Uniform Dose Research Articles

Validation of a 3D printed bolus for radiotherapy: a proof-of-concept study.

3D-printed boluses in radiation therapy are of increasing interest for enhancing treatment precision and patient comfort. A comprehensive clinical validation of these boluses remains to be established. This study aims to confirm the effectiveness of a 3D-printed bolus through a proof-of-concept comparative validation, by implementing in a clinical setting a bolus made of PLA and designed to ensure uniform dose coverage for a case in the eye region. In this study the 3D-printed bolus was compared to two commercially available boluses (one thermoplastic and one skin type) by using a refecence where no bolus was present (with the optimal dose distribution scenario). All boluses were placed on an anthropomorphic head phantom and BeOSL detectors were used to measure dose values to determine the level of their effectiveness on delivery. During the scanning process, a thermoplastic mask was used to prevent bolus movement and to accurately reproduce clinical scenarios. Differences in dose values at Dmax and D50% revealed the performance of each bolus. The treatment planning system (TPS) and BeOSL readings for the 3D printed bolus were within 2% (the clinical tolerance), with 0.66% dose difference for the customized 3D-printed bolus. Although the thermoplastic bolus had the closest value to the detector reading, with a score of 0.30%, this result was influenced by improper shaping of the bolus on the phantom and the presence of a wide air gap, which caused lack of eye covering. Whereas, the skin bolus, due to higher volume of air between phantom surface and bolus, showed a 1.29% dose difference between the TPS values and the OSL detector readings. We provide a comparative validation for the use of 3D printed boluses and highlight that proper bolus fitting is essential in clinical settings to avoid air gaps and maintain dose distribution over multiple treatment sessions.

Automated contouring for breast cancer radiotherapy in the isocentric lateral decubitus position: aneural network-based solution for enhanced precision and efficiency.

Adjuvant radiotherapy is essential for reducing local recurrence and improving survival in breast cancer patients, but it carries arisk of ischemic cardiac toxicity, which increases with heart exposure. The isocentric lateral decubitus position, where the breast rests flat on asupport, reduces heart exposure and leads to delivery of amore uniform dose. This position is particularly beneficial for patients with unique anatomies, such as those with pectus excavatum or larger breast sizes. While artificial intelligence (AI) algorithms for autocontouring have shown promise, they have not been tailored to this specific position. This study aimed to develop and evaluate aneural network-based autocontouring algorithm for patients treated in the isocentric lateral decubitus position. In this single-center study, 1189 breast cancer patients treated after breast-conserving surgery were included. Their simulation CT scans (1209 scans) were used to train and validate aneural network-based autocontouring algorithm (nnU-Net). Of these, 1087 scans were used for training, and 122 scans were reserved for validation. The algorithm's performance was assessed using the Dice similarity coefficient (DSC) to compare the automatically delineated volumes with manual contours. Aclinical evaluation of the algorithm was performed on 30additional patients, with contours rated by two expert radiation oncologists. The neural network-based algorithm achieved asegmentation time of approximately 4 min, compared to 20 min for manual segmentation. The DSC values for the validation cohort were 0.88 for the treated breast, 0.90 for the heart, 0.98 for the right lung, and 0.97 for the left lung. In the clinical evaluation, 90% of the automatically contoured breast volumes were rated as acceptable without corrections, while the remaining 10% required minor adjustments. All lung contours were accepted without corrections, and heart contours were rated as acceptable in 93.3% of cases, with minor corrections needed in 6.6% of cases. This neural network-based autocontouring algorithm offers apractical, time-saving solution for breast cancer radiotherapy planning in the isocentric lateral decubitus position. Its strong geometric performance, clinical acceptability, and significant time efficiency make it avaluable tool for modern radiotherapy practices, particularly in high-volume centers.

Unique Research for Developing a Full Factorial Design Evaluated Liquid Chromatography Technique for Estimating Budesonide and Formoterol Fumarate Dihydrate in the Presence of Specified and Degradation Impurities in Dry Powder Inhalation.

A simple LC method has been developed and validated for estimating budesonide (epimer B + A) and formoterol fumarate dihydrate in dry powder inhalation. The development results of this study make it very significant. The degradation and process impurities in EP and ChP were identified in addition to budesonide and formoterol fumarate. As of yet, no one has reported all impurities using a single method. It is a unique research because it analyzes APSD (Aerodynamic Particle Size Distribution), DDU (Delivered Dose Uniformity), BU (Blend Uniformity), Assay, and cleaning test samples. It enhances the quality of medicine and separates all organic impurities and isomers through a suitable stationary phase (YMC-Pack Pro C18, 150 × 4.6 mm × 3 μm). We optimized the chromatographic conditions: Injection volume was 20 μL, and flow rate was 1.0 mL/min. The wavelength was optimized at 220 nm. After experimental and validation results. An example is A, which contains sodium dihydrogen orthophosphate monohydrate, sodium 1-decane sulfonate, adjusted pH 3.0, and acetonitrile at a ratio of 80:20 (v/v), and B, which contains pH 3.0 buffer and acetonitrile at a ratio of 20:80 (v/v) respectively. In addition to being optimized, the test method was validated according to ICH Q2(R2).

Quantitative assessment of delivered dose in carbon ion spatially fractionated radiotherapy (C-SFRT) and biological response to C-SFRT

Objective. Applying carbon ion beams, which have high linear energy transfer and low scatter within the human body, to Spatially Fractionated Radiation Therapy (SFRT) could benefit the treatment of deep-seated or radioresistant tumors. This study aims to simulate the dose distributions of spatially fractionated beams (SFB) to accurately determine the delivered dose and model the cell survival rate following SFB irradiation.Approach. Dose distributions of carbon ion beams are calculated using the Triple Gaussian Model. The sensitive volume of the detector used in measurements was also considered. If the measurements and simulations show good agreement, the dose distribution and absolute dose delivered by SFB can be accurately estimated. Three types of dose distributions were delivered to human salivary gland cells (HSGc-C5): uniform dose distribution (UDD), and one-dimensional (1D) grid-like dose distributions (GDD) with 6 mm and 8 mm spacing. These provided high (Peak-to-Valley Dose Ratio, PVDR = 4.0) and low (PVDR = 1.64) dose differences between peak and valley doses, respectively. Linear-Quadratic (LQ) model parameters for HSGc-C5 were derived from the UDD and cell survival fractions (SF) were simulated for 1D GDD using these values.Main results. Good agreement was observed between measurements and simulations when accounting for detector volume. However, the TPS results overestimated dose in steep gradient region, likely due to the 2.0 mm calculation resolution. LQ parameters for HSGc-C5 wereα= 0.34 andβ= 0.057. The 1D GDD with 6 mm spacing showed good agreement between simulations and experiments, but the 8.0 mm spacing resulted in lower experimental cell survival.Significance. We successfully simulated the GDD and conducted SF simulations. The results suggest potential cell-killing effects due to high-dose differences in SFB.

P-1659. Clinical and Safety Outcomes of Uniform Thrice-Weekly Daptomycin Dosing Based on Adjusted Body Weight in Patients Receiving Intermittent Hemodialysis

Abstract Background Limited evidence exists on optimal dosing of daptomycin (DAP) in patients receiving intermittent dialysis (HD). Current labeling recommends every 48 hour (q48h) dosing which often causes additional DAP doses to be given throughout the week when the schedules become unaligned. Alternatively, current recommendations for thrice weekly dosing suggest a larger dose for the 72-hour interdialytic interval, which makes operationalization difficult within current inpatient electronic systems. Methods A retrospective observational cohort study comparing clinical and safety outcomes of adult patients receiving DAP with HD was performed between 01/2021 and 04/2024. Updated dosing recommendations for DAP with HD was modified on 1/2023 to indication based uniform adjusted body weight (AdjBW) dosing with each HD session compared to the previous recommendation of q48h based on total body weight. Clinical outcomes included microbiologic recurrence and escalation of dose or antibiotic therapy. Safety outcomes included CK elevation and development of rhabdomyolysis. Patients were excluded if they were on DAP prior to admission or received < 2 DAP doses. Results In total, 79 patients met inclusion. BMI, acuity of infection, length of stay, and duration of therapy were similar between the q48h (n=42) and the with each HD groups (n=37). There was a significant reduction in total weekly AdjBW DAP received in the with each HD group (23.8mg/kg vs 28.8 mg/kg, p < .0001) despite a higher utilization of the 8 mg/kg strategy (64.9% vs 26.2%). There was no significant difference in the clinical failure (5.4% vs 4.8%, p = 0.90) or safety outcomes (0% vs 6.5%, p = 0.12) between the post- and pre-groups, including after propensity matching based on BMI, AdjBW dose received, and receipt of source control. Conclusion Utilizing uniform DAP doses with each HD compared to standard q48h frequency in patients receiving HD did not result in worse clinical or safety outcomes while reducing the overall weekly exposure to DAP. This strategy further supports the use of AdjBW as the preferred dosing weight for DAP, including in HD patients, who have been underrepresented in previous studies. This method could also be useful in the outpatient setting to help optimize DAP exposure. Disclosures All Authors: No reported disclosures

Protein-functionalized and intrinsically radiolabeled [188Re]ReOx nanoparticles: advancing cancer therapy through concurrent radio-photothermal effects.

Enhancing therapeutic effectiveness is crucial for translating anticancer nanomedicines from laboratory to clinical settings. In this study, we have developed radioactive rhenium oxide nanoparticles encapsulated in human serum albumin ([188Re]ReOx-HSA NPs) for concurrent radiotherapy (RT) and photothermal therapy (PTT), aiming to optimize treatment outcomes. [188Re]ReOx-HSA NPs were synthesized by a controlled reduction of 188ReO4- in HSA medium and extensively characterized. The anticancer effect of [188Re]ReOx-HSA NPs was demonstrated in vitro in murine melanoma (B16F10) cell line. In vivo SPECT/CT imaging, autoradiography and biodistribution studies were performed after intratumoral injection of [188Re]ReOx-HSA NPs in melanoma tumor-bearing C57BL/6 mice. The potential of [188Re]ReOx-HSA NPs for combined RT and PTT treatment was also demonstrated in the aforesaid mice model. [188Re]ReOx-HSA NPs (size 4-6nm) were synthesized with high colloidal and radiochemical stability. Upon laser (808nm) exposure on B16F10 cells incubated with [188Re]ReOx-HSA NPs, only < 20% of cells were alive demonstrating high therapeutic efficacy under in vitro settings. Uniform dose distribution and retention of the radiolabeled NPs in the tumor volume were observed via SPECT/CT imaging and autoradiography studies. Tumor growth in mice model was significantly arrested with ~ 1.85 MBq dose of [188Re]ReOx-HSA NPs and simultaneous laser irradiation, demonstrating synergistic benefit of RT and PTT. These results demonstrate that intrinsically radiolabeled [188Re]ReOx-HSA NPs having unique features such as high photothermal effects and favorable nuclear decay characteristics for combined RT/PTT, hold great promise for clinical translation.

Randomized Evaluation of the PET-Adjusted IMRT for NSCLC Trial (REPAINT).

Standard radiotherapy (RT) for locally advanced NSCLC (LA-NSCLC) employs a uniform dose of approximately 60 Gy. Recent trials demonstrated that radiotherapy dose escalation may not improve outcomes and may cause added toxicity. XXX previously performed a single-arm trial testing a personalized, risk-adapted, and de-intensified RT strategy. We now report findings from a randomized trial testing this novel approach. LA-NSCLC patients with ECOG performance status 0-2 were eligible for this trial. Metabolic tumor volume (MTV) for each pulmonary tumor and involved lymph node was calculated using FDG-PET. Participants were randomized 1:1 to receive standard RT (60 Gy in 30 fractions delivered to pulmonary tumors and involved lymph nodes) versus dose-painted RT (55 Gy delivered to tumors and lymph nodes with metabolic volume exceeding 20 cm3 and 44-48 Gy to other lesions, all in 20 fractions). Concurrent chemotherapy and standard adjuvant therapy were given in both arms. The primary objective was to characterize patient-reported outcomes utilizing PRO-CTCAE. Secondary objectives included comparing outcomes between study arms. Fifty patients were enrolled. The most common grade 3 patient-reported adverse events within 90 days of RT completion were dysphagia (38%), fatigue (38%), cough (32%), and wheezing (28%). The median progression-free survival (PFS) duration is 18 months, and the median overall survival (OS) duration is 42 months. PFS and OS rates are similar across study arms (logrank p=0.562 and 0.765, respectively). There have been three cases of in-field disease progression, with one in the control arm and two in the dose-painted arm. Grade 3-4 lymphopenia was reduced with dose-painted RT (48% v. 81%, chi-square p=0.012). High-grade patient-reported toxicity in LA-NSCLC patients who are treated with concurrent chemoradiotherapy is common. We found no evidence that risk-adapted radiotherapy de-escalation compromises clinical outcomes. Follow-up studies testing the ability of this approach to improve the safety profile of chemoradiotherapy are warranted.

Simulation of Spread-Out Bragg Peak for Proton Therapy in Prostate Cancer Treatment Using MATLAB Linear Least Squares Method

Delivering an accurate dose to the target in radiotherapy is crucial for maximizing the effectiveness of prostate cancer treatment while minimizing side effects. Proton therapy offers significant potential advantages over conventional radiotherapy due to its unique physical properties, particularly the ability to precisely deposit energy at a specific depth using the Spread-Out Bragg Peak (SOBP) technique. The SOBP ensures a uniform dose distribution across the tumor, sparing surrounding healthy tissues. However, challenges remain in designing an optimal SOBP that achieves precise dose delivery, especially given the complex interplay of proton energies and target depths. This study addresses these challenges by utilizing Geant4 simulations to model SOBP generation through the use of multiple proton pencil beam energies. Additionally, the MATLAB Linear Least Squares (lsqlin) optimization tool was employed to determine optimal beam weighting configurations for achieving desired dose distributions. The results demonstrate that an optimized SOBP can be successfully achieved, offering a promising foundation for enhancing proton therapy in prostate cancer treatment.

Development of Novel Fluticasone/Salmeterol/Tiotropium-Loaded Dry Powder Inhaler and Bioequivalence Assessment to Commercial Products in Rats.

Background/Objectives: Inhaler devices have been developed for the effective delivery of inhaled medications used in the treatment of pulmonary diseases. However, differing operating procedures across the devices can lead to user errors and reduce treatment efficacy, especially when patients use multiple devices simultaneously. To address this, we developed a novel dry powder inhaler (DPI), combining fluticasone propionate (FP), salmeterol xinafoate (SX), and tiotropium bromide (TB) into a single device designed for bioequivalent delivery compared to existing commercial products in an animal model. Methods: The micronized FP/SX/TB-loaded capsule was prepared by sieving, blending, and filling capsules. Capsule suitability of the drugs was investigated from the comparison of the stability of drugs within various capsule formulations to that of commercial products. The particle size of the drugs was adjusted using spiral air jet milling, and the ratio of lactose hydrate carriers was optimized by comparing the aerodynamic particle size distribution (APSD) with that of commercial products. To investigate the bioequivalence of micronized FP/SX/TB-loaded DPI to commercial products, the dissolution profile of FP/SX/TB particles and pharmacokinetics in rats were evaluated and compared to commercial products. Results: Capsules with hydroxypropyl methylcellulose (HPMC) without a gelling agent showed superior stability of the drugs compared to commercial products. The deposition pattern was influenced by the particle size of the drugs, and fine particle mass exhibited a significant correlation with the amount of fine carrier. Micronized FP/SX/TB-loaded DPI gave a similar APSD and dissolution profile compared to the commercial products and showed dose uniformity by the DPI device. Furthermore, micronized FP/SX/TB-loaded DPI exhibited bioequivalence to commercial products, as evidenced by no significant differences in pharmacokinetic parameters following intratracheal administration in rats. Conclusions: A novel triple-combination DPI containing FP/SX/TB was successfully developed, demonstrating comparable pharmacological performance to commercial products. Optimized FP/SX/TB-loaded DPI with HPMC capsule achieved bioequivalence in rat studies, suggesting its potential for improved patient compliance and therapeutic outcomes. This novel single-device DPI offers a promising alternative for triple therapy in pulmonary diseases.

Quantitative Assessment of Delivered Dose in Carbon Ion Spatially Fractionated Radiotherapy (C-SFRT) and Biological Response to C-SFRT

Abstract Objective&amp;#xD;Applying carbon ion beams, which have high linear energy transfer and low scatter within the human body, to Spatially Fractionated Radiation Therapy (SFRT) could benefit the treatment of deep-seated or radioresistant tumors. This study aims to simulate the dose distributions of spatially fractionated beams (SFB) to accurately determine the delivered dose and model the cell survival rate following SFB irradiation.&amp;#xD;Approach&amp;#xD;Dose distributions of carbon ion beams are calculated using the Triple Gaussian Model. The sensitive volume of the detector used in measurements was also considered. If the measurements and simulations show good agreement, the dose distribution and absolute dose delivered by SFB can be accurately estimated. Three types of dose distributions were delivered to human salivary gland cells (HSGc-C5): uniform dose distribution (UDD), and one-dimensional (1D) grid-like dose distributions (GDD) with 6 mm and 8 mm spacing. These provided high (Peak-to-Valley Dose Ratio, PVDR=4.0) and low (PVDR=1.64) dose differences between peak and valley doses, respectively. Linear-Quadratic (LQ) model parameters for HSGc-C5 were derived from the UDD and cell survival fractions (SF) were simulated for 1D GDD using these values.&amp;#xD;Main results&amp;#xD;Good agreement was observed between measurements and simulations when accounting for detector volume. However, the TPS results overestimated dose in steep gradient region, likely due to the 2.0 mm calculation grid size. LQ parameters for HSGc-C5 were α = 0.34 and β = 0.057. The 1D GDD with 6 mm spacing showed good agreement between simulations and experiments, but the 8.0 mm spacing resulted in lower experimental cell survival.&amp;#xD;Significance&amp;#xD;We successfully simulated grid-like dose distributions and conducted SF simulations. The results suggest potential cell-killing effects due to high-dose differences in SFB.&amp;#xD;

Assessment of dose uniformity and optimal CT number for virtual bolus in breast VMAT planning

Background: ICRU Report No. 83 proposes using the Flash Region in the strategic design of breast cancer treatment. However, concerns persist regarding the delivery of the designated radiation dose to breast cancer patients undergoing Volumetric Modulated Arc Therapy (VMAT) with virtual bolus in the irradiation plan. Objective: This study aimed to assess dose uniformity in breast VMAT treatment with a virtual bolus, validate the planning dose by comparing it with nanoDotTM measurements on a Rando phantom, and determine the optimal CT number for the virtual bolus in breast VMAT planning. Materials and Materials and methods: To assess dose uniformity in the breast VMAT plan, nine nanoDot™ dosimeters were placed on the breast of Rando phantom, followed by CT simulation and VMAT treatment planning. The clinical target volume (CTV) and organs at risk were contoured, and the planning target volume (PTV) boundaries were expanded by 5 mm and 10 mm for virtual bolus thicknesses of 10 mm and 15 mm, respectively. The CT number of the virtual bolus varied from 0 to -700 HU. The planning doses at 9 points were determined, and the coefficient of variation (%CV) was calculated. Additionally, measurements at these 9 points were performed using nanoDot™ dosimeters. The calculated and measured doses were then compared. Finally, VMAT treatment plans with a virtual bolus were implemented in 10 breast cancer patients, using the virtual bolus with varying CT numbers as in the phantom study to evaluate the optimal CT number of the bolus. Results: The doses among the 9 points for each plan were uniform, with a %CV of less than 4. For calculated dose validation, the percentage differences between the measured and calculated dose for all treatment plans, with variations in the CT number and the bolus thickness, were within ±5%. To determine the optimal CT number for the virtual bolus, the breast cancer treatment plan that met the dose criteria for tumors and organs at risk was the plan with a CT number of 0 HU for both virtual bolus thicknesses of 10 and 15 mm. Conclusion: Virtual bolus provides uniform dose distribution for breast VMAT planning, which measurements from nanoDotTM can validate. The appropriate CT number for the virtual bolus is 0 HU for both bolus thicknesses. In future studies, measurements should be conducted on actual patients.

Superior Anti-Tumor Response After Microbeam and Minibeam Radiation Therapy in a Lung Cancer Mouse Model

Objectives: The present study aimed to compare the tumor growth delay between conventional radiotherapy (CRT) and the spatially fractionated modalities of microbeam radiation therapy (MRT) and minibeam radiation therapy (MBRT). In addition, we also determined the influence of beam width and the peak-to-valley dose ratio (PVDR) on tumor regrowth. Methods: A549, a human non-small-cell lung cancer cell line, was implanted subcutaneously into the hind leg of female CD1-Foxn1nu mice. The animals were irradiated with sham, CRT, MRT, or MBRT. The spatially fractionated fields were created using two specially designed multislit collimators with a beam width of 50 μm and a center-to-center distance (CTC) of 400 μm for MRT and a beam width of 500 μm and 2000 μm CTC for MBRT. Additionally, the concept of the equivalent uniform dose (EUD) was chosen in our study. A dose of 20 Gy was applied to all groups with a PVDR of 20 for MBRT and MRT. Tumor growth was recorded until the tumors reached at least a volume that was at least three-fold of their initial value, and the growth delay was calculated. Results: We saw a significant reduction in tumor regrowth following all radiation modalities. A growth delay of 11.1 ± 8 days was observed for CRT compared to the sham, whereas MBRT showed a delay of 20.2 ± 7.3 days. The most pronounced delay was observed in mice irradiated with MRT PVDR 20, with 34.9 ± 26.3 days of delay. Conclusions: The current study highlights the fact that MRT and MBRT modalities show a significant tumor growth delay in comparison to CRT at equivalent uniform doses.

Development of a low-dose strategy for propagation-based imaging helical computed tomography (PBI-HCT): high image quality and reduced radiation dose

Background. Propagation-based imaging computed tomography (PBI-CT) has been recently emerging for visualizing low-density materials due to its excellent image contrast and high resolution. Based on this, PBI-CT with a helical acquisition mode (PBI-HCT) offers superior imaging quality (e.g., fewer ring artifacts) and dose uniformity, making it ideal for biomedical imaging applications. However, the excessive radiation dose associated with high-resolution PBI-HCT may potentially harm objects or hosts being imaged, especially in live animal imaging, raising a great need to reduce radiation dose.Methods. In this study, we strategically integrated Sparse2Noise (a deep learning approach) with PBI-HCT imaging to reduce radiation dose without compromising image quality. Sparse2Noise uses paired low-dose noisy images with different photon fluxes and projection numbers for high-quality reconstruction via a convolutional neural network (CNN). Then, we examined the imaging quality and radiation dose of PBI-HCT imaging using Sparse2Noise, as compared to when Sparse2Noise was used in low-dose PBI-CT imaging (circular scanning mode). Furthermore, we conducted a comparison study on the use of Sparse2Noise versus two other state-of-the-art low-dose imaging algorithms (i.e., Noise2Noise and Noise2Inverse) for imaging low-density materials using PBI-HCT at equivalent dose levels.Results. Sparse2Noise allowed for a 90% dose reduction in PBI-HCT imaging while maintaining high image quality. As compared to PBI-CT imaging, the use of Sparse2Noise in PBI-HCT imaging shows more effective by reducing additional radiation dose (30%-36%). Furthermore, helical scanning mode also enhances the performance of existing low-dose algorithms (Noise2Noise and Noise2Inverse); nevertheless, Sparse2Noise shows significantly higher signal-to-noise ratio (SNR) value compared to Noise2Noise and Noise2Inverse at the same radiation dose level.Conclusions and significance. Our proposed low-dose imaging strategy Sparse2Noise can be effectively applied to PBI-HCT imaging technique and requires lower dose for acceptable quality imaging. This would represent a significant advance imaging for low-density materials imaging and for future live animals imaging applications.

Influence of absorbing layers on the average dose and dose uniformity during irradiation with 1–3 MEV electrons

Electron beams with energies up to 3 MeV, widely used in technological and research practice, have a relatively low penetration depth into matter, and the nonuniformity of energy absorption can reach 30% per 1 mm of path. High nonuniformity, as well as the high cost of radiation, requires the researcher to have skills in optimizing the uniformity of irradiation and reducing energy losses. This work presents the dependence of the average absorbed dose and dose nonuniformity when irradiating a liquid with a horizontal beam in test tubes or pipes with different glass wall thicknesses (0.2–2 mm Pyrex). The dependencies are applicable to clarify, predict and analyze the distribution of absorbed dose in materials.

Highs and Lows of Spatially Fractionated Radiation Therapy: Dosimetry and Clinical Outcomes.

Spatially fractionated radiation therapy (SFRT) intentionally delivers a heterogeneous dose distribution characterized by alternating regions of high and low doses throughout a tumor. This modality may enhance response to subsequent whole tumor radiation in bulky and radioresistant lesions that are historically less responsive to conventional radiation doses alone. The current study presents a single institution experience with modern era SFRT using predominantly a volumetric modulated arc therapy (VMAT) lattice technique. Patients treated with SFRT between 10/2019 and 6/2022 were included for analysis. Patient characteristics, tumor characteristics, and dosimetric parameters were collected retrospectively as part of an institutional review board approved registry and protocol. Descriptive statistics were used to collate patient data and Kaplan Meier analysis were generated for overall survival and local control. Univariate analyses were used to investigate factors associated with outcomes. A total of 176 patients with 186 sites treated were included. Median age was 64 and the most commonly treated histologies were non-small cell lung cancer and sarcoma. The most common SFRT dose was 20 Gy in 1 fraction with 88% of patients receiving follow-up whole tumor radiotherapy to a median EQD2 dose of 32.5 Gy (α/β=10). Median gross tumor volume (GTV) was 480.5 cc (7.8-10,897.8). Median follow-up was 322 days with 1 year overall survival 37% and 1 year local control 81%. Local control was available in 138 treated sites (131 patients. SFRT factors including dose to 10% (D10%), dose to 90% (D90%), equivalent uniform dose, and mean dose were highly predictive of local control. Grade 3 toxicity occurred in 9 patients. All of these patients received follow-up whole tumor radiation and at least two of these were attributable to unexpected rapid regression of tumor. SFRT is a promising technique that appears to confer good local control across a disparate group of patients with bulky and radioresistant tumors. Dosimetric parameters of SFRT treatment plans may be independent predictors of local control. Further investigation is warranted as are prospective trials to evaluate the role of SFRT in both the palliative and definitive setting.

Hydrogen-Generating Magnesium Alloy Seed Strand Sensitizes Solid Tumors to Iodine-125 Brachytherapy.

Radioactive iodine-125 (125I) seed implantation, a brachytherapy technique, effectively kills tumor cells via X-rays and gamma rays, serving as an alternative therapeutic option following the failure of frontline treatments for various solid tumors. However, tumor radioresistance limits its efficacy. Hydrogen gas has anticancer properties and can enhance the efficacy of immunotherapy. However, its role in radiotherapy sensitization has rarely been reported. Many current hydrogen delivery methods involve hydrogen-generating nanomaterials, such as magnesium-based nanomaterials. This study introduces an AZ31 magnesium alloy 125I seed strand (termed AMASS) with pH-dependent slow-release hydrogen characteristics and excellent mechanical properties. AMASS can be implanted into tumors via minimally invasive surgery, releasing hydrogen around the 125I seeds. In vitro experiments showed that hydrogen from AMASS degradation significantly inhibited tumor proliferation, increased apoptosis, disrupted redox homeostasis and mitochondrial membrane potential, reduced adenosine triphosphate levels, and induced DNA damage due to 125I radiation. In mouse xenograft and rabbit liver tumor models, hydrogen from AMASS showed superior therapeutic effects compared with 125I seeds alone, with no noticeable side effects. In addition, AMASS has a uniform radiation dose distribution and simple implantation. Therefore, hydrogen from AMASS enhanced 125I seed efficacy, supporting the further promotion and application of 125I seed implantation in cancer therapy.

The LET enhancement of energy-specific collimation in pencil beam scanning proton therapy.

To computationally characterize the LET distribution during dynamic collimation in PBS and quantify its impact on the resultant dosedistribution. Monte Carlo simulations using Geant4 were used to model the production of low-energy proton scatter produced in the collimating components of a novel PBS collimator. Custom spectral tallies were created to quantify the energy, track- and dose-averaged LET resulting from individual beamlet and composite fields simulated from a model of the IBA dedicated nozzle system. The composite dose distributions were optimized to achieve a uniform physical dose coverage of a cubical and pyramidal target, and the resulting dose-average LET distributions were calculated for uncollimated and collimated PBS deliveries and used to generate RBE-weighted dosedistributions. For collimated beamlets, the scattered proton energy fluence is strongly dependent on collimator position relative to the central axis of the beamlet. When delivering a uniform profile, the distribution of dose-average LET was nearly identical within the target and increased between 1 and within 10mm surrounding the target. Dynamic collimation resulted in larger dose-average LET changes: increasing the dose-average LET between 1 and within 10mm of a pyramidal target while reducing the dose-average LET outside this margin by as much as . Biological dose distributions are improved with energy-specific collimation in reducing the lateralpenumbra. The presence of energy-specific collimation in PBS can lead to dose-average LET changes relative to an uncollimated delivery. In some clinical situations, the placement and application of energy-specific collimation may require additional planning considerations based on its reduction to the lateral penumbra and increase in high-dose conformity. Future applications may embody these unique dosimetric characteristics to redirect high-LET portions of a collimated proton beamlet from healthy tissues while enhancing the dose-average LET distribution withintarget.

Multi-collimator proton minibeam radiotherapy with joint dose and PVDR optimization.

The clinical translation of proton minibeam radiation therapy (pMBRT) presents significant challenges, particularly in developing an optimal treatment planning technique. A uniform target dose is crucial for maximizing anti-tumor efficacy and facilitating the clinical acceptance of pMBRT. However, achieving a high peak-to-valley dose ratio (PVDR) in organs-at-risk (OAR) is essential for sparing normal tissue. This balance becomes particularly difficult when OARs are located distal to the beam entrance or require patient-specific collimators. This work proposes a novel pMBRT treatment planning method that can achieve high PVDR at OAR and uniform dose at target simultaneously, via multi-collimator pMBRT (MC-pMBRT) treatment planning method with joint dose and PVDR optimization (JDPO). MC-pMBRT utilizes a set of generic and premade multi-slit collimators with different center-to-center distances and does not need patient-specific collimators. The collimator selection per field is OAR-specific and tailored to maximize PVDR in OARs while preserving target dose uniformity. Then, the inverse optimization method JDPO is utilized to jointly optimize target dose uniformity, PVDR, and other dose-volume-histogram based dose objectives, which is solved by iterative convex relaxation optimization algorithm and alternating direction method of multipliers. The need and efficacy of MC-pMBRT is demonstrated by comparing the single-collimator (SC) approach with the multi-collimator (MC) approach. While SC degraded either PVDR for OAR or dose uniformity for the target, MC provided a good balance of PVDR and target dose uniformity. The proposed JDPO method is validated in comparison with the dose-only optimization (DO) method for MC-pMBRT, in reference to the conventional (CONV) proton RT (no pMBRT). Compared to CONV, MC-pMBRT (DO and JDPO) preserved target dose uniformity and plan quality, while providing unique PVDR in OAR. Compared to DO, JDPO further improved PVDR via PVDR optimization during treatment planning. A novel pMBRT treatment planning method called MC-pMBRT is proposed that utilizes a set of generic and premade collimators with joint dose and PVDR optimization algorithm to optimize OAR-specific PVDR and target dose uniformity simultaneously.

Dosimetric evaluation of different cylinder diameters in three-dimensional vaginal brachytherapy for early-stage endometrial cancer

PurposeTo evaluate the dosimetric, radiobiological, and toxicity differences between different cylinder diameters (d) in high-dose-rate three-dimensional computed-tomography-guided vaginal brachytherapy (VBT) for early-stage endometrial cancer (EC).MethodsFrom January 2019 to January 2024, postoperative EC patients treated with exclusive VBT using cylinders were classified by the cylinder diameter (d ≤ 2.6 cm: small-size; d ≥ 3.0 cm: large-size) and matched according to 1:2 propensity score matching. Vaginal clinical target volume (CTV) was a 3-mm expansion around the cylinder surface. Dosimetric parameters in equivalent dose in 2 Gy (EQD2) (α/β = 3 Gy) and equivalent uniform dose (EUD) of vaginal_CTV and organs at risk (OARs) were evaluated. Urinary, gastrointestinal, and vaginal toxicities were assessed using CTCAE v5.0.ResultsAfter matching, 132 patients (small-size: 44; large-size: 88) were analyzed. For vaginal_CTV, the small-size group had higher doses to 2%, 5%, 0.1 cc, 1 cc, and 2 cc of the volume (D2, D5, D0.1 cc, D1cc, and D2cc) than the large-size group while lower doses to the 95%, 98%, and 100% volume (D95, D98, and D100). The D2cc and D5cc of bladder and all dosimetric parameters of rectum were smaller in the small-size group. The EUD of vaginal_CTV, bladder, and rectum showed no significant differences. No significant differences in toxicities were found within the median follow-up of 26.8 months.ConclusionCylinders with smaller diameters produced more nonuniform dose distributions in the target and delivered lower doses to bladder and rectum than large-size cylinders. However, the dosimetric differences did not translate into significant differences of radiobiological parameters or outcomes.

Optimization Function for Determining Optimal Dose Range for Beef and Seed Potato Irradiation.

The objective of this study is to develop a universally applicable approach for establishing the optimal dose range for the irradiation of plant and animal products. The approach involves the use of the optimization function for establishing the optimal irradiation dose range for each category of plant and animal product to maximize the suppression of targeted pathogens while preserving the surrounding molecules and biological structures. The proposed function implies that pathogens found in the product can be efficiently suppressed provided that irradiation is performed with the following criteria in mind: a high irradiation dose uniformity, a high probability of irradiation hitting pathogens and controlled heterogeneity of radiobiological sensitivity of pathogens. This study compares the optimal dose ranges for animal and plant products using beef tenderloin and seed potato tubers as examples. In a series of experiments, our team traced the dose dependencies of myoglobin oxidation in beef and the amount of potential damage to albumin's native structure. The behavior patterns of myoglobin derivatives and the amount of potential damage to albumin found in this study determined the optimal dose range, which appeared to be wider for beef irradiation compared to that for seed potato tubers, as they do not require uniform irradiation of the entire volume since targeted phytopathogens are predominantly found within the surface layers of the tubers. The use of proprietary methods involving spectrophotometry and high-performance liquid chromatography-mass spectrometry provides a novel perspective on the quantitative assessment of the myoglobin oxidation level and the potential damage to albumin's native structure.