Dose-volume Histogram Analysis Research Articles

Pre-therapy PET-based voxel-wise dosimetry prediction by characterizing intra-organ heterogeneity in PSMA-directed radiopharmaceutical theranostics

Abstract Background and objective Treatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET. Methods 23 patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA I&T RPT were retrospectively included. 48 treatment cycles with pre-treatment PET imaging and at least 3 post-therapeutic SPECT/CT imaging were selected. The distribution of PET tracer and RPT dose was compared for kidney, liver and spleen, characterizing intra-organ heterogeneity differences. Pharmacokinetic simulations were performed to enhance the understanding of the correlation. Two strategies were explored for pre-therapy voxel-wise dosimetry prediction: (1) organ-dose guided direct projection; (2) deep learning (DL)-based distribution prediction. Physical metrics, dose volume histogram (DVH) analysis, and identity plots were applied to investigate the predicted absorbed dose map. Results Inconsistent intra-organ patterns emerged between PET imaging and dose map, with moderate correlations existing in the kidney (r = 0.77), liver (r = 0.5), and spleen (r = 0.58) (P < 0.025). Simulation results indicated the intra-organ pharmacokinetic heterogeneity might explain this inconsistency. The DL-based method achieved a lower average voxel-wise normalized root mean squared error of 0.79 ± 0.27%, regarding to ground-truth dose map, outperforming the organ-dose guided projection (1.11 ± 0.57%) (P < 0.05). DVH analysis demonstrated good prediction accuracy (R2 = 0.92 for kidney). The DL model improved the mean slope of fitting lines in identity plots (199% for liver), when compared to the theoretical optimal results of the organ-dose approach. Conclusion Our results demonstrated the intra-organ heterogeneity of pharmacokinetics may complicate pre-therapy dosimetry prediction. DL has the potential to bridge this gap for pre-therapy prediction of voxel-wise heterogeneous dose map.

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.

Dosimetric impact of CT metal artifact reduction for spinal implants in stereotactic body radiotherapy planning.

Metal artifacts due to spinal implants may affect the accuracy of dose calculation for radiotherapy. However, the dosimetric impact of metal artifact reduction (MAR) for spinal implants in stereotactic body radiotherapy (SBRT) plans has not been well studied. The objective of this study was to evaluate the dosimetric impact of MAR in spinal SBRT planning with three clinically common dose calculation algorithms. Gammex phantom and 10 patients' computed tomography (CT) images were studied to investigate the effects of titanium implants. A commercial orthopedic MAR algorithm was employed to reduce artifacts. Dose calculations for SBRT were conducted on both artifact-corrected and uncorrected images using three commercial algorithms [analytical anisotropic algorithm (AAA), Acuros XB (AXB), and Monte Carlo (MC)]. Dose discrepancies between artifact-corrected and uncorrected cases were appraised using a dose-volume histogram (DVH) and 3-dimensional (3D) gamma analysis with different distance to agreement (DTA) and dose difference criteria. The gamma agreement index (GAI) was denoted as G(∆D, DTA). Statistical analysis of t-test was utilized to evaluate the dose differences of different algorithms. The phantom study demonstrated that titanium metal artifacts can be effectively reduced. The patient cases study showed that dose differences between the artifact-corrected and uncorrected datasets were small evaluated by gamma index and DVH. Gamma analysis found that even the strict criterion local G(1,1) had average values ≥93.9% for the three algorithms. For all DVH metrics, average differences did not exceed 0.7% in planning target volume (PTV) and 2.1% in planning risk volume of spinal cord (PRV-SC). Statistical analysis showed that the observed dose differences of MC method were significantly larger than those of AAA (P<0.01 for D98% of PTV and P<0.001 for D0.1cc of spinal cord) and AXB methods (P<0.001 for D98% and P<0.0001 for D0.1cc). Dosimetric impact of artifacts caused by titanium implants is not significant in spinal SBRT planning, which indicates that dose calculation algorithms might not be very sensitive to CT number variation caused by titanium inserts.

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

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

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 Comparison Study Between Free Breathing and Breath Hold Techniques in Patients Treated by Liver-Directed Stereotactic Body Radiation Therapy.

Background Breathing motion management is the key to delivering stereotactic body radiation therapy (SBRT) for liver lesions. This study aimed to compare the dosimetric parameters of liver SBRT using two different techniques: free breathing and breath hold. Method The study included 11 patients with liver metastases or hepatocellular carcinoma who underwent liver-directed SBRT. A dosimetric comparison was performed using dose-volume histogram analysis, evaluating parameters such as the maximum dose to 5 cc of bowel volume, mean liver dose (MLD), and liver V20and V30. Statistical analyses were performed to compare results. Results The findings revealed that the breath hold technique resulted in significantly lower doses to the bowel and smaller volumes of normal liver tissue receiving 20 Gy (V20) and 30 Gy (V30) than the free breathing. Although there was no statistically significant difference in the MLD between the two techniques, the breath hold technique resulted in a lower MLD. Conclusion This dosimetric comparison study suggests that the breath hold technique is associated with lower radiation exposure to the bowel and normal liver tissues. Although this may not be feasible for all patients, it may be an appropriate procedure for selected individuals. Further research is needed to validate these findings in different patient populations and explore their impact on clinical outcomes and patient-reported quality of life.

Absorbed dose calculation for a realistic CT-derived mouse phantom irradiated with a standard Cs-137 cell irradiator using a Monte Carlo method.

Computed tomography (CT) derived Monte Carlo (MC) phantoms allow dose determination within small animal models that is not feasible with in-vivo dosimetry. The aim of this study was to develop a CT-derived MC phantom generated from a mouse with a xenograft tumour that could then be used to calculate both the dose heterogeneity in the tumour volume and out of field scattered dose for pre-clinical small animal irradiation experiments. A BEAMnrc Monte-Carlo model has been built of our irradiation system that comprises a lead collimator with a 1 cm diameter aperture fitted to a Cs-137 gamma irradiator. The MC model of the irradiation system was validated by comparing the calculated dose results with dosimetric film measurement in a polymethyl methacrylate (PMMA) phantom using a 1D gamma-index analysis. Dose distributions in the MC mouse phantom were calculated and visualized on the CT-image data. Dose volume histograms (DVHs) were generated for the tumour and organs at risk (OARs). The effect of the xenographic tumour volume on the scattered out of field dose was also investigated. The defined gamma index analysis criteria were met, indicating that our MC simulation is a valid model for MC mouse phantom dose calculations. MC dose calculations showed a maximum out of field dose to the mouse of 7% of Dmax. Absorbed dose to the tumour varies in the range 60%-100% of Dmax. DVH analysis demonstrated that tumour received an inhomogeneous dose of 12 Gy-20 Gy (for 20 Gy prescribed dose) while out of field doses to all OARs were minimized (1.29 Gy-1.38 Gy). Variation of the xenographic tumour volume exhibited no significant effect on the out of field scattered dose to OARs. The CT derived MC mouse model presented here is a useful tool for tumour dose verifications as well as investigating the doses to normal tissue (in out of field) for preclinical radiobiological research.

Comparison of intensity-modulated radiation therapy (IMRT), 3D conformal proton therapy and intensity-modulated proton therapy (IMPT) for the treatment of metastatic brain cancer.

The purpose of this study has been to compare photon intensity modulated radiation therapy (IMRT) against both conformal and intensity modulated proton therapy (IMPT) plans for metastatic brain cancer. Ten IMRT patients with brain cancer were chosen retrospectively, with prescription doses in the range of 20 to 40 Gy, delivered in 3 to 5 fractions using Varian TrueBeam STx machine. Three proton plans with proton double scattering, single collimation static-IMPT, and energy layer by layer collimation dynamic-IMPT were then generated for the same patients using the Mevion S250 system for conformal plans and the S250i system for IMPT plans. Each plan had respective treatment planning systems that include Brainlab iPlan for IMRT, Varian Eclipse for proton double scattering, and RaySearch Raystation for IMPT. Dosimetric and radiobiologic comparisons were made through dose-volume histogram (DVH) analysis of the target and the organs at risk (OAR); and with parameters of equivalent uniform dose (EUD), tumor control probability (TCP), and normal tissue complication probability (NTCP), respectively. A set of variables α/β ratio, survival fraction, and clonogenic cell density were selected and varied to observe their effect on the abovementioned parameters. Doses were observed to be more homogeneous for patients with brain malignancies with photon IMRT treatments, while dose conformity is improved with proton PBS treatments. Normal tissue is, on average, spared more through both proton treatment options. The minimum doses, closely approximated by dose to 98% of the target volume, are similar across treatment modalities with slight variations.

Effects of reconstruction methods on dose distribution for lung stereotactic body radiotherapy treatment plans.

The aim of the present study was to investigate the effect of tumour motion on various imaging strategies as well as on treatment plan accuracy for lung stereotactic body radiotherapy treatment (SBRT) cases. The ExacTrac gating phantom and paraffin were used to investigate respiratory motion and represent a lung tumour, respectively. Four-dimensional computed tomography (4DCT) imaging was performed, while the phantom was moving sinusoidally with 4s cycling time with three different amplitudes of 8, 16, and 24mm. Reconstructions were done with maximum (MIP) and average intensity projection (AIP) methods. Comparisons of target density and volume were performed using two reconstruction techniques and references values. Volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) were planned based on reconstructed computed tomography (CT) sets, and it was examined how density variations affect the dose-volume histogram (DVH) parameters. 4D cone beam computed tomography (CBCT) was performed with the Elekta Versa HD linac imaging system before irradiation and compared with 3D CBCT. Thus, various combinations of 4DCT reconstruction methods and treatment alignment methods have been investigated. Point measurements as well as 2 and 3D dose measurements were done by optically stimulated luminescence (OSL), gafchromic films, and electronic portal imaging devices (EPIDs), respectively. The mean volume reduction was 7.8% for the AIP and 2.6% for the MIP method. The obtained Hounsfield Unit (HU) values were lower for AIP and higher for MIP when compared with the reference volume density. In DVH analysis, there were no statistical differences for D95%, D98%, and Dmean (p > 0.05). However, D2% was significantly affected by HU changes (p < 0.01). A positional variation was obtained up to 2mm in moving direction when 4D CBCT was applied after 3D CBCT. Dosimetric measurements showed that the main part of the observed dose deviation was due to movement. In lung SBRT treatment plans, D2% doses differ significantly according to the reconstruction method. Additionally, it has been observed that setups based on 3D imaging can cause a positional error of up to 2mm compared to setups based on 4D imaging. It is concluded that MIP has advantages over AIP in defining internal target volume (ITV) in lung SBRT applications. In addition, 4D CBCT and 3D EPID dosimetry are recommended for lung SBRT treatments.

Craniospinal Irradiation: A Dosimetric Comparison Between O-Ring Linac and Conventional C-arm Linac

PurposeThe aim of this study was to perform a dosimetric evaluation between craniospinal irradiation volumetric modulated arc therapy plans designed for an O-Ring and a conventional C-arm Linac. Methods and MaterialsTwo adult patients were selected for this study. Two plans were designed one for a TrueBeam Edge and one for Halcyon O-ring Linac for each patient. The evaluation of the plans was conducted in terms of dose volume histogram analysis of the target volume and organs at risk (OARs) along with total plan monitor units and beam-on time. Paired sample t test was performed to compare Dmax and Dmean of OARs for each plan's comparison. The delivery of volumetric modulated arc therapy plans was evaluated using Octavius 4D phantom. ResultsAll plans demonstrated dose distributions with sufficient planned target volume conformity and homogeneity. The Homogeneity Index and Conformity Index for all plans were found comparable. The paired sample t test did not demonstrate significant difference in terms of Dmax and Dmean of OARs between plans for both patients. All plans met the threshold of 90%, with Halcyon plans having higher gamma passing rates. ConclusionsCraniospinal irradiation plans generated for Halcyon and Edge are equivalent in terms of plan quality and dose sparing at OARs. The small variations may have originated from the differences in beam profile or mean energy, the degree of the modulation for each plan and characteristics of multi leaf collimators for each treatment unit. Halcyon is able to deliver a distinctly faster treatment, but Edge provides an automatic rotational correction for patient positioning.

Detailed analysis of failure patterns using deformable image registration in hypopharyngeal cancer patients treated with sequential boost intensity-modulated radiotherapy.

Sequential boost intensity-modulated radiotherapy (SQB-IMRT) uses two different planning CTs (pCTs) and treatment plans. SQB-IMRT is a form of adaptive radiotherapy that allows for responses to changes in the shape of the tumour and organs at risk (OAR). On the other hand, dose accumulation with the two plans can be difficult to evaluate. The purpose of this study was to analyse patterns of loco-regional failure using deformable image registration (DIR) in hypopharyngeal cancer patients treated with SQB-IMRT. Between 2013 and 2019, 102 patients with hypopharyngeal cancer were treated with definitive SQB-IMRT at our institution. Dose accumulation with the 1st and 2nd plans was performed, and the dose to the loco-regional recurrent tumour volume was calculated using the DIR workflow. Failure was classified as follows: (i) in-field (≥95% of the recurrent tumour volume received 95% of the prescribed dose); (ii) marginal (20-95%); or (iii) out-of-field (<20%). After a median follow-up period of 25months, loco-regional failure occurred in 34 patients. Dose-volume histogram analysis showed that all loco-regional failures occurred in the field within 95% of the prescribed dose, with no marginal or out-of-field recurrences observed. The dosimetric analysis using DIR showed that all loco-regional failures were within the high-dose region. More aggressive treatment may be required for gross tumours.

Near-Maximum Rib Dose is the Most Relevant Risk Factor for Ipsilateral Spontaneous Rib Fracture: A Dosimetric Analysis of Breast Cancer Patients after Radiotherapy

<h3>Purpose/Objective(s)</h3> Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. <h3>Materials/Methods</h3> We retrospectively reviewed 2,204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). <h3>Results</h3> Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In multivariate analysis of all patients, a hypofractionated dose scheme and abnormally low bone density were significant clinical risk factors for ipsilateral SRF. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cutoff value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. <h3>Conclusion</h3> Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. Additionally, we suggest that the dose for the rib be constrained to D2cc EQD2 < 52 Gy to minimize the risk of ipsilateral SRF.

3D-CRT, IMRT and VMAT for flank irradiation due to pediatric Wilms tumor: A comparative planning study with XCAT phantoms

PurposeTo compare the dosimetric parameters and radiogenic risks from 3D-CRT, IMRT and VMAT for flank irradiation due to pediatric Wilms tumor. MethodsTwo computational XCAT phantoms simulating an average 5- and 10-year-old patient were used. Four different planning target volumes (PTVs) for right flank (RF) and left flank (LF) irradiation with or without paraaortic lymph nodes (LNs) and eight surrounding organs-at-risk (OARs) were contoured on the phantoms’ CT sections. Forty-eight 3D-CRT, IMRT and VMAT plans were created using 6 and 10-MV photons on the two phantoms. The target coverage index (TCI), homogeneity index (HI), conformity index (CI), conformation number (CN) and OAR exposure were determined through dose-volume histogram (DVH) analysis. Second cancer risks were estimated using a non-linear model and DVH data. ResultsThe IMRT and VMAT for LF + LN and RF + LN irradiation reduced the radiation dose to four to six out of the eight OARs compared to 3D-CRT. Conventional treatment provided a better organ sparing for RF and LF irradiation. The IMRT and VMAT led to superior planning parameters in respect to 3D-CRT for all PTVs and both patient’s ages (3D-CRT: TCI = 59.80 % - 82.26 %, CI = 0.55–0.81, CN = 0.40–0.64, HI = 1.11–1.15; IMRT: TCI = 96.04 % - 99.72 %, CI = 0.85–0.91, CN = 0.85–0.88, HI = 1.03–1.05; VMAT: TCI = 96.02 % - 99.69 %, CI = 0.86–0.91, CN = 0.85–0.89, HI = 1.03–1.06). The excess-absolute-risk for developing secondary small intestine, liver and stomach malignancies from 3D-CRT were (7.99–19.32) × 10-4, (0.29–3.83) × 10-4 and (0.37–4.50) × 10-4 persons-year, respectively. The corresponding risks from intensity modulated techniques reached to 22.26 × 10-4, 4.58 × 10-4 and 5.42 × 10-4 persons-year. ConclusionsThis dataset related to plan quality, radiation dose and risks to OARs allows the selection of the proper treatment technique for flank irradiation based on the patient’s age and target site.

A deep learning approach to generate synthetic CT in low field MR-guided radiotherapy for lung cases

IntroductionThis study aims to apply a conditional Generative Adversarial Network (cGAN) to generate synthetic Computed Tomography (sCT) from 0.35 Tesla Magnetic Resonance (MR) images of the thorax. MethodsSixty patients treated for lung lesions were enrolled and divided into training (32), validation (8), internal (10,TA) and external (10,TB) test set. Image accuracy of generated sCT was evaluated computing the mean absolute (MAE) and mean error (ME) with respect the original CT. Three treatment plans were calculated for each patient considering MRI as reference image: original CT, sCT (pure sCT) and sCT with GTV density override (hybrid sCT) were used as Electron Density (ED) map. Dose accuracy was evaluated comparing treatment plans in terms of gamma analysis and Dose Volume Histogram (DVH) parameters. ResultsNo significant difference was observed between the test sets for image and dose accuracy parameters. Considering the whole test cohort, a MAE of 54.9 ± 10.5 HU and a ME of 4.4 ± 7.4 HU was obtained.Mean gamma passing rates for 2%/2mm, and 3%/3mm tolerance criteria were 95.5 ± 5.9% and 98.2 ± 4.1% for pure sCT, 96.1 ± 5.1% and 98.5 ± 3.9% for hybrid sCT: the difference between the two approaches was significant (p = 0.01). As regards DVH analysis, differences in target parameters estimation were found to be within 5% using hybrid approach and 20% using pure sCT. ConclusionThe DL algorithm here presented can generate sCT images in the thorax with good image and dose accuracy, especially when the hybrid approach is used. The algorithm does not suffer from inter-scanner variability, making feasible the implementation of MR-only workflows for palliative treatments.

Comparative assessment of passive scattering and active scanning proton therapy techniques using Monte Carlo simulations

Background: in this study, two proton beam delivery designs, i.e. passive scattering proton therapy (PSPT) and pencil beam scanning (PBS), were quantitatively compared in terms of dosimetric indices. The GATE Monte Carlo (MC) particle transport code was used to simulate the proton beam system; and the developed simulation engines were benchmarked with respect to the experimental measurements. Method: a water phantom was used to simulate system energy parameters using a set of depth-dose data in the energy range of 120–235 MeV. To compare the performance of PSPT against PBS, multiple dosimetric parameters including Bragg peak width (BP W50), peak position, range, peak-to-entrance dose ratio, penumbra(90-10)%, penumbra(80-20)%, M 95% and dose volume histogram have been analyzed under the same conditions. Furthermore, the clinical test cases introduced by AAPM TG-119 were simulated in both beam delivery modes to compare the relevant clinical values obtained from Dose Volume Histogram (DVH) analysis. Results: the parametric comparison in the water phantom between the two techniques revealed that the value of peak-to-entrance dose ratio in PSPT is considerably higher than that from PBS by a factor of 8%. In addition, the BP_W50, penumbra(90-10)%, penumbra(80-20)%, and M 95% in PSPT was increased by a factor of 7, 51, 37, and 2.7%, respectively compared to the corresponding value obtained from PBS model. TG-119 phantom simulations showed that the difference of PTV mean dose between PBS and PSPT techniques are up to 1.8% while the difference of max dose to organ at risks (OARs) exceeds 50%. Conclusion: the results of this simulation show that although the passive scattering design method has a slightly higher ability to adjust the dose in target volume, but the active scanning proton therapy systems was superior in dose painting, and lower out-of-field dose compared to passive scattering design.

Compensation for radiotherapy treatment interruptions due to a cyberattack: An isoeffective DVH‐based dose compensation decision tool

Unscheduled interruptions to radiotherapy treatments lead to decreased tumor control probability (TCP). Rapid cell repopulation in the tumor increases due to the absence of radiation dose, resulting in the loss of TCP. Compensation for this loss is required to prevent or reduce an extension of the patient's overall treatment time and regain the original TCP. The cyberattack on the Irish public health service in May 2021 prevented radiotherapy treatment delivery resulting in treatment interruptions of up to 12 days. Current standards for treatment gap calculations are performed using the Royal College of Radiologists (RCR) methodology, using a point‐dose for planning target volume (PTV) and the organs at risk (OAR).An in‐house tool, named EQD2VH, was created in Python to perform treatment gap calculations using the dose–volume histogram (DVH) information in DICOM data extracted from commercial treatment planning system plans. The physical dose in each dose bin was converted into equivalent dose in 2‐Gy fractions (EQD2), accounting for tumor cell repopulation. This EQD2‐based DVH provides a 2D representation of the impact of treatment gap compensation strategies on both PTV and OAR dose distributions compared to the intended prescribed treatment plan. This additional information can aid clinicians’ choice of compensation options. EQD2VH was evaluated using five high‐priority patients experiencing a treatment interruption when the cyberattack occurred. Compensation plans were created using the RCR methodology to evaluate EQD2VH as a decision‐making tool.The EQD2VH method demonstrated that the comparison of compensated treatment plans alongside the original intended treatment plans using isoeffective DVH analysis can be achieved. It enabled a visual and quantitative comparison between treatment plan options and provided an individual analysis of each structure in a patient's plan. It demonstrated potential to be a useful decision‐making tool for finding a balance between optimizing dose to PTV while protecting OARs.

Assessment of dose perturbations for metal stent in photon and proton radiotherapy plans for hepatocellular carcinoma

BackgroundThe present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.MethodsWith computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior–posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter. The difference in dose distributions and dosimetric parameters were compared depending on the stent's positions (the bile duct (GB) and intestinal tract (GI)) and angles (0°, 45°, and 90°). Additionally, the dose variation in the target volume including the stent was comparatively evaluated through dose volume histogram (DVH) analysis. And the comparison of clinical cases was carried out in the same way.ResultsPercentage differences in the dosimetric parameters calculated by MC ranged from − 7.0 to 3.9% for the photon plan and − 33.7 to 4.3% for the proton plan, depending on the angle at which the GB and GI stents were placed, compared to those without the stent. The maximum difference was observed at the minimum dose (Dmin), which was observed in both photon and proton plans in the GB and GI stents deployed at a 90° incidence angle. The parameter differences were greater in the proton plan than in photon plan. The target volume showed various dose variations depending on positions and angles of stent for both beams. Compared with no-stent, the doses within the target volume containing the GI and GB stents for the photon beam were overestimated in the high-dose area at 0°, nearly equal within 1% at 45°, and underestimated at 90°. These doses to the proton beam were underestimated at all angles, and the amount of underdose to the target volume increased with an increase in the stent angle. However, the difference was significantly greater with the proton plan than the photon plan.ConclusionsDose perturbations within the target volume due to the presence of the metal stent were not observed in the TPS calculations for photon and proton beams, but MC was used to confirm that there are dose variations within the target volume. The MC results found that delivery of the treatment beam avoiding the stent was the best method to prevent target volume underdose.

Near-maximum rib dose is the most relevant risk factor for ipsilateral spontaneous rib fracture: adosimetric analysis of breast cancer patients after radiotherapy.

Spontaneous rib fracture (SRF) is acommon late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. We retrospectively reviewed 2204patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3years after RT. The median time to develop ipsilateral SRF was 15months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests.

Radiobiological analysis of preliminary results of a phase II study of pelvic hypofractionated and accelerated radiotherapy for high-risk prostate cancer patients.

PurposeConventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the same time, the safety and efficacy of HypoAR for pelvic node irradiation remain obscure.Material and MethodsIn a phase II study, we evaluated the feasibility of pelvic HypoAR in 22 high-risk prostate cancer patients. The RT scheme delivers 14 consecutive fractions of 3.67 Gy (total 51.38 Gy) to the prostate, 3.5 Gy (total 49 Gy) to the seminal vesicles, and 2.7 Gy (total 37.8 Gy) to the lymph nodes, using image-guided volumetric modulated arc therapy. A comparative radiobiological analysis of dose-volume histogram is performed (HypoAR vs. hypothetical equivalent CRT regimens, without and with time correction).ResultsOur clinical experience shows impressively low early and short-term late toxicities, without any grade III events, within a median follow-up of 30 months. Only one biochemical relapse was recorded 30 months after irradiation. In radiobiological analysis, considering an α/β-value of 4 Gy and a λ-value of 0.2 Gy/day for late effects, all comparisons predicted significantly lower toxicity for the HypoAR regimen (p < 0.05). For early toxicities (α/β = 10 Gy), a λ-value lower than 0.4 Gy/day favors the HypoAR regimen, which is along with the clinical results.ConclusionRadiobiological analysis favors HypoAR as a safe and effective regimen for high-risk prostate cancer patients, which is confirmed in the current phase II clinical study.

Effect of dosimetric parameters on postoperative respiratory morbidity in locally advanced esophageal cancer treated with preoperative chemoradiotherapy (CRT).

e16075 Background: Postoperative pulmonary complications are common after neoadjuvant CRT of locally advanced esophageal cancers. Using data from the French multicenter randomized phase II PROTECT trial (NCT02359968), we aimed to evaluate the dosimetric parameters which could be associated with the occurrence of postoperative respiratory morbidities in patients (pts) who underwent preoperative CRT. Methods: Key eligibility criteria for the PROTECT trial were stage II or III resectable adenocarcinoma or squamous cell carcinoma of the esophagus located below the carina. Pts received FOLFOX or Carboplatin-Paclitaxel, combined with radiotherapy (RT): total dose of 41.4 Gy, 5 fractions of 1.8 Gy per week, starting at day 1 of chemotherapy. The patient's position and definition of the target volumes and organs at risk were the same as in the CROSS trial (van Hagen, 2012). Pts were treated using 3D conformal RT or IMRT. Surgery occurred 4 to 8 weeks after completion of CRT through a transthoracic or mini-invasive approach with a two field extended lymphadenectomy. Pts recruited in the PROTECT trial up to Sept. 2019 who underwent surgery after CRT were eligible for this ancillary study. The primary endpoint of our translational study was the occurrence of postoperative respiratory morbidity, of any grade (Clavien-Dindo classification for early morbidity &lt; 31 days; NCI-CTCAE v4 for later events), up to 1 year following surgery, considering disease progression or death as competing events. Cause-specific Cox models were used to model the risk of respiratory morbidity, considering the following factors: performance status, BMI, smoking, histological subtype, tumor site, FEV1, RT technique, time interval between CRT and surgery, and dosimetric parameters derived from the Dose-Volume Histogram analysis (mean lung dose, V10Gy, V20Gy and V30Gy, as other parameters strongly correlated to these 4 ones). Results: Among the 98 pts recruited in the PROTECT trial from Feb. 2015 to Sept. 2019, 78 underwent surgery after CRT and were included in our translational study. Median age was 63.5 years (range 33 to 79). Tumor was located at the middle or lower third of the esophagus for 67% of pts. Mean lung dose was 10.2 Gy (sd = 3.2). Mean PTV volume was 566 cc (sd = 272). A total of 33 pts experienced at least one respiratory morbidity (16 pneumonia, 7 pleural effusion, 4 ARDS, 21 miscellaneous events). The cumulative incidence of respiratory morbidity was 42% one month after surgery (95% CI, 32-54), 44% at 3 months (32-54), and 46% at 6 months (35-57). None of the dosimetric parameters and other studied factors appeared associated with postoperative respiratory morbidity. Conclusions: We did not identify dosimetric factors that could predict the risk of postoperative respiratory morbidity after treatment with preoperative CRT with FOLFOX or Carboplatin-Paclitaxel. Clinical trial information: NCT02359968.