Dose Region Research Articles

Dose prediction of CyberKnife Monte Carlo plan for lung cancer patients based on deep learning: robust learning of variable beam configurations

BackgroundAccurate calculation of lung cancer dose using the Monte Carlo (MC) algorithm in CyberKnife (CK) is essential for precise planning. We aim to employ deep learning to directly predict the 3D dose distribution calculated by the MC algorithm, enabling rapid and accurate automatic planning. However, most current methods solely focus on conventional intensity-modulated radiation therapy and assume a consistent beam configuration across all patients. This study seeks to develop a more versatile model incorporating variable beam configurations of CK and considering the patient’s anatomy.MethodsThis study proposed that the AB (anatomy and beam) model be compared with the control Mask (only anatomy) model. These models are based on a 3D U-Net network to investigate the impact of CK beam encoding information on dose prediction. The study collected 86 lung cancer patients who received CK′s built-in MC algorithm plans using different beam configurations for training/validation (66 cases) and testing (20 cases). We compared the gamma passing rate, dose difference maps, and relevant dose-volume metrics to evaluate the model’s performance. In addition, the Dice similarity coefficients (DSCs) were calculated to assess the spatial correspondence of isodose volumes.ResultsThe AB model demonstrated superior performance compared to the Mask model, particularly in the trajectory dose of the beam. The DSCs of the AB model were 20–40% higher than that of the Mask model in some dose regions. We achieved approximately 99% for the PTV and generally more than 95% for the organs at risk (OARs) referred to the clinical planning dose in the gamma passing rates (3 mm/3%). Relative to the Mask model, the AB model exhibited more than 90% improvement in small voxels (p < 0.001). The AB model matched well with the clinical plan’s dose-volume histograms, and the average dose error for all organs was 1.65 ± 0.69%.ConclusionsOur proposed new model signifies a crucial advancement in predicting CK 3D dose distributions for clinical applications. It enables planners to rapidly and precisely predict MC doses for lung cancer based on patient-specific beam configurations and optimize the CK treatment process.

Pneumonitis after normofractionated radioimmunotherapy: a method for dosimetric evaluation

BackgroundPost-Therapy-Pneumonitis (PTP) is a critical side effect of both, thoracic radio(chemo)therapy (R(C)T) and immune checkpoint inhibition (ICI). However, disease characteristics and patient-specific risk factors of PTP after combined R(C)T + ICI are less understood. Given that RT-triggered PTP is strongly dependent on the volume and dose of RT [1], driven by inflammatory mechanisms, we hypothesize that combination therapy of R(C)T with ICI influences the dose-volume-effect correlation for PTP. This study focuses on the development of a method for evaluation of alterations of dosimetric parameters for PTP after R(C)T with and without ICI.Methods and materialsPTP volumes were delineated on the follow-up diagnostic Computed Tomography (CT) and deformably matched to the planning CT for patients with PTP after thoracic R(C)T + ICI or R(C)T. Dose data was converted to 2-Gy equivalent doses (EQD2) and dosimetrically analyzed. Dosimetric and volumetric parameters of the segmented PTP volumes were analyzed. The method was exemplarily tested on an internal patient cohort including 90 patients having received thoracic R(C)T + ICI (39) and R(C)T (51). Thirtytwo patients with PTP were identified for further analysis. Additional data on previous chemotherapy, RT, smoking status and pulmonary co-morbidity were conducted. A matched pair analysis with regard to planning target volumes (PTV) was conducted for curative intended (definitive) and palliative patient cohorts individually.ResultsThe presented method was able to quantify and compare the dosimetric parameters of PTP for the different therapies. For our study group, no significant differences between R(C)T + ICI and R(C)T only was observed. However, the dosimetric analysis revealed large volumetric fractions (55%) of the PTP volumes to be located outside of high dose (EQD2 < 40 Gy) regions for R(C)T + ICI. There was a non-significant trend towards increased area under the curve of the dose volume histogram (AUC) values for R(C)T + ICI compared to R(C)T only (3743.6 Gy∙% vs. 2848.8 Gy∙%; p-value = 0.171). In contrast to the data for the palliative intended treatment group, for definitive R(C)T + ICI, data tended towards increased volumes with higher doses.ConclusionsThe proposed method was capable to quantify dosimetric differences in the dose-volume-effect relationship of PTP for patients with R(C)T + ICI and patients with R(C)T only. In this exploratory analysis, no significant dosimetric differences within PTP volumes for the different groups could be observed. However, our observations suggest, that for safe application of thoracic R(C)T + ICI, further careful investigation of dosimetric prescription and analysis concepts with larger and conformer study groups is recommendable.

Relationship between radiation dose and cerebral microbleed formation in dogs with intracranial tumors.

Cerebral microbleeds (CMBs) are a possible sequela in human brain tumor patients treated with radiation therapy (RT). No such association is reported in dogs. To investigate whether CMBs occur in dogs after radiotherapy, and if there is an association between number and dose, and an increase over time. Thirty-four client-owned dogs irradiated for primary intracranial neoplasia. ≥2 magnetic resonance imaging (MRI) scans including susceptibility-weighted imaging (SWI) were required. Retrospective, observational, single-center study. Cerebral microbleeds identified on 3 T SWI were counted within the entire brain, and within low- (<20 Gy), intermediate- (20-30 Gy), and high- (>30 Gy) dose regions. A generalized linear mixed-effects model was used to analyze the relationship between the CMBs count and the predictor variables (irradiation dose, time after treatment). Median follow-up time was 12.6 months (range, 1.8-37.6 months). Eighty-three MR scans were performed. In 4/15 dogs (27%, 95% CI, 10%-52%) CMBs were present at baseline. ≥1 CMBs after RT were identified in 21/34 dogs (62%, 95% CI, 45%-77%). With each month, the number of CMBs increased by 14% (95% CI, 11%-16%; P < .001). The odds of developing CMBs in the high-dose region are 4.7 times (95% CI, 3.9-5.6; P < .001) greater compared with the low-dose region. RT is 1 possible cause of CMBs formation in dogs. Cerebral microbleeds are most likely to occur in the peritumoral high-dose volume, to be chronic, and to increase in number over time. Their clinical relevance remains unknown.

Clinical Application of Equivalent Uniform Dose in Intensity-Modulated Rotational Radiotherapy Based on Eclipse TPS

To investigate the application of equivalent uniform dose (EUD) in intensity-modulated rotational radiotherapy and to explore optimization methods for improving the quality of modulated treatment plans. The impact of the parameter a in the EUD formula on the characteristics of the EUD curve was analyzed using Python. Thirty cases of head and neck tumors, thoracic tumors, and pelvic tumors were randomly selected for treatment planning. Dose optimization for the target area and organs at risk were performed using a physics-based optimization approach or an optimization approach that combines physical constraints with the EUD function. The dose distribution and compliance with constraints of the two groups of plans were compared, while also observing the effect of different values of a on the planning outcomes. The impact of the value of a on the changes in EUD curve characteristics was consistent with its impact on the results of EUD plan optimization. When -15≤ a≤-5, the dose distribution in the target area was more uniform; when 1≤ a≤7, the effect on the uniform dose and low-dose regions in organs at risk was more noticeable; when 10≤ a≤30, the effect of constraining the high-dose regions in organs at risk was more pronounced, with the EUD for the target area and organs at risk exhibiting different expressions under different a values. The study also found that the target dose distribution and the protection of organs at risk in the EUD optimization group were better than those in the physical optimization group only. The a-value has a significant impact on the, the dose distribution in the target area and the organ at risk, providing a reference for the setting of a-value while using EUD to optimize the intensity modulation plan. The using of EUD optimization method can not only achieve excellent dose distribution in the target area, but also significantly reduce the normal tissue dose and the probability of complications, which has certain clinical application value.

Evaluation of Inverse Planned and Forward Planned Intensity Modulated Radiotherapy Techniques in Breast Cancer

Introduction: The objective of this study is to compare the dosimetric parameters of radiation to the whole breast between the two intensity-modulated radiotherapy (IP IMRT) techniques, i.e. Inverse planned IMRT (IP IMRT) and Forward Planned IMRT (FP IMRT) with regard to target coverage (PTV) and irradiation of organs at risk (OAR). Material and Methods: Plain and Contrast enhanced computed tomography (CECT) datasets were created for 41 patients treated with whole breast radiation therapy. CT simulation and treatment is performed using deep inspiratory breath hold technique (DIBH). Radiotherapy treatment Planning is done using Eclipse Treatment Planning System (version 13.7) with a prescription dose of 40 Gy in 15#. The developed treatment plans were subjected to objective comparison of PTV and OARs using dose volume histograms (DVH). Results: IP IMRT plans provided better coverage (99.5% vs 97.6%), comparable though higher maximum dose (Dmax 45.0 VS 44.1 Gy), higher hot spot (PTV105% 49.2 vs 33), lower volumes receiving 20, 25, 30 Gy (V20, V25, V30) for heart, more homogeneous (homogeneity index 0.10 vs. 0.14) and conformal dose distribution (conformity Index 1.0 vs 0.98) compared to FP IMRT. Regarding OAR dosimetry it is observed that FP IMRT showed reduced mean dose to Coronary artery (LADCA), Contralateral Lung (CL), Contralateral breast (CB) along with reduction in low dose region (V5) to all OARs under study. It was also observed that Monitor units used and planning time were lower for FP IMRT. Conclusion: On weighing different dosimetric factors, both the techniques have displayed their own advantages and disadvantages. Choosing a planning technique needs to be customized taking into consideration various factors such as breast topography, size and volumes of breast, availability of expertise planning skills and resources.

Online Adaptive Proton Therapy Facilitated by Artificial Intelligence–Based Autosegmentation in Pencil Beam Scanning Proton Therapy

PurposeOnline adaptive proton therapy (oAPT) is essential to address interfractional anatomical changes in patients receiving pencil beam scanning proton therapy (PBSPT). Artificial intelligence (AI)-based auto-segmentation can increase the efficiency and accuracy. Linear energy transfer (LET)-based biological effect evaluation can potentially mitigate possible adverse events caused by high LET. New spot arrangement based on the verification CT (vCT) can further improve the re-plan quality. We propose an oAPT workflow that incorporates all these functionalities and validate its clinical implementation feasibility with prostate patients. Methods and MaterialsAI-based auto-segmentation tool AccuContourTM (Manteia, Xiamen, China) was seamlessly integrated into oAPT. Initial spot arrangement tool on the vCT for re-optimization was implemented using raytracing. An LET-based biological effect evaluation tool was developed to assess the overlap region of high dose and high LET in selected OARs. Eleven prostate cancer patients were retrospectively selected to verify the efficacy and efficiency of the proposed oAPT workflow. The time cost of each component in the workflow was recorded for analysis. ResultsThe verification plan showed significant degradation of the CTV coverage and rectum and bladder sparing due to the interfractional anatomical changes. Re-optimization on the vCT resulted in great improvement of the plan quality. No overlap regions of high dose and high LET distributions were observed in bladder or rectum in re-plans. 3D Gamma analyses in PSQA confirmed the accuracy of the re-plan doses before delivery (Gamma passing rate = 99.57 ± 0.46%), and after delivery (98.59 ± 1.29%). The robustness of the re-plans passed all clinical requirements. The average time for the complete execution of the workflow was 9.12 ± 0.85 minutes, excluding manual intervention time. ConclusionThe AI-facilitated oAPT workflow was demonstrated to be both efficient and effective by generating a re-plan that significantly improved the plan quality in prostate cancer treated with PBSPT.

Inversion-recovery ultrashort-echo-time (IR-UTE) MRI-based detection of radiation dose heterogeneity in gynecologic cancer patients treated with HDR brachytherapy

PurposeTo evaluate the relationship between delivered radiation (RT) and post-RT inversion-recovery ultrashort-echo-time (IR-UTE) MRI signal-intensity (SI) in gynecologic cancer patients treated with high-dose-rate (HDR) brachytherapy (BT).MethodsSeven patients underwent whole-pelvis RT (WPRT) followed by BT to the high-risk clinical target volume (HR-CTV). MR images were acquired at three time-points; pre-RT, post-WPRT/pre-BT, and 3–6 months post-BT. Diffuse-fibrosis (FDiffuse) was imaged with a non-contrast dual-echo IR (inversion time [TI] = 60 ms) UTE research application, with image-subtraction of the later echo, only retaining the ultrashort-echo SI. Dense-fibrosis (FDense) imaging utilized single-echo Late-Gadolinium-Enhanced IR-UTE, acquired ∼ 15 min post-Gadavist injection. Resulting FDiffuse and FDense SI were normalized to the corresponding gluteal-muscle SI. Images were deformably registered between time-points based on normal tissue anatomy. The remnant tumor at both time-points was segmented using multi-parametric MRI. Contours corresponding to the 50%, 100%, 150%, and 200% isodose lines (IDLs) of the prescription BT-dose were created. Mean FDiffuse and FDense SI within (i) each IDL contour and (ii) the remnant tumor were calculated. Post-BT FDiffuse and FDense SI were correlated with prescribed BT-dose. To determine the relationship between BT-dose and IR-UTE SI, the differences in the post-BT FDense across IDLs was determined using paired t-tests with Bonferroni correction.ResultsFDense was higher in regions of higher dose for 6/7 patients, with mean ± SD values of 357 ± 103% and 331 ± 97% (p = .03) in the 100% and 50% IDL, respectively. FDense was higher in regions of higher dose in the responsive regions with mean ± SD values of 380 ± 122% and 356 ± 135% (p = .03) in the 150% and 50% IDL, respectively. Within the segmented remnant tumor, an increase in prescribed dose correlated with an increase in FDense post-BT (n = 5, r = .89, p = .04). Post-BT FDiffuse inversely correlated (n = 7, r = -.83, p = .02) with prescribed BT-dose within the 100% IDL.ConclusionsResults suggest that FDense SI 3–6 months post-BT is a sensitive measure of tissue response to heterogeneous BT radiation-dose. Future studies will validate whether FDiffuse and FDense are accurate biomarkers of fibrotic radiation response.

Development and first implementation of a novel multi-modality cardiac motion and dosimetry phantom for radiotherapy applications.

Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real-time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT). This work describes the development and implementation of a novel multi-modality and magnetic resonance (MR)-compatible cardiac phantom. The patient-informed 3D model was derived from manual contouring of a contrast-enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post-processed to simulate female heart with an average volume. The model was 3D-printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR-safe programmable motor to supply cardiac and respiratory motion in superior-inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR-linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient-derived cardiac (sine waveform, 4.3mm peak-to-peak, 60 beats/min), respiratory (cos4 waveform, 30mm peak-to-peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4mm peak-to-peak, 70 beats/min) and respiratory (cos4 waveform, 24mm peak-to-peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4mm × 2.4mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT-based VT treatment plan was delivered twice under cone-beam CT guidance and cumulative stationary doses to multi-point PSDs were evaluated. No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3±25.8%/66.9±14.0%, 97.0±2.2%/96.4±1.7%, and 90.4±4.8%/89.3±3.5% of prescription for cardiac, respiratory, and cardio-respiratory motion profiles for the 2-chamber (PSD) and 12-substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was<2% from expected using the IC module. Real-time dose measured for the PSDs at 10Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio-respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was<1% from expected (5-6 cGy deviation of 5.9Gy/fraction) and high gradient/low dose regions had deviations<3.6% (6.3 cGy less than expected 1.73Gy/fraction). A novel multi-modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR-linac. Our phantom was capable of mimicking cardiac, cardio-respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time-resolved PSDs with small sensitive volumes appear promising for low-amplitude/high-frequency motion and multi-point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy.

Informing solar blind radioluminescence imaging through a calibrated spectrum

While direct radiation detection methods offer great insight into the origin of ionizing particles and photons, their use to locate contaminated areas or concealed radioactive sources can lead to undue exposure of personnel and equipment to ionizing radiation or the potential for contamination. These same sources induce ultraviolet (UV) optical photon fluorescence in air – a process referred to as radioluminescence – that may be imaged from low dose regions over larger attenuation lengths than ionizing radiation. However, most optical detection methods are limited to low lighting conditions to image the more abundant ultraviolet-A (UV-A) photons. To extend this capability to room light or daytime conditions, the solar blind region (Ultraviolet-C (UV–C), <280 nm) can be tapped. Though the emission yield of UV-C photons is roughly two orders of magnitude lower than that in the UV-A regime, the UV-C offers dramatic improvements in signal-to-noise ratios under bright lighting conditions due to decreased background interferences. The yield of specific UV-C lines, if present in the literature at all, varies widely, which has a large impact in modeling and analyzing standoff UV-C measurement scenarios. Thus, we have captured improved radioluminescence spectra over 250–400 nm and identified observed emission peaks in ambient air. Many of the UV-C photons produced by ionizing radiation excitation result from high-energy, molecular nitrogen Gaydon-Herman transitions which have had limited study to date for this application. Relating these findings to published UV-A yields, we estimate emissions between 0.15 and 0.19 photons/MeV over 250–280 nm. We also use a commercial corona-discharge imaging camera to demonstrate outdoor UV-C radiation mapping of alpha and gamma emitters from 50 to 75 m standoffs, respectively. The imaged “counts” are compared to optically modeled values and show the same trend over distance.

Impact of delivery variations on 3D dose distributions for volumetric modulated arc therapy plans of various complexity.

Delivery variations during radiotherapy can cause discrepancies between planned and delivered dose distribution. These variations could arise from random and systematic offsets in certain machine parameters or systematic offsets related to the calibration process of the treatment unit. The aim of this study was to present a novel simulation-based methodology to evaluate realistic delivery variations in three dimensions (3D). Additionally, we investigated the dosimetric impact of delivery variations for volumetric modulated arc therapy (VMAT) plans for different treatment sites and complexities. Twelve VMAT plans for different treatment sites (prostate-, head & neck-, lung-, and gynecological cancer) were selected. The clinical plan used for the treatment of each patient was reoptimized to create one plan with reduced complexity (i.e., simple plan) and one of higher complexity (i.e., complex plan). This resulted in a total of 36 plans. Delivery variations were simulated by randomly introducing offsets in multi-leaf collimator position, jaw position, gantry angle and collimator angle simultaneously. Twenty simulations were carried out for each of the 36 plans, yielding 720 simulated deliveries. To explore the impact of individual offsets, additional simulations were conducted for each type of offset separately. A 3D dose calculation was performed for each simulation using the same calculation engine as for the clinical plan. Two standard deviations (2SD) of dose were determined for every voxel for 3D-spatial evaluations. The dose variation in certain DVH metrics, that is, D2% and D98% for the clinical target volume and five different DVH metrics for selected organs at risk, was calculated for the twenty simulated deliveries of each plan. For comparison, the effect of delivery variations was assessed by conducting measurements with the Delta4 phantom. The volume of voxels with 2SD above 1% of the prescribed dose was consistently larger for the complex plans in comparison to their corresponding simple and clinical plans. 2SDs larger than 1% were in many cases, found to accumulate outside the planning target volume. For complex plans, regions with 2SDs larger than 1% were detected also inside the high dose region, exhibiting, on average, a size six times larger volume, than those observed in simple plans. Similar results were found for all treatment sites. Variation in the selected DVH metrics for the simulated deliveries was generally largest for the complex plans with few exceptions. When comparing the 2SD distribution of the measurements with the 2SD distribution from the simulations, the spatial information showed deviations outside the PTV in both simulations and measurements. However, the measured values were, on average, 35% higher for the prostate plans and 10% higher for the head & neck plans compared to the simulated values. The presented methodology effectively quantified and localized dose deviations due to delivery offsets. The 3D analysis provided information that was undetectable using the analysis based on DVH metrics. Dosimetric uncertainties due to delivery variations were prominent at the edge of the high-dose region irrespective of treatment site and plan complexity. Dosimetric uncertainties inside the high-dose region was more profound for plans of higher complexity.

A treatment-site-specific evaluation of commercial synthetic computed tomography solutions for proton therapy

Background and purposeDespite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system. Materials and methodsThe evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with “ground truth” deformed CTs. ResultsThe choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the “ground truth”, while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm. ConclusionsThis study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows.

Dosimetry with the TruView gel on a 0.35 T MR-Linac: A feasibility study

The purpose of this work is to assess the feasibility of performing dosimetry with the TruView (ModusQA, London, Ontario, Canada) MTB Fricke gel by MRI reading on a low field MR-Linac (0.35 T). Radiochromic TruView gels were manufactured at IRSN. A 4 echoes time (TE) single-shot fast spin echo sequence (HASTE) was used for 2D images acquisitions. Raw MRI images were denoised (MP-PCA) and transversal relaxation rates (R2) maps were extracted using a homemade Matlab routine. Temperature influences on R2 as well as gel homogeneity were investigated. A dosimetric evaluation of the TruView gel was conducted implying four gels made from the same batch, with three of them dedicated to calibration, and the fourth one received a simple dosimetric plan. Results showed the TruView gel to be sensitive to temperature drift. A protocol was thus developed to ensure thermal stability with the use of a dedicated temperature-controlled water bath. An inhomogeneity that manifests as a R2 increase near the air/gel interface was found to cause a 4% amplitude deviation in R2 along unirradiated gels. Air sealing drastically reduced the inhomogeneity. Dose versus R2 calibration was established. TruView gel sensitivity was found to be low (0.0093 Gy−1 s−1). 1D and 2D comparison to planned dose distribution displayed overall agreement with global gamma index (5%/3 mm) evaluation with an 87 % passing rate. Main discrepancies in the low and gradient dose regions were attributable to the calibration range and diffusion effects. This study demonstrated the feasibility of using the TruView gel for dosimetric evaluation on a low field MR-Linac. The protocol developed needs to be extended to a full 3D evaluation to enable patient QA and may require modifications to the gel formulation to increase its overall sensitivity and ensure limited dependence on temperature drift.

The response of radiation detectors in modulated fields for small targets

Intensity-modulated delivery techniques in radiotherapy are advanced methods that use the superposition of small fields to create complex dose distributions. These techniques result in intense gradients and inhomogeneous dose regions, making the dosimetry of composite fields challenging, especially when the sub-fields superposition does not restore charged particle equilibrium. This work aims to address the response of radiation detectors in non-equilibrium conditions. Two ionization chambers and a micro-diamond detector were irradiated using composite fields from VMAT plans with spherical targets with diameters ranging from 0.5 to 8 cm. The radiation detectors' response and the dose delivered by the VMAT plans were measured using a plastic scintillator detector and radiochromic film as reference detectors. It was observed that an under-response of the ionization chambers was up to 13% and an over-response of the micro-diamond detector was up to 2.5%. Additionally, output correction factors were derived and used to measure the absorbed dose in composite plans using the radiation detectors. The measured dose was compared with that measured with radiochromic film. A dose difference was found within radiochromic film uncertainties (<2.5%). The results of this work suggest that radiation detectors require output correction factors when non-equilibrium conditions persist in composite fields. However, a link between static and composite fields could not be established because the field size cannot be determined accurately.

Investigation of zinc polycarboxylate cement used in dental treatments in terms of retrospective dosimeter.

Zinc polycarboxylate cement is one of the few dental materials that demonstrate true adhesion to tooth structure. It is suitable for use in living organisms without causing harm. Its strong adhesion to teeth and low level of irritancy are two important parameters for the dental applications. In this study, the dosimetry properties of zinc polycarboxylate cement using thermoluminescence (TL) method were investigated and determined the effectiveness of its use as a good dosimeter. According to the results of this study, the sample shows a good TL properties with three main peaks found around 140°C, 220°C and 330°C. It has a wide linear dose response between 72 Gy and 2.3kGy and good reusability of the TL peak found at 330°C. Unfortunately, the TL peak intensity values are rapidly faded within a short waiting time interval. Zinc polycarboxylate cement, which is frequently used in dental crowns, can be used as a retrospective dosimeter for measuring the amount of radiation in space studies and nuclear accidents due to its wide linear dose-response curve in the high dose region.

Salvage Ablative Radiotherapy for Isolated Local Recurrence of Pancreatic Adenocarcinoma following Definitive Surgery.

Introduction: The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume. Methods: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan. Results: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively. Conclusions: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.

Treatment planning with high-resolution 3D dose maps in preclinical and translational synchrotron microbeam radiation therapy

Background and PurposeMicrobeam Radiation Therapy (MRT) aims to deliver higher doses to the target while minimizing radiation damage to healthy tissues using synchrotron x-ray microbeams. Translational MRT research has now started, driven by promising results from preclinical studies. This study aimed to propose a first dose-outcome model by analyzing micrometric dose distributions obtained with high-resolution 3D dose calculations, accounting for the inherent physical dose distribution complexity in MRT. The feasibility of integrating penMRT, our full Monte Carlo multiscale dose calculation algorithm based on PENELOPE into translational research on veterinary patients was also investigated. Material and MethodsMicrometric dose distributions were calculated in tumor-bearing rats and for a veterinary patient with penMRT, for conformal multi-directional MRT treatment plans. Absorbed dose maps were obtained with 0.005 × 0.005 × 1 mm3 voxel sizes. High-resolution dose-volume histograms were extracted and analyzed against radiobiology studies. ResultsThe complexity of the MRT dose distribution was properly rendered at a micrometer scale on 3D dose maps, with well separated dose regions observed on the differential dose-volume histograms. The median survival time of glioma-bearing rats varied linearly with the volume fraction of the planning target volume that received doses higher than 50 Gy (R2 = 0.98). The feasibility of using penMRT for treatment planning in large volumes has been shown on a veterinary patient. ConclusionsThis study demonstrated the significant added value of penMRT for planning and prescribing MRT treatments. It also shed light on the correlation between the high-resolution 3D dose distributions and the treatment outcome.

Interactions of plumbagin with five common antibiotics against Staphylococcus aureus in vitro.

Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S. aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) values against S. aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S. aureus, and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.

Clinical benchmarking of a commercial software for skin dose estimation in cardiac, abdominal, and neurology interventional procedures.

Radiation exposure from interventional radiology (IR) could lead to potential risk of skin injury in patients. Several dose monitoring software like radiation dose monitor (RDM) were developed to estimate the patient skin dose (PSD) distribution in IR. This study benchmarked the accuracy of RDM software in estimating PSD as compared to GafChromic film baseline in-vivo measurements on patients during cardiac, abdominal, and neurology IR procedures. The prospective study conducted in four IR departments included 81 IR procedures (25 cardiac, 31 abdominal, and 25 neurology procedures) on three angiographic systems. PSD and field geometry were measured by placing GafChromic film under the patient's back. Statistical analyses were performed to compare the software estimation and film measurement results in terms of PSD and geometric accuracy. Median values of measured/calculated PSD were 1140/1005, 591/655.9, and 538/409.7mGy for neurology, cardiac, and abdominal procedures, respectively. For all angiographic systems, the median (InterQuartile Range, IQR) difference between calculated and measured PSD was -10.2% (-21.8%-5.7%) for neurology, -4.5% (-19.5%-15.5%) for cardiac, and -21.9% (-38.7%--3.6%) for abdominal IR procedures. These differences were not significant for all procedures (p>0.05). Discrepancies increased up to -82% in lower dose regions where the measurement uncertainties are higher. Regarding the geometric accuracy, RDM correctly reproduced the skin dose map and estimated PSD area dimensions closely matched those registered on films with a median (IQR) difference of 0cm (-1-0.8cm). RDM is proved to be a useful solution for the estimation of PSD and skin dose distribution during abdominal, cardiac and neurology IR procedures despite a geometry phantom which is not specific to the latter type of IR procedures.

Streamlined pin-ridge-filter design for single-energy proton FLASH planning.

FLASH radiotherapy (FLASH-RT) with ultra-high dose rate has yielded promising results in reducing normal tissue toxicity while maintaining tumor control. Planning with single-energy proton beams modulated by ridge filters (RFs) has been demonstrated feasible for FLASH-RT. This study explored the feasibility of a streamlined pin-shaped RF (pin-RF) design, characterized by coarse resolution and sparsely distributed ridge pins, for single-energy proton FLASH planning. An inverse planning framework integrated within a treatment planning system was established to design streamlined pin RFs for single-energy FLASH planning. The framework involves generating a multi-energy proton beam plan using intensity-modulated proton therapy (IMPT) planning based on downstream energy modulation strategy (IMPT-DS), followed by a nested pencil-beam-direction-based (PBD-based) spot reduction process to iteratively reduce the total number of PBDs and energy layers along each PBD for the IMPT-DS plan. The IMPT-DS plan is then translated into the pin-RFs and the single-energy beam configurations for IMPT planning with pin-RFs (IMPT-RF). This framework was validated on three lung cases, quantifying the FLASH dose of the IMPT-RF plan using the FLASH effectiveness model. The FLASH dose was then compared to the reference dose of a conventional IMPT plan to measure the clinical benefit of the FLASH planning technique. The IMPT-RF plans closely matched the corresponding IMPT-DS plans in high dose conformity (conformity index of <1.2), with minimal changes in V7Gy and V7.4Gy for the lung (<3%) and small increases in maximum doses (Dmax) for other normal structures (<3.4Gy). Comparing the FLASH doses to the doses of corresponding IMPT-RF plans, drastic reductions of up to nearly 33% were observed in Dmax for the normal structures situated in the high-to-moderate-dose regions, while negligible changes were found in Dmax for normal structures in low-dose regions. Positive clinical benefits were seen in comparing the FLASH doses to the reference doses, with notable reductions of 21.4%-33.0% in Dmax for healthy tissues in the high-dose regions. However, in the moderate-to-low-dose regions, only marginal positive or even negative clinical benefit for normal tissues were observed, such as increased lung V7Gy and V7.4Gy (up to 17.6%). A streamlined pin-RF design was developed and its effectiveness for single-energy proton FLASH planning was validated, revealing positive clinical benefits for the normal tissues in the high dose regions. The coarsened design of the pin-RF demonstrates potential advantages, including cost efficiency and ease of adjustability, making it a promising option for efficient production.

Effects of nuclear interaction corrections and trichrome fragment spectra modelling on dose and linear energy transfer distributions in carbon ion radiotherapy

Background and PurposeNuclear interaction correction (NIC) and trichrome fragment spectra modelling improve relative biological effectiveness-weighted dose (DRBE) and dose-averaged linear energy transfer (LETd) calculation for carbon ions. The effect of those novel approaches on the clinical dose and LET distributions was investigated. Materials and MethodsThe effect of the NIC and trichrome algorithm was assessed, creating single beam plans for a virtual water phantom with standard settings and NIC + trichrome corrections. Reference DRBE and LETd distributions were simulated using FLUKA version 2021.2.9. Thirty clinically applied scanned carbon ion treatment plans were recalculated applying NIC, trichrome and NIC + trichrome corrections, using the LEM low dose approximation and compared to clinical plans (base RS). Four treatment sites were analysed: six prostate adenocarcinoma, ten head and neck, nine locally advanced pancreatic adenocarcinoma and five sacral chordoma. The FLUKA and clinical plans were compared in terms of DRBE deviations for D98%, D50%, D2% for the clinical target volume (CTV) and D50% in ring-like dose regions retrieved from isodose curves in base RS plans. Additionally, region-based median LETd deviations and global gamma parameters were evaluated. ResultsDose deviations comparing baseRS and evaluation plans were within ± 1% supported by γ-pass rates over 97% for all cases. No significant LETd deviations were reported in the CTV, but significant median LETd deviations were up to 80% for very low dose regions. ConclusionOur results showed improved accuracy of the predicted DRBE and LETd. Considering clinically relevant constraints, no significant modifications of clinical protocols are expected with the introduction of NIC + trichrome.