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.

Characterization of a commercial plastic scintillator for electron FLASH dosimetry.

PURPOSE: This study investigated the potential of a commercially available plastic scintillator, the Exradin W2, as a real-time dosimeter for ultra-high-dose-rate (UHDR) electron beams. This work aimed to characterize this system's performance under UHDR conditions and addressed limitations inherent to other conventional dosimetry systems. METHODS AND MATERIALS: We assessed the W2's performance as a UHDR electron dosimeter using a 16 MeV UHDR electron beam from the FLASH research extension (FLEX) system. Additionally, the vendor provided a beta firmware upgrade to better handle the processing of the high signal generated in the UHDR environment. We evaluated the W2 regarding dose-per-pulse, pulse repetition rate, charge versus distance, and pulse linearity. Absorbed dose measurements were compared against those from a plane-parallel ionization chamber, optically stimulated luminescent dosimeters and radiochromic film. RESULTS: We observed that the 1 × 1 mm W2 scintillator with the MAX SD was more suitable for UHDR dosimetry compared to the 1 × 3 mm W2 scintillator, capable of matching film measurements within 2% accuracy for dose-per-pulse up to 3.6 Gy/pulse. The W2 accurately ascertained the inverse square relationship regarding charge versus virtual source distance with R2 of ∼1.00 for all channels. Pulse linearity was accurately measured with the W2, demonstrating a proportional response to the delivered pulse number. There was no discernible impact on the measured charge of the W2 when switching between the available repetition rates of the FLEX system (18-180 pulses/s), solidifying consistent beam output across pulse frequencies. CONCLUSIONS: This study tested a commercial plastic scintillator detector in a UHDR electron beam, paving the way for its potential use as a real-time, patient-specific dosimetry tool for future FLASH radiotherapy treatments. Further research is warranted to test and improve the signal processing of the W2 dosimetry system to accurately measure in UHDR environments using exceedingly high dose-per-pulse and pulse numbers.

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.

A simple calibration routine for small inorganic scintillation detectors for in vivo dosimetry during brachytherapy.

BACKGROUND: In vivo dosimetry (IVD) is rarely performed in brachytherapy (BT), allowing potential dose misadministration to go unnoticed. This study presents a clinical routine-calibration method of detectors for IVD in high (HDR) and pulsed dose rate (PDR) Ir-192 BT. PURPOSE: To evaluate the dosimetric precision and feasibility of an in-clinic calibration routine of detectors for IVD in afterloading BT. METHODS: Calibrations were performed in a PMMA phantom with two needles inserted 20 mm apart. The source was loaded in one of the needles at 15 dwells for 10 s. The detector was placed in the other needle, and its signal was recorded. The mean signal at each dwell position was fitted to the expected dose rate with the calibration factor and the detector's longitudinal position being free parameters. The method was tested with an inorganic scintillation detector using one Ir-192 FlexiSource HDR and two Ir-192 GammaMedPlus PDR sources and followed by validation measurements in water. RESULTS: The standard measurement uncertainty (k = 1) of the calibration factor in absolute terms (Gy/s) was 3.2/3.4% for the HDR/PDR source. The uncertainty was dominated by source strength uncertainty, and the precision of the method was <1%. The mean ± 1SD of the difference in measured and expected dose rate during validation was 1.5 ± 4.7% (HDR) and 0.0 ± 4.1% (PDR) with a positional uncertainty in the setup of 0.33/0.23 mm (HDR/PDR) (k = 1). CONCLUSION: A precise and feasible in-clinic calibration method for IVD and source strength consistency tests in BT was presented.

On the acceptance, commissioning, and quality assurance of electron FLASH units.

Background & Purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an example of commissioning. Methods: A protocol for acceptance, commissioning, and QA of UHDR linear accelerators was established by combining and adapting standards and professional recommendations for standard linear accelerators based on the experience with UHDR at four clinical centers that use different UHDR devices. Non-standard dosimetric beam parameters considered included pulse width, pulse repetition frequency, dose per pulse, and instantaneous dose rate, together with recommendations on how to acquire these measurements. Results: The 6- and 9-MeV beams of an UHDR electron device were commissioned by using this developed protocol. Measurements were acquired with a combination of ion chambers, beam current transformers (BCTs), and dose-rate-independent passive dosimeters. The unit was calibrated according to the concept of redundant dosimetry using a reference setup. Conclusions: This study provides detailed recommendations for the acceptance testing, commissioning, and routine QA of low-energy electron UHDR linear accelerators. The proposed framework is not limited to any specific unit, making it applicable to all existing eFLASH units in the market. Through practical insights and theoretical discourse, this document establishes a benchmark for the commissioning of UHDR devices for clinical use.

A high-throughput focused collimator for OAR-sparing preclinical proton FLASH studies: commissioning and validation.

Objective. To fabricate and validate a novel focused collimator designed to spare normal tissue in a murine hemithoracic irradiation model using 250 MeV protons delivered at ultra-high dose rates (UHDRs) for preclinical FLASH radiation therapy (FLASH-RT) studies.Approach. A brass collimator was developed to shape 250 MeV UHDR protons from our Varian ProBeam. Six 13 mm apertures, of equivalent size to kV x-ray fields historically used to perform hemithorax irradiations, were precisely machined to match beam divergence, allowing concurrent hemithoracic irradiation of six mice while sparing the contralateral lung and abdominal organs. The collimated field profiles were characterized by film dosimetry, and a radiation survey of neutron activation was performed to ensure the safety of staff positioning animals.Main results. The brass collimator produced 1.2 mm penumbrae radiation fields comparable to kV x-rays used in preclinical studies. The penumbrae in the six apertures are similar, with full-width half-maxima of 13.3 mm and 13.5 mm for the central and peripheral apertures, respectively. The collimator delivered a similar dose at an average rate of 52 Gy s-1for all apertures. While neutron activation produces a high (0.2 mSv h-1) initial ambient equivalent dose rate, a parallel work-flow in which imaging and setup are performed without the collimator ensures safety to staff.Significance. Scanned protons have the greatest potential for future translation of FLASH-RT in clinical treatments due to their ability to treat deep-seated tumors with high conformality. However, the Gaussian distribution of dose in proton spots produces wider lateral penumbrae compared to other modalities. This presents a challenge in small animal pre-clinical studies, where millimeter-scale penumbrae are required to precisely target the intended volume. Offering high-throughput irradiation of mice with sharp penumbrae, our novel collimator-based platform serves as an important benchmark for enabling large-scale, cost-effective radiobiological studies of the FLASH effect in murine models.

Radiation safety of ultra-high dose rate electron accelerators for FLASH radiotherapy.

BACKGROUND: An ultra-high dose rate (UHDR) electron accelerator for FLASH radiotherapy (RT) produces very intense bremsstrahlung by the interaction of the electron beam with objects both inside and outside of the accelerator. The bremsstrahlung dose per pulse is typically 1-2 orders of magnitude larger than that of conventional RT x-ray treatment of the same energy, and for electron energies above 10 MeV, the bremsstrahlung produces substantially more induced radioactivity outside the accelerator than for conventional RT. Therefore, a thorough radiation safety assessment is mandatory prior to the operation of a UHDR electron accelerator. PURPOSE: To evaluate the radiation safety of a prototype FLASH-enabled Varian TrueBeam accelerator and to develop a general framework for assessment of all key radiation safety properties of a UHDR electron accelerator for FLASH RT. METHODS: Production of bremsstrahlung and induced radioactivity by a UHDR electron accelerator is modeled by various analytical methods. The analytical modeling is compared with National Institute of Standards and Technology (NIST) bremsstrahlung yield data as well as measurements of primary bremsstrahlung outside the bunker and induced radioactivity of irradiated thick targets for a FLASH-enabled 16 MeV Varian TrueBeam electron accelerator. In addition, the analytical modeling is complemented by measurements of secondary bremsstrahlung inside/outside the bunker and neutrons at the maze entrance. RESULTS: Calculated bremsstrahlung yields deviate maximum 8.5% from NIST data, and all measurements of primary bremsstrahlung and induced radioactivity agree with calculations, validating the analytical tools. In addition, it is found that scattering foil bremsstrahlung dominates primary bremsstrahlung and the main source of secondary bremsstrahlung is the irradiated object outside the accelerator. It follows that primary and secondary bremsstrahlung outside the bunker can be calculated using the same simple formalism as that used for conventional RT. Measured primary bremsstrahlung tenth-value layers for concrete of the simple formalism are in good agreement with NCRP and IAEA data, while measured secondary bremsstrahlung tenth-value layers for concrete are considerably lower than NCRP and IAEA data. All calculations and measurements form a general framework for assessment of all key radiation safety properties of a UHDR electron accelerator. CONCLUSIONS: The FLASH-enabled Varian TrueBeam accelerator is safe for normal operation (max. 99 pulses per irradiation) in a bunker designed for at least 15 MV conventional x-ray treatment unless the UHDR workload is much larger than the x-ray workload. A similar finding applies to other UHDR electron accelerators. However, during beam tuning, radiation survey, or other tests with extended irradiation time, the UHDR workload may become very large, necessitating the implementation of additional safety measures.

Validation and reproducibility of in vivo dosimetry for pencil beam scanned FLASH proton treatment in mice.

PURPOSE: To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber. METHODS AND MATERIALS: 227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector. RESULTS: Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R2 values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ±â€¯3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ±â€¯0.8 Gy/s and mean local average dose rate of 160.6 ±â€¯3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose. CONCLUSION: In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.

FLASH Effect Is Not Always Induced by Ultra-high Dose-rate Proton Irradiation Under Hypoxic Conditions.

BACKGROUND/AIM: Pre-clinical studies have shown that irradiation with electrons at an ultra-high dose-rate (FLASH) spares normal tissue while maintaining tumor control. However, most in vitro experiments with protons have been conducted using a non-clinical irradiation system in normoxia alone. This study evaluated the biological response of non-tumor and tumor cells at different oxygen concentrations irradiated with ultra-high dose-rate protons using a clinical system and compared it with the conventional dose rate (CONV). MATERIALS AND METHODS: Non-tumor cells (V79) and tumor cells (U-251 and A549) were irradiated with 230 MeV protons at a dose rate of >50 Gy/s or 0.1 Gy/s under normoxic or hypoxic (<2%) conditions. The surviving fraction was analyzed using a clonogenic cell survival assay. RESULTS: No significant difference in the survival of non-tumor or tumor cells irradiated with FLASH was observed under normoxia or hypoxia compared to the CONV. CONCLUSION: Proton irradiation at a dose rate above 40 Gy/s, the FLASH dose rate, did not induce a sparing effect on either non-tumor or tumor cells under the conditions examined. Further studies are required on the influence of various factors on cell survival after FLASH irradiation.

Single- versus Multi-computed Tomography Simulation for High-dose-rate Postoperative Gynecological Intracavitary Brachytherapy.

Introduction: This study aimed to investigate whether there is a dosimetric difference of implementing single instead of multi-computed tomography (CT) simulation treatment planning for high-dose-rate postoperative gynecological intracavitary brachytherapy (BT). Materials and Methods: Eighty patients were registered in the study. They received three BT fractions of 7 Gy/week (three CTs, three original plans). The organs at risk (OAR), the rectal wall, and the clinical target volume (CTV) were delineated. The delivered doses for the 2cc of OARs (D2cc), 1cc of rectal wall (D1cc), as well as for the 90% and 100% of CTV volume (DCTV90%, DCTV100%) were evaluated. To evaluate the values of the above parameters if the single-CT-simulation method has been chosen, the time of the first treatment plan was corrected for the decay and applied as the second and third CT, retrospectively, creating the next fractions (two revised plans). Results: No statistically significant (P > 0.05) differences were found between the original and revised plans for the OARs and CTV. However, for the single-CT-simulation method, it was noted that the dose constraints for the total rectal dose were exceeded in some cases (36.3%). Conclusion: The fact that rectal dose constraints were exceeded in 1/3 of patients with the single-CT-simulation method is dosimetrically significant.

A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy.

BACKGROUND: Quality assurance (QA) for ultra-high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH-RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH-RT. PURPOSE: To develop a comprehensive pre-treatment QA program for cyclotron-based proton pencil beam scanning (PBS) FLASH-RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG-224 recommendations. METHODS: A 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months. RESULTS: The relative dosimetries were compliant with TG-224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam-to-beam absolute output on the same day reached up to 2.14%, the day-to-day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session. CONCLUSIONS: A comprehensive QA program for FLASH-RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH-RT field.

The FLASH effect-an evaluation of preclinical studies of ultra-high dose rate radiotherapy.

FLASH radiotherapy (FLASH-RT) is a novel radiotherapy approach based on the use of ultra-high dose radiation to treat malignant cells. Although tumours can be reduced or eradicated using radiotherapy, toxicities induced by radiation can compromise healthy tissues. The FLASH effect is the observation that treatment delivered at an ultra-high dose rate is able to reduce adverse toxicities present at conventional dose rates. While this novel technique may provide a turning point for clinical practice, the exact mechanisms underlying the causes or influences of the FLASH effect are not fully understood. The study presented here uses data collected from 41 experimental investigations (published before March 2024) of the FLASH effect. Searchable databases were constructed to contain the outcomes of the various experiments in addition to values of beam parameters that may have a bearing on the FLASH effect. An in-depth review of the impact of the key beam parameters on the results of the experiments was carried out. Correlations between parameter values and experimental outcomes were studied. Pulse Dose Rate had positive correlations with almost all end points, suggesting viability of FLASH-RT as a new modality of radiotherapy. The collective results of this systematic review study suggest that beam parameter qualities from both FLASH and conventional radiotherapy can be valuable for tissue sparing and effective tumour treatment.

Plastic scintillator-based dosimeters for ultra-high dose rate (UHDR) electron radiotherapy.

This paper reports the development of dosimeters based on plastic scintillating fibers imaged by a charge-coupled device camera, and their performance evaluation through irradiations with the electron Flash research accelerator located at the Centro Pisano Flash Radiotherapy. The dosimeter prototypes were composed of a piece of plastic scintillating fiber optically coupled to a clear optical fiber which transported the scintillation signal to the readout systems (an imaging system and a photodiode). The following properties were tested: linearity, capability to reconstruct the percentage depth dose curve in solid water and to sample in time the single beam pulse. The stem effect contribution was evaluated with three methods, and a proof-of-concept one-dimensional array was developed and tested for online beam profiling. Results show linearity up to 10 Gy per pulse, and good capability to reconstruct both the timing and spatial profiles of the beam, thus suggesting that plastic scintillating fibers may be good candidates for low-energy electron Flash dosimetry.

Mechanisms of Action in FLASH Radiotherapy: A Comprehensive Review of Physicochemical and Biological Processes on Cancerous and Normal Cells.

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy.

A Novel Positive-Contrast Magnetic Resonance Imaging Line Marker for High-Dose-Rate (HDR) MRI-Assisted Radiosurgery (MARS).

Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer.

Electron beam response corrections for an ultra-high-dose-rate capable diode dosimeter.

BACKGROUND: Ultra-high-dose-rate (UHDR) electron beams have been commonly utilized in FLASH studies and the translation of FLASH Radiotherapy (RT) to the clinic. The EDGE diode detector has potential use for UHDR dosimetry albeit with a beam energy dependency observed. PURPOSE: The purpose is to present the electron beam response for an EDGE detector in dependence on beam energy, to characterize the EDGE detector's response under UHDR conditions, and to validate correction factors derived from the first detailed Monte Carlo model of the EDGE diode against measurements, particularly under UHDR conditions. METHODS: Percentage depth doses (PDDs) for the UHDR Mobetron were measured with both EDGE detectors and films. A detailed Monte Carlo (MC) model of the EDGE detector has been configured according to the blueprint provided by the manufacturer under an NDA agreement. Water/silicon dose ratios of EDGE detector for a series of mono-energetic electron beams have been calculated. The dependence of the water/silicon dose ratio on depth for a FLASH relevant electron beam was also studied. An analytical approach for the correction of PDD measured with EDGE detectors was established. RESULTS: Water/silicon dose ratio decreased with decreasing electron beam energy. For the Mobetron 9 MeV UHDR electron beam, the ratio decreased from 1.09 to 1.03 in the build-up region, maintained in range of 0.98-1.02 at the fall-off region and raised to a plateau in value of 1.08 at the tail. By applying the corrections, good agreement between the PDDs measured by the EDGE detector and those measured with film was achieved. CONCLUSIONS: Electron beam response of an UHDR capable EDGE detector was derived from first principles utilizing a sophisticated MC model. An analytical approach was validated for the PDDs of UHDR electron beams. The results demonstrated the capability of EDGE detector in measuring PDDs of UHDR electron beams.

Reply to comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.

Liew and Mairani commented on our paper 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation' (Shiraishiet al2024aPhys. Med. Biol.69015017), which proposed a biophysical model to predict the dose-response curve of surviving cell fractions after ultra-high dose rate irradiation following conventional dose rate irradiation by considering DNA damage yields. They suggested the need to consider oxygen concentration in our prediction model and possible issues related to the data selection process used for the benchmarking test in our paper. In this reply, we discuss the limitations of both the present model and the available experimental data for determining the model's parameters. We also demonstrate that our proposed model can reproduce the experimental survival data even when using only the experimental DNA damage data measured reliably under normoxic conditions.

Salvage percutaneous high-dose-rate brachyablation after stereotactic body radiation therapy for early-stage non-small cell lung cancer.

Patients with primary tumor progression after stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) have a second chance at complete tumor eradication with salvage local therapies, including lung resection, repeat course of SBRT, and percutaneous ablative therapies. In this paper, we presented our institution's initial experience with percutaneous high-dose-rate (HDR) brachyablation for a relapsed stage I NSCLC that had been treated with SBRT 4.3 years earlier. Lung tumor measuring approximately 5 cm in maximum tumor dimension at the time of relapse was histopathologically confirmed to be persistent squamous cell carcinoma, and successfully treated with a single fraction of 24 Gy with HDR brachyablation. Treatment was delivered via two percutaneous catheters inserted under CT-guidance, and treated in less than 20 minutes. The patient was discharged home later the same day without the need for a chest tube, and has been monitored with serial surveillance scans every 3 to 6 months without evidence of further lung cancer progression or complications at 2.8 years post-HDR brachyablation procedure and 7.8 years after initial SBRT.