea, proctitis, cystitis, and dysuria. The most significant predictors of acute ≥G2 GI toxicity were rectum V47 and V46 (p < 0.001 and p < 0.001) and rectum wall V46 (p = 0.001), whereas the most significant predictors of late ≥G2 GI AEs were rectum wall V47 and V48 (p = 0.019 and p = 0.021). None of the bladder or bladder wall parameters was significantly associated with the risk of acute toxicity. The minimum doses to bladder wall (p = 0.004) and bladder (p = 0.005) were the most significant predictors of late ≥G2 GU toxicity. Postoperative radiotherapy is associated with a clinically relevant risk of AEs, which is associated with DVH parameters, and remains even in patients who fulfil commonly accepted dose constraints. Considering the lack of survival benefit of postoperative adjuvant RT, our results support delaying treatment through an early salvage approach to avoid or defer toxicity.

Dosimetric comparison of four-dimensional computed tomography based internal target volume against variations in respiratory motion during treatment between volumetric modulated arc therapy and three-dimensional conformal radiotherapy in lung stereotactic body radiotherapy.

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose-volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were - 2.9 ± 4.4% (- 16.0 - 1.2%) and - 2.0 ± 2.8% (- 11.2 - 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV.

Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Dose-Volume Parameters to the Urinary Tract Sub-Volumes and Predictors of Genitourinary Acute Toxicity in a Phase 2 Clinical Trial Assessing MRI-Guided Prostate Boost for Localized Prostate Cancer - The Miami BlastM Trial.

The relationship between radiotherapy dose to the sub-volumes of the genitourinary (GU) tract and GU toxicity is poorly understood, particularly in prostate cancer patients treated with an intraprostatic dominant lesion (IDL) boost. While the use of IDL boost improves outcomes, it results in higher doses to GU structures and potentially increased toxicity. We investigated the association between dose-volume histogram (DVH) parameters for urinary tract sub-volumes and GU toxicity in the context of IDL boost in patients enrolled in the Miami BlastM Trial. DVH data were assessed for patients enrolled in the Miami BlastM, a randomized phase 2 trial (NCT20140627) evaluating upfront versus integrated IDL boost. IDL GTV boost consisted of either 12-14 Gy administered on day 1 or integrated boost of 2.4 Gy per fraction (91.2 Gy total, 98.5 Gy 2.0 Equiv), with the prostate receiving 76 Gy in 38 fractions. Bladder trigone (BTg) and urethra sub-volumes were contoured retrospectively on planning CT scans. GU toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE) version 4 and International Prostate Symptom Score (IPSS). DVHs of the bladder, BTg, bladder minus BTg, prostatic urethra, and bulbomembranous urethra were examined. The primary composite endpoint was CTCAE GU acute toxicity grade (G) ≥2 and/or IPSS increase of ≥10 from baseline. Secondary endpoints were GU acute toxicity G≥2, GU late toxicity G≥2, and IPSS increase of ≥10 from baseline. Univariable and multivariable logistic regression analyses were performed. A total of 129 patients treated between February 2015 and January 2022 were eligible for analysis. One hundred and one (78%) patients developed either GU acute toxicity G≥2 (68%) and/or an IPSS increase of ≥10 from baseline (30%). Less than 2% of patients developed GU toxicity G≥3. BTg V30 Gy was significantly associated with IPSS increase ≥10 (p = 0.046). The bulbomembranous urethral maximum dose was significantly associated with GU acute toxicity G≥2 and GU late toxicity G≥2 (p <0.05 for both). Average maximum and mean urethral doses were 88.9 and 81.5 Gy, respectively. The BTg maximum dose, V20 Gy, V30 Gy, and V40 Gy were not significantly associated with the primary composite endpoint (p = 0.56, 0.75, 0.89, 0.82, respectively). On multivariable analysis, a higher bulbomembranous urethral maximum dose was significantly associated with GU acute toxicity G≥2 and/or IPSS increase of ≥10 from baseline (p = 0.019). Our data suggest a dose-effect relationship between maximum doses to the bulbomembranous urethra and GU toxicity. A better understanding of RT-related changes to specific sub-volumes of the urethra and strategies to mitigate urethral dose could enhance the therapeutic ratio in prostate cancer patients treated with MRI-guided IDL boost.

Inter-fractional Assessment during MR-guided Online Adaptive Radiotherapy for Glioblastoma

Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study aimed to assess the feasibility and potential benefits of MR-guided online adaptive radiotherapy (MRgOART) for patients with glioblastoma. Twenty consecutive patients with glioblastoma were treated with MRgOART of 60 Gy in 30 fractions by the 1.5 T MR-Linac. The MRgOART fractions employed daily MR scans and the contours were utilized to create each adapted plan. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on MRI of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3 ... Fx30) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume (∆V), Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. The reference treatment plans were generated using step-and-shoot IMRT and utilized 7-9 beam groups on original CT. Before the treatment, a synthetic CT (sCT) quality assurance (QA) process was performed to assess the dose accuracy of bulk relative electron density (rED) assignment for online MRI based treatment plan in terms of gamma analysis, point dose comparison and dose volume histogram (DVH) parameters. Then, the online adaptative treatment plans were obtained by re-optimizing based on the contours on daily pre-treatment MRI by "adapt to shape" workflow. Non-adaptive plans for each patient were generated by recalculating the dose from the reference plans on daily online MRI by "adapt to position" workflow. GTV and CTV coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. For both criteria, the 1%/1mm (98.58%±0.15%) and 2%/2mm (99.88%±0.18%) gamma passing rate results were always clinically acceptable in sCT QA process. The differences on point dose and DVH parameters between the plans based on sCT and original CT were less than 1%. A total of 20 patients with 600 fractions were evaluated. The results showed that large inter-fractional changes for GTV limited the efficacy of radiation therapy (DSC: 0.78±0.08, HD: 20.94±3.64mm, ∆V: 2.92%±6.36%). The inter-fractional CTV changes were smaller (DSC: 0.91±0.04, HD: 15.31±3.09mm, ∆V: 1.41%±1.29%). GTV coverage of non-adaptive plans was below the prescribed coverage in 228/600 fractions (38%), with 90 (15%) failing by more than 10%. For CTV coverage of non-adaptive plans, the changes were less than 5%. Online adaptative plans improved GTV and CTV coverage significantly (p<0.001) to 99%. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p<0.001). Significant inter-fractional tumor changes could be found during radiotherapy in patients with glioblastoma treated by the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions.

The Predictive Value of Changes in Basal Myocardial F-18 Fluorodeoxyglucose Uptake for Cardiotoxicity in Locally Advanced Esophageal Cancer Patients Receiving Definitive Radiotherapy

To investigate the predictive value of changes in myocardial 18F-FDG uptake for major adverse cardiac events (MACEs) in locally advanced esophageal cancer patients receiving definitive radiotherapy. Between August 2012 and January 2018, 400 patients with stage II-III esophageal cancer receiving definitive radiotherapy at two institutions were divided into the training (n = 240) and external validation cohorts (n = 160). All patients underwent FDG-PET imaging within 1 week before treatment and 3 months after treatment. Myocardium delineation was performed by Carimas software (version 2.10) based on the AHA 17-segment model. When contouring the left ventricle, the myocardium was automatically divided into basal (segments 1-6), middle (segments 7-12), and apical (segments 13-16) regions, and the mean dose and FDG uptake parameters of each region were obtained by Carimas. Our primary endpoint was MACEs. Patient clinicopathologic factors, dosimetric parameters for the whole heart and cardiac substructures, and myocardial changes within the three regions on 18F-FDG PET were utilized to seek the best predictive models for cardiotoxicity. To avoid multicollinearity between dose-volume histogram (DVH) parameters, we selected the variables with the lowest Akaike Information Criterion (AIC) value from the DVH parameters of the same cardiac structure for the actual modeling procedure. Competing risk analysis and Cox regressions analysis were performed. The predictive performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score. At a median follow-up interval of 78 months, 28 patients (11.7%) developed MACEs. The basal region of the myocardium received the highest radiation dose, followed by the middle and the apex region. The basal myocardial SUVmax and SUVmean significantly increased after radiotherapy while the apical and middle myocardial SUVmax and SUVmean not significantly increased. In univariate analysis, age, pre-existing cardiac disease, changes in pre- and post-treatment basal myocardial SUVmax and SUVmean (∆SUVmax and ∆SUVmean), and dosimetric parameters for MHD, mean LCX, mean LAD, and mean LV dose were associated with an increased hazard of MACEs. Multivariate analysis showed that basal ∆SUVmean retained significance after adjusting for age, pre-existing cardiac disease, and dosimetric parameters for whole heart and cardiac substructures. The AUCs and Brier scores demonstrated favorable predictive accuracies of the model's integrating variables with significant difference in multivariate analysis when predicting MACEs in the training and validation cohorts. ∆SUVmean was an independent indicator of MACE in locally advanced esophageal cancer patients receiving definitive radiotherapy. Changes in basal myocardial FDG uptake is a promising biomaker for predicting radiation-induced cardiotoxicity.

Quality Assurance of Protocol Compliance in a Multicenter Randomized Trial Investigating the Role of Hypofractionated Comprehensive Reginal Nodal Irradiation in Node-Positive Breast Cancer (HARVEST)

The HARVEST trial (NCT03829553) is a phase III, multicenter, randomized clinical trial to explore efficacy and safety of hypofractionated irradiation (HFI) involving regional nodal irradiation (RNI, including internal mammary nodes, IMN) in N+ breast cancer patients treated with mastectomy or breast conserving surgery (BCS). Current study aims to analyze the dosimetric quality assurance so as to evaluate the compliance to the trial protocol. Eligible patients were randomly assigned (1:1) to receive conventional fractionated irradiation (CFI: 50 Gy/25Fx) or HFI (40.05 Gy/15Fx), which is delivered to ipsilateral chest wall or whole breast (CW/WB) with tumor bed boost (HFI: 10.68 Gy/4Fx; CFI: 10 Gy/5Fx) and comprehensive RNI (supra/infraclavicular nodes and IMN in each patient, lower axilla if indicated) by using IMRT technique. The plan quality was evaluated based on dose distribution, dose volume histogram (DVH) and field parameters. The target coverage, including planning target volume of CW/WB (PTV1) and tumor bed (PTV2) and doses of the organs at risk (OARs) were evaluated. The LQ model was used to convert doses of OARs in HFI group using α/β = 3 Gy (EQD23) for comparison. Between Feb 21, 2019 and Feb 14, 2022, 801 patients were enrolled at 8 centers with 401 and 400 in CFI and HFI group, respectively. There were 182 patients received BCS and 387 patients were with more than three positive lymph nodes. In the CFI group, the D90 and V45 of PTV1 reached the prescribed dose in 70.6% and 96.0% of the patients, respectively. In the HFI group, the D90 and V36 of PTV1 reached the prescribed dose in 87.8% and 95.5% of the patients, respectively. When the tumor bed was irradiated, the D90 of PTV2 reached the prescribed dose in 95.6% in the CFI group and 100% in the HFI group, respectively. The mean D90 of PTV1 and PTV2 were 50.09±0.65 Gy and 60.63±0.91 Gy in CFI group while 40.11±0.56 Gy and 50.79±2.03 Gy in HFI group. For OARs constraints, protocol compliance was all above 95% (heart: 95.3%; ipsilateral lung: 95.5%; contralateral lung: 97.1%; humeral head: 98.2% and spinal cord: 100%) with no significant difference between CFI and HFI groups. For patients with left-sided breast cancer, the Dmean of the heart was 5.10±1.75 Gy vs. 4.59±1.86 Gy (EQD23) in CFI and HFI groups (p = 0.51), respectively. No significant differences in Dmean of the heart (1.45±0.71 Gy vs. 1.33±0.77 Gy (EQD23), p = 0.40) was found either between two groups in right-sided patients. The differences were significant in the Dmean of the ipsilateral lung (13.37±1.99 Gy vs. 11.17±3.50 Gy (EQD23), p<0.01), contralateral lung (0.88±0.73 Gy vs. 0.74±0.61 Gy (EQD23), p<0.01) and the ipsilateral humeral head (15.27±7.62 Gy vs. 13.05±6.19 Gy (EQD23), p<0.01) and the Dmax of spinal cord (21.40±8.82 Gy vs. 19.47±7.99 Gy (EQD23), p = 0.05) between CFI and HFI groups. A high degree of compliance with protocol dose constraints was found for treatment plans in the HARVEST trial and doses to the most of OARs decreased in HFI group.