Point Dose Research Articles

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Development of a 3D printed phantom for commissioning and quality assurance of multiple brain targets stereotactic radiosurgery

Single plan techniques for multiple brain targets (MBT) stereotactic radiosurgery (SRS) are now routine. Patient specific quality assurance (QA) for MBT poses challenges due to the limited capabilities of existing QA tools which necessitates several plan redeliveries. This study sought to develop an SRS QA phantom that enables flexible MBT patient specific QA in a single delivery, along with complex SRS commissioning. PLA marble and PLA StoneFil materials were selected based on the literature and previous research conducted in our department. The HU numbers were investigated to determine the appropriate percentage infill for skull and soft-tissue equivalence. A Prusa MK3S printer in conjunction with the above-mentioned filaments were used to print the SRS QA phantom. Quality control (QC) was performed on the printed skull, film inserts and plugs for point dose measurements. EBT3 film and point dose measurements were performed using a CC04 ionisation chamber. QC demonstrated that the SRS QA phantom transverse, coronal and sagittal film planes were orthogonal within 0.5°. HU numbers for the skull, film inserts and plugs were 858 ± 20 and 35 ± 12 respectively. Point and EBT3 film dose measurements were within 2.5% and 3%/2 mm 95% gamma pass rate, respectively except one Gross Tumour Volume (GTV) that had a slightly lower gamma pass rate. Dose distributions to five GTVs were measured with EBT3 film in a single plan delivery on CyberKnife. In conclusion, an SRS QA phantom was designed, and 3D printed and its use for performing complex MBT patient specific QA in a single delivery was demonstrated.

Optically stimulated luminescence dosimeters for simultaneous measurement of point dose and dose-weighted LET in an adaptive proton therapy workflow.

To demonstrate the suitability of optically stimulated luminescence detectors (OSLDs) for accurate simultaneous measurement of the absolute point dose and dose-weighted linear energy transfer (LETD) in an anthropomorphic phantom for experimental validation of daily adaptive proton therapy. A clinically realistic intensity-modulated proton therapy (IMPT) treatment plan was created based on a CT of an anthropomorphic head-and-neck phantom made of tissue-equivalent material. The IMPT plan was optimized with three fields to deliver a uniform dose to the target volume covering the OSLDs. Different scenarios representing inter-fractional anatomical changes were created by modifying the phantom. An online adaptive proton therapy workflow was used to recover the daily dose distribution and account for the applied geometry changes. To validate the adaptive workflow, measurements were performed by irradiating Al2O3:C OSLDs inside the phantom. In addition to the measurements, retrospective Monte Carlo simulations were performed to compare the absolute dose and dose-averaged LET (LETD) delivered to the OSLDs. The online adaptive proton therapy workflow was shown to recover significant degradation in dose conformity resulting from large anatomical and positioning deviations from the reference plan. The Monte Carlo simulations were in close agreement with the OSLD measurements, with an average relative error of 1.4% for doses and 3.2% for LETD. The use of OSLDs for LET determination allowed for a correction for the ionization quenched response. The OSLDs appear to be an excellent detector for simultaneously assessing dose and LET distributions in proton irradiation of an anthropomorphic phantom. The OSLDs can be cut to almost any size and shape, making them ideal for in-phantom measurements to probe the radiation quality and dose in a predefined region of interest. Although we have presented the results obtained in the experimental validation of an adaptive proton therapy workflow, the same approach can be generalized and used for a variety of clinical innovations and workflow developments that require accurate assessment of point dose and/or average LET.

Verifying institutionally developed hybrid 3D-printed coaxial cylindrical phantom for patient-specific quality assurance in stereotactic body radiation therapy of hepatocellular carcinoma.

An accurate and reliablepatient-specific quality assurance (PSQA) is crucial to ensure the safety and precision of Stereotactic body radiation therapy (SBRT) in treating Hepatocellular carcinoma (HCC). This study examines the effectiveness of a novel hybrid 3D-printed hybrid coaxial cylindrical phantom for PSQA in the SBRT of HCC. The study compared three different point dose verification techniques for PSQA: a traditional solid water phantom, two dimensional detector array I'MatriXX, and a newly developed hybrid 3D-printed phantom. Thirty SBRT HCC liver cases were examined using these techniques, and point doses were measured and compared to planned doses using the perpendicular composite method with solid water and I'MatriXX phantoms. Unlike the other two methods, the point dose was compared in true composite geometry using the hybrid 3D-printed phantom, which enhanced the accuracy and consistency of PSQA. The study aims to assess the statistical significance and accuracy of the hybrid 3D-printed phantom compared to other methods. The results showed all techniques complied with the institutional threshold criteria of within ± 3% for point-dose measurement discrepancies. The hybrid 3D-printed phantom was found to have better consistency with a lower standard deviation than traditional methods. Statistical analysis using Student's t-test revealed the statistical significance of the hybrid 3D-printed phantom technique in patient-specific point-dose assessments with a p-value < 0.01. The hybrid 3D-printed phantom developed institutionally is cost-effective and easy to handle. It has been proven to be a valuable tool for PSQA in SBRT for the treatment of HCC and has demonstrated its practicality and reliability.

Calculation of Organ Dose Distribution (in-field and Out-of-field) in Breast Cancer Radiotherapy on RANDO Phantom Using GEANT4 Application for Tomographic Emission (Gate) Monte Carlo Simulation.

Organ dose distribution calculation in radiotherapy and knowledge about its side effects in cancer etiology is the most concern for medical physicists. Calculation of organ dose distribution for breast cancer treatment plans with Monte Carlo (MC) simulation is the main goal of this study. Elekta Precise linear accelerator (LINAC) photon mode was simulated and verified using the GEANT4 application for tomographic emission. Eight different radiotherapy treatment plans on RANDO's phantom left breast were produced with the ISOgray treatment planning system (TPS). The simulated plans verified photon dose distribution in clinical tumor volume (CTV) with TPS dose volume histogram (DVH) and gamma index tools. To verify photon dose distribution in out-of-field organs, the point dose measurement results were compared with the same point doses in the MC simulation. Eventually, the DVHs for out-of-field organs that were extracted from the TPS and MC simulation were compared. Based on the implementation of gamma index tools with 2%/2 mm criteria, the simulated LINAC output demonstrated high agreement with the experimental measurements. Plan simulation for in-field and out-of-field organs had an acceptable agreement with TPS and experimental measurement, respectively. There was a difference between DVHs extracted from the TPS and MC simulation for out-of-field organs in low-dose parts. This difference is due to the inability of the TPS to calculate dose distribution in out-of-field organs. Based on the results, it was concluded that the treatment plans with the MC simulation have a high accuracy for the calculation of out-of-field dose distribution and could play a significant role in evaluating the important role of dose distribution for second primary cancer estimation.

Comprehensive dosimetric commissioning of proton minibeam radiotherapy on a single gantry proton system.

Proton minibeam radiation therapy (pMBRT) can deliver spatially fractionated dose distributions with submillimeter resolution. These dose distributions exhibit significant heterogeneity in both depth and lateral directions. Accurate characterization of pMBRT doses requires dosimetry devices with high spatial resolution and a wide dynamic range. Furthermore, the dependency of dosimetric measurements on Linear Energy Transfer (LET), as observed in conventional proton therapy, is also present in pMBRT depth dose measurements. This work demonstrates the process of performing comprehensive dosimetric measurements to characterize the pMBRT collimator on a clinical single-gantry proton machine, utilizing commercially available dosimetry devices. The minibeam collimator is designed to be mounted on the clinical nozzle as a beam-modifying accessory. Three collimators, each with a slit opening of 0.4 mm, are thoroughly evaluated. The center-to-center (c-t-c) distances of the slits for these collimators are 2.8 mm, 3.2 mm, and 4.0 mm, respectively. High spatial resolution dosimetry devices are essential for PMBRT dose characterizations. To meet this requirement, two-dimensional (2D) dose measurement devices, Gafchromic films, are used to measure lateral profiles at various depths. Films are also used for depth dose profile measurements in solid water. Additionally, high-resolution point dose detectors, microDiamond, and Razor diode detectors are employed for lateral profile measurements at various depths. Percent depth dose (PDD) measurements of pMBRT in solid water, with various proton energies, collimators, and air gaps, are performed using Gafchromic films. The film's LET dependency for proton beams is corrected to ensure accurate pMBRT PDD measurements. The Monte Carlo simulation tool TOPAS is utilized to compare and validate all experimental measurements. At depths where LET is not a concern, film dose measurements were consistent with microDiamond and Razor diode point measurements. The point detectors need to be orientated with the thin side aligned to the incoming beam. Comparison of the lateral dose profiles extracted from TOPAS simulations, films, microDiamond, and Razor diode detectors shows a passing rate exceeding 98% in 1D gamma analysis at 3% 0.1 mm criteria.However, when the microDiamond detector is orientated to face the pMBRT beam, its spatial resolution may not be sufficient to capture the peak and valley dose accurately. Nevertheless, an accuracy within 2% can still be achieved when comparing the average dose. The PDD measurements show that the peak valley dose ratio (PVDR) of pMBRT can be altered at different depths with different air gaps using the same collimator or different collimators of different c-t-c distances. Our study demonstrates that comprehensive dose measurements for pMBRT can be conducted using standard clinical dose measurement devices. These measurements are indispensable for guiding and ensuring accurate dose reporting in pre-clinical studies using the pMBRT technique.

Feasibility and clinical implementation of MRI-guided surface brachytherapy.

Best practices for high-dose-rate surface applicator brachytherapy treatment (SABT) have long relied on computed tomography (CT)-based imaging to visualize diseased sites for treatment planning. Compared with magnetic resonance (MR)-based imaging, CT provides insufficient soft tissue contrast. This work described the feasibility of clinical implementation of MR-based imaging in SABT planning to provide individualized treatment optimization. A 3D-printed phantom was used to fit Freiberg flap-style (Elekta, The Netherlands) applicator. Images were taken using an optimized pointwise encoding time reduction with radial acquisition (PETRA) MR sequence for catheter visualization, and a helical CT scan to generate parallel treatment plans. This clinical study included three patients undergoing SABT for Dupuytren's contracture/palmar fascial fibromatosis imaged with the same modalities.SABT planning was performed in Oncentra Brachy (Elekta Brachytherapy, The Netherlands) treatment planning software. A geometric analysis was conducted by comparing CT-based digitization with MR-based digitization. CT and MR dwell positions underwent a rigid registration, and average Euclidean distances between dwell positions were calculated. A dosimetric comparison was performed, including point-based dose difference calculations and volumetric segmentations with Dice similarity coefficient (DSC) calculations. Euclidean distances between dwell positions from CT-based and MR-based plans were on average 0.68 ±0.05 mm and 1.35 ±0.17 mm for the phantom and patients, respectively. The point dose difference calculations were on average 0.92% for the phantom and 1.98% for the patients. The D95 and D90 DSC calculations were both 97.9% for the phantom, and on average 93.6% and 94.2%, respectively, for the patients. The sub-millimeter accuracy of dwell positions and high DSC's (> 0.95) of the phantom demonstrated that digitization was clinically acceptable, and accurate treatment plans were produced using MR-only imaging. This novel approach, MRI-guided SABT, will lead to individualized prescriptions for potentially improved patient outcomes.

Investigation of Effect of Air Gap between Surface and Bolus on Dose Distribution for 6 MV Photon Beam

In radiotherapy, tissue equivalent boluses are frequently used in the treatment of superficially located tumors. The air gap between the patient's skin and the bolus may cause dosimetric uncertainties. This study aims to dosimetrically investigate the effect of the air gap between the surface and the bolus on dose distribution. Computed tomography (CT) images of the phantom were obtained and transferred to the treatment planning system (TPS). In the TPS, a bolus was placed on the phantom surface and then air gaps were created between the bolus and the surface. The effect of the air gaps between the surface and the 5 mm thick bolus on the dose distribution was analyzed with the point doses obtained from the TPS. For the 6 MV X-ray, it was observed that the air gap negatively affected the surface doses calculated by TPS. Accordingly, an inverse correlation was found between air gap and surface dose. It is recommended that bolus use, especially in curved anatomical regions, should be applied before CT scanning as much as possible. When using bolus material in radiotherapy, it is recommended to be careful not to leave an air gap between the surface and the bolus.

A comprehensive investigation to the fate of phosphorus in full-scale wastewater treatment plants using aluminum salts for enhanced phosphorus removal

This study investigated the fate of phosphorus (P) in 8 full-scale municipal wastewater treatment plants (WWTPs) in Shanghai, China, in which both biological nutrient removal and aluminum-based chemical phosphorus removal were used. The results showed that 83.8–98.9 % P was transferred to the sludge in the 8 WWTPs by both chemical and biological reactions. P speciation analysis indicated that chemical P precipitates accounted for 84.3 % in the activated sludge, of which crystalline AlPO4 and amorphous iron‑phosphorus compounds (FePs) were the main components. Sludge with more water-soluble and weakly adsorbed P was generated in the anaerobic-anoxic-oxic (A/A/O) process than in other processes. Among the 8 WWTPs, the one with the largest flow rate and relatively short sludge retention time (SRT) had the best potential to release P from all types of sludge. The recovery potential of P from thickened sludge can be improved by separately thickening the sludge produced in the high-efficiency sedimentation tank or feeding it into the dewatering process directly. Different P removal chemicals and dosing points changed the amount of chemical precipitate formed but had little effect on the composition of P accumulating organisms (PAOs) at the genus level. Although aluminum-based coagulants were applied in the investigated WWTPs, Fe in wastewater had the most positive effect on the proliferation of PAOs. The synthesis of polyphosphate was also related to the metabolism of PAOs as it affected transmembrane inorganic phosphate (Pi) transport and polyhydroxybutyrate (PHB) synthesis. The in-depth understanding of the fate of P is beneficial to improve P recovery efficiency in WWTPs.

CLINICAL RESULTS OF CERVIX CANCER USING VARIOUS TECHNOLOGIES IN RADIATION THERAPY

Background: clinical results of patients with cervical cancer (CC) who treated with different methodological approaches of radiotherapy (RT) in the transforming from conventional to conformal RT and brachytherapy (BT).&#x0D; Purpose: to evaluate long-term results of treatment, locoregional and distant control.&#x0D; Methods: 137 patients with CC IIb - IIIb in 2013-2016 were analysed: 70 (51%) - conventional gamma therapy and brachytherapy (BT) with two-dimensional planning (2D) 60Сo alone or in combination with cisplatin 40 mg/m2 two groups of n=35. The total dose (TD) for point A 75.08 0.57 Gy, point B 57.9 0.43 Gy. In 67 (49%) with conform radiotherapy following BT with three-dimensional planning (3D) 192Ir alone or in combination with cisplatin 40 mg/m2 - two groups n = 35 and 32, respectively. TD CTV-HR D90 95.0 Gy 0.67 EQD2.&#x0D; Results: 3 and 5-year overall survival with 3D RT versus 2D RT was 84.6 4.5% and 63.1 6.0%; 84.6 4.5% versus 56.1 6.0%, respectively (p = 0.030). It was revealed that modern technologies are important in improving overall survival with image-guided RT: 88.2 6.6% of patients are alive for 3 years versus 59.0 8.4%, respectively (p=0.027). The use of chemoradiotherapy (CRT) showed an advantage of 3-year event-free survival in groups with 2D RT - 67.9 8.4% versus 55.2 8.6% (p = 0.042) in 3D RT - no statistically significant differences. Locoregional control was higher in the 3D RT groups at 3 years follow-up: 97.0 2.9% versus 82.9 5.3%, p = 0.050. CRT allows to reduce the number of local failures in the pelvis in the follow-up period up to 6 months, regardless of the RT technologies. The number of relapses and metastases in pelvis is lower in 3D RT - 3.0 2.1% versus 2D - 15.7 4.4% (p = 0.05). The frequency of metastases did not show statistically significant differences: 2D RT - 5.7 2.8% versus 3D RT - 9.0 3.5% (p 0.05).&#x0D; Conclusion: the study proves the improvement of local control in the treatment of cervical cancer in cases of conformal RT and 3D BT.

Impact of Maximum Point Dose Within the Planning Target Volume on Local Control of Nonsmall Cell Lung Cancer Treated With Stereotactic Body Radiotherapy.

No consensus exists on the maximum dose delivered to the planning target volume (PTV) in the delivery of stereotactic body radiotherapy (SBRT) for primary lung cancer. We investigated whether higher biologically effective doses (BED) within the PTV were associated with improved tumor control. We reviewed patients with early-stage, node-negative nonsmall cell lung cancer who received curative-intent SBRT between 2005 and 2018. We calculated the maximum BED (maxBED) within the PTV for all patients, analyzing outcomes using the cumulative incidence method and Fine-Gray test statistics to assess prognostic impact. We analyzed 171 patients (median age, 70.2; range, 43 to 90y) with 181 lung nodules. Median follow-up was 2.7 years (range, 0.1 to 12y) for all patients and 4.2 years (range, 0.2 to 8.4y) for living patients. Median maximum tumor diameter was 1.9cm (range, 0.7 to 5.6cm). Patients received a prescription of 48 or 50 Gy in 4 or 5 fractions, respectively, except for one who received 60 Gy in 5 fractions. Median maxBED was 120 Gy (range, 101 to 171 Gy). There was no difference in the 3-year local control (LC) rate among patients treated with a maxBED<120 Gy versus ≥120 Gy ( P =0.83). No significant differences in LC were observed between patients with early-stage nonsmall cell lung cancer treated with SBRT in 4 or 5 fractions with a maxBED≥120 Gy. However, a higher maxBED trended toward improved LC rates, suggesting a maxBED threshold greater than 120 Gy may be needed to improve LC rates.

Simulated galactic cosmic ray exposure activates dose-dependent DNA repair response and down regulates glucosinolate pathways in arabidopsis seedlings.

Outside the protection of Earth's magnetic field, organisms are constantly exposed to space radiation consisting of energetic protons and other heavier charged particles. With the goal of crewed Mars exploration, the production of fresh food during long duration space missions is critical for meeting astronauts' nutritional and psychological needs. However, the biological effects of space radiation on plants have not been sufficiently investigated and characterized. To that end, 10-day-old Arabidopsis seedlings were exposed to simulated Galactic Cosmic Rays (GCR) and assessed for transcriptomic changes. The simulated GCR irradiation was carried out in the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Lab (BNL). The exposures were conducted acutely for two dose points at 40 cGy or 80 cGy, with sequential delivery of proton, helium, oxygen, silicon, and iron ions. Control and irradiated seedlings were then harvested and preserved in RNAlater at 3 hrs post irradiation. Total RNA was isolated for transcriptomic analyses using RNAseq. The data revealed that the transcriptomic responses were dose-dependent, with significant upregulation of DNA repair pathways and downregulation of glucosinolate biosynthetic pathways. Glucosinolates are important for plant pathogen defense and for the taste of a plant, which are both relevant to growing plants for spaceflight. These findings fill in knowledge gaps of how plants respond to radiation in beyond-Earth environments.

Chronic intermittent convection-enhanced delivery of vigabatrin to the bilateral subthalamic nucleus in an acute rat seizure model

Targeted intracerebral drug delivery is an attractive experimental approach for the treatment of drug-resistant epilepsies. In this regard, the subthalamic nucleus (STN) represents a focus-independent target involved in the remote modulation and propagation of seizure activity. Indeed, acute and chronic pharmacological inhibition of the STN with vigabatrin (VGB), an irreversible inhibitor of GABA transaminase, has been shown to produce antiseizure effects. This effect, however, is lost over time as tolerance develops with chronic, continuous intracerebral pharmacotherapy. Here we investigated the antiseizure effects of chronic intermittent intra-STN convection-enhanced delivery of VGB in an acute rat seizure model focusing on circumventing tolerance development and preventing adverse effects. Timed intravenous pentylenetetrazol (PTZ) seizure threshold testing was conducted before and after implantation of subcutaneous drug pumps and bilateral intra-STN cannulas. Drug pumps infused vehicle or VGB twice daily (0.4 µg) or once weekly (2.5 µg, 5 µg) over three weeks. Putative adverse effects were evaluated and found to be prevented by intermittent compared to previous continuous VGB delivery. Clonic seizure thresholds were more clearly raised by intra-STN VGB compared to myoclonic twitch. Both twice daily and once weekly intra-STN VGB significantly elevated clonic seizure thresholds depending on dose and time point, with responder rates of up to 100% observed at tolerable doses. However, tolerance could not be completely avoided, as tolerance rates of 40–75% were observed with chronic VGB treatment. Results indicate that the extent of tolerance development after intermittent intra-STN VGB delivery varies depending on infusion dose and regimen.

Comparison of Rapid Arc and Intensity Modulated Radiotherapy in a True Beam Linear Accelerator for 6 MV: Application of AAPM TG‐119 tests in treatment planning and quality assurance

AbstractObjectiveWe developed rapid arc (RA) and intensity‐modulated radiotherapy (IMRT) plans based on the American Association of Physicists in Medicine Task Group‐119 (AAPM TG‐119) proposals and compared the planning and quality assurance results.Materials and MethodsTwo treatment plans were used for each study patient: one using 7–9 IMRT fields and the other using the two full‐arc RA methods. Plan optimization and dose calculations were performed using 6 MV photons and EclipseTM with the anisotropic analytical algorithm (AAA). Task group (TG)‐119 described the planning objectives used to evaluate the treatment plans generated for this study. Point dose, planar fluence measurement, and trajectory log file analysis are used for quality assurance.ResultsThe conformity index (CI) for treatment plans varied between 0.76–0.91 when using IMRT and 0.75–0.93 when using RA. The homogeneity index (HI) was approximately 0.10–0.24 (IMRT) and 0.07–0.23 (RA). The ratio of the total number of monitor units required for IMRT to that required for RA was between 0.87 and 2.14. The treatment log files exhibited higher gamma passing with RA than with IMRT.ConclusionRA plans were more effective than IMRT plans in achieving the test goals. Point dose measurements and electronic portal imaging device (EPID)‐based planar fluence measurements showed statistically insignificant differences between the IMRT and RA plan quality assurance (QA) results. However, the trajectory log file analysis exhibited better gamma‐passing results for RA than for IMRT.

Vaginal Dose Reduction by Changing the Ovoid Loading Pattern in Image Guided Intracavitary Brachytherapy of Cervix.

Locally advanced cervical cancer is frequently treated using a combination of external beam radiotherapy and brachytherapy. Radiotherapy often leads to vaginal morbidity, which poses a significant problem. This study aims to analyze the impact of reducing ovoid loading on dosimetry. We analyzed forty-five CT-based intracavitary brachytherapy plans from fifteen patients. Three plan sets were created for the 45 applications: a standard loading plan (A), a plan with reduced ovoid loading (B), and a tandem-only loading plan (C). We generated Dose-Volume Histograms and recorded dose volume parameters for the three plan sets. The D90 for the Clinical Target Volume (CTV) did not show significant differences among the three plan sets (p = 0.20). The average D90 values for plans A, B, and C were 8.15Gy, 8.16Gy, and 7.4Gy, respectively. No statistically significant differences were observed in D2cc bladder (p = 0.09) (average values: 6.8Gy, 6.5Gy, and 5.9Gy for plans A, B, and C, respectively) and D2cc sigmoid (p = 0.43) (average values: 2.8Gy, 2.6Gy, and 2.4Gy, respectively) among the three plan sets. However, there was a statistically significant difference in D2cc rectum (p < 0.001) (average values: 4Gy, 3.3Gy, and 1.8Gy, respectively), as well as in vaginal dose points (p < 0.001). Reducing ovoid loading significantly decreased the doses to vaginal dose points and the rectum without compromising the dose to the Clinical Target Volume (CTV). Therefore, in carefully selected cases, the adoption of tandem-only loading or reduced ovoid loading could be considered to minimize vaginal morbidity following high dose rate intracavitary brachytherapy.

Association between selective serotonin reuptake inhibitor use and developing irritable bowel syndrome through retrospective analysis.

Serotonin affects the balance and integrity of the gut microbiome; however, studies have confirmed the influence of selective serotonin reuptake inhibitors (SSRIs) on irritable bowel syndrome (IBS). We evaluated the association between SSRI use and subsequent IBS occurrence in a real-world setting. A multivariate Cox proportional hazard model was adopted, and the National Health Insurance Service cohort claims database between 2010 and 2019 was used. Non-SSRI users were selected using the propensity score matching method. Subgroup analyses were performed using the point of use, cumulative dose, and duration of SSRI use. Additional analysis was performed using a control group without psychiatric medications. We included 2901 SSRI users and 2727 non-SSRI users. After adjusting covariates, the risk of developing IBS in SSRI users was 1.54 times that in non-SSRI users (95% confidence interval [CI]: 1.01-2.33). The hazard ratio (HR) of the recent, heavy, and short-term user groups were 3.19 (95% CI: 2.03-4.99), 2.22 (95% CI: 1.50-3.29), and 4.83 (95% CI: 3.02-7.73), respectively, compared with that of non-users. In patients without a history of psychiatric medications, the risk of IBS incidence after SSRI use increased significantly (HR: 1.61, 95% CI: 1.06-2.42), whereas HR was insignificant in patients with a history of psychiatric medications (HR: 1.25, 95% CI: 0.98-1.60). The risk of subsequent IBS occurrence following SSRI use was high in patients who initially took a heavy SSRI dose and those who did not have a history of psychiatric drug use.

Clinical and pathomorphological changes in the rabbit retina after an injection of various doses of the cytostatic melphalan

Background: In recent years, there have been individual reports on intracameral chemotherapy (ICC) for aqueous seeding in retinoblastoma. The effect of melphalan on the structures of the ocular anterior segment (including the cornea, iris and anterior lens capsule) is however, still unknown, since no relevant experimental studies have been carried out so far. Purpose: To experimentally assess the changes in the rabbit anterior segment induced by intracameral injection of various concentrations of the alkylating cytostatic melphalan. Material and Methods: Twelve adult Chinchilla rabbits (22 eyes; age, 5–6 months; weight, 2.5–3 kg) were involved in this experimental study and maintained in the vivarium of the Filatov institute in separate cages under standard conditions. Results: After a 5-µg melphalan injection, corneal and iris changes were reversible and the lens was still clear. With an increase in melphalan concentration in injection solution (to 10, 15 and 20 µg) and time point (to 1 month and 3 weeks) after injection, degenerative changes in some epithelial cells of the iris became irreversible, anterior capsular cataract developed, but the cornea and anterior chamber aqueous remained clear. After a single 20-µg intracameral injection of melphalan, there was depigmentation of the iris, posterior synechia and anterior capsular cataract. Conclusion: Clinical and ultrastructural responses of ocular anterior segment tissue to intracameral melphalan injection depended on the injected dose and time point after injection. Most cells of examined tissues showed the capability to restore their ultrastructure following ceasing of the toxic effect of the drug.

Can we skip the simulation step for radiation treatment planning in patients with symptomatic bone metastases?

255 Background: Patients with bone metastases may require urgent radiation treatment (RT) due to severe pain, neurologic or other symptoms. Conventional approaches typically involve a 3-step process: initial consultation, followed several days later by a planning CT (pCT) simulation and dosimetric planning, and finally RT delivery. The time frame from consultation to RT can be up to 2 weeks, overly lengthy for severely symptomatic patients. We explored the viability of using diagnostic CT (dCT) imaging, usually available to radiation oncologists at the time of consultation, for RT planning - with the ultimate goal of removing the simulation step to reduce the interval from consultation to RT. In this initial phase of the project, we set out to compare differences in key dosimetric parameters from dCT- and pCT- generated RT plans. Methods: We retrospectively reviewed patients (n=28) treated for bone metastases at a single academic institution from 2020-2023. We utilized rigid image registration to transfer physician contours from pCT images to dCT images to account for changes in patient positioning. Beam arrangements, energies, and administered monitor units were also transferred from the pCT to the dCT for accurate dose calculation. We calculated RT dose coverage of each target metastasis using “V100”, or the percentage of the target lesion receiving 100% of the RT prescription dose. Correspondingly, the “V95” and the maximum point dose (“hotspot”) in patients were also calculated. Results: Out of 28 patients, 24 were treated to single and 4 to multiple (2-4) bone metastases. We excluded patients who had no dCT (n=7) or whose body positioning on the dCT (e.g. arms) created obstructions for beam arrangements (n=2). Eventually, 24 clinical plans made from 19 patients’ pCTs were migrated to their dCTs to generate comparable dosimetric plans. For all 24 dCT-based plans (12 spines and 12 extremities), the mean full dose coverage V100 decreased by 7.14% ± 15.89%. Overall, the plans had 91.14% ± 18.6% for V95 to PTV. Hotspots rose by 2.75% ± 3.61%. Two cases were observed to have full-dose-coverage drop over 40%: one was caused by patient’s outline change induced by different couches used for diagnosis and simulation, and the other one had an initial coverage of 57.6% for V100 in the original clinical plan. The remaining plans had a drop of 3.14% ± 8.37% on V100, and 96.1% ± 8.2% for V95. Conclusions: It was feasible to generate radiation treatment plans for bone metastases with good tumor coverage using dCT imaging. Patient selection plays a crucial role in dCT-based treatment planning, as the dose distribution is highly sensitive to anatomical variations resulting from patient positioning. This treatment planning approach circumvents the simulation step and would reduce patients' wait time for RT, thereby enabling more rapid access to RT for patients suffering with symptoms from bone metastases.

Study of peripheral dose from low-dose CT to adaptive radiotherapy of postoperative prostate cancer.

The increasing use of computed tomography (CT) for adaptive radiotherapy (ART) has raised concerns about the peripheral radiation dose. This study investigates the feasibility of low-dose CT (LDCT) for postoperative prostate cancer ART to reduce the peripheral radiation dose, and evaluates the peripheral radiation dose of different imaging techniques and propose an image enhancement method based on deep learning for LDCT. A linear accelerator integrated with a 16-slice fan-beam CT from UIH (United Imaging Healthcare, China) was utilized for prostate cancer ART. To reduce the tube current of CT for ART, LDCT was acquired. Peripheral doses of normal-dose CT (NDCT), LDCT, and mega-voltage computed tomography (MV-CT) were measured using a cylindrical Virtual Water™ phantom and an ion chamber. A deep learning model of LDCT for abdominal and pelvic-based cycle-consistent generative adversarial network was employed to enhance the image quality of LDCT. Six postoperative prostate cancer patients were selected to evaluate the feasibility of low-dose CT network restoration images (RCT) by the deep learning model for ART. The three aspects among NDCT, LDCT, and RCT were compared: the Hounsfield Unit (HU) of the tissue, the Dice Similarity Coefficient (DSC) criterion of target and organ, and dose calculation differences. In terms of peripheral dose, the LDCT had a surface measurement point dose of approximately 1.85 mGy at the scanning field, while the doses of NDCT and MV-CT were higher at 22.85 mGy and 29.97 mGy, respectively. However, the image quality of LDCT was worse than NDCT. When compared to LDCT, the tissue HU value of RCT showed a significant improvement and was closer to that of NDCT. The DSC results for target CTV between RCT and NDCT were also impressive, reaching up to 94% for bladder and femoral heads, 98% for rectum, and 94% for the target organ. Additionally, the dose calculation differences for the ART plan based on LDCT and NDCT were all within 1%. Overall, these findings suggest that RCT can provide an effective alternative to NDCT and MV-CT with similar or better outcomes in HU values of tissue and organ damage. More testing is required before clinical application.

Extended in-field and out-of-field validation of a compact Monte Carlo model of an IBA PROTEUS®ONE proton beam in TOPAS/GEANT4

Objective: This study evaluates a compact Monte Carlo (MC) model of a pencil beam scanning clinical proton beam using TOPAS to estimate the dose out-of-field (OOF). Compact modelling means that the model starts from a pristine proton beam at the nozzle exit, customised based on acceptance and commissioning data, instead of modelling the full treatment head and room. Approach: First, in-field validation tests were performed. Then, the OOF dose was validated in an RW3 phantom with bubble detectors for personal neutron dosimetry (measuring the neutron dose equivalent) and thermoluminiescent detectors (measuring the absorbed dose by protons and gammas). Measurements were performed at 15 and 35 cm from the distal edge of the field for five different irradiation plans, covering different beam orientations, proton energies and a 40 mm range shifter. TOPAS simulations were performed with QGSP Binary Cascade HP (BIC) and QGSP Bertini HP (Bertini) hadron physics lists. Main results: In-field validation shows that MC simulations agree with point dose measurements within −2.5 % and +1.5 % at locations on- and off-axis and before, in and after the Bragg peak or plateau. The gamma passing rate 2%/3mm of four simulated treatment plans compared to the dose distribution calculated by the TPS exceeds 97 % agreement score. OOF dose simulations showed an average overestimation of 27 % of the neutron dose equivalent for the BIC hadron physics list and an average underestimation of 20 % for the Bertini hadron physics list. The simulated absorbed dose of protons and gammas showed a systematic underestimation which was on average 21 % and 51 % for BIC and Bertini respectively. Significance: Our study demonstrates that a compact MC model can reliably produce in-field data, while out-of-field dose data are within the uncertainties of the detector systems and MC simulations nuclear models, and do so with shorter modelling and faster calculation time.