Automatic end-to-end VMAT treatment planning for rectal cancers.

BACKGROUND: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear. PURPOSE: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs. METHODS: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the rectum. We trained, validated, and tested deep learning auto-segmentation models using nnU-Net architecture for clinical target volume (CTV), bowel bag, large bowel, small bowel, total bowel, femurs, bladder, bone marrow, and female and male genitalia. For the CTV, we identified 174 patients with clinically drawn CTVs. We used data for 18 patients for all structures other than the CTV. The structures were contoured under the guidance of and reviewed by a gastrointestinal (GI) radiation oncologist. The predicted results for CTV in 35 patients and organs at risk (OAR) in six patients were scored by the GI radiation oncologist using a five-point Likert scale. For auto-planning, a RapidPlan knowledge-based planning solution was modeled for VMAT delivery with a prescription of 25 Gy in five fractions. The model was trained and tested on 20 and 34 patients, respectively. The resulting plans were scored by two GI radiation oncologists using a five-point Likert scale. Finally, the end-to-end pipeline was evaluated on 16 patients, and the resulting plans were scored by two GI radiation oncologists. RESULTS: In 31 of 35 patients, CTV contours were clinically acceptable without necessary modifications. The CTV achieved a Dice similarity coefficient of 0.85 (±0.05) and 95% Hausdorff distance of 15.25 (±5.59) mm. All OAR contours were clinically acceptable without edits, except for large and small bowel which were challenging to differentiate. However, contours for total, large, and small bowel were clinically acceptable. The two physicians accepted 100% and 91% of the auto-plans. For the end-to-end pipeline, the two physicians accepted 88% and 62% of the auto-plans. CONCLUSIONS: This study demonstrated that the VMAT treatment planning technique for rectal cancer can be automated to generate clinically acceptable and safe plans with minimal human interventions.

High-Density Glass Scintillators for Proton Radiography-Relative Luminosity, Proton Response, and Spatial Resolution.

Proton radiography is a promising development in proton therapy, and researchers are currently exploring optimal detector materials to construct proton radiography detector arrays. High-density glass scintillators may improve integrating-mode proton radiography detectors by increasing spatial resolution and decreasing detector thickness. We evaluated several new scintillators, activated with europium or terbium, with proton response measurements and Monte Carlo simulations, characterizing relative luminosity, ionization quenching, and proton radiograph spatial resolution. We applied a correction based on Birks's analytical model for ionization quenching. The data demonstrate increased relative luminosity with increased activation element concentration, and higher relative luminosity for samples activated with europium. An increased glass density enables more compact detector geometries and higher spatial resolution. These findings suggest that a tungsten and gadolinium oxide-based glass activated with 4% europium is an ideal scintillator for testing in a full-size proton radiography detector.

Protocol-in-a-Day Workshop: Expediting IRB Approval for Junior and Senior Faculty.

Delays in research protocol development may be a single factor that hinders the career progression of academic faculty. Structured educational guidance during this phase proves crucial in mitigating setbacks in Institutional Review Board (IRB) approval and expediting trial implementation. To address this, the Protocol-in-a-Day (PIAD) workshop, a comprehensive 1-day event involving members from six critical facets of RO clinical trial implementation, was established, offering significant input to individual protocols. Efficacy and satisfaction of the PIAD workshop were assessed through a 5-question survey and the average time from submission to IRB initial approval. The normality of the data was analyzed using the Shapiro-Wilk Test. Nonparametric data was analyzed using a Mann-Whitney U test for significance. A total of 18 protocols that went through the PIAD workshop were activated. The mean time to IRB approval for protocols that went through PIAD was 39.8 days compared to 58.4 days for those that did not go through the PIAD workshop. Based on survey results, 100% of PIAD participants said the PIAD workshop was useful and 94% of participants stated that the PIAD workshop improved the overall quality of their protocol. Participant surveys further highlighted substantial improvements in trial quality, language, and statistical design and revealed that all participants found the workshop helpful. Therefore, both junior and senior faculty benefitted from this educational program during protocol development, as both groups demonstrated shorter times to IRB approval than non-participants. This acceleration not only fosters efficient trial implementation but also supports academic faculty in their career development.

Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma. METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six academic sites in the USA. Eligible patients were randomly assigned (1:1), with block randomisation (block sizes of 6-12) with a maximum of 24 patients per group, to receive daily avasopasem (90 mg) or placebo intravenously directly before (ie, within 180 min) SBRT (50, 55, or 60 Gy in five fractions, adaptively assigned in real time by Bayesian estimates of 90-day safety and efficacy). Patients and physicians were masked to treatment group allocation, but not to SBRT dose. The primary objective was to find the optimal dose of SBRT with avasopasem or placebo as determined by the late onset EffTox method. All analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT03340974, and is complete. FINDINGS: Between Jan 25, 2018, and April 29, 2020, 47 patients were screened, of whom 42 were enrolled (median age was 71 years [IQR 63-75], 23 [55%] were male, 19 [45%] were female, 37 [88%] were White, three [7%] were Black, and one [2%] each were unknown or other races) and randomly assigned to avasopasem (n=24) or placebo (n=18); the placebo group was terminated early after failing to meet prespecified efficacy parameters. At data cutoff (June 28, 2021), the avasopasem group satisfied boundaries for both efficacy and toxicity. Late onset EffTox efficacy response was observed in 16 (89%) of 18 patients at 50 Gy and six (100%) of six patients at 55 Gy in the avasopasem group, and was observed in three (50%) of six patients at 50 Gy and nine (75%) of 12 patients at 55 Gy in the placebo group, and the Bayesian model recommended 50 Gy or 55 Gy in five fractions with avasopasem for further study. Serious adverse events of any cause were reported in three (17%) of 18 patients in the placebo group and six (25%) of 24 in the avasopasem group. In the placebo group, grade 3 adverse events within 90 days of SBRT were abdominal pain, acute cholangitis, pyrexia, increased blood lactic acid, and increased lipase (one [6%] each); no grade 4 events occurred. In the avasopasem group, grade 3-4 adverse events within 90 days of SBRT were acute kidney injury, increased blood alkaline phosphatase, haematoma, colitis, gastric obstruction, lung infection, abdominal abscess, post-surgical atrial fibrillation, and pneumonia leading to respiratory failure (one [4%] each).There were no treatment-related deaths but one late death in the avasopasem group due to sepsis in the setting of duodenal obstruction after off-study treatment was reported as potentially related to SBRT. INTERPRETATION: SBRT that uses 50 or 55 Gy in five fractions can be considered for patients with localised pancreatic ductal adenocarcinoma. The addition of avasopasem might further enhance disease outcomes. A larger phase 2 trial (GRECO-2, NCT04698915) is underway to validate these results. FUNDING: Galera Therapeutics.

Dual beam-current transformer design for monitoring and reporting of electron ultra-high dose rate (FLASH) beam parameters.

PURPOSE: To investigate the usefulness and effectiveness of a dual beam-current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real-time, and to inform on the usefulness of this design for future eFLASH beam control. METHODS: Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW), pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower-to-upper BCT signal. RESULTS: A linear relationship was observed between the absorbed dose measured on Gafchromic film and the BCT signals for both the upper and lower BCT (R2  > 0.99). A linear relationship was also observed in the BCT signals as a function of the number of pulses delivered regardless of the PW, DPP, or PRF (R2  > 0.99). The lower-to-upper BCT ratio was found to correlate strongly with the energy of the eFLASH beam due to differential beam attenuation caused by the secondary scattering foil. The BCTs were also able to provide accurate information about the PW, PRF, energy, and DPP for each individual pulse delivered in real-time. CONCLUSION: The dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse-by-pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real-time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.

Automation of radiation treatment planning for rectal cancer.

PURPOSE: To develop an automated workflow for rectal cancer three-dimensional conformal radiotherapy (3DCRT) treatment planning that combines deep learning (DL) aperture predictions and forward-planning algorithms. METHODS: We designed an algorithm to automate the clinical workflow for 3DCRT planning with field aperture creations and field-in-field (FIF) planning. DL models (DeepLabV3+ architecture) were trained, validated, and tested on 555 patients to automatically generate aperture shapes for primary (posterior-anterior [PA] and opposed laterals) and boost fields. Network inputs were digitally reconstructed radiographs, gross tumor volume (GTV), and nodal GTV. A physician scored each aperture for 20 patients on a 5-point scale (>3 is acceptable). A planning algorithm was then developed to create a homogeneous dose using a combination of wedges and subfields. The algorithm iteratively identifies a hotspot volume, creates a subfield, calculates dose, and optimizes beam weight all without user intervention. The algorithm was tested on 20 patients using clinical apertures with varying wedge angles and definitions of hotspots, and the resulting plans were scored by a physician. The end-to-end workflow was tested and scored by a physician on another 39 patients. RESULTS: The predicted apertures had Dice scores of 0.95, 0.94, and 0.90 for PA, laterals, and boost fields, respectively. Overall, 100%, 95%, and 87.5% of the PA, laterals, and boost apertures were scored as clinically acceptable, respectively. At least one auto-plan was clinically acceptable for all patients. Wedged and non-wedged plans were clinically acceptable for 85% and 50% of patients, respectively. The hotspot dose percentage was reduced from 121% (σ = 14%) to 109% (σ = 5%) of prescription dose for all plans. The integrated end-to-end workflow of automatically generated apertures and optimized FIF planning gave clinically acceptable plans for 38/39 (97%) of patients. CONCLUSION: We have successfully automated the clinical workflow for generating radiotherapy plans for rectal cancer for our institution.

Characterization of the Plastic Scintillator Detector System Exradin W2 in a High Dose Rate Flattening-Filter-Free Photon Beam.

(1) Background: The Exradin W2 is a commercially available scintillator detector designed for reference and relative dosimetry in small fields. In this work, we investigated the performance of the W2 scintillator in a 10 MV flattening-filter-free photon beam and compared it to the performance of ion chambers designed for small field measurements. (2) Methods: We measured beam profiles and percent depth dose curves with each detector and investigated the linearity of each system based on dose per pulse (DPP) and pulse repetition frequency. (3) Results: We found excellent agreement between the W2 scintillator and the ion chambers for beam profiles and percent depth dose curves. Our results also showed that the two-voltage method of calculating the ion recombination correction factor was sufficient to correct for the ion recombination effect of ion chambers, even at the highest DPP. (4) Conclusions: These findings show that the W2 scintillator shows excellent agreement with ion chambers in high DPP conditions.

Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience.

BACKGROUND: We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC). METHODS: We retrospectively evaluated all patients with CRC treated with IORT at our institution from 2001 to 2010. IORT was delivered using high-dose-rate brachytherapy (median 12.5-Gy). We analyzed factors associated with postoperative morbidity, local control (LC), and overall survival (OS). RESULTS: One hundred patients were evaluated with 70% received IORT for recurrent tumors. R0 resection rate was 58%. Postoperative Grade ≥3 complications (33%) were independently associated with transfusions ≥3 units packed red blood cells (P = 0.016) and body mass index (BMI) ≥35 (P = 0.0499). Eighty-two patients underwent external beam radiation therapy (EBRT) before IORT. Five-year LC was 94%, for primary and 56%, for recurrent tumors, respectively (P = 0.007). Microscopic positive (R1) margins were not associated with LC (P = 0.316). BMI ≥30 (P = 0.048) and post-discharge complications (P = 0.041) were independent risk factors for worse LC. Median post-IORT OS was 67.7 (95% CI 51.1-84.3) months for all patients. CONCLUSION: For patients with primary or recurrent locally advanced CRC, treatment with radical surgery and IORT achieved excellent LC outcomes irrespective of microscopic margin status. IORT may be indicated for tumors suspected to have close or positive microscopic margins.

A comprehensive investigation of the performance of a commercial scintillator system for applications in electron FLASH radiotherapy.

BACKGROUND: Dosimetry in ultra-high dose rate (UHDR) beamlines is significantly challenged by limitations in real-time monitoring and accurate measurement of beam output, beam parameters, and delivered doses using conventional radiation detectors, which exhibit dependencies in ultra-high dose-rate (UHDR) and high dose-per-pulse (DPP) beamline conditions. PURPOSE: In this study, we characterized the response of the Exradin W2 plastic scintillator (Standard Imaging, Inc.), a water-equivalent detector that provides measurements with a time resolution of 100 Hz, to determine its feasibility for use in UHDR electron beamlines. METHODS: The W2 scintillator was exposed to an UHDR electron beam with different beam parameters by varying the pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude settings of an electron UHDR linear accelerator system. The response of the W2 scintillator was evaluated as a function of the total integrated dose delivered, DPP, and mean and instantaneous dose rate. To account for detector radiation damage, the signal sensitivity (pC/Gy) of the W2 scintillator was measured and tracked as a function of dose history. RESULTS: The W2 scintillator demonstrated mean dose rate independence and linearity as a function of integrated dose and DPP for DPP ≤ 1.5 Gy (R2 > 0.99) and PRF ≤ 90 Hz. At DPP > 1.5 Gy, nonlinear behavior and signal saturation in the blue and green signals as a function of DPP, PRF, and integrated dose became apparent. In the absence of Cerenkov correction, the W2 scintillator exhibited PW dependence, even at DPP values <1.5 Gy, with a difference of up to 31% and 54% in the measured blue and green signal for PWs ranging from 0.5 to 3.6 µs. The change in signal sensitivity of the W2 scintillator as a function of accumulated dose was approximately 4%/kGy and 0.3%/kGy for the measured blue and green signal responses, respectively, as a function of integrated dose history. CONCLUSION: The Exradin W2 scintillator can provide output measurements that are both dose rate independent and linear in response if the DPP is kept ≤1.5 Gy (corresponding to a mean dose rate up to 290 Gy/s in the used system), as long as proper calibration is performed to account for PW and changes in signal sensitivity as a function of accumulated dose. For DPP > 1.5 Gy, the W2 scintillator's response becomes nonlinear, likely due to limitations in the electrometer related to the high signal intensity.

Evaluation of ion chamber response for applications in electron FLASH radiotherapy.

Ion chambers are required for calibration and reference dosimetry applications in radiation therapy (RT). However, exposure of ion chambers in ultra-high dose rate (UHDR) conditions pertinent to FLASH-RT leads to severe saturation and ion recombination, which limits their performance and usability. The purpose of this study was to comprehensively evaluate a set of commonly used commercially available ion chambers in RT, all with different design characteristics, and use this information to produce a prototype ion chamber with improved performance in UHDR conditions as a first step toward ion chambers specific for FLASH-RT. The Advanced Markus and Exradin A10, A26, and A20 ion chambers were evaluated. The chambers were placed in a water tank, at a depth of 2 cm, and exposed to an UHDR electron beam at different pulse repetition frequency (PRF), pulse width (PW), and pulse amplitude settings on an IntraOp Mobetron. Ion chamber responses were investigated for the various beam parameter settings to isolate their dependence on integrated dose, mean dose rate and instantaneous dose rate, dose-per-pulse (DPP), and their design features such as chamber type, bias voltage, and collection volume. Furthermore, a thin parallel-plate (TPP) prototype ion chamber with reduced collector plate separation and volume was constructed and equally evaluated as the other chambers. The charge collection efficiency of the investigated ion chambers decreased with increasing DPP, whereas the mean dose rate did not affect the response of the chambers (± 1%). The dependence of the chamber response on DPP was found to be solely related to the total dose within the pulse, and not on mean dose rate, PW, or instantaneous dose rate within the ranges investigated. The polarity correction factor (Ppol ) values of the TPP prototype, A10, and Advanced Markus chambers were found to be independent of DPP and dose rate (± 2%), while the A20 and A26 chambers yielded significantly larger variations and dependencies under the same conditions. Ion chamber performance evaluated under different irradiation conditions of an UHDR electron beam revealed a strong dependence on DPP and a negligible dependence on the mean and instantaneous dose rates. These results suggest that modifications to ion chambers design to improve their usability in UHDR beamlines should focus on minimizing DPP effects, with emphasis on optimizing the electric field strength, through the construction of smaller electrode separation and larger bias voltages. This was confirmed through the production and evaluation of a prototype ion chamber specifically designed with these characteristics.

Characterization of a novel time-resolved, real-time scintillation dosimetry system for ultra-high dose rate radiation therapy applications.

Background: Scintillation dosimetry has promising qualities for ultra-high dose rate (UHDR) radiotherapy (RT), but no system has shown compatibility with mean dose rates (DR-) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillator dosimetry system with the potential of accommodating UHDRs. Methods and Materials: A thorough dosimetric characterization of the system was performed on an UHDR electron beamline. The system's response as a function of dose, DR-,Dp, and the pulse dose rate DRp was investigated, together with the system's dose sensitivity (signal per unit dose) as a function of dose history. The capabilities of the system for time-resolved dosimetric readout were also evaluated. Results: Within a tolerance of ±3%, the system exhibited dose linearity and was independent of DR- and Dp within the tested ranges of 1.8-1341 Gy/s and 0.005-7.68 Gy, respectively. A 6% reduction in the signal per unit dose was observed as DRp was increased from 8.9e4-1.8e6 Gy/s. Additionally, the dose delivered per integration window of the continuously sampling photodetector had to remain between 0.028 and 11.64 Gy to preserve a stable signal response per unit dose. The system accurately measured Dp of individual pulses delivered at up to 120 Hz. The day-to-day variation of the signal per unit dose at a reference setup varied by up to ±13% but remained consistent (<±2%) within each day of measurements and showed no signal loss as a function of dose history. Conclusions: With daily calibrations and DRp specific correction factors, the system reliably provides real-time, millisecond-resolved dosimetric measurements of pulsed conventional and UHDR beams from typical electron linacs, marking an important advancement in UHDR dosimetry and offering diverse applications to FLASH-RT and related fields.

Integrated-mode proton radiography with 2D lateral projections.

Integrated-mode proton radiography leading to water equivalent thickness (WET) maps is an avenue of interest for motion management, patient positioning, andin vivorange verification. Radiographs can be obtained using a pencil beam scanning setup with a large 3D monolithic scintillator coupled with optical cameras. Established reconstruction methods either (1) involve a camera at the distal end of the scintillator, or (2) use a lateral view camera as a range telescope. Both approaches lead to limited image quality. The purpose of this work is to propose a third, novel reconstruction framework that exploits the 2D information provided by two lateral view cameras, to improve image quality achievable using lateral views. The three methods are first compared in a simulated Geant4 Monte Carlo framework using an extended cardiac torso (XCAT) phantom and a slanted edge. The proposed method with 2D lateral views is also compared with the range telescope approach using experimental data acquired with a plastic volumetric scintillator. Scanned phantoms include a Las Vegas (contrast), 9 tissue-substitute inserts (WET accuracy), and a paediatric head phantom. Resolution increases from 0.24 (distal) to 0.33 lp mm-1(proposed method) on the simulated slanted edge phantom, and the mean absolute error on WET maps of the XCAT phantom is reduced from 3.4 to 2.7 mm with the same methods. Experimental data from the proposed 2D lateral views indicate a 36% increase in contrast relative to the range telescope method. High WET accuracy is obtained, with a mean absolute error of 0.4 mm over 9 inserts. Results are presented for various pencil beam spacing ranging from 2 to 6 mm. This work illustrates that high quality proton radiographs can be obtained with clinical beam settings and the proposed reconstruction framework with 2D lateral views, with potential applications in adaptive proton therapy.

Establishing a fingerprinting method for fast catheter identification in HDR brachytherapy in vivo dosimetry.

PURPOSE: To use quantities measurable during in vivo dosimetry to build unique channel identifiers, that enable detection of brachytherapy errors. MATERIALS AND METHODS: Treatment plan of 360 patients with prostate cancer who underwent high-dose-rate brachytherapy (range, 16-25 catheters; mean, 17) were used. A single point virtual dosimeter was placed at multiple positions within the treatment geometry, and the source-dosimeter distance and dwell time were determined for each dwell position in each catheter. These values were compared across all catheters, dwell position by dwell position, simulating a treatment delivery. A catheter was considered uniquely identified if, for a given dwell position, no other catheters had the same measured values. The minimum number of dwell positions needed to identify a specific catheter and the optimal dosimeter location uniquely were determined. The radial (r) and vertical (z) dimensions of the source-dosimeter distance were also examined for their utility in discriminating catheters. RESULTS: Using a virtual dosimeter with no uncertainties, all catheters were identified in 359 of the 360 cases with 9 dwell position measurements. When only the dwell time were measured, all catheters were uniquely identified after 1 dwell position. With a 2-mm spatial accuracy (r,z), all catheters were identified in 94% of the plans. Simultaneous measurement of source-dosimeter distance and dwell time ensured full catheter identification in all plans ranging from 2 to 6 dwell positions. The number of dwell positions needed to uniquely identify all catheters was lower when the distance from the implant center was higher. CONCLUSIONS: The most efficient fingerprinting approach involved combining source-dosimeter distance (i.e., source tracking) and dwell time. The further the dosimeter is placed from the center of the implant the better it can uniquely identify catheters.

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.

Phase I trial of single-photon emission computed tomography-guided liver-directed radiotherapy for patients with low functional liver volume.

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312.

Comparison of reconstructed prompt gamma emissions using maximum likelihood estimation and origin ensemble algorithms for a Compton camera system tailored to proton range monitoring.

Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm. To this end, we exploit experimental and Monte Carlo (MC) simulation data acquired with the Polaris-J Compton Camera (CC) prototype. The differences between the proton beam range (RD) defined as the 80% distal dose fall-off and the PG range (RPG), obtained by fitting the distal end of the reconstructed profile with a sigmoid function, were quantified. A comparable performance of both reconstruction algorithms was found. For both experimental and simulated irradiation scenarios, the correlation between RD and RPG was within 5 mm. These values were consistent with the ground truth distance (RD-RPGg≈ 3 mm) calculated by using the expected PG emission available from MC simulation. Furthermore, shifts of 3 mm in the proton beam range were resolved with the MLEM algorithm by calculating the relative difference between the RPG for each reconstructed profile. In non-homogeneous targets, the spatial changes in the PG emission due to the different materials could not be fully resolved from the reconstructed profiles; however, the fall-off region still resembled the ground truth emission. For this scenario, the PG correlation (RD-RPG) varied from 0.1 mm to 4 mm, which is close to the ground truth correlation (3 mm). This work provides a framework for the evaluation of the range monitoring capabilities of a CC device for PG imaging. The two investigated image reconstruction algorithms showed a comparable and consistent performance for homogeneous and heterogeneous targets.

Dose Escalation for Pancreas SBRT: Potential and Limitations of using Daily Online Adaptive Radiation Therapy and an Iterative Isotoxicity Automated Planning Approach.

Purpose: To determine the dosimetric limitations of daily online adaptive pancreas stereotactic body radiation treatment by using an automated dose escalation approach. Methods and Materials: We collected 108 planning and daily computed tomography (CT) scans from 18 patients (18 patients × 6 CT scans) who received 5-fraction pancreas stereotactic body radiation treatment at MD Anderson Cancer Center. Dose metrics from the original non-dose-escalated clinical plan (non-DE), the dose-escalated plan created on the original planning CT (DE-ORI), and the dose-escalated plan created on daily adaptive radiation therapy CT (DE-ART) were analyzed. We developed a dose-escalation planning algorithm within the radiation treatment planning system to automate the dose-escalation planning process for efficiency and consistency. In this algorithm, the prescription dose of the dose-escalation plan was escalated before violating any organ-at-risk (OAR) dose constraint. Dose metrics for 3 targets (gross target volume [GTV], tumor vessel interface [TVI], and dose-escalated planning target volume [DE-PTV]) and 9 OARs (duodenum, large bowel, small bowel, stomach, spinal cord, kidneys, liver, and skin) for the 3 plans were compared. Furthermore, we evaluated the effectiveness of the online adaptive dose-escalation planning process by quantifying the effect of the interfractional dose distribution variations among the DE-ART plans. Results: The median D95% dose to the GTV/TVI/DE-PTV was 33.1/36.2/32.4 Gy, 48.5/50.9/40.4 Gy, and 53.7/58.2/44.8 Gy for non-DE, DE-ORI, and DE-ART, respectively. Most OAR dose constraints were not violated for the non-DE and DE-ART plans, while OAR constraints were violated for the majority of the DE-ORI patients due to interfractional motion and lack of adaptation. The maximum difference per fraction in D95%, due to interfractional motion, was 2.5 ± 2.7 Gy, 3.0 ± 2.9 Gy, and 2.0 ± 1.8 Gy for the TVI, GTV, and DE-PTV, respectively. Conclusions: Most patients require daily adaptation of the radiation planning process to maximally escalate delivered dose to the pancreatic tumor without exceeding OAR constraints. Using our automated approach, patients can receive higher target dose than standard of care without violating OAR constraints.

Endoscopic Ultrasound-Guided Fiducial Placement for Stereotactic Body Radiation Therapy in Patients with Pancreatic Cancer.

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. Most patients included in the study had either locally advanced disease (32 patients, 39%) or borderline resectable disease (29 patients, 35%). Eighty-two PC patients underwent the placement of 230 fiducial markers under EUS guidance. The technical success rate of the fiducial placement was 98%. No immediate EUS-related adverse events were reported. The average time to the simulation CT after fiducial placement was 3.1 days. Of the 216 fiducial markers used for the SBRT delivery, 202 fiducial markers were visible on both the simulation CT and the cone beam CT scan. A median dose of 40cGY was given to all the patients in five fractions. Of these, 41% of the patients reported no SBRT-related toxicities during the follow-up. Fatigue and nausea were the most reported SBRT-related toxicities, which were seen in 35% of the patients post-SBRT. Our results demonstrate that EUS-guided fiducial placement is safe and effective in target volume delineation, facilitating SBRT delivery in PC patients. Further clinical trials are needed to determine the SBRT-related survival benefits in patients with pancreatic cancer.

Dosimetric performance and array assessment of plastic scintillation detectors for stereotactic radiosurgery quality assurance.

PURPOSE: To compare the performance of plastic scintillation detectors (PSD) for quality assurance (QA) in stereotactic radiosurgery conditions to a microion-chamber (IC), Gafchromic EBT2 films, 60 008 shielded photon diode (SD) and unshielded diodes (UD), and assess a new 2D crosshair array prototype adapted to small field dosimetry. METHODS: The PSD consists of a 1 mm diameter by 1 mm long scintillating fiber (BCF-60, Saint-Gobain, Inc.) coupled to a polymethyl-methacrylate optical fiber (Eska premier, Mitsubishi Rayon Co., Ltd., Tokyo, Japan). Output factors (S(c,p)) for apertures used in radiosurgery ranging from 4 to 40 mm in diameter have been measured. The PSD crosshair array (PSDCA) is a water equivalent device made up of 49 PSDs contained in a 1.63 cm radius area. Dose profiles measurements were taken for radiosurgery fields using the PSDCA and were compared to other dosimeters. Moreover, a typical stereotactic radiosurgery treatment using four noncoplanar arcs was delivered on a spherical phantom in which UD, IC, or PSD was placed. Using the Xknife planning system (Integra Radionics Burlington, MA), 15 Gy was prescribed at the isocenter, where each detector was positioned. RESULTS: Output Factors measured by the PSD have a mean difference of 1.3% with Gafchromic EBT2 when normalized to a 10 × 10 cm(2) field, and 1.0% when compared with UD measurements normalized to the 35 mm diameter cone. Dose profiles taken with the PSD crosshair array agreed with other single detectors dose profiles in spite of the presence of the 49 PSDs. Gamma values comparing 1D dose profiles obtained with PSD crosshair array with Gafchromic EBT2 and UD measured profiles shows 98.3% and 100.0%, respectively, of detector passing the gamma acceptance criteria of 0.3 mm and 2%. The dose measured by the PSD for a complete stereotactic radiosurgery treatment is comparable to the planned dose corrected for its SD-based S(c,p) within 1.4% and 0.7% for 5 and 35 mm diameter cone, respectively. Furthermore, volume averaging of the IC can be observed for the 5 mm aperture where it differs by as much as 9.1% compared to the PSD measurement. The angular dependency of the UD is also observed, unveiled by an under-response around 2.5% of both 5 and 35 mm apertures. CONCLUSIONS: Output Factors and dose profiles measurements performed, respectively, with the PSD and the PSDCA were in agreement with those obtained with the UD and EBT2 films. For stereotactic radiosurgery treatment verification, the PSD gives accurate results compared to the planning system and the IC once the latter is corrected to compensate for the averaging effect of the IC. The PSD provides precise results when used as a single detector or in a dense array, resulting in a great potential for stereotactic radiosurgery QA measurements.

Validating plastic scintillation detectors for photon dosimetry in the radiologic energy range.

PURPOSE: Photon dosimetry in the kilovolt (kV) energy range represents a major challenge for diagnostic and interventional radiology and superficial therapy. Plastic scintillation detectors (PSDs) are potentially good candidates for this task. This study proposes a simple way to obtain accurate correction factors to compensate for the response of PSDs to photon energies between 80 and 150 kVp. The performance of PSDs is also investigated to determine their potential usefulness in the diagnostic energy range. METHODS: A 1-mm-diameter, 10-mm-long PSD was irradiated by a Therapax SXT 150 unit using five different beam qualities made of tube potentials ranging from 80 to 150 kVp and filtration thickness ranging from 0.8 to 0.2 mmAl + 1.0 mmCu. The light emitted by the detector was collected using an 8-m-long optical fiber and a polychromatic photodiode, which converted the scintillation photons to an electrical current. The PSD response was compared with the reference free air dose rate measured with a calibrated Farmer NE2571 ionization chamber. PSD measurements were corrected using spectra-weighted corrections, accounting for mass energy-absorption coefficient differences between the sensitive volumes of the ionization chamber and the PSD, as suggested by large cavity theory (LCT). Beam spectra were obtained from x-ray simulation software and validated experimentally using a CdTe spectrometer. Correction factors were also obtained using Monte Carlo (MC) simulations. Percent depth dose (PDD) measurements were compensated for beam hardening using the LCT correction method. These PDD measurements were compared with uncorrected PSD data, PDD measurements obtained using Gafchromic films, Monte Carlo simulations, and previous data. RESULTS: For each beam quality used, the authors observed an increase of the energy response with effective energy when no correction was applied to the PSD response. Using the LCT correction, the PSD response was almost energy independent, with a residual 2.1% coefficient of variation (COV) over the 80-150-kVp energy range. Monte Carlo corrections reduced the COV to 1.4% over this energy range. All PDD measurements were in good agreement with one another except for the uncorrected PSD data, in which an over-response was observed with depth (13% at 10 cm with a 100 kVp beam), showing that beam hardening had a non-negligible effect on the PSD response. A correction based on LCT compensated very well for this effect, reducing the over-response to 3%. CONCLUSION: In the diagnostic energy range, PSDs show high-energy dependence, which can be corrected using spectra-weighted mass energy-absorption coefficients, showing no considerable sign of quenching between these energies. Correction factors obtained by Monte Carlo simulations confirm that the approximations made by LCT corrections are valid. Thus, PSDs could be useful for real-time dosimetry in radiology applications.