Analysis of hydrogen peroxide production in pure water: Ultrahigh versus conventional dose-rate irradiation and mechanistic insights.

BACKGROUND: Ultrahigh dose-rate radiation (UHDR) produces less hydrogen peroxide (H2O2) in pure water, as suggested by some experimental studies, and is used as an argument for the validity of the theory that FLASH spares the normal tissue due to less reactive oxygen species (ROS) production. In contrast, most Monte Carlo simulation studies suggest the opposite. PURPOSE: We aim to unveil the effect of UHDR on H2O2 production in pure water and its underlying mechanism, to serve as a benchmark for Monte Carlo simulation. We hypothesized that the reaction of solvated electrons ( e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ ) removing hydroxyl radicals (•OH), the precursor of H2O2, is the reason why UHDR leads to a lower G-value (molecules/100 eV) for H2O2 (G[H2O2]), because: 1, the third-order reaction between e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ and •OH is more sensitive to increased instantaneous ROS concentration by UHDR than a two-order reaction of •OH self-reaction producing H2O2; 2, e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ has two times higher diffusion coefficient and higher reaction rate constant than that of •OH, which means e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ would dominate the competition for •OH and benefit more from the inter-track effect of UHDR. Meanwhile, we also experimentally verify the theory of long-lived radicals causing lower G(H2O2) in conventional irradiation, which is mentioned in some simulation studies. METHODS AND MATERIALS: H2O2 was measured by Amplex UltraRed assay. 430.1 MeV/u carbon ions (50 and 0.1 Gy/s), 9 MeV electrons (600 and 0.62 Gy/s), and 200 kV x-ray tube (10 and 0.1 Gy/s) were employed. For three kinds of water (real hypoxic: 1% O2; hypoxic: 1% O2 and 5% CO2; and normoxic: 21% O2), unbubbled and bubbled samples with N2O, the scavenger of e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , were irradiated by carbon ions and electrons with conventional and UHDR at different absolute dose levels. Normoxic water dissolved with sodium nitrate (NaNO3), another scavenger of e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , and bubbled with N2O was irradiated by x-ray to verify the results of low-LET electron beam. RESULTS: UHDR leads to a lower G(H2O2) than conventional irradiation. O2 and CO2 can both increase G(H2O2). N2O increases G(H2O2) of both UHDR and conventional irradiation and eliminates the difference between them for carbon ions. However, N2O decreases G(H2O2) in electron conventional irradiation but increases G(H2O2) in the case of UHDR, ending up with no dose-rate dependency of G(H2O2). Three-spilled carbon UHDR does not have a lower G(H2O2) than one-spilled UHDR. However, the electron beam shows a lower G(H2O2) for three-spilled UHDR than for one-spilled UHDR. Normoxic water with N2O or NaNO3 can both eliminate the dose rate dependency of H2O2 production for x-ray. CONCLUSIONS: UHDR has a lower G(H2O2) than the conventional irradiation for both high LET carbon and low LET electron and x-ray beams. Both scavengers for e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ , N2O and NaNO3, eliminate the dose-rate dependency of G(H2O2), which suggests e aq - ${\mathrm{e}}_{{\mathrm{aq}}}^ - $ is the reason for decreased G(H2O2) for UHDR. Three-spilled UHDR versus one-spilled UHDR indicates that the assumption of residual radicals reducing G(H2O2) of conventional irradiation may only be valid for low LET electron beam.

Commissioning considerations for the Bravos high-dose-rate afterloader: Towards improving treatment delivery accuracy.

BACKGROUND AND PURPOSE: The upgrade of major equipment can be disruptive to clinical operations and introduce risk as policy and procedures need to adapt to new technical possibilities and constraints. We describe here the transition from GammaMedPlus-iX to Bravos in a busy brachytherapy clinic, involving four afterloaders across two sites. MATERIAL AND METHODS: Our clinic employs three high-dose-rate remote afterloaders in four dedicated treatment vaults at the main site and a fourth afterloader at a regional location. Of more than 600 new HDR treatment plans performed annually, most are planned and treated intraoperatively. Most treatments are for prostate cancer, followed by GYN, intraoperative brachytherapy, GI, and other sites. Applicators used include vendor-provided applicators as well as third party applicators and in-house 3D-printed devices to provide interstitial, intracavitary, intraluminal, and surface treatments. All applicators were commissioned according to recommended guidelines. The choice of tolerances and the design of new procedures were informed by current guidelines and leveraged new HDR afterloader functionalities. A review of clinical operations in the 4 months postupgrade was conducted to evaluate the feasibility of new tolerances and the effectiveness of new procedures. RESULTS: The procedures outlined improved and standardized afterloader QA and treatment protocols with clear actionable steps for staff to follow to ensure treatments are delivered as planned. Re-commissioning of applicators yielded results similar to those previously reported by other investigators. A review of initial treatment data revealed that in one case, due to the implementation of tight tolerances, obstruction near the tip of the channel was detected and corrected prior to treatment. It confirms that the implementation of the tolerances adopted is feasible and effective in flagging treatment deviations. CONCLUSION: Enhanced procedures and QA processes were implemented successfully. We established clear actionable steps to follow by staff to ensure that treatments are delivered accurately.

Dose rate correction for the novel 2D diode array MapCHECK 3.

PURPOSE: To investigate the dose rate dependence of MapCHECK3 and its influence on measurement accuracy, as well as the effect of dose rate correction. MATERIALS AND METHODS: The average and instantaneous dose rate dependence of MapCHECK2 and MapCHECK3 were studied. The accuracy of measurements was investigated where the dose rate differed significantly between dose calibration of the MapCHECK and the measurement. Measurements investigated include: the central axis dose for different fields at different depths, off-axis doses outside the field, and off-axis doses along the wedge direction. Measurements using an ion chamber were taken as the reference. Exponential functions were fit to account for average and instantaneous dose rate dependence for MapCHECK3 and used for dose rate correction. The effect of the dose rate correction was studied by comparing the differences between the measurements for MapCHECK (with and without the correction) and the reference. RESULTS: The maximum dose rate dependence of MapCHECK3 is greater than 2.5%. If the dose calibration factor derived from a 10 × 10 cm2 open field at 10 cm depth was used for measurements, the average differences in central diode dose were 0.8% ± 1.0% and 1.0% ± 0.8% for the studied field sizes and measurement depths, respectively. The introduction of wedge would not only induce -1.8% ± 1.3% difference in central diode dose, but also overestimate the effective wedge angle. After the instantaneous dose rate correction, above differences can be changed to 1.9% ± 8.1%, 0.2% ± 0.1%, and 0.0% ± 0.9%. The pass rate can be improved from 98.4% to 98.8%, 98.3%-100.0%, and 96.3%-100.0%, respectively. CONCLUSION: Compared with MapCHECK2 (SunPoint1 diodes), the more pronounced dose rate dependence of MapCHECK3 (SunPoint2 diodes) should be carefully considered. To ensure highly accurate measurement, it is suggested to perform the dose calibration at the same condition where measurement will be performed. Otherwise, the dose rate correction should be applied.

Protocol-based CT-guided brachytherapy for patients with prostate cancer and previous rectal extirpation-a curative approach.

OBJECTIVE: There are numerous curative treatment possibilities for prostate cancer. In patients who have undergone rectal extirpation for rectal cancer treatment, curative options are limited due to anatomic changes and previous irradiation of the pelvis. In this analysis, we validate the feasibility of CT-guided transperineal interstitial brachytherapy for this specific scenario. PATIENTS AND METHODS: We analyzed the treatment procedures and outcomes of 5 patients with metachronic nonmetastatic prostate cancer. Ultrasound-guided brachytherapy was not possible in any of the patients. Of these 5 patients, 3 were treated for prostate cancer using temporary brachytherapy with Ir-192 only, and 2 were treated with external-beam radiation therapy and temporary brachytherapy as a boost. CT-guided brachytherapy was performed in all patients. We analyzed the feasibility, efficacy, treatment-related toxicity, and quality of life (EORTC-30, IEFF, IPSS, and ICIQ questionnaires) of the treatments. RESULTS: Median follow-up was 35 months. Two out of five patients received boost irradiation (HDR 2â€¯× 9 Gy, PDR 30 Gy). Three out of five patients were treated with PDR brachytherapy in two sessions up to a total dose of 60 Gy. Dosimetric parameters were documented as median values as follows: V100 94.7% (94.5-98.4%), D2bladder 64.3% (50.9-78.3%), D10urethra 131.05% (123.2%-141.2%), and D30urethra 122.45% (116.2%-129.5%). At the time of analysis, no biochemical recurrence had been documented. Furthermore, neither early nor late side effects exceeding CTCAE grade 2 were documented. CONCLUSION: CT-guided transperineal brachytherapy of the prostate in patients with previous rectal surgery and radiation therapy is safe and represents a possible curative treatment option. Brachytherapy can be considered for patients with metachronic prostate cancer in this specific scenario, albeit preferably in experienced high-volume centers.

Scatter radiation levels in X-ray rooms during chest radiography.

This research focused on the determination of scatter radiation levels in x-ray rooms during chest radiography. 108 patients were examined. Four x-ray machines (A, B, C, and D) were used during the research from three centers. Three positions were considered in this study; position Q just beside the (Bucky stand), position R, which is 150 cm from the left of the Bucky stand towards the door and position T, 200 cm from the Bucky stand to the radiographer's protective screen respectively. Two machines (A and B) from center 1 and one machine from center 2 (C) and one machine from center 3 (D). The body mass index (BMI) of the participants ranged from 20 to 25 kgm-2 with mean value of 23.97 kgm-2. The background radiation level was read using Radalert 100 m before any exposure, and the mean background level was 0.298 mR/h. The mean of the scatter radiation doses obtained from positions Q with respect to the four machines A, B, C, and D, were 0.109, 0.201, 0.204, 0.200 mR/h (9.166, 16.903, 17.156, 16.819 mSv/yr) and their standard deviations were ±0.052, ±0.053, ±0.064, and ±0.081 respectively. The results were comparable with previous studies. The study recommends staff education and training in determination of radiation levels for enhanced work safety.

Time structures of proton pencil beam scanning delivery on a microsecond scale measured with a pixelated semiconductor detector Timepix3.

PURPOSE: The time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non-invasive technique based on scattered particle tracking. METHODS: A pixelated semiconductor detector, AdvaPIX-Timepix3, with a temporal resolution of 1.56 ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high-flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty. RESULTS: The uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub-milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7 µs and 1 ms repetition time for the synchrocyclotron accelerator. CONCLUSION: The AdvaPIX-Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files.

Investigation of the beam quality and dose rate dependence of PAKAG polymer gel dosimeter in optical readout technique.

This study aims to evaluate the optical response dependence of the PAKAG polymer gel dosimeter on photon energy and dose rate. The produced gel dosimeters were irradiated using a Varian CL 21EX medical linear accelerator with delivered doses of 0, 2, 4, 6, 8, and 10 Gy. To examine the response dependence on the delivered dose rate, dose rates of 50, 100, 200, and 350 cGy/min were investigated. Additionally, two incident beam qualities of 6 and 18 MV were examined to study the response dependence on the incident beam energy. The irradiated polymer gel dosimeters were readout using a UV Vis spectrophotometer in the 300 to 800 nm scan range. The results reveal that a wide variation in dose rate (50-350 cGy.min-1) influences the absorbance-dose response and the sensitivity of PAKAG polymer gel dosimeter. However, smaller variations did not show a significant effect on the response. Furthermore, the response changed insignificantly with beam quality for investigated energies. It was concluded that the optical reading response of the PAKAG polymer gel dosimeter is satisfactorily independent of external parameters, including dose rate and incident beam quality. .

Implementing high-dose rate surface mould brachytherapy for carcinoma of eyelid: a practical approach and weekly review.

Surface mould brachytherapy is a conformal radiotherapy technique that can deliver high dose to the target while sparing nearby normal structures, Here, we aim to describe the procedurals details for high-dose rate (HDR) surface mould brachytherapy in sebaceous carcinoma of eyelid in a 54-year old lady. She was hesitant for surgery and any form of invasive intervention like interstitial brachytherapy. So, she was treated with surface mould HDR brachytherapy to a total dose of 52 Gy in 13 fractions at a dose of 4 Gy per fraction delivered twice daily using Iridium-192 isotope with no acute side effects. She was evaluated on a weekly basis for any radiation side effects and now she is disease-free for 6 months post-treatment with only mild dry eye. A detailed step-by-step procedure of surface mould technique, simulation procedure, dose prescription, planning, plan evaluation and treatment has been described in this paper. Surface mould HDR brachytherapy can be safely used as organ preserving modality of treatment for eyelid carcinoma.

Dramatic Radiographic Response of Pelvis-Filling Locally Advanced Cervical Cancer Treated With Radiation and Chemotherapy.

Locally advanced cervical cancers are often treated with palliative intent due to concerns that the tumor is too far advanced or too large to be treated curatively. Also, patients greater than 65 years of age with cervical cancer are sometimes regarded as being too old or too frail to be cured with combined radiation and chemotherapy. These patients are often treated with radiation alone or with palliative therapy. Understanding the treatment modalities for cervical cancer is essential, as they can be complex and unique to each patient's specific diagnosis. This case report aims to describe the dramatic response to treatment with combined radiation and chemotherapy for a patient greater than 65 years of age with pelvis-filling cervical cancer with right-sided hydronephrosis. After a five-week course of concurrent chemoradiation, the cervical mass radiographically completely disappeared, with no evidence of disease noted on pelvic MRI.

Dosimetric evaluation of a novel modular cell irradiation platform for multi-modality in vitro studies including high dose rate brachytherapy.

PURPOSE: High dose-rate (HDR) brachytherapy is integral for the treatment of numerous cancers. Preclinical studies involving HDR brachytherapy are limited. We aimed to describe a novel platform allowing multi-modality studies with clinical HDR brachytherapy and external beam irradiators, establish baseline dosimetry standard of a preclinical orthovoltage irradiator, to determine accurate dosimetric methods. METHODS: A dosimetric assessment of a commercial preclinical irradiator was performed establishing the baseline dosimetry goals for clinical irradiators. A 3D printed platform was then constructed with 14 brachytherapy channels at 1cm spacing to accommodate a standard tissue culture plate at a source-to-cell distance (SCD) of 1 cm or 0.4 cm. 4-Gy CT-based treatment plans were created in clinical treatment planning software and delivered to 96-well tissue culture plates using an Ir192 source or a clinical linear accelerator. Standard calculation models for HDR brachytherapy and external beam were compared to corresponding deterministic model-based dose calculation algorithms (MBDCAs). Agreement between predicted and measured dose was assessed with 2D-gamma passing rates to determine the best planning methodology. RESULTS: Mean (±standard deviation) and median dose measured across the plate for the preclinical irradiator was 423.7 ± 8.5 cGy and 430.0 cGy. Mean percentage differences between standard and MBDCA dose calculations were 9.4% (HDR, 1 cm SCD), 0.43% (HDR, 0.4 cm SCD), and 2.4% (EBRT). Predicted and measured dose agreement was highest for MBDCAs for all modalities. CONCLUSION: A 3D-printed tissue culture platform can be used for multi-modality irradiation studies with great accuracy. This tool will facilitate preclinical studies to reveal biologic differences between clinically relevant radiation modalities.

Long-term outcomes of high-dose-rate brachytherapy and external beam radiotherapy without hormone therapy for high-risk localized prostate cancer.

PURPOSE: Until March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment. MATERIALS AND METHODS: Patients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39-45 Gy/13-25 fractions. and 16.5-22 Gy/2-4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined. RESULTS: Seventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively. CONCLUSION: HDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy.

The Bacau (Romania) phosphogypsum stacks as a source of radioactive threat: a case study.

For a detailed characterization of the 5.7 106 mt phosphogypsum (PG) stack in the vicinity of Bacau city, Romania, the air dose rate (ADR) was measured in 72 points covering the stack surface, while 10 samples of stack material were collected for future analysis. Radiometric determinations showed for the ADR values varying between 364 ± 53 and 489 ± 8 nSv/h, with some extreme values of 2775 ± 734 nSv/h, significantly exceeding 90 nSv/h, the average value reported for the Romanian territory. High-resolution gamma-ray spectroscopy (HRGS), performed on 10 samples collected from the entire PG stack evidenced only the presence of 226Ra as the major radioactive element with a specific activity varied between 820 ± 150 and 5278 ± 264 Bq/kg for hot spots. Further analysis performed on a similar number of samples by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF), scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDX), evidenced, beside gypsum as the main component, traces of brushite (CaHPO4·2H2O) and ardealite (Ca2(PO3OH)(SO4)·4H2O), as well as the presence of small acicular celestine (SrSO4) agglomerates. XRF determinations of the mass fractions of major elements evidenced values such as SiO2 (2.31 ± 0.73 %), TiO2 (0.07 ± 0.01 %), Al2O3 (0.17 ± 0.04 %), Fe2O3 (0.87 ± 0.18 %), MnO (0.01 ± 0.01 %), MgO (0.17 ± 0.02 %), CaO (32.5 ± 0.82 %), Na2O (0.04 ± 0.04 %), K2O (0.05 ± 0.01 %), P2O5 (2.12 ± 0.51 %), LOI (20.2 ± 0.3 %), i.e. closer to literature reported data for PG of different provenience while the data concerning the distribution of 20 trace elements, including incompatible Sc, La, Ce, and Th were relatively closer to the upper continental crust (UCC).

Radioactivity estimation of radioactive hotspots using a Compton camera and derivation of dose rates in the surrounding environment.

At the Fukushima Daiichi Nuclear Power Station, radiation sources released in the accident were deposited on various equipment and building structures. During decommissioning, it is crucial to understand the distribution of radiation sources and ambient dose equivalent rates to reduce worker exposure and implement detailed work planning. In this study, the author introduces a method for visualizing radiation sources, estimates their radioactivity using a Compton camera, and derives the dose rate around the radiation sources. In the demonstration test, the Compton camera was used to visualize radioactive hotspots caused by 137Cs radiation sources deposited in the outdoor environment and estimated the radioactivity. Furthermore, the dose rate around the hotspots was calculated from the estimated radioactivity, which confirmed that the calculated dose rate correlated with the dose rate measured using a survey meter. This approach is novel, where a series of analyses were conducted using the Compton camera to visualize radioactive hotspots, estimate the radioactivity, and derive the dose rate in the surrounding environment.

Salvage low-dose-rate brachytherapy for locally recurrent prostate cancer after definitive irradiation.

Purpose: The optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center. Patients and methods: A total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups. Conclusion: The efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta-analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary.

Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors.

Introduction: FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors. Methods: Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post-treatment to evaluate treatment efficiency and adverse effects. Results: Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression. Discussion: Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT.

Commissioning an ultra-high-dose-rate electron linac with end-to-end tests.

Objective. The FLASH effect can potentially be used to improve the therapeutic ratio of radiotherapy (RT) through delivery of Ultra-high-dose-rate (UHDR) irradiation. Research is actively being conducted to translate UHDR-RT and for this purpose the Mobetron is capable of producing electron beams at both UHDR and conventional dose rates for FLASH research and translation. This work presents commissioning of an UHDR Mobetron with end-to-end tests developed for preclinical research.Approach. UHDR electron beams were commissioned with an efficient approach utilizing a 3D-printed water tank and film to fully characterize beam characteristics and dependences on field size, pulse width (PW) and pulse repetition frequency (PRF). This commissioning data was used to implement a beam model using the GAMOS Monte Carlo toolkit for the preclinical research. Then, the workflow for preclinical FLASH irradiation was validated with end-to-end tests delivered to a 3D-printed mouse phantom with internal inhomogeneities.Main results.PDDs, profiles and output factors acquired with radiochromic films were precisely measured, with a PRF that showed little effect on the UHDR beam energy and spatial characteristics. Increasing PW reduced theDmaxand R50by 2.08 mmµs-1and 1.28 mmµs-1respectively. An end-to-end test of the preclinical research workflow showed that both profiles in head-foot and lateral directions were in good agreement with the MC calculations for the heterogeneous 3D printed mouse phantom with Gamma index above 93% for 2 mm/2% criteria, and 99% for 3 mm/3%.Significance. The UHDR Mobetron is a versatile tool for FLASH preclinical research and this comprehensive beam model and workflow was validated to meet the requirements for conducting translational FLASH research.

Dosimetry of microbeam radiotherapy by flexible hydrogenated amorphous silicon detectors.

Objective.Detectors that can provide accurate dosimetry for microbeam radiation therapy (MRT) must possess intrinsic radiation hardness, a high dynamic range, and a micron-scale spatial resolution. In this work we characterize hydrogenated amorphous silicon detectors for MRT dosimetry, presenting a novel combination of flexible, ultra-thin and radiation-hard features.Approach.Two detectors are explored: an n-type/intrinsic/p-type planar diode (NIP) and an NIP with an additional charge selective layer (NIP + CSC).Results.The sensitivity of the NIP + CSC detector was greater than the NIP detector for all measurement conditions. At 1 V and 0 kGy under the 3T Cu-Cu synchrotron broadbeam, the NIP + CSC detector sensitivity of (7.76 ± 0.01) pC cGy-1outperformed the NIP detector sensitivity of (3.55 ± 0.23) pC cGy-1by 219%. The energy dependence of both detectors matches closely to the attenuation coefficient ratio of silicon against water. Radiation damage measurements of both detectors out to 40 kGy revealed a higher radiation tolerance in the NIP detector compared to the NIP + CSC (17.2% and 33.5% degradations, respectively). Percentage depth dose profiles matched the PTW microDiamond detector's performance to within ±6% for all beam filtrations except in 3T Al-Al due to energy dependence. The 3T Cu-Cu microbeam field profile was reconstructed and returned microbeam width and peak-to-peak values of (51 ± 1)µm and (405 ± 5)µm, respectively. The peak-to-valley dose ratio was measured as a function of depth and agrees within error to the values obtained with the PTW microDiamond. X-ray beam induced charge mapping of the detector revealed minimal dose perturbations from extra-cameral materials.Significance.The detectors are comparable to commercially available dosimeters for quality assurance in MRT. With added benefits of being micron-sized and possessing a flexible water-equivalent substrate, these detectors are attractive candidates for quality assurance,in-vivodosimetry and in-line beam monitoring for MRT and FLASH therapy.

Comparison of perioperative and subacute postoperative complications between LDR and HDR monotherapy brachytherapy for prostate cancer.

PURPOSE: We aim to investigate perioperative and subacute postoperative complications in patients undergoing LDR or HDR monotherapy for prostate cancer. We hypothesize a low rate of complications, and a favorable toxicity profile in patients treated with HDR compared to LDR. MATERIALS AND METHODS: A prospectively collected institutional database was queried for patients treated with HDR or LDR prostate monotherapy between 1998 and 2021. Toxicities were determined per CTCAE. Claims based billing codes were obtained to identify additional events. Events occurring within 4 months of treatment were defined as perioperative or subacute postoperative complications. RESULTS: 759 patients were identified, 446 received LDR with 125I, and 313 received HDR with 192Ir. HDR patients had higher risk features: 75.7% with Gleason score 7+ versus 2.4% of LDR, and 16% with initial PSA 10+ ng/mL versus 2.7% of LDR. Toxicities were mild with the most common being grade 1 GU frequency and nocturia at ∼50%. HDR patients had significantly less grade 2 dysuria (2.6% vs. 9.0%), frequency (4.8% vs. 9.4%), hematuria (1.0% vs. 5.2%), nocturia (3.8% vs. 9.4%), and urinary obstructive symptoms (7.3% vs. 11.2%), all statistically significant. 11 (1.4%) patients had infection requiring antibiotics: 8 (1.8%) from the LDR group and 3 (1%) from the HDR group. Cardiopulmonary events were low at <2% overall, without difference between HDR and LDR. CONCLUSIONS: Overall toxicity rates support the safety of prostate brachytherapy. HDR monotherapy is associated with significantly less perioperative and subacute postoperative GU events when compared to LDR monotherapy. Cardiopulmonary events were equally rare in both groups.

Impact of dose distribution by a 3D planning system for brachytherapy with 198Au grains for head and neck cancer.

BACKGROUND: There has been no study in which the correlation between clinical results and dosimetry based on a 3D treatment planning system in patients with 198Au grains for head and neck cancer was evaluated. METHODS: Thirty-two patients who were treated with 198Au grains for head and neck cancer were reviewed. Twenty-five patients were treated with brachytherapy alone and seven patients were treated with a combination of brachytherapy and neoadjuvant external beam radiation therapy. RESULTS: With a median observation period of 60 months, the 5-year local control rate was 82.9%. V85Gy of CTV in patients with local recurrence tended to be lower than that in patients without local recurrence (p = 0.07). The maximum dose of the keratinized gingiva in patients in whom bone exposure occurred was significantly higher than that in patients in whom bone exposure did not occur (p = 0.001). CONCLUSIONS: Dose distribution with 198Au grains can predict local control and late adverse events.

Single-dose high-dose-rate brachytherapy versus two and three fractions for locally advanced prostate cancer.

BACKGROUND: Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. MATERIALS AND METHODS: 293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. RESULTS: At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. CONCLUSIONS: Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.