Vertebral compression fracture (VCF) is a potential serious complication of spinal stereotactic body radiotherapy (SBRT). Previously we noted a correlation between advanced Spinal Instability Neoplastic Score (SINS), tumor-related endplate (EP) disruption, and certain primary pathologies with increased VCF risk. Here, we report on an expanded patient cohort to further examine EP disruption’s role in VCF. This retrospective cohort study was conducted at a single institution, gathering demographic and treatment data from patients who underwent spinal SBRT between 2013 and 2020. EP disruption was identified on pre-SBRT CT scans. Chronic steroid use was defined as steroids administered for 4 weeks or more. The 1-year cumulative incidence of VCF was evaluated by follow-up MRI and CT scans at 3-month intervals post-treatment. Based on multivariate analysis, a nomogram was created using four independent predictors: EP disruption, steroid use, SINS ≥ 7, and adverse histology. A total of 173 patients were included. The median follow-up was 19 months. Approximately 69 patients (40

Purpose. Commercial electron FLASH platforms deliver ultra-high dose rate doses at discrete combinations of pulse parameters including pulse width (PW), pulse repetition frequency (PRF) and number of pulses (N), which dictate unique combinations of dose and dose rates. Additionally, collimation, source to surface distance, and airgaps also vary the dose per pulse (DPP). Currently, obtaining pulse parameters for the desired dose and dose rate is a cumbersome manual process involving creating, updating, and looking up values in large spreadsheets for every treatment configuration. This work presents a pulse parameter optimizer application to match intended dose and dose rate precisely and efficiently. Methods. Dose and dose rate calculation methods have been described for a commercial electron FLASH platform. A constrained optimization for the dose and dose rate cost function was modelled as a mixed integer problem in MATLAB (The MathWorks Inc., Version9.13.0 R2022b, Natick, Massachusetts). The beam and machine data required for the application were acquired using GafChromic film and alternating current current transformers (ACCTs). Variables for optimization included DPP for every collimator, PW and PRF measured using ACCT and airgap factors. Results. Using PW, PRF, N and airgap factors as parameters, a software was created to optimize dose and dose rate, reaching the closest match if exact dose and dose rates are not achievable. Optimization took 20 s or less to converge to results. This software was validated for accuracy of dose calculation and precision in matching prescribed dose and dose rate. Conclusion. A pulse parameter optimization application was built for a commercial electron FLASH platform to increase efficiency in dose, dose rate, and pulse parameter prescription process. Automating this process reduces safety concerns associated with manual look up and calculation of these parameters, especially when many subjects at different doses and dose rates are to be safely managed.

Background: Ventricular arrhythmias (VAs) are the most lethal arrhythmias. Established therapies to prevent VAs include anti-arrhythmic drugs (AADs) and catheter ablation (CA). For patients with recurrent VAs despite AADs and CA, novel therapies such as cardiac sympathetic denervation (CSD) and stereotactic body radiation therapy (SBRT) exist. This study reports outcomes of CSD and SBRT at a tertiary care academic center. Methods: Study comprises all patients undergoing CSD or SBRT at one center from 10/2018 - 10/2021. Patients with less than 2 months of follow-up were excluded. Retrospective chart review was performed to collate data for demographics, clinical characteristics, arrhythmia burden before and after novel therapies (maximum 12 months), and treatment complications. VA burden in the form of anti-tachycardia pacing (ATP) episodes and defibrillator shocks was assessed as primary efficacy outcome. Treatment complications were assessed as primary safety outcome. Results: Overall, 25 patients underwent novel therapies for VAs, and 13 were excluded for insufficient follow up. Five, 4, and 3 patients underwent CSD, SBRT, and both, respectively. Median age was 66 years (55-72), and 10 (83%) were male. Median left ventricular ejection fraction was 30% (25%-34%). Four patients (33%) had ischemic cardiomyopathy. Median number of AADs and CA prior to novel therapies was 3 (2-5) and 1 (0-2), respectively. Follow up was available for a median of 12 (12-12) months before and 12 (9-12) months after treatment. Overall, VA burden was reduced in 11 of 12 patients (Figure 1). Mean number of ATP and shock episodes was significantly lower after novel therapies (39±43 vs 3±6; p= 0.008). No procedure-related complications were observed. Conclusion: Novel VA treatment modalities are associated with a significantly reduced arrhythmia burden in this single center study. There is a promising role of these therapies as an adjunct to the existing treatment modalities of CA and AADs.

K. Dibs: None. J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.A. Olausson: None. E. Bourekas: None. D. Boulter: None. A.S. Ayan: None. E.R. Cochran: None. V. Yildiz: None. J.C. Grecula: None. A.L. Arnett: None. R. Raval: None. S. Beyer: None. T. Scharschmidt: None. J.B. Elder: None. A. Chakravarti: None. E. Mendel: None. D.M. Blakaj: None.

A 3-D dosimeter fills the need for treatment plan and delivery verification required by every modern radiation-therapy method used today. This report summarizes a proof-of-concept study to develop a water-equivalent solid 3-D dosimeter that is based on novel radiation-hard scintillating material. The active material of the prototype dosimeter is a blend of radiation-hard peroxide-cured polysiloxane plastic doped with scintillating agent P-Terphenyl and wavelength-shifter BisMSB. The prototype detector was tested with 6 MV and 10 MV x-ray beams at Ohio State University's Comprehensive Cancer Center. A 3-D dose distribution was successfully reconstructed by a neural network specifically trained for this prototype. This report summarizes the material production procedure, the material's water equivalency investigation, the design of the prototype dosimeter and its beam tests, as well as the details of the utilized machine learning approach and the reconstructed 3-D dose distributions.

Hypofractionation can be beneficial for patients with prostate cancer, but higher dose per fraction with reduced margins can be difficult to achieve due to intrafraction motion. The goal of this prospective study is to validate the use of periodic imaging during treatment with fiducial marker detection algorithm by using radiofrequency transponders for prostate cancer patients undergoing treatment for radiation therapy. Kilovoltage (kV) imaging collected during radiotherapy treatment automatically detect fiducial markers from images and compares their real-time location to their expected location from the treatment plan. This information is useful clinically to pause the treatment beam if the region of interest has moved during the course of treatment. We are currently accruing male patients treated for prostate cancer with three implanted beacons emitting a radiofrequency. Ten (10) patients are being accrued for the study and data is collected for five (5) treatment sessions for each patient. Periodic imaging during treatment with fiducial marker detection algorithm was used to collect kV images during the patient treatment. Since the treatment plans are arc-based, an image was collected every 10 degrees of gantry rotation. A typical prostate treatment plan involves two full treatment arcs for approximately 72 images per fraction. The position data from the periodic imaging during treatment with fiducial marker detection algorithm was compared to the positions from the data from the radiofrequency beacons projected on KV detector plane to evaluate the positional accuracy of the system. We present the preliminary data from the first five patients which include data reported from beacons detected within a 5 mm threshold (N = 4335). The analysis of the data using a two-sample t-test fail to reject the null hypothesis at 0.05 significance level (P = 0.714) meaning that the detected marker locations are the same. The difference between the two technologies was found to be 0 ± 1.4 mm in the x-direction and 0.5 ± 1.8 mm in the y-direction. The commercially available fiducial marker detection algorithm allows imaging during treatment to automatically detect fiducial markers and compare their real-time location to their expected location from the treatment plan based on kV images. Determination of fiducial marker location between periodic imaging during treatment with fiducial marker detection algorithm could provide a cost-effective alternative to an additional real-time tracking and positioning system. This technology can provide an alternate solution to patients with contraindications to the use or implantation of beacons emitting a radiofrequency.

Radiation treatment deviations from the prescribed dose may lead to unexpected radiation treatment complications or long-term consequences including worse overall outcomes. Yet factors contributing to these radiation treatment (RT) deviations are often not explored in a systemic fashion, and there is paucity of data available to evaluate factors associated with these events. We conducted an IRB approved, single-institution retrospective review of all patients with dosimetric RT deviations from 2016-2019. Type of deviations were separated into 4 categories: set-up (improper placement of the bolus, table board, dental stent, head rest, rails, vac bag, or body part), localization (table shift, patient positioning on imaging, or SSD), procedural (gantry-table collisions, 1 isocenter for 2 distinct PTVs, incorrectly cut bolus, or free breathing instead of breath hold), or wrong site. Patient characteristics (disease site, stage, and histology), late toxicity, overall survival (OS), and RT details including the planned and actual treatment dose and fractions were collected. Of the 55 patients identified, 34 (62%) patients were treated definitively and 21 (38%) were treated with palliative intent. Most common treatment sites included 21 (38.2%) breast/chest wall, 12 (21.8%) bone, 10 (18.2%) head and neck. The majority of events were set-up errors (n = 40, 73%), followed by localization (n = 8, 14.5%), procedural (n = 6, 11%), and wrong site (n = 1). Fourteen (25%) patients at the time of the treatment deviation were receiving concurrent treatment to 2+ sites. For treatment plans that were recreated with the actual treatment delivery dose, the median absolute percentage difference in total PTV dose was 0.41% (range 0-7%). Only 1 case met state criteria as a reportable radiation dose deviation. The median number of days from start of RT to event was 5 (range 0-48 days), with the first RT deviation events occurring significantly later in the treatment course for palliative patients (60% through treatment time) compared to definitive intent (22% through treatment time) (p = 0.00222). No late toxicities were attributed to dosimetric deviations. For patients treated with palliative RT, 12 (57%) died with a median of 2 months (range 0.8-6 months). For patients treated definitively, median follow-up was 19 months (range 2-48 months). Radiation treatment deviation events represent an opportunity for quality improvement in radiation treatment planning and delivery. The most common events at our institution represent set-up error, but overall, the impact on total PTV percentage differences is minimal and not associated with a treatment site, prescription dose, or late toxicity. Of note, RT deviations occur significantly later in the course of palliative treatments versus definitive treatments, suggesting an element of procedural learning in definitive radiation treatment course.

To identify post-treatment dosimetric and pre-treatment clinical factors that predict for Yttrium-90 (90Y) radioembolization (RE) response for patients with hepatic metastases from colorectal cancer. From January 2014-October 2017, 21 patients treated at our institution with biopsy confirmed colon adenocarcinoma hepatic metastases treated with one (38%) or two (62%) courses of 90Y RE were retrospectively identified and 54 hepatic tumors were identified with at least 6 month of imaging follow up. Following retrospective tumor and liver contouring, dose-volume histograms (DVHs) were calculated from the same day post-treatment Bremsstrahlung SPECT scan to calculate 90Y dose deposition. Dosimetric factors (maximum dose, minimum dose, tumor V50%, mean tumor dose (MTD), tumor volume, liver volume, number of RE treatments, liver mean dose) and clinical characteristics were associated with disease control rate (DCR) (i.e. complete response, partial response, or stable disease via RECIST criteria) at 6 months. Receiver operating characteristic (ROC) curves were generated to determine area under the curves (AUC) and optimal cutoff points to predict for local tumor control. Local progression free survival (LPFS) and overall survival (OS) analyses were performed (Kaplan-Meier). DCR at 6 months was 64.8% (35/54). The two year OS rate for patients who had ≥ 1 non-responsive tumor(s) (n=11) was 11.8% vs. 52.3% in patients with complete disease control (n=10) (log rank p=0.021). Tumor responders had a significantly higher max dose, MTD, and V50% compared to non-responders, (p<0.05). Clinical factors which were significantly higher in responsive tumors were: older age, longer time from diagnosis to RE, lower number of prior systemic therapies, and prior liver directed therapy (e.g. ablation, surgery, or liver infusion pump). The ROC curve for 6 month response and MTD AUC was significant (p=0.007), and the optimal cutoff point was determined to be 50 Gy. The MTD was 57.4 Gy (SD, 18.4) vs. 42.1 Gy (SD, 14.6) for responders vs. non-responders, respectively (two-tailed t-test p=0.005). Two-year local control was 57.3% vs 21.2% for tumors treated with a MTD ≥50 Gy vs <50 Gy respectively (log rank p=0.003). On univariate cox regression analysis the significant predictors for LPFS were: increasing max tumor dose, MTD ≥50 Gy, increasing V50%, increasing age, shorter time from diagnosis to RE, and prior liver directed therapy. On multivariate cox regression analysis, the only two significant variables for LPFS were prior liver directed therapy and MTD ≥50 Gy. We report MTD ≥ 50 Gy and prior liver directed therapies predict for higher local control rates following 90Y RE. These results provide a rationale to include pre-90Y RE tumor contouring and optimizing dose prescription to reach a minimum MTD of 50 Gy. Further studies are required to validate these findings.

Salivary gland shrinkage is known to occur with radiation therapy (RT) for head and neck cancer. Adaptive Radiation Therapy (ART) is commonly performed during the course of Intensity-Modulated Radiation Therapy (IMRT) due to weight loss and/or tumor shrinkage. Our goal was to investigate changes in parotid (PG) and submandibular gland (SMG) volumes measured on initial and replanning CT. We hypothesize that dose received by gland at the time of replan predicts for quantitative gland volume reduction. Replanning thus has the potential to reduce this effect which ultimately may reduce severity of xerostomia. We analyzed 100 patients who underwent adaptive re-planning (200 plans) between December 2014 to August 2017. Volumetric Modified Arc Therapy (VMAT) based IMRT was used in all. All patients had an initial CT simulation scan (Plan 1) used for radiation planning and a subsequent new CT simulation for adaptive replan (Plan 2). Dose-volume histograms were used to measure mean and maximum doses to right and left PG and SMG. We then correlated these doses to PG and SMG volume changes noted at the time of replan (PG1-PG2; SMG1-SMG2). Univariate and multivariate analyses were performed to identify factors contributing to gland volume changes. Tumor site included 9 oral cavity, 50 oropharynx, 14 Larynx, 7 Nasopharynx, and 20 others. Treatments were definitive chemo-RT in 67%, adjuvant chemo-RT in 20%, or adjuvant RT alone in 10%. Chemo used was Cisplatin-based 36%, Carboplatin-based 22%, or Cetuximab-based in 28%. Median total RT dose was 70 Gy (60-70 Gy in 30-35 daily fractions). Median time to performing replan was at fraction #21 (42 Gy) and around day 37 of therapy (13-66 days). Mean weight loss at time of replan was -4.3% (-21.3 to +17.5%). Analysis included 181 PG and 116 SMG. Mean dose received at time of replan with corresponding volume change: RPG = 1548 cGy, -13.6%; LPG = 1647 cGy, -14.6%; RSMG = 3359 cGy, -12.7%; LSMG = 3366 cGy, -14.4%. The correlation values of dose received and volume change: RPG r = 0.17, LPG r = -0.21, RSMG r = -0.33, and LSMG r = -0.27 (all with P<.05 except RPG, P=.13). Anatomic changes during radiation can result in increased doses to normal tissues and increased risk of toxicity. Our results show a significant change in gland volume in 3 of 4 salivary glands at the time of replanning with a direct correlation to dose received to the gland. Adaptive replan has the potential to reduce salivary gland doses.

Recent studies have demonstrated a correlation between hematologic toxicity (HT) and radiation dose to the bone marrow (BM) in lung cancer (LuC). We set to perform normal tissue complication probability (NTCP) modeling in patients receiving chemoradiation (CRT) for LuC and to explore the feasibility of BM-sparing (BMS) in a subgroup of these patients. We analyzed 218 patients receiving CRT for LuC. Thoracic BM (TBM) was contoured as the T1-T10 vertebral bodies. Acute HT was defined as grade≥3 leukopenia, neutropenia, thrombocytopenia and/or anemia (HT3+). NTCP was evaluated with the Lyman-Kutcher-Burman (LKB) model. Twenty patients with high TBM mean dose were randomly selected with a BMS-IMRT objective of mean TBM<23 Gy. Dose to the planning target volume (PTV), heart, lung, esophagus, and spinal cord were compared on the pre- and post-BMS-sparing plans using the Wilcoxon signed-rank test. The HT3+ rate was 48%. Optimization of the LKB model for HT3+ yielded the parameters: n=1, m=1.62, and TD50=23.4 Gy. Compared to patients with TBM mean<23 Gy, patients with TBM mean≥23 Gy had a 1.8-fold increase in the odds of developing HT3+ [OR=1.78, p=0.038]. BMS-IMRT was able to significantly reduce the TBM mean, TBM V5-V20 and the spinal cord maximum dose (Table). PTV dose was not significantly reduced by BMS-IMRT. There were no significant increases in radiation dose to the heart, lung, or esophagus with BMS-IMRT LKB modeling confirms the expectation that TBM acts like a parallel organ (n=1). BMS-IMRT appears feasible without compromising plan quality. Prospective evaluation of BMS-IMRT is needed to determine if this approach results in clinically significant reductions in HT.Abstract 3045; Table 1Non-BMSMedian (range)BMSMedian (Range)% changeMedian (range)p-valueBone Marrow Mean (Gy) V5 (%) V10 (%) V20 (%)32.7 (25.6-41.4)82.5 (59.6-100)77.2 (55.2-100)69.9 (50.7-97.5)24.3 (19.6-30.9)80.2 (57.1-100)70.4 (50.8-95.8)50.5 (32.9-72.8)-23.7 (-40.3 to -6.5)-2.5 (-5.0 to 0.0)-7.7 (-22.2 to -0.7)-23.7 (-54.1 to5.6)<0.001<0.001<0.001<0.001PTV D95 (Gy) Mean (Gy)60.0 (56.4-61.2)62.7 (60.4-68.2)60.0 (58.2-62.7)62.5 (60.9-66.3)0.0 (0.0-5.2)0.3 (-2.7 to 1.6)0.070.38Heart Mean (Gy) V30 (%) V40 (%) V60 (%)17.6 (5.9-36.1)21.4 (4-92.9)11.1 (2.2-37.1)2.2 (0.1-19.2)16.3 (5.2-35.3)18.1 (2.7-91.6)10.7 (1.7-38.9)1.9 (0.0-19.9)0.5 (-15.3 to 18.7)-2.0 (-38.4 to 31.2)-9.2 (-65.2 to 54.9)-1.8 (-85.7 to 29.4)0.850.330.440.78Lung Mean (Gy) V5 (%) V20 (%)16.7 (12.5-19.2)74.1 (45.4-97.3)31.2 (17.8-36.4)16.3 (11.3-19.6)74.4 (41.3-96.8)30.1 (12.4-36.7)-2.2 (-11.5 to 6.6)0.1 (-9.0 to 33.2)-1.2 (-34.7 to 8.1)0.070.820.21Esophagus Mean (Gy) V50 (%) V60 (%)31.5 (20.5-48.5)34.8 (10.2-68.0)16.4 (1.0-59.2)30.9 (22.2-48.5)37.3 (8.4-66.0)22.0 (1.2-57.3)-1.4 (-9.0 to 8.6)-3.4 (-29.0 to 34.0)7.4 (-38.3 to 509.1)0.500.180.16Spinal Cord Max (Gy)42.0 (33.1-47.2)38.3 (25.6-45.5)-7.8 (-37.7 to 11.5)0.002 Open table in a new tab

We report the measurement of the one-dimensional charged kaon correlation functions using 600 GeV/c Sigma(-), pi(-) and 540 GeV/c p beams from the SELEX (E781) experiment at the Fermilab Tevatron. (KK +/-)-K-+/- correlation functions are studied for three transverse pair momentum, k(T), ranges and parameterized by a Gaussian form. The emission source radii, R, and the correlation strength, lambda, are extracted. The analysis shows a decrease of the source radii with increasing kaon transverse pair momentum for all beam types. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background and Purpose: To perform a retrospective in vivo dosimetry study of 129 total body irradiation (TBI) on leukemia and bone marrow transplant patients treated in our clinic from 2008 to 2011 and to find out if there is any indication of the necessity of developing a new efficient TBI approach. Materials and Methods: The in vivo dosimetry data of 129 patients treated with TBI between 2008 and 2011 were retrieved from the database and analyzed. These patients were mostly treated with the regime of a single fraction or 6 fractions with some exceptions of 8-fraction or 2-fraction treatments depending on the protocols that were applied. For every fraction of treatment, 10 pairs of diode dosimeters were used to monitor the doses to the midline of head, neck, arms, mediastinum, left lung, right lung, umbilicus, thigh, knee, and ankle for both AP and PA fields. The doses to the midline of the above body parts were considered to be the average of the AP and PA readings of each diode pair. Dose deviation from the prescribed value for each body part was studied by plotting the histogram of the frequency versus deviation and comparing this with the dose delivered to the midline of the umbilicus to where the dose was prescribed. The correlation of dose deviation to body part thickness was also studied. By studying the dose deviations, we can find the uniformity of general dose distributions for conventional TBI treatments. Results: The retrospective dosimetry study of the 129 TBI patient treatments indicates that for most of the patients treated in our clinic, the doses received by different body parts monitored with in vivo dosimetry were within the window of 10% difference from the prescribed dose. The inhomogeneity of dose on different body parts could be manually improved by using compensators, but the method is cumbersome and time consuming. The dose deviation in many histograms ranging from about ?10% to 10% indicates some incongruity of dose distribution. This could be due to the method of using lead compensators for a manual dose adjustment which could not ideally compensate for different body thicknesses everywhere. Conclusions: The conventional TBI could give uniform dose to the major body parts under the online in vivo dosimetry monitoring at the level of 10%, but the treatment procedure is cumbersome and time consuming. This implies the importance of developing a new and efficient TBI method by adopting modern radiation therapy technique.

To analyze the inter-fraction tumor volume changes during Stereotactic Body Radiation Therapy (SBRT) of early stage non-small cell lung cancer (NSCLC) with respect to deposited doses and patient characteristics. Tumor volumes of 15 consecutive patients (age 57-86) treated with SBRT at our institution between November 1, 2011 and June 1, 2012 were retrospectively analyzed. Patients were treated with a total dose of 45-54 Gy in 3-5 fractions. Kilovoltage cone-beam CT (CBCT) images obtained immediately prior to each administered dose were used to delineate gross tumor volume (GTV) resulting in 84 sets of contours from 18 tumors. The sum of the differential dose-volume histogram (DVH) of structures contoured prior to treatment was used to determine the average dose and cumulative radiation delivered. Pearson's r and Spearman's ρ correlation as well as partial correlation analysis were performed to study tumor volume changes with respect to patient and tumor characteristics as well as radiation delivered. Relative to their original volume, most tumors increased in size and then decreased during the treatment course. The baseline CBCT tumor volume during the first treatment was between 0.41 and 43.9 mL. An average maximum increase of 15% relative to the baseline volume and regression of 11% were observed in tumor size, corresponding to a 26% average inter-fraction tumor volume range. The PTV size was inversely correlated to inter-fraction tumor volume changes (r = −0.59, p = 0.013 and ρ = −0.62, p = 0.0090), whereas age was proportional to the interval between the first treatment and the time point when the largest volume increase was observed (r = +0.52, p = 0.031 and ρ = +0.63, p = 0.0062). Partial correlation between radiation dose and inter-fraction volume revealed that the average PTV dose (r = +0.60, p = 0.031 and ρ = +0.58, p = 0.038) and cumulative dose in the ipsilateral normal lung (lung minus PTV) (ρ = +0.72, p = 0.0059) are each directly correlated to the inter-fraction volume range. The average enlargement of squamous cell carcinomas was greater than adenocarcinomas; however, the difference was not statistically significant. The observed CBCT volume changes during treatment had minimal effect on treatment planning dose coverage. Our preliminary data suggest that for ablative SBRT doses significant changes in inter-fraction tumor volume exist that are correlated to age, cumulative radiation dose in lung tissue and average PTV dose. The frequently observed increase followed by decrease in tumor volume suggests the presence of competing physiological processes during ablative radiation, and may be related to acute vascular injury, edema and inflammation, as well as tumor cell death and normal tissue effects of radiation.

Using data taken by SELEX during the 1996–1997 fixed target run at Fermilab, we study the production of charmed hadrons on copper and carbon targets with Σ −, p, π −, and π + beams. Parametrizing the dependence of the inclusive production cross section on the atomic number A as A α , we determine α for D +, D 0, D s + , D +(2010), Λ c + , and their respective anti-particles, as a function of their transverse momentum p t and scaled longitudinal momentum x F . Within our statistics there is no dependence of α on x F for any charm species for the interval 0.1<x F <1.0. The average value of α for charm production by pion beams is α meson=0.850±0.028. This is somewhat larger than the corresponding average α baryon=0.755±0.016 for charm production by baryon beams (Σ −, p).