Accurate dosimetry in small-field and flattening-filter-free (FFF) photon beams is essential for quality assurance in modern radiotherapy, but conventional detectors often face trade-offs in spatial resolution, stability, and response linearity. Diamond offers an attractive alternative due to its wide bandgap, tissue equivalence, and radiation hardness. In this work, we characterize high-purity single-crystal chemical vapor deposition (SC-CVD) diamond detectors under clinical 6 MV and 10 MV LINAC beams. We evaluate current-voltage behavior, dose linearity, temporal stability, and output factor performance in a water phantom. The detector exhibits excellent linearity across clinically relevant dose rates (Fowler exponent approximate to 0.997), submillimeter resolution, and <0.1 % signal drift over 60 s. The device provides stable response and sub-millimeter resolution, supporting its use in small-field dosimetry. These results establish a quantitative baseline for high-purity diamond sensors in clinical dosimetry and support their integration into future transparent x-ray beam imagers with sub 50 mu m spatial resolution.

BACKGROUND:Stereotactic body radiation therapy (SBRT) is increasingly used for bone metastases, but inconsistent endpoint definitions and reporting hinder evidence synthesis and clinical application. This study aimed to establish international consensus recommendations for standardised endpoints, definitions, and reporting parameters in SBRT studies for bone metastases. METHODS:A systematic review of prospective SBRT studies (2014-2024) informed a three-round modified Delphi consensus process conducted from 2024 to 2025. Consensus was predefined as at least 75% agreement. Candidate items were refined through iterative online surveys, qualitative feedback, and a final prioritisation vote by an international multidisciplinary expert panel. RESULTS:Of 114 invited experts, 82 from 20 countries participated in at least one Delphi round. Review of 58 prospective studies showed substantial variability in endpoint definitions, pain and toxicity assessment, radiological response criteria, and timing of outcome evaluation. The panel endorsed 46 reporting items (41 required, 5 recommended) and prioritised core endpoint sets across three clinical contexts: oligometastatic, oligoprogressive, and asymptomatic high-risk bone metastases. Strong consensus was reached for definitions of vertebral compression fracture (92%), time to salvage local therapy (93%), duration of pain response (92%), and time to local progression (90%); pain flare achieved 89% agreement. A revised clinical response framework (C-BRAC), introducing a stable disease category, achieved 91% agreement and was recommended for exploratory use alongside existing criteria. CONCLUSIONS:These recommendations provide a structured framework for designing and reporting SBRT studies in bone metastases and may improve consistency, comparability, and future guideline development.

A novel Bragg peak FLASH proton radiation therapy facility using the fixed-magnetic-field synchrotron with kinetic energy range between 10 and 250 MeV will be built at Stony Brook University Hospital. The permanent magnet synchrotron has the shape of a racetrack where the two arcs are made of combined nonlinear fields magnets. This design can provide fixed betatron tunes for the extraordinary kinetic energy, and allow FLASH radiation to be delivered at 40 Gy/s in 100 ms. The permanent magnet accelerator should reduce overall operating cost. This facility can fit into a 7 × 11 m2 space. As the first step to investigate proton beam lateral profiles and penetration distribution in tissue, we tested physical properties of proton FLASH beams starting from lower energy 28 MeV beam. The beam width was 7.45 mm in both the horizontal and vertical directions. The measured Bragg peak depth was 6.5 mm and peak gap was 8.97 mm. This particular low energy beam distribution would be suitable for the planned small animal studies.

[This corrects the article DOI: 10.1016/j.adro.2025.101881.].

Background: High-dose-rate (HDR) brachytherapy delivers focused radiation to tumors using radioactive sources like Ir-192, commonly used in prostate, breast, gynecologic, and skin cancers. It serves as a primary treatment or a boost after external beam radiation therapy. Precise applicator placement, accurate source positioning, and appropriate dwell times are critical for effective treatment. While imaging confirms planned source and applicator locations, real-time validation during treatment remains a challenge. Purpose: This study evaluates the dosimetric effects of HDR brachytherapy applicator misalignment, source mispositioning, and dwell time errors on the target and organs at risk (OARs) to propose strategies for minimizing these issues. Methods: Gynecologic HDR treatments were planned using the Henschke applicator and BrachyVision. Plans were analyzed in RadCalc, where applicator misalignment, source mispositioning, and dwell time errors were simulated. Volumetric doses to the target and OARs were compared between BrachyVision and RadCalc. Results: Applicator misalignment in all directions similarly affected target coverage, with lateral misalignments exceeding 3 mm significantly impacting the small bowel. Anterior and posterior misalignments predominantly affected the bladder and rectum, with 5 mm movements having the most significant bowel impact. Superior and inferior misalignments, interpreted as source mispositioning, caused the largest rectal dose deviations at displacements above 3 mm. Dwell time errors impacted all OARs, most notably the sigmoid, and reduced target coverage by up to 6 percent per second. Conclusions: Minimizing applicator misalignment, source mispositioning, and dwell time errors is crucial for accurate HDR brachytherapy dose delivery and adherence to dose constraints. The observed reductions in target coverage may compromise local tumor control, while increased dose to organs at risk, particularly the small bowel, bladder, and rectum, may increase the risk of radiation-related toxicity. These findings highlight the importance of accurate treatment delivery and support the future development of real-time verification techniques in HDR brachytherapy.

Pain from spinal metastases can result in significant impact to patients' quality of life. Conventional external beam radiation therapy (cEBRT) has long been shown to be effective in the pain control of patients with spinal metastases. With the advancement in radiation therapy, stereotactic body radiation therapy (SBRT) has been increasingly adopted for the treatment of spinal metastases. Multiple randomised controlled trials (RCT) have been performed to evaluate whether SBRT provides better pain relief compared to cEBRT. Previous meta-analyses showed that SBRT have significantly better complete pain response at 3 months compared to cEBRT. This report updates meta-analyses by incorporating the complete pain response data obtained from personal communication with the NRG Oncology Radiation Therapy Oncology Group (RTOG) 0631 principal investigator and the recently published RCT by Guckenberger et al. The results demonstrate that the results for complete pain response at 3 months have now changed and no longer favour SBRT. It is postulated that inconsistent definitions and reporting of study endpoints, specifically regarding vertebral compression fractures induced by radiation therapy, could be possible reasons for the difference in meta-analyses results. A consensus for standardizing study endpoints for future clinical trials in SBRT for painful bone metastases is needed to allow for better interpretation of study results.

Purpose:Radiation-induced morphea (RIM) is a very rare but devastating side effect of breast radiation therapy, characterized by progressive skin induration, pain, and discoloration, with no effective treatments currently available. This is a proof-of-concept study that aims to identify radiomic features from pretreatment magnetic resonance imaging (MRI) scans associated with the development of RIM in patients with breast cancer undergoing radiation therapy. Methods and Materials:This is a retrospective analysis of a single institutional registry of patients who received diagnosis of RIM following breast radiation therapy from 2008 to 2022. Clinical and histopathological data were reviewed. Pretreatment MRI scans of these patients and matched controls were analyzed. Radiomic features were extracted from whole breast and fibroglandular tissue regions of interest. A total of 528 radiomic features were compared between patients who developed RIM and those who did not, using the Wilcoxon rank-sum test to identify statistically significant differences. Results:We evaluated 10 patients who received clinical diagnosis of RIM, with a mean age of 63 years (range, 44-75 years). Among these, 7 patients had biopsy-proven RIM. Both clinical and histologic findings were correlated with radiomic analyses. Forty percent of the patients had a history of autoimmune disorders, including hypothyroidism, Graves' disease, systemic sclerosis, and systemic lupus erythematosus. Radiomic analysis identified 11 significant features, primarily related to tissue structure and texture. Nine of these features were from the contralateral breast, and 2 were from the ipsilateral breast. Conclusions:This is a pilot study on a small sample that demonstrates that radiomic features extracted from pretreatment MRI scans can serve as potential predictors for the development of RIM in patients with breast cancer. The integration of clinical and histopathological data with radiomic analysis highlights the distinct changes in breast tissue architecture that precede RIM onset. These findings pave the way for the early identification of patients at risk, allowing for more personalized surveillance and management strategies.

Purpose:This systematic review evaluated variability in study endpoints among stereotactic body radiation therapy (SBRT) studies for bone metastases. Heterogeneity in endpoint definitions and reporting may hinder cross-study comparability and the establishment of consistent treatment protocols. Methods:A comprehensive search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials identified prospective studies, including cohort studies, phase I/II trials, and randomised controlled trials (RCTs), published between 2014-01-01 and 2024-11-12. Studies were eligible if they: (1) included adult patients with bone metastases treated with SBRT, (2) were prospective, and (3) reported pre-defined clinical endpoints. Results:A total of 58 studies were included: eight cohort studies, 37 phase I/II trials, and 13 RCTs. Pain-related endpoints were the most frequently reported primary endpoints, with pain response reported in 28% (16 studies). Other primary endpoints included toxicities (22%, 13 studies), survival metrics (12%, seven studies), and local control (9%, five studies). Secondary endpoints varied, with survival-related endpoints reported in 60% (35 studies) and toxicity in 41% (24 studies). Endpoint selection differed by clinical scenario, reflecting distinct objectives such as symptom relief, local control, and progression-free survival. Variability in definitions for endpoints, particularly pain flare and vertebral compression fracture, along with inconsistent radiological response criteria, was noted. Conclusion:Considerable heterogeneity in endpoint selection, definitions, and measurement tools across SBRT reflects diverse clinical objectives. Consensus-driven standardisation of endpoints, response criteria, and follow-up schedules is essential to enhance comparability, facilitate evidence synthesis, and support integration of SBRT research findings into clinical practice.

Peer review is an essential part of the patient treatment process that examines and, where necessary, recommends revisions to clinical data, therapeutic parameters, and potential alternative approaches to treatment. Our hypothesis is that artificial intelligence (AI) and machine language technologies can enhance peer-review efficacy by screening cases for potential treatment interruptions caused by re-planning and treatment cessation. Fifty-five features of clinical and therapeutic parameters from 3881 radiotherapy patients (7142 plans) treated from 2014 to 2021 were used as input for two AI models: a multivariable least absolute shrinkage and selection operator (LASSO) logistic regression model and a pattern recognition feed-forward neural network (NN). The dataset was split into 70% training and 30% testing, with the training set divided into five groups for cross-validation. Analysis was performed on the full cohort and on subsets based on treatment site. Performance metrics of accuracy, sensitivity, and specificity were calculated. Overall, 8.1% of all cases had treatment interruptions, most commonly in the head and neck region compared to other sites (19% vs 6%-9%, P<.01). For the LASSO model, test set sensitivity, specificity, and accuracy ranged from 37%-70%, 59%-78%, and 60%-76%, respectively, with higher specificity than sensitivity for site subsets. For the NN model, test set sensitivity, specificity, and accuracy ranged from 41%-68%, 53%-79%, and 53%-78%, respectively. Both models demonstrated the highest accuracy in the brain subset. For the full cohort, NN accuracy (58%) was similar to LASSO (60%). The largest accuracy differences between LASSO and NN were in the lung/breast/chest (LASSO: 71% vs NN: 57%) and spine/extremity (LASSO: 66% vs NN: 54%) subsets. Our results provide proof-of-concept that AI- and ML-based technologies have potential as screening tools to aid peer review in radiation oncology. Early identification of patients at risk for radiation therapy interruptions using these tools could translate into higher treatment completion rates. The study is being continued to include more clinical features and to optimize model hyperparameters.

Abstract Background: Preclinical studies with transplanted GL261 glioma in mouse brain treated with radiosurgery and checkpoint blockade showed dramatic improvement of tumor cure and prolonged survival, associated with activated macrophage infiltration in the tumor site. We perform phase I study in patients with glioblastoma to assess safety and local tumor response by combined radiosurgery and checkpoint inhibitor given during window-of-opportunity prior to surgical resection, and progression-free survival and overall survival. Method and Procedure: Biopsy-proven WHO grade 4 glioblastoma patients were enrolled to the study (NCT05423210). Patients were treated with two doses of intravenous Atezolizumab at the beginning and at the end of the two-week period, concomitantly with fractionated radiosurgery (8 Gy x 4 to the grossly enhancing tumor) over 4 days during the course of 2 weeks. Maximal safe surgical resection was subsequently performed within 2 weeks from completion of radiosurgery. Adjuvant radiation 50 Gy over 5 weeks and Temozolomide were given as per standard treatment of GBM along with continuation of Atezolizumab until unacceptable toxicity or tumor progression. The initial biopsy specimen and surgical specimen were collected for laboratory examination of immune profiles. Results: The study plans to enroll total 12 histologically confirmed CNS WHO Grade 4 GBM patients also planned for surgical resection. Six patients were enrolled after consenting so far. There was no grade 3 or 4 toxicity from the window-of-opportunity combination treatment, all 6 patients successfully completing the treatment. Three patients reported fatigue and two patients had skin rash. There was one patient experiencing metallic taste. At present, five patients survive progression-free at 25, 18, 16 and 6 months since the treatment. An unanticipated finding is that there was significantly less intraoperative bleeding in the surgical field than usual brain tumor surgery. Conclusion: Preoperative fractionated radiosurgery and Atezolizumab was well tolerated so far, and appear to improve tumor control. We continue enroll the patients. Lab study of immune cell profile is underway. Citation Format: Samuel Ryu, Alexander Stessin, Charles Mikell, Agnieszka Kowalska, Roberta Seidman, Steven West, Kartik Mani. Interim report of Phase I study of window-of-opportunity fractionated stereotactic radiotherapy combined with checkpoint blockade prior to surgical resection for newly diagnosed glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B010.

Radiomic graph analysis of pretreatment CT enables holistic analysis of head and neck squamous cell carcinoma tumors and their surrounding environment, showing good performance in local-regional recurrence and distant metastasis prediction and unique model interpretability.

Purpose Stereotactic radiosurgery/radiotherapy (SRS/SRT) has increasingly been used to treat brain metastases. However, the development of distant brain metastases (DBMs) in the untreated brain remains a serious complication. We sought to develop a spatially aware radiomic signature to model the time-to-DBM development in a cohort of patients leveraging pre-treatment magnetic resonance imaging (MRI) and radiotherapy treatment planning data including radiation dose distribution maps. Methods and Materials We retrospectively analyzed a cohort of 105 patients with brain metastases treated by SRS/SRT with pre-treatment multi-parametric MRI (T1, T1 post-contrast, T2, FLAIR). 3D radiomic features were extracted from each MRI sequence within 5 isodose regions of interest (ROIs) identified via radiation dose distribution maps and gross target volume (GTV) contours. Clinical features including patient performance status, number of lesions treated, tumor volume, and tumor stage were collected to serve as a baseline for comparison. Cox proportional hazards (CPH) modelling and Kaplan Meier analysis were used to model time-to-DBM development. Results CPH models trained using radiomic features achieved a mean concordance index (c-index) of 0.63 (std=0.08) compared to a c-index of 0.49 (std=0.09) for CPH models trained using clinical factors. A CPH model trained using both radiomic and clinical features achieved a c-index of 0.69 (std=0.08). The identified radiomic signature was able to stratify patients into distinct risk groups with statistically significant differences (p=0.00007) in time-to-DBM development as measured by log-rank test. Clinical features were unable to do the same. Radiomic features from the peritumoral 50-75% isodose ROI and GTV region were most predictive of DBM development. Conclusions Our results suggest that radiomic features extracted from pre-treatment MRI and multiple isodose ROIs can model time-to-DBM development in patients receiving SRS/SRT for brain metastases, outperforming clinical feature baselines. Notably, we believe we are the first to leverage SRS/SRT dose maps for ROI identification and subsequent radiomic analysis of peritumoral and untargeted brain regions using multi-parametric MRI. We observed that the peritumoral environment may be implicated in DBM development for SRS/SRT-treated brain metastases. Our preliminary results might enable the identification of patients with predisposition to DBM development and prompt subsequent changes in disease management.

Purpose/Objective(s) Stereotactic body radiation therapy (SBRT) represents a paradigm shift in the precision oncologic management of spinal metastases, leveraging advanced image-guidance and motion management techniques to deliver ablative doses with sub-millimetric accuracy. This study assesses the comparative efficacy and safety of various SBRT regimens for spinal metastases using a network meta-analysis (NMA) approach, integrating both direct and indirect evidence from randomized controlled trials (RCTs). Materials/Methods A comprehensive search of Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was conducted through March 1, 2023 to identify RCTs comparing SBRT with conventional external beam radiotherapy (cEBRT) in treating spinal metastases. The primary outcomes included overall and complete pain response, local tumor progression, and overall survival. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random-effects model. Heterogeneity was assessed with the Cochran Q and I² statistics, and the P-score method was employed to rank treatment efficacy. Results Three RCTs involving 642 patients were included. The SBRT regimens were 24 Gy in a single fraction, 24 Gy in 2 daily fractions, and 16 or 18 Gy in a single fraction, all compared against cEBRT. The regimen of 16 or 18 Gy in a single fraction showed a statistically significant lower overall pain response at 3 months compared to 24 Gy in 2 daily fractions (RR 0.58, 95% CI, 0.37–0.89; P = 0.013), with no significant differences at 6 months. Complete pain response at 3 and 6 months did not significantly differ across SBRT dose-fractionations, with data missing from one trial. Side effects were rare and similar across regimens, although 24 Gy in 2 fractions was associated with fewer compression fractures compared to 24 Gy in a single fraction (RR 0.11, 95% CI, 0.01–0.98; P = 0.047). There were no significant differences in local progression and overall survival at 6 months across fractionation regimens. Conclusion This NMA suggests that different SBRT regimens offer comparable safety profiles and efficacy for the treatment of spinal metastases, with specific dose-fractionations showing advantages in certain outcomes. These findings underscore the necessity of tailored treatment strategies to optimize patient outcomes. Future research should prioritize elucidating patient and disease characteristics that predict the most benefit from specific SBRT protocols, thereby enhancing personalized care in spinal metastases management.

Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter. Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter. Main Results: Couch movement magnitude (mean +/- SD) in vertical, longitudinal and lateral directions were -0.7 +/- 2.5, 1.4 +/- 2.9 and -0.1 +/- 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 +/- 2%) and less than 10% for PTV (-10 +/- 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: Delta D10%:184 +/- 466 cGy, Delta D40%:139 +/- 241 cGy, Bowel: Delta D1 cm3:54 +/- 129 cGy; Delta D5 cm3:44 +/- 116 cGy, Urethra: Delta D0.03 cm3:1 +/- 1%). Doses to the rectum tended to decrease (Rectum: Delta D1 cm3:-206 +/- 564 cGy, Delta D10%:-97 +/- 426 cGy; Delta D20%:-50 +/- 251 cGy). Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.

Purpose: The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. Materials/methods: Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40-50 Gy/ 20-25 fractions). SBRT dose was 30-40 Gy in 5 fractions for patients treated with SBRT alone and 25-32 Gy in 4-5 fractions for those treated with SBRT + WBRT. LC and overall survival (OS) were estimated using KaplanMeier curves. Response was also assessed using RECIST guidelines. Results: Median follow-up was 32 (range: 3.4-70.4) months. Imaging at median 2.2 (0.6-8.1) months post-SBRT showed median 43.2 % (range: 2-100 %) decrease in the largest diameter and median 68.7 % (range: 27.9-100 %) SUV reduction. There were 3 cases of local progression at 8.7-10.6 months. Estimated LC was 100 % at 6 months and 71.6 % at 12, 24 and 36 months. Estimated median OS was 100 % at 6 months, 76.9 % at 12 months, and 61.5 % at 24 and 36 months. Acute toxicity (n = 13; 92.9 %) included grade (G)1 (n = 8), G2 (n = 4), and G4 (necrosis; n = 1). Late toxicity included G2 edema (n = 1) and G4 necrosis (n = 2, including 1 consequential late effect). Only patients treated with SBRT + WBRT experienced acute/late G4 toxicity, managed with resection or steroids. Conclusions: SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n = 2) occurred in the SBRT + WBRT group, it was successfully salvaged.

Purpose: Stereotactic radiosurgery/radiation therapy (SRS/SRT) increasingly has been used to treat brain metastases. However, the development of distant brain metastases (DBMs) in the untreated brain remains a serious complication. We sought to develop a spatially aware radiomic signature to model the time-to-DBM development in a cohort of patients leveraging pretreatment magnetic resonance imaging (MRI) and radiation therapy treatment planning data including radiation dose distribution maps. Methods and Materials: We retrospectively analyzed a cohort of 105 patients with brain metastases treated by SRS/SRT with pretreatment multiparametric MRI (T1, T1 postcontrast, T2, fl uid -attenuated inversion recovery). Three-dimensional radiomic features were extracted from each MRI sequence within 5 isodose regions of interest (ROIs) identi fi ed via radiation dose distribution maps and gross target volume (GTV) contours. Clinical features including patient performance status, number of lesions treated, tumor volume, and tumor stage were collected to serve as a baseline for comparison. Cox proportional hazards (CPH) modeling and Kaplan - Meier analysis were used to model time-to-DBM development. Results: CPH models trained using radiomic features achieved a mean concordance index (c -index) of 0.63 (standard deviation [SD], 0.08) compared with a c -index of 0.49 (SD, 0.09) for CPH models trained using clinical factors. A CPH model trained using both radiomic and clinical features achieved a c -index of 0.69 (SD, 0.08). The identi fi ed radiomic signature was able to stratify patients into distinct risk groups with statistically signi fi cant differences ( P = .00007) in time-to-DBM development as measured by log -rank test. Clinical features were unable to do the same. Radiomic features from the peritumoral 50% to 75% isodose ROI and GTV region were most predictive of DBM development. Conclusions: Our results suggest that radiomic features extracted from pretreatment MRI and multiple isodose ROIs can model timeto-DBM development in patients receiving SRS/SRT for brain metastases, outperforming clinical feature baselines. Notably, we believe we are the fi rst to leverage SRS/SRT dose maps for ROI identi fi cation and subsequent radiomic analysis of peritumoral and untargeted brain regions using multiparametric MRI. We observed that the peritumoral environment may be implicated in DBM development for SRS/SRT-treated brain metastases. Our preliminary results might enable the identi fi cation of patients with predisposition to DBM development and prompt subsequent changes in disease management.

Background When arsenic trioxide (ATO) was combined with radiation for treatment of transplanted murine gliomas in the brain, tumor response improved with disrupted tumor blood flow and survival was significantly prolonged.Methods Total of 31 patients with newly diagnosed glioblastoma were accrued to a multi-institutional, NCI-funded, phase I study to determine the maximum tolerated dose (MTD) of ATO administered with radiation. Secondary objectives were survival and pharmacodynamic changes in perfusion on magnetic resonance imaging (MRI). Patients (unknown MGMT and IDH status) received ATO either once or twice weekly during radiation without concurrent or adjuvant temozolomide.Results Median age: 54.9 years, male: 68%, KPS >= 90: 77%, debulking surgery: 77%. Treatments were well-tolerated: 81% of patients received all the planned ATO doses. Dose-limiting toxicities included elevated liver function tests, hypokalemia, and edema. The MTD on the weekly schedule was 0.4 mg/kg and on the biweekly was 0.3 mg/kg. The median survival (mOS) for all patients was 17.7 months. Survival on the biweekly schedule (22.8 months) was longer than on the weekly schedule (12.1 months) (P = .039) as was progression-free survival (P = .004). Similarly, cerebral blood flow was significantly reduced in patients treated on the biweekly schedule (P = .007).Conclusions ATO with standard radiation is well tolerated in patients with newly diagnosed glioblastoma. Even without temozolomide or adjuvant therapy, the overall survival of all patients (17.7 months) and especially patients who received biweekly ATO (22.8 months) is surprising and accompanied by pharmacodynamic changes on MRI. Further studies of this regimen are warranted. Glioblastoma (GBM) is a common form of brain cancer. Most patients with GBM eventually die from the disease even after aggressive treatment with surgery, radiation, and chemotherapy. Studies in mice have shown that a compound called arsenic trioxide (ATO) could improve the ability of radiation to kill tumor cells. This study was designed to test the safety of ATO in human patients with GBM and find out the best treatment dose. To do this, the authors recruited 31 patients in a safety trial of the drug. Their results demonstrate that most patients were able to take the drug without major side effects. Patients taking twice a week survived significantly longer than those taking it weekly. Larger clinical trials are needed to confirm these findings.