A Prospective Trial of Single-Fraction Radiation to the Tumor Bed with a Novel Breast-Specific Stereotactic Radiation Therapy Device: The GammaPod.

Purpose: Radiation therapy for early-stage breast cancer is typically delivered in a hypofractionated regimen to the whole breast followed by a tumor bed boost. This results in a treatment course of approximately 4 weeks. In this study, the tumor bed boost was delivered in a single fraction as part of a safety and feasibility study for FDA clearance of the device. Methods and Materials: Eligible women with early-stage breast cancer underwent lumpectomy followed by radiation therapy. Patients underwent breast immobilization using a system specific to the GammaPod followed by CT simulation, boost treatment planning, and boost treatment delivery all in a single treatment day. Patients then started whole-breast radiation therapy within 1 week of the boost treatment. Patients and treatments were assessed for safety and feasibility. Acute toxicities were recorded. Results: A single-fraction boost of 8 Gy was delivered to the tumor bed before a course of whole-breast radiation. The GammaPod treatment was successfully delivered to 14 of 17 enrolled patients. Acute toxicities from all radiation therapy, inclusive of the boost and whole-breast radiation, were limited to grade 1 events. Conclusions: The GammaPod device successfully delivered a single-fraction boost treatment to the tumor bed with no change in expected acute toxicities. The results of this study led to FDA clearance of the device through the Investigational Device Exemption process at the FDA. The GammaPod is in clinical use at 4e institutions nationally and internationally, with additional sites pending in 2023.

How many brain metastases can be treated with stereotactic radiosurgery before the radiation dose delivered to normal brain tissue rivals that associated with standard whole brain radiotherapy?

INTRODUCTION: Clinical trial data comparing outcomes after administration of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) to patients with brain metastases (BM) suggest that SRS better preserves cognitive function and quality of life without negatively impacting overall survival. Here, we estimate the maximum number of BM that can be treated using single and multi-session SRS while limiting the dose of radiation delivered to normal brain tissue to that associated with WBRT. METHODS: Multiple-tumor SRS was simulated using a Monte Carlo - type approach and a pre-calculated dose kernel method. Tumors with diameters ≤36 mm were randomly placed throughout the contoured brain parenchyma until the brain mean dose reached 3 Gy, equivalent to the radiation dose delivered during a single fraction of a standard course of WBRT (a total dose of 30 Gy in 10 daily fractions of 3 Gy). Distribution of tumor sizes, dose coverage, selectivity, normalization, and maximum dose data used in the simulations were based on institutional clinical metastases data. RESULTS: The mean number of tumors treated, mean volume of healthy brain tissue receiving > 12 Gy (V12) per tumor, and total tumor volume treated using mixed tumor size distributions were 12.7 ± 4.2, 2.2 cc, and 12.9 cc, respectively. Thus, we estimate that treating 12-13 tumors per day over 10 days would deliver the dose of radiation to healthy brain tissue typically associated with a standard course of WBRT. CONCLUSION: Although in clinical practice, treatment with SRS is often limited to patients with ≤15 BM, our findings suggest that many more lesions could be targeted while still minimizing the negative impacts on quality of life and neurocognition often associated with WBRT. Results from this in silico analysis require clinical validation.

Correlation of treatment time to target volume for GammaPod treatments: A simple second calculation.

PURPOSE: The GammaPod is a novel device for stereotactic breast treatments that employs 25 rotating Co-60 sources while the patient is continuously translated in three axes to deliver a highly conformal dose to the target. There is no commercial software available for independent second calculations. The purpose of this study is to determine an efficient way to estimate GammaPod treatment times based on target volume and use it as a second calculation for patient-specific quality assurance. METHODS: Fifty-nine GammaPod (Xcision Medical Systems, LLC.) breast cancer patient treatments were used as the fitting dataset for this study. Similar to the Curie-seconds concept in brachytherapy, we considered dose-rate × time/(prescribed dose) as a function of target volumes. Using a MATLAB (Mathworks, Natick, MA, USA) script, we generated linear (with 95% confidence interval (CI)) and quadratic fits and tested the resulting equations on an additional set of 30 patients. RESULTS: We found a strong correlation between the dose-rate × time/(prescribed dose) and patients' target volumes for both the linear and quadratic models. The linear fit was selected for use and using the polyval function in MATLAB, a 95% CI graph was created to depict the accuracy of the prediction for treatment times. Testing the model on 30 additional patients with target volumes ranging from 20 to 188 cc yielded treatment times from 10 to 25 min that in all cases were within the predicted CI. The average absolute difference between the predicted and actual treatment times was 1.0 min (range 0-3.3 min). The average percent difference was 5.8% (range 0%-18.4%). CONCLUSION: This work has resulted in a viable independent calculation for GammaPod treatment times. This method has been implemented as a spreadsheet that is ready for clinical use to predict and verify the accuracy of breast cancer treatment times.

Radiation shielding and safety implications following linac conversion to an electron FLASH-RT unit.

PURPOSE: Due to their finite range, electrons are typically ignored when calculating shielding requirements in megavoltage energy linear accelerator vaults. However, the assumption that 16 MeV electrons need not be considered does not hold when operated at FLASH-RT dose rates (~200× clinical dose rate), where dose rate from bremsstrahlung photons is an order of magnitude higher than that from an 18 MV beam for which shielding was designed. We investigate the shielding and radiation protection impact of converting a Varian 21EX linac to FLASH-RT dose rates. METHODS: We performed a radiation survey in all occupied areas using a Fluke Biomedical Inovision 451P survey meter and a Wide Energy Neutron Detection Instrument (Wendi)-2 FHT 762 neutron detector. The dose rate from activated linac components following a 1.8-min FLASH-RT delivery was also measured. RESULTS: When operated at a gantry angle of 180° such as during biology experiments, the 16 MeV FLASH-RT electrons deliver ~10 µSv/h in the controlled areas and 780 µSv/h in the uncontrolled areas, which is above the 20 µSv in any 1-h USNRC limit. However, to exceed 20 µSv, the unit must be operated continuously for 92 s, which corresponds in this bunker and FLASH-RT beam to a 3180 Gy workload at isocenter, which would be unfeasible to deliver within that timeframe due to experimental logistics. While beam steering and dosimetry activities can require workloads of that magnitude, during these activities, the gantry is positioned at 0° and the dose rate in the uncontrolled area becomes undetectable. Likewise, neutron activation of linac components can reach 25 µSv/h near the isocenter following FLASH-RT delivery, but dissipates within minutes, and total doses within an hour are below 20 µSv. CONCLUSION: Bremsstrahlung photons created by a 16 MeV FLASH-RT electron beam resulted in consequential dose rates in controlled and uncontrolled areas, and from activated linac components in the vault. While our linac vault shielding proved sufficient, other investigators would be prudent to confirm the adequacy of their radiation safety program, particularly if operating in vaults designed for 6 MV.

Simplified method for determining dose to a non-water phantom through the use of ND,w and IAEA TRS 483 for the GammaPod.

PURPOSE: GammaPod, a breast stereotactic radiosurgery device, utilizes 25 rotating Co-60 sources to deliver highly conformal dose distributions. The GammaPod system requires that reference dosimetry be performed in a specific vendor-supplied poly-methylmethacrylate (PMMA) phantom. The nonstandard nature of GammaPod dosimetry, in both the phantom material and machine-specific reference (msr), prohibits use of the American Association of Physicists in Medicine Task Group 51 (TG-51) protocol. This study proposes a practical method using TRS 483 to make the reference dosimetry procedure simpler and to reduce overall uncertainties. METHODS: The dose to PMMA (DPMMA) is determined under msr conditions using TRS 483 with an Exradin A1SL chamber placed in a PMMA phantom. The conversion factor, which converts from the dose-to-water (Dw) in broad-beam Co-60 reference geometry to DPMMA in the msr small field Co-60 (Qmsr) geometry, is derived using the Monte Carlo simulations and procedure described in TRS 483. RESULTS: The new conversion factor value for an Exradin A1SL chamber is 0.974. When combined with ND,w, DPMMA differs by 0.5% from the TG-21/Nx method and 0.2% from the IROC values. Uncertainty decreased from 2.2% to 1.6%. CONCLUSION: We successfully implemented TRS 483 reference dosimetry protocols utilizing ND,w for the GammaPod in the PMMA phantom. These results show not only agreement between measurements performed with the previously published method and independent thermoluminescent dosimetry measurements but also reductions in uncertainty. This also provides readers with a pathway to develop their own IAEA TRS 483 factor for any new small field machine that may be developed.

Reproducibility of a novel, vacuum-assisted immobilization for breast stereotactic radiotherapy.

A novel, breast-specific stereotactic radiotherapy device has been developed for delivery of highly conformal, accelerated partial breast irradiation. This device employs a unique, vacuum-assisted, breast cup immobilization system that applies a gentle, negative pressure to the target breast with the patient in the prone position. A device-specific patient loader is utilized for simulation scanning and device docking. Prior to clinical activation, a prospective protocol enrolled 25 patients who had been or were to be treated with breast conservation surgery and adjuvant radiotherapy for localized breast cancer. The patients underwent breast cup placement and two separate CT simulation scans. Surgical clips within the breast were mapped and positions measured against the device's integrated stereotactic fiducial/coordinate system to confirm reproducible and durable immobilization during the simulation, treatment planning, and delivery process for the device. Of the enrolled 25 patients, 16 were deemed eligible for analysis. Seventy-three clips (median, 4; mean, 4.6; range, 1-8 per patient) were mapped in these selected patients on both the first and second CT scans. X, Y, and Z coordinates were determined for the center point of each clip. Length of vector change in position was determined for each clip between the two scans. The mean displacement of implanted clips was 1.90 mm (median, 1.47 mm; range, 0.44-6.52 mm) (95% CI, 1.6-2.20 mm). Additional analyses stratified clips by position within the breast and depth into the immobilization cup. Overall, this effort validated the clinically utilized 3-mm planning target volume margin for accurate, reliable, and precise employment of the device.

Immune checkpoint inhibition in patients treated with stereotactic radiation for brain metastases.

PURPOSE: Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI. METHODS AND MATERIALS: Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed. RESULTS: One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC. CONCLUSION: These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.

The Impact of Radiation Energy on Dose Homogeneity and Organ Dose in the Göttingen Minipig Total-Body Irradiation Model.

Animal models of total-body irradiation (TBI) are used to elucidate normal tissue damage and evaluate the efficacy of medical countermeasures (MCM). The accuracy of these TBI models depends on the reproducibility of the radiation dose-response relationship for lethality, which in turn is highly dependent on robust radiation physics and dosimetry. However, the precise levels of radiation each organ absorbs can change dramatically when different photon beam qualities are used, due to the interplay between their penetration and the natural variation of animal sizes and geometries. In this study, we evaluate the effect of varying the radiation energy, namely cobalt-60 (Co-60); of similar penetration to a 4-MV polyenergetic beam), 6 MV and 15 MV, in the absorbed dose delivered by TBI to individual organs of eight Göttingen minipigs of varying weights (10.3-24.1 kg) and dimensions (17.5-25 cm width). The main organs, i.e. heart, lungs, esophagus, stomach, bowels, liver, kidneys and bladder, were contoured by an experienced radiation oncologist, and the volumetric radiation dose distribution was calculated using a commercial treatment planning system commissioned and validated for Co-60, 6-MV and 15-MV teletherapy units. The dose is normalized to the intended prescription at midline in the abdomen. For each animal and each energy, the body and organ dose volume histograms (DVHs) were computed. The results show that more penetrating photon energies produce dose distributions that are systematically and consistently more homogeneous and more uniform, both within individual organs and between different organs, across all animals. Thoracic organs (lungs, heart) received higher dose than prescribed while pelvic organs (bowel, bladder) received less dose than prescribed, due to smaller and wider separations, respectively. While these trends were slightly more pronounced in the smallest animals (10.3 kg, 19 cm abdominal width) and largest animals (>20 kg, ∼25 cm abdominal width), they were observed in all animals, including those in the 9-15 kg range typically used in MCM models. Some organs received an average absorbed dose representing <80% of prescribed dose when Co-60 was used, whereas all organs received average doses of >87% and >93% when 6 and 15 MV were used, respectively. Similarly, average dose to the thoracic organs reached as high as 125% of the intended dose with Co-60, compared to 115% for 15 MV. These results indicate that Co-60 consistently produces less uniform dose distributions in the Göttingen minipig compared to 6 and 15 MV. Moreover, heterogeneity of dose distributions for Co-60 is accentuated by anatomical and geometrical variations across various animals, leading to different absorbed dose delivered to organs for different animals. This difference in absorbed radiation organ doses, likely caused by the lower penetration of Co-60 and 6 MV compared to 15 MV, could potentially lead to different biological outcomes. While the link between the dose distribution and variation of biological outcome in the Göttingen minipig has never been explicitly studied, more pronounced dose heterogeneity within and between organs treated with Co-60 teletherapy units represents an additional confounding factor which can be easily mitigated by using a more penetrating energy.

Technical Note: Dosimetric feasibility of lattice radiotherapy for breast cancer using GammaPod.

PURPOSE: Studies on Lattice radiotherapy (LRT) for breast cancer have been largely lacking. This study investigates the dosimetric feasibility of using Gamma Pod, a stereotactic radiotherapy apparatus originally designed for breast SBRT, to deliver LRT to large, bulky breast tumor as a noninvasive treatment option. METHODS: The GammaPod-based LRT was simulated using Geant4 Gate Monte Carlo software. The simulated GammaPod was equipped with 5 mm diameter non-coplanar circular beams that span 28° latitudinally from 18° to 43° off the horizontal plane. Two degrees longitudinal intervals were used to simulate rotating sources. To simulate the treatments to different breast sizes, three water-equivalent hemisphere volumes with diameters of 10, 15, and 20 cm were analyzed. The lattice was planned by spacing focal points 2 cm apart in the transverse and sagittal planes and 2.5 cm in the coronal plane. This resulted in 22-172 shots for full breast treatment. The maximum dose for each individual shot was 20 Gy. The peak-to-valley dose differences and skin dose were analyzed. To verify the feasibility of delivering LRT, a test plan was created and delivered to a commercial diode array dose verification device using a clinical GammaPod system with 15 mm collimators. RESULTS: The dose profiles showed the average peak-to-valley dose percent differences of 94.10% in the 10 cm hemispherical volume, 88.95% in the 15 cm hemispherical volume, and 83.60% in the 20 cm hemispherical volume. Average skin dose was 1.27, 1.72, and 2.13 Gy for the 10, 15, and 20 cm irradiation volumes, respectively. The LRT plan delivered using a clinical GammaPod system with larger collimators verified the feasibility of LRT plan delivery. CONCLUSION: GammaPod-based lattice radiotherapy is a viable treatment option and its application can be extended to treating large bulky breast tumors.

A multi-center analysis of single-fraction versus hypofractionated stereotactic radiosurgery for the treatment of brain metastasis.

BACKGROUND: Hypofractionated-SRS (HF-SRS) may allow for improved local control and a reduced risk of radiation necrosis compared to single-fraction-SRS (SF-SRS). However, data comparing these two treatment approaches are limited. The purpose of this study was to compare clinical outcomes between SF-SRS versus HF-SRS across our multi-center academic network. METHODS: Patients treated with SF-SRS or HF-SRS for brain metastasis from 2013 to 2018 across 5 radiation oncology centers were retrospectively reviewed. SF-SRS dosing was standardized, whereas HF-SRS dosing regimens were variable. The co-primary endpoints of local control and radiation necrosis were estimated using the Kaplan Meier method. Multivariate analysis using Cox proportional hazards modeling was performed to evaluate the impact of select independent variables on the outcomes of interest. Propensity score adjustments were used to reduce the effects confounding variables. To assess dose response for HF-SRS, Biologic Effective Dose (BED) assuming an α/ß of 10 (BED10) was used as a surrogate for total dose. RESULTS: One-hundred and fifty six patients with 335 brain metastasis treated with SF-SRS (n = 222 lesions) or HF-SRS (n = 113 lesions) were included. Prior whole brain radiation was given in 33% (n = 74) and 34% (n = 38) of lesions treated with SF-SRS and HF-SRS, respectively (p = 0.30). After a median follow up time of 12 months in each cohort, the adjusted 1-year rate of local control and incidence of radiation necrosis was 91% (95% CI 86-96%) and 85% (95% CI 75-95%) (p = 0.26) and 10% (95% CI 5-15%) and 7% (95% CI 0.1-14%) (p = 0.73) for SF-SRS and HF-SRS, respectively. For lesions > 2 cm, the adjusted 1 year local control was 97% (95% CI 84-100%) for SF-SRS and 64% (95% CI 43-85%) for HF-SRS (p = 0.06). On multivariate analysis, SRS fractionation was not associated with local control and only size ≤2 cm was associated with a decreased risk of developing radiation necrosis (HR 0.21; 95% CI 0.07-0.58, p < 0.01). For HF-SRS, 1 year local control was 100% for lesions treated with a BED10 ≥ 50 compared to 77% (95% CI 65-88%) for lesions that received a BED10 < 50 (p = 0.09). CONCLUSIONS: In this comparison study of dose fractionation for the treatment of brain metastases, there was no difference in local control or radiation necrosis between HF-SRS and SF-SRS. For HF-SRS, a BED10 ≥ 50 may improve local control.

Dosimetry evaluation of the GammaPod stereotactic radiosurgery device based on established AAPM and IAEA protocols.

PURPOSE: The GammaPod is a novel dedicated prone breast stereotactic radiosurgery (SRS) device recently developed at the University of Maryland Medical Center. This device utilizes multiple rotating Co-60 sources to create highly conformal dose distributions for breast treatments, including boosts, partial breast irradiation, or presurgery SRS. However, due to its small field sizes and nonstandard geometry, existing calibration protocols cannot be directly applied. In this study, we adapt and implement the American Association of Physicists in Medicine Task Group 21 (TG-21) and International Atomic Energy Agency (IAEA) Technical Report Series 483 (TRS 483) protocols for reference dose measurements for the GammaPod. This represents the first published dosimetric investigation GammaPod and is meant to serve as a reference to future users commissioning and calibrating these devices. METHODS: Reference dose measurements were performed following the TG-21/IAEA TRS 483 protocols using an ADCL-calibrated Exradin A1SL thimble chamber in a polymethyl methacrylate (PMMA) breast-mimicking phantom. Monte Carlo calculations and measurements were also performed in water to determine chamber-specific k PMMA Q m s r , Q 0 f msr , f ref quality conversion factor converting reference field size (fref ) to machine-specific field sizes (fmsr ) (25-mm) as well as k PMMA f clin , f msr , the conversion factor from the (fmsr ) to the clinical field size (fclin ) (15mm). Verification was performed using the thermoluminescent dosimeter remote monitoring service from the Imaging and Radiation Oncology Core (IROC) in Houston, TX. RESULTS: The (fref ) to (fmsr ) chamber-specific factor k PMMA Q m s r , Q 0 f msr , f ref was 0.992 while the (fmsr ) to (fclin ) chamber-specific k PMMA f clin , f msr factor was 1.014. The radiation absorbed dose to water measured in the PMMA phantom based on the TG-21/IAEA TRS 483 formalism agreed with IROC values to within 1% and 2% for the 25- and 15-mm collimators, respectively. CONCLUSION: We successfully implemented the TG-21 and TRS 483 reference dosimetry protocols for the GammaPod. These results show agreement between measurements performed with different reference dosimetry protocols and independent thermoluminescent measurements.

A Dose of Reality: How 20 Years of Incomplete Physics and Dosimetry Reporting in Radiobiology Studies May Have Contributed to the Reproducibility Crisis.

PURPOSE: A large proportion of preclinical or translational studies using radiation have poor replicability. For a study involving radiation exposure to be replicable, interpretable, and comparable, its experimental methodology must be well reported, particularly in terms of irradiation protocol, including the amount, rate, quality, and geometry of radiation delivery. Here we perform the first large-scale literature review of the current state of reporting of essential experimental physics and dosimetry details in the scientific literature. METHODS AND MATERIALS: For 1758 peer-reviewed articles from 469 journals, we evaluated the reporting of basic experimental physics and dosimetry details recommended by the authoritative National Institute of Standards and Technology symposium. RESULTS: We demonstrate that although some physics and dosimetry parameters, such as dose, source type, and energy, are well reported, the majority are not. Furthermore, highly cited journals and articles are systematically more likely to be lacking experimental details related to the irradiation protocol. CONCLUSIONS: These findings show a crucial deficiency in the reporting of basic experimental details and severely affect the reproducibility and translatability of a large proportion of radiation biology studies.

Development and validation of a comprehensive patient-specific quality assurance program for a novel stereotactic radiation delivery system for breast lesions.

PURPOSE: The GammaPod is a dedicated prone breast stereotactic radiosurgery (SRS) machine composed of 25 cobalt-60 sources which rotate around the breast to create highly conformal dose distributions for boosts, partial-breast irradiation, or neo-adjuvant SRS. We describe the development and validation of a patient-specific quality assurance (PSQA) system for the GammaPod. METHODS: We present two PSQA methods: measurement based and calculation based PSQA. The measurements are performed with a combination of absolute and relative dose measurements. Absolute dosimetry is performed in a single point using a 0.053-cc pinpoint ionization chamber in the center of a polymethylmethacrylate (PMMA) breast phantom and a water-filled breast cup. Relative dose distributions are verified with EBT3 film in the PMMA phantom. The calculation-based method verifies point doses with a novel semi-empirical independent-calculation software. RESULTS: The average (± standard deviation) breast and target sizes were 1263 ± 335.3 cc and 66.9 ± 29.9 cc, respectively. All ion chamber measurements performed in water and the PMMA phantom agreed with the treatment planning system (TPS) within 2.7%, with average (max) difference of -1.3% (-1.9%) and -1.3% (-2.7%), respectively. Relative dose distributions measured by film showed an average gamma pass rate of 97.0 ± 3.2 when using a 3%/1 mm criteria. The lowest gamma analysis pass rate was 90.0%. The independent calculation software had average agreements (max) with the patient and QA plan calculation of 0.2% (2.2%) and -0.1% (2.0%), respectively. CONCLUSION: We successfully implemented the first GammaPod PSQA program. These results show that the GammaPod can be used to calculate and deliver the predicted dose precisely and accurately. For routine PSQA performed prior to treatments, the independent calculation is recommended as it verifies the accuracy of the planned dose without increasing the risk of losing vacuum due to prolonged waiting times.

Commissioning and acceptance guide for the GammaPod.

The GammaPod breast treatment device has been introduced to provide stereotactic radiation therapy to the breast to patients in the prone position. The GammaPod, using a stereotactic coordinate system, dynamically delivers dose to the target by rotating 25 non-overlapping Co-60 beams while the patient's breast is translated continuously in three axes on the couch during delivery. From simulation to treatment, the patient's breast is immobilized using mild negative pressure (150 mm Hg below atmospheric pressure) through a device-specific dual-cup system with stereotactic fiducials. This technology can be used for boost, multi-fraction partial-breast steterotactic body radiotherapy (SBRT), or single-fraction stereotactic radiosurgery (SRS). This paper reports the commissioning of the system for clinical use. The GammaPod device has four major subsystems: mechanical, dosimetric, radiation safety, and safety interlocks. Detailed methods for testing each subsystem have been identified and quantified. Mechanical systems include couch motion and accuracy along with couch sag. Dosimetric tests include absolute dose calibration, dose profiles, timer error, and plan verifications. Radiation safety includes room and wall surveys, along with device leakage measurements. Safety interlocks deal with power systems, immobilization, and treatment interrupts. The absolute dose rate of the 25 mm collimator was determined using TG-21 dosimetry protocol. The relative output factor for the 15 mm collimator was 0.94. The difference of the full-width-at-half-maximum of the single shot of the 25 mm collimator between the treatment planning system and the measurement was 0.2 mm. All interlocks were found to perform correctly, and the shield was within state and Nuclear Regulatory Commission limits. The items and techniques for commissioning the GammaPod have been developed and tested using the methods reported here.

Dosimetric effects of the kV based image-guided radiation therapy of prone breast external beam radiation: Towards the optimized imaging frequency.

PURPOSE: For prone breast treatment, daily image-guided radiation therapy (IGRT) allows couch shifting to correct breast position relative to the treatment field. This work investigates the dosimetric effect of reducing kV imaging frequencies and the feasibility of optimizing the frequency using patient anatomy or their first 3-day shifts. METHOD: Thirty-seven prone breast patients who had been treated with skin marker alignment followed by daily kV were retrospectively analyzed. Three IGRT schemes (daily-kV, weekly-kV, no-kV) were simulated, assuming that fractions with kV imaging deliver a dose distribution equivalent to that in computed tomography (CT) planning, whereas other fractions yield a dose distribution as recreated by shifting the CT plan isocenter back to its position before the couch shift was applied. Treatment dose to targets (breast and lumpectomy cavity [LPC]) and organs at risks (OAR)s (heart, ipsilateral lung) in different schemes were calculated. Patient anatomy information on CT plans and first 3-day couch shift data were analyzed to investigate whether these factors could guide imaging scheme optimization. RESULTS: When kV imaging frequency was reduced, the percentage dose changes (δD) for breast and LPC objectives (average <1%) were smaller than those for heart and lung (average 28%-31% for Dmean ). In general, the δD of no-kV imaging was approximately that of weekly kV imaging × a factor of 1.2-1.4. Although most dose objectives were not affected, the potential higher heart dose may be of concern. No strong correlation was found between δD for different kV frequencies and patient anatomy size/distance or the first 3-day couch shift data. CONCLUSIONS: Despite resulting in lower imaging dose, time, cost, and similar target coverage, a reduction in kV imaging frequency may introduce higher heart complication risk. Daily kVs are needed more in left-sided breast patients. A less frequent imaging schedule, if considered, cannot be individually optimized using CT anatomic features or early shift data.

Correlation of radiation dose and activity with clinical outcomes in metastatic colorectal cancer after selective internal radiation therapy using yttrium-90 resin microspheres.

PURPOSE: Yttrium-90 (Y)-resin microspheres are prescribed using activity. We evaluated overall survival (OS) and radiographic tumor response after selective internal radiation therapy (SIRT) with resin microspheres in patients with liver metastases from colorectal cancer. PATIENTS AND METHODS: We retrospectively reviewed 60 metastatic colorectal cancer patients treated at our institution with SIRT using Y-resin microspheres. Each patient underwent pre-SIRT MRI or computed tomography imaging of the liver with intravenous contrast. Patients underwent post-treatment imaging at 2-3-month intervals with response assessed according to unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as published three-dimensional volumetric criteria. We then related the prescribed activity established by the body surface area method and the corresponding prescribed dose to radiographic treatment response and OS. RESULTS: The median follow-up after the first SIRT treatment was 8.9 months. The mean prescribed activity and the prescribed dose were 26.6 mCi and 52.8 Gy, respectively. OS was not significantly associated with either prescribed activity or prescribed dose. Prescribed dose was also not related to response. However, a significant relationship was found between a higher prescribed activity and an improved radiographic response by RECIST (P=0.04) at the second follow-up. CONCLUSION: The prescribed activity of Y-resin microspheres may be correlated with radiographic response by RECIST criteria at 4-6 months post-treatment. For a more accurate prediction of response, a valid dose calculation model based on post-Y PET dosimetry is likely needed given the heterogeneous dose delivery seen in SIRT.

Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis.

BACKGROUND: Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] in vivo and in patients with ulcerative colitis (UC). METHODS: Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. RESULTS: Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo versus the treated group (p < 0.05). Selenium was the more active component. The contribution of green tea was minor. In the TNBS model, the Wallace scores for macroscopic lesions were 4.8 ± 1.5 (treatment) and 8.2 ± 0.5 (placebo) (p = 0.01). In humans, Coltect was well tolerated and effective. Fourteen subjects (70%) improved: nine (45%) went into complete remission, four (20%) experienced marked improvement and one (5%) experienced moderate improvement at the end of the trial. Clinical activity index decreased significantly at 4 and 8 weeks (p < 0.001). Two patients had no change in their symptoms, and one withdrew after 4 weeks. Flare-up in four subjects caused three to withdraw from the study after less than 4 weeks. Endoscopic improvement was observed in 11 (69%) patients, and four patients (25%) achieved complete remission. CONCLUSIONS: Coltect may serve as a first-line or add-on therapy in patients with mild-to-moderate UC.

Collision indicator charts for gantry-couch position combinations for Siemens ONCOR and Elekta Infinity linacs.

Noncoplanar radiation fields from a linear accelerator can be used to deliver radiation dose distributions that are superior to those delivered using coplanar radiation fields. Noncoplanar radiation field arrangements are especially valuable when delivering stereotactic body radiation therapy (SBRT). Noncoplanar radiation fields, however, are geometrically more challenging to deliver than coplanar radiation fields, and are associated with a greater risk of collisions between the gantry, treatment couch, and patient. Knowledge of which treatment couch offset, treatment couch angle, and gantry angle combinations provide a collision-free radiotherapy delivery is useful in the treatment planning process, as the risk of requiring replanning due to improperly selected treatment parameters can be minimized. Such tables are by default specific to the linear accelerator make and model used for treatment. In this work a set of plots is presented indicating which combination of treatment couch lateral offsets (-10 cm to 10 cm), couch angles (270° to 90°), and gantry angles (0° to 360°), will result in collision-free radiation delivery using Siemens ONCOR linear accelerators equipped with a 160-leaf multileaf collimator and a 550 TxT treatment table, and a Elekta Infinity linear accelerator with an MLCi2 and Elekta iBEAM evo Couchtop EP. The patient was assumed to have a width of 50 cm and a height of 25 cm.