Overview of medical physics education and research programs in a non-academic environment.

Northwest Medical Physics Center (NMPC) is a nonprofit organization that provides clinical physics support to over 35 radiation therapy facilities concentrated in the Pacific Northwest. Although clinical service is the primary function of NMPC, the diverse array of clinical sites and physics expertise has allowed for the establishment of structured education and research programs, which are complementary to the organization's clinical mission. Three clinical training programs have been developed at NMPC: a therapy medical physics residency program accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), an Applied Physics Technologist (APT) program, and a summer undergraduate internship program. A partnership has also been established with a major radiation oncology clinical vendor for the purposes of validating and testing new clinical devices across multiple facilities. These programs are managed by a dedicated education and research team at NMPC, made up of four qualified medical physicists (QMPs). The education and research work has made a significant contribution to the organization's clinical mission, and it has provided new training opportunities for early-career physicists across many different clinical environments. Education and research can be incorporated into nonacademic clinical environments, improving the quality of patient care, and increasing the number and type of training opportunities available for medical physicists.

Determination of commissioning criteria for multileaf-collimator, stereotactic radiosurgery treatments on Varian TrueBeam and Edge machines using a novel anthropomorphic phantom.

An anthropomorphic phantom has been developed by Varian Medical Systems for commissioning multileaf-collimator (MLC), stereotactic radiosurgery (SRS) treatments on Varian TrueBeam and Edge linear accelerators. Northwest Medical Physics Center (NMPC) has collected end-to-end data on these machines, at six independent clinical sites, to establish baseline dosimetric and geometric commissioning criteria for SRS measurements with this phantom. The Varian phantom is designed to accommodate four interchangeable target cassettes, each designed for a specific quality assurance function. End-to-end measurements utilized the phantom to verify the coincidence of treatment isocenter with a hidden target in a Winston-Lutz cassette after localization using cone-beam computed tomography (CBCT). Dose delivery to single target (2 cm) and single-isocenter, multitarget (2 and 1 cm) geometries was verified using ionization chamber and EBT3 film cassettes. A nominal dose of 16 Gy was prescribed for each plan using a site's standard beam geometry for SRS cases. Measurements were performed with three Millennium and three high-definition MLC machines at beam energies of 6-MV and 10-MV flattening-filter-free energies. Each clinical site followed a standardized procedure for phantom simulation, treatment planning, quality assurance, and treatment delivery. All treatment planning and delivery was performed using ARIA oncology information system and Eclipse treatment planning software. The isocenter measurements and irradiated film were analyzed using DoseLab quality assurance software; gamma criteria of 3%/1 mm, 3%/0.5 mm, and 2%/1 mm were applied for film analysis. Based on the data acquired in this work, the recommended commissioning criteria for end-to-end SRS measurements with the Varian phantom are as follows: coincidence of treatment isocenter and CBCT-aligned hidden target < 1 mm, agreement of measured chamber dose with calculated dose ≤ 5%, and film gamma passing > 90% for gamma criteria of 3%/1 mm after DoseLab auto-registration shifts ≤ 1 mm in any direction.

Identification of miRNA Associated with Reduced Survival after Whole-Thorax Lung Irradiation in Non-Human Primates.

Thoracic exposure to ionizing radiation can lead to delayed injuries to the heart and lung that are serious and even life-threatening. These injuries are difficult to predict since they manifest over many weeks and months. To identify noninvasive, tissue-specific biomarkers for the early detection of late radiation injury, circulating microRNA (miRNA) levels were measured in non-human primates (NHP, Macaca mulatta) that received a single exposure of whole-thorax lung irradiation (WTLI) at a dose likely to result in 20% or 75% mortality within 180 days (9.8 or 10.7 Gy). Animals were observed for 270 days after WTLI. Approximately 58% of 9.8 Gy WTLI animals (7 of 12) and 94% of 10.7 Gy WTLI animals (15 out of 16) did not survive to the primary end point. Evidence of pulmonary fibrosis/pneumonitis was observed in all animals. Animals that received 10.7 Gy WTLI experienced more severe and early-onset pneumonitis, as indicated by reduced aerated lung volume, high non-sedated respiratory rate, earlier and more frequent dexamethasone treatments, and evidence of onset of heart disease. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days postirradiation, before the manifestation of symptoms, and included miRNA sequences known to regulate pathways associated with pulmonary fibrosis (TGF-ß/SMAD signaling) and pneumonitis/inflammation (p53 signaling). The abundance of several circulating miRNA differentially expressed at day 6 or 15, such as miR-199a-3p and miR-25-3p, correlated with statistically significant differences in survival. This study supports the hypothesis that it is feasible to use plasma miRNA profiles to identify individuals at high risk of organ-specific late radiation injury. These miRNA profiles could improve radiation oncology clinical practice and serve as biomarkers to predict who might develop late complications in the aftermath of a radiological or nuclear (RAD-NUC) incident.

A gottingen minipig model of radiation-induced coagulopathy.

PURPOSE: Total body irradiation of the Gottingen minipig results in a characteristic hematopoietic response, including anemia, neutropenia, lymphocytopenia, and thrombocytopenia. Currently, there are no well-characterized large or small animal models for radiation-induced thrombocytopenia. The study described here using the Gottingen minipig was focused on understanding which aspects of the coagulation cascade leads to radiation-induced coagulopathy. In this study, multiple clinical pathology parameters were determined prior to and for 45-days following total body irradiation using a 6 MV photon linear accelerator. MATERIALS AND METHODS: Following irradiation, frequent analyses of conventional hematology and coagulation parameters provided time-course information on the onset and recovery of thrombocytopenia. In addition, thromboelastography (TEG) was utilized to monitor coagulation dysfunction, namely clotting time, clot formation time, clot strength, and fibrinolysis. Coagulation factor activity levels were measured for factors II, V, VII, VIII, IX, X, XI, XII, XIII, Protein C, fibrin monomers, antiplasmin and D-dimer using a Siemen's coagulation analyzer to provide time course information of changes in activity post irradiation exposure. RESULTS: These analyses revealed that in total body irradiated minipigs, TEG tracings demonstrate long R (time to initial clot formation) and K (time to achieve a certain clot strength) times, and low alpha-angle (rate of clot formation) and MA (overall stability of the clot) during onset of thrombocytopenia (typically post irradiation day 10-15). Low alpha-angle and MA directly correlated with decreased platelet counts. A long R time is suggestive of a deficiency in clotting factors and was compared to measured activity levels of individual coagulation factors. The data indicates that coagulation factors are significantly changed early after irradiation exposure prior to thrombocytopenia and factors VIII, XI, XII and XIII are markedly altered during the critical point of thrombocytopenia. CONCLUSION: These data support the continued use of multiple approaches to evaluate the coagulation cascade in order to provide the most meaningful interpretation of the hematopoietic changes that occur post irradiation.

The impact of supportive care on survival in large animal models of total body irradiation.

PURPOSE: Well-characterized animal models that mimic the human response to potentially lethal doses of radiation are necessary in order to assess the efficacy of candidate medical countermeasures under the criteria of the U.S. Food and Drug Administration 'Animal Rule'. Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity under scenarios likely to be present in the human population during mass casualty situations. These scenarios include understanding the impact of medical management on survival of the hematopoietic acute radiation syndrome (H-ARS). Little information is available to compare the impact of medical management under identical study conditions. The work presented here provides a comparison of the impact of different levels of medical management (supportive care) on the survival outcome in two large animal models: the male Gottingen minipig and the male rhesus macaque (NHP). MATERIALS AND METHODS: In the context of this comparison, limited supportive care consisted of administration of analgesics only, standard supportive care consisted of prophylactic administration of analgesics, antibiotics and fluids (minipigs) or analgesics, antibiotics, antidiarrheals, nutritional and fluid support (NHP) on a set schedule regardless of indication, and full supportive care (NHP only) consisted of analgesics, antibiotics, antidiarrheals, nutritional and fluid support, antiemetics and blood transfusions on an individual animal, trigger-to-treat regimen. Regardless of level of supportive care, minipigs were exposed to total body irradiation using a Co60 source and NHPs were exposed to total body irradiation using 6 MV photon energy. RESULTS: Based on estimated LD50 values, the inclusion of antimicrobial or broad-spectrum antibiotics provided a dose modifying factor (DMF) of 1.09 in the minipig, and by 1.15 in the NHP (standard supportive care to limited supportive care ratio. For the NHP, the administration of supportive care based on symptomology rather than a set schedule, and inclusion of blood transfusions yielded a DMF of 1.05 (full supportive care to standard supportive care ratio). Conversely, comparison of the estimated LD50 values between full supportive care and limited supportive care in the NHP provided a DMF of 1.21. CONCLUSION: The study reported here provides a comparison of the impact of antibiotic administration on radiation-induced lethality.

VMAT testing for an Elekta accelerator.

Volumetric-modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity-modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability.