In Vivo Verification of Electron Paramagnetic Resonance Biodosimetry Using Patients Undergoing Radiation Therapy Treatment.

PURPOSE: Electron paramagnetic resonance (EPR) biodosimetry, used to triage large numbers of individuals incidentally exposed to unknown doses of ionizing radiation, is based on detecting a stable physical response in the body that is subject to quantifiable variation after exposure. In vivo measurement is essential to fully characterize the radiation response relevant to a living tooth measured in situ. The purpose of this study was to verify EPR spectroscopy in vivo by estimating the radiation dose received in participants' teeth. METHODS AND MATERIALS: A continuous wave L-band spectrometer was used for EPR measurements. Participants included healthy volunteers and patients undergoing head and neck and total body irradiation treatments. Healthy volunteers completed 1 measurement each, and patients underwent measurement before starting treatment and between subsequent fractions. Optically stimulated luminescent dosimeters and diodes were used to determine the dose delivered to the teeth to validate EPR measurements. RESULTS: Seventy measurements were acquired from 4 total body irradiation and 6 head and neck patients over 15 months. Patient data showed a linear increase of EPR signal with delivered dose across the dose range tested. A linear least-squares weighted fit of the data gave a statistically significant correlation between EPR signal and absorbed dose (P < .0001). The standard error of inverse prediction (SEIP), used to assess the usefulness of fits, was 1.92 Gy for the dose range most relevant for immediate triage (≤7 Gy). Correcting for natural background radiation based on patient age reduced the SEIP to 1.51 Gy. CONCLUSIONS: This study demonstrated the feasibility of using spectroscopic measurements from radiation therapy patients to validate in vivo EPR biodosimetry. The data illustrated a statistically significant correlation between the magnitude of EPR signals and absorbed dose. The SEIP of 1.51 Gy, obtained under clinical conditions, indicates the potential value of this technique in response to large radiation events.

Dosimetric response of Gafchromic™ EBT-XD film to therapeutic protons.

EBT-XD model of Gafchromic™ films has a broader optimal dynamic dose range, up to 40 Gy, compared to its predecessor models. This characteristic has made EBT-XD films suitable for high-dose applications such as stereotactic body radiotherapy and stereotactic radiosurgery, as well as ultra-high dose rate FLASH radiotherapy. The purpose of the current study was to characterize the dependence of EBT-XD film response on linear energy transfer (LET) and dose rate of therapeutic protons from a synchrotron. A clinical spot-scanning proton beam was used to study LET dependence at three dose-averaged LET (LETd) values of 1.0 keV/µm, 3.6 keV/µm, and 7.6 keV/µm. A research proton beamline was used to study dose rate dependence at 150 Gy/second in the FLASH mode and 0.3 Gy/second in the non-FLASH mode. Film response data from LETd values of 0.9 keV/µm and 9.0 keV/µm of the proton FLASH beam were also compared. Film response data from a clinical 6 MV photon beam were used as a reference. Both gray value method and optical density (OD) method were used in film calibration. Calibration results using a specific OD calculation method and a generic OD calculation method were compared. The four-parameter NIH Rodbard function and three-parameter rational function were compared in fitting the calibration curves. Experimental results showed that the response of EBT-XD film is proton LET dependent but independent of dose rate. Goodness-of-fit analysis showed that using the NIH Rodbard function is superior for both protons and photons. Using the "specific OD + NIH Rodbard function" method for EBT-XD film calibration is recommended.

Preliminary dosimetric comparison between fixed and rotating source stereotactic radiosurgery systems.

PURPOSE: The Akesis Galaxy RTi (AK) is a novel rotational 60 Co-based cranial stereotactic radiosurgery (SRS) system. While similar systems have been compared against the fixed-source Leksell Gamma Knife (GK) system using stylized phantoms, dosimetric plan quality with realistic anatomy has yet to be characterized for this or any other rotating system versus GK. This study aims to benchmark AK dosimetric performance against GK by retrospectively replanning previously-treated GK patients at our institution. METHODS: Thirteen patients, previously treated on a GK Icon, were re-planned on the AK treatment planning system using the same prescription doses and isodoses as the original GK plans. The cohort includes patients treated for brain metastases, schwannomas, pituitary adenomas, trigeminal neuralgias, and arteriovenous malformations. Plans are evaluated with target coverage metrics (Dmin , Dmean , D95% , V150% ) and dose conformality indices: Radiation Therapy Oncology Group conformity index (CI), selectivity, Paddick CI (PCI), gradient index (GI). RESULTS: AK plans use fewer shots and larger collimation compared to GK plans, resulting in statistically significant reductions in treatment time (p = 0.047) by as much as 88.4 minutes while maintaining comparable target V100% . For most metastatic cases, GK produces higher Dmin (16.0-25.9 vs. 12.5-24.3 Gy, p = 0.008) while AK produces higher V150% (0.03-14.92 vs. 0.02-11.59 cc, p = 0.028). For non-metastatic cases, GK provides superior CI (p = 0.025) and GI (p = 0.044). No statistically significant differences were found in the remaining metrics. CONCLUSION: This cohort demonstrates that the AK system is able to achieve largely comparable dosimetric results to GK, typically with shorter treatment times. Further investigation with a larger cohort is underway.

Frequency of errors in the transfer of treatment parameters from the treatment planning system to the oncology information system in a multi-vendor environment.

BACKGROUND: Technological advancements have made it possible to improve patient outcomes in radiotherapy, sparing both normal tissues and increasing tumour control. However, these advancements have resulted in an increase in the number of software systems used, which each require data inputs to function. For institutions with multiple vendors for their treatment planning systems and oncology information systems, the transfer of data between them is potentially error prone and can lead to treatment errors. PURPOSE: The goal of this work was to determine the frequency of errors in data transfers between the Varian Eclipse treatment planning system and the Elekta Mosaiq oncology information system. METHODS: An in-house program was used to quantify the number of errors for 2700 unique plans over an 8-month period. Using this information, the frequency of the errors were calculated. A risk priority number was calculated using the calculated frequencies to determine the impact on the clinic. RESULTS: The most common errors discovered were backup timer settings (10.7%), Field label (8.5%), DRR associations (3.3%), imaging field types (3.1%), dose rate (1%), Field Id (0.8%), imaging isocenter (0.7% and SSD (0.7%). Based on the risk priority numbers, the DRR association error was ranked as having the highest potential impact on the patient. CONCLUSIONS: The results of the work show that the most effort should be focused on checking the manual steps performed in the transfer process, while items that are imported directly from DICOM-RT without modification are highly likely to be transferred accurately. The data can be used to help guide the implementation of future automated tools and process improvement in the clinic.

A small footprint couch-top support device for image-guided radiotherapy of heavy patients.

PURPOSE: Patients with body weights close to or above 400 lbs present unique challenges in radiation therapy since the weight limit of most treatment couches decreases as the couch-top extends toward the treatment gantry. The purpose of this work was to develop a small footprint couch-top support platform to safely perform image-guided radiotherapy (IGRT) for extremely heavy patients. METHODS: One way to protect the couch-top from damage and prevent a catastrophic breakdown is to provide additional support as the couch extends toward the treatment gantry. To allow a maximal range of gantry movement, a small-footprint adjustable jack stand, placed underneath the couch-top, was chosen and modified from a commercial jack stand (with 1100 lbs capacity). The couch could be easily extended longitudinally and laterally with a modified 8-ball-transfer plate mounted at the top. The operation of a couch-top support platform was used for two heavy patients after phantom testing. kV and MV imaging options and ranges were quantified. RESULTS: The custom-constructed couch-top support platform was found to provide stable support with smooth couch shifts. The small footprint allowed gantry rotation from 133° to 227°, which would allow both fixed beam radiotherapy and partial-arc volumetric modulated arc therapy (VMAT). For IGRT, orthogonal 2D kV-kV image pairs with source angles of 40o and 130o were acquired and tested successfully. With the support platform, two clinical cases with patient weights greater than 415 lbs were successfully treated with image-guided partial arc VMAT radiotherapy. The study demonstrated the safety and efficiency of using this new couch-top support platform to prevent couch failure from treating heavy patients. CONCLUSIONS: A new couch-top support platform has been designed, assembled, and tested for IGRT. The new support platform is easy to use, cost-effective, and allows extremely heavy patients to be treated safely and robustly with IGRT and VMAT.

Use of CT simulation and 3-D radiation therapy treatment planning system to develop and validate a total-body irradiation technique for the New Zealand White rabbit.

PURPOSE: Well-controlled ionizing radiation injury animal models for testing medical countermeasure efficacy require robust radiation physics and dosimetry to ensure accuracy of dose-delivery and reproducibility of the radiation dose-response relationship. The objective of this study was to establish a simple, convenient, robust and accurate technique for validating total body irradiation (TBI) exposure of the New Zealand White rabbit. METHODS: We use radiotherapy techniques such as computed tomography simulation and a 3 D-conformal radiation therapy treatment planning system (TPS) on three animals to comprehensively design and preplan a TBI technique for rabbits. We evaluate the requirement for bolus, treatment geometry, bilateral vs anterior-posterior treatment delivery, the agreement between monitor units calculated using the TPS vs a traditional hand calculation to the mid-plane, and resulting individual organ doses. RESULTS: The optimal technique irradiates animals on the left-decubitus position using two isocentric bilateral parallel-opposed 6 MV x-ray beams. Placement of a 5 mm bolus and 8.5 mm beam spoiler was shown to increase the dose to within ≤5 mm of the surface, improving dose homogeneity throughout the body of the rabbit. A simple hand calculation formalism, dependent only on mid-abdominal separation, could be used to calculate the number of monitor units (MUs) required to accurately deliver the prescribed dose to the animal. For the representative animal, the total body volume receiving > 95% of the dose, V95% > 99%, V100% > 95%, and V107% < 20%. The area of the body receiving >107% of the prescribed dose was mainly within the limbs, head, and around the lungs of the animal, where the smaller animal width reduces the x-ray attenuation. Individual organs were contoured by an experienced dosimetrist, and each received doses within 95-107% of the intended dose, with mean values ∼104%. Only the bronchus showed a maximal dose >107% (113%) due to the decreased attenuation of the lungs. To validate the technique, twenty animals were irradiated with four optically-stimulated luminescence dosimeters (OSLDs) placed on the surface of each animal (two on each side in the center of the radiation beam). The average dose over all animals was within <0.1% from intended values, with no animal receiving an average dose more than ±3.1% from prescription. CONCLUSION: The TBI technique developed in this pilot study was successfully used to establish the dose-response relationship for 45-day lethality across the dose-range to induce the hematopoietic-subsyndrome of the acute radiation syndrome (ARS).

Clinically-implementable template plans for multidwell treatments using Leipzig-style applicators in 192Ir surface brachytherapy.

PURPOSE: Multiple dwell positions ("multidwell") within a Leipzig-style applicator can be used to increase dose uniformity and treatment area. Model-based dose calculation algorithms (MBDCAs) are necessary for accurate calculations involving these applicators because of their nonwater equivalency and complex geometry. The purpose of this work was to create template plans from MBDCA calculations and present their dwell times and positions for users of these applicators without access to MBDCAs. METHODS AND MATERIALS: The Leipzig-style solid applicator model within our treatment planning system was used to design template plans. Five template plans, normalized to 0.3 cm depth within a water phantom, were optimized using the treatment planning system MBDCA. Each template plan contained unique dwell positions, times, and active lengths (0.5-1.5 cm). A single-dwell distribution was optimized for comparison. The stem of this applicator stops within the shell; therefore, one template plan contained an intrafraction rotation to determine the largest dose distribution achievable. Effects of imperfect applicator rotation were quantified by inserting rotational offsets and comparing the V100%, D95%, and minimum dose coverage for planning target volumes created from 80%/90% isodose lines. RESULTS: The 90% (80%) isodose line dimensions at 0.3 cm depth for single-dwell increased from 0.94 × 0.97 (1.53 × 1.57) cm2 to 2.09 × 1.24 (2.75 × 1.88) cm2 in the largest template plan. Manually inserted angular offsets up to ±10° for the template plan requiring rotation preserved V100%, D95%, and minimum dose within 2.0%, 1.9%, and 8.0%, respectively. CONCLUSION: A set of template plans was created to provide accessibility to the multidwell methodology, even for users without access to MBDCAs. Each template plan should be reviewed before clinical implementation.

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.

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.

Hematological Effects of Non-Homogenous Ionizing Radiation Exposure in a Non-Human Primate Model.

Detonation of a radiological or nuclear device in a major urban area will result in heterogenous radiation exposure, given to the significant shielding of the exposed population due to surrounding structures. Development of biodosimetry assays for triage and treatment requires knowledge of the radiation dose-volume effect for the bone marrow (BM). This proof-of-concept study was designed to quantify BM damage in the non-human primate (NHP) after exposure to one of four radiation patterns likely to occur in a radiological/nuclear attack with varying levels of BM sparing. Rhesus macaques (11 males, 12 females; 5.30-8.50 kg) were randomized by weight to one of four arms: 1. bilateral total-body irradiation (TBI); 2. unilateral TBI; 3. bilateral upper half-body irradiation (UHBI); and 4. bilateral lower half-body irradiation (LHBI). The match-point for UHBI vs. LHBI was set at 1 cm above the iliac crest. Animals were exposed to 4 Gy of 6 MV X rays. Peripheral blood samples were drawn 14 days preirradiation and at days 1, 3, 5, 7 and 14 postirradiation. Dosimetric measurements after irradiation indicated that dose to the mid-depth xiphoid was within 6% of the prescribed dose. No high-grade fever, weight loss >10%, dehydration or respiratory distress was observed. Animals in the bilateral- and unilateral TBI arms presented with hematologic changes [e.g., absolute neutrophil count (ANC) <500/ll; platelets <50,000/ll] and clinical signs/symptoms (e.g., petechiae, ecchymosis) characteristic of the acute radiation syndrome. Animals in the bilateral UHBI arm presented with myelosuppression; however, none of the animals developed severe neutropenia or thrombocytopenia (ANC remained >500/µl; platelets >50,000/µl during 14-day follow-up). In contrast, animals in the LHBI arm (1 cm above the ilieac crest to the toes) were protected against BM toxicity with no marked changes in hematological parameters and only minor gross pathology [petechiae (1/5), splenomegaly (1/5) and mild pulmonary hemorrhage (1/5)]. The model performed as expected with respect to the dose-volume effect of total versus partial-BM irradiation, e.g., increased shielding resulted in reduced BM toxicity. Shielding of the major blood-forming organs (e.g., skull, ribs, sternum, thoracic and lumbar spine) spared animals from bone marrow toxicity. These data suggest that the biological consequences of the absorbed dose are dependent on the total volume and pattern of radiation exposure.