Initial experience with an electron FLASH research extension (FLEX) for the Clinac system.

PURPOSE: Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. METHODS: A linear accelerator (Clinac 23EX) was modified to include a non-clinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. RESULTS: The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached a maximum dose rate >3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10 × 10 cm2 . The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. CONCLUSION: Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists.

Predictors of patient radiation exposure during transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes patients to radiation. OBJECTIVES: We sought to identify factors associated with higher radiation exposure and to quantify their relative influence, which may inform reduction of this hazard. METHODS: All TAVR procedures at Rhode Island Hospital between March 20, 2012 and February 12, 2017 were included. Procedures were performed by two co-primary operators using a Siemens Artis Zeego system. Radiation metrics were generated by the imaging system. The primary metric was dose-area product (DAP, Gy*cm2 ), and secondary metrics were reference point air kerma (mGy) and fluoroscopy time (minutes). Data collected for the STS/ACC TVT Registry were utilized to develop a multivariable linear regression model predicting DAP. RESULTS: In 294 TAVRs, median DAP was 169 Gy*cm2 [interquartile range (IQR) 106-238]. The r2 values for the full 27-variable DAP model and reduced eight-variable model were 0.457 and 0.420, respectively. Valve area, aortic insufficiency, and procedure year (suggesting absence of a learning curve) were non-significant predictors in the full model, while increasing weight, cutdown transfemoral access, higher pre-procedure creatinine and hemoglobin, and vascular complications predicted higher DAP in both models. Results were unchanged when DAP was log-transformed. Secondary models for air kerma and fluoroscopy time revealed similar predictors. CONCLUSION: Factors associated with increased procedural complexity and duration as well as radiation attenuation and scatter predict increased patient radiation exposure during TAVR. Modification of procedural technique, especially using percutaneous femoral vascular access, may facilitate reduction in exposure.

Addressing a radiation safety sentinel event alert: one state's experience.

The Joint Commission issued a Sentinel Event Alert in August 2011 to address the radiation risks related to diagnostic medical imaging. The University of Nebraska Medical Center (UNMC) and Nebraska Coalition for Patient Safety (NCPS) sent a survey to Nebraska hospital radiology departments in May 2012 to solicit responses regarding radiation safety management practices. Survey results demonstrate that Nebraska hospitals perform well in many radiation safety efforts, but lack in others, as well as the need for additional research to track or compare progress. Nebraska's experience can serve as a model for other states to perform similar radiation safety management research.

Patient Radiation Dosage During Lower Extremity Endovascular Intervention.

OBJECTIVES: The aims of this study were to determine the incidence of actionably high radiation dosages and to identify predictors of increased patient dosage. BACKGROUND: Peripheral endovascular intervention using fluoroscopic imaging has become a mainstay of treatment for lower extremity peripheral artery disease but exposes patients to ionizing radiation. METHODS: Patient radiation dosage, quantified as dose-area product (DAP), was obtained from the National Cardiovascular Data Registry Peripheral Vascular Intervention Registry. The percentage of procedures exceeding a DAP of 500 Gy · cm2, the threshold above which follow-up for radiation-related adverse effects is indicated by the National Council on Radiation Protection and Measurements, was determined. A multivariate regression model was generated to identify patient and procedural factors associated with increasing DAP. RESULTS: Among 17,174 procedures performed at 73 sites, patient DAP exceeded 500 Gy · cm2 in 7%. Independent predictors of increased patient DAP in order from greatest magnitude of effect included more proximal lesion location, bifurcation lesion, male sex, diabetes, hypertension, prior percutaneous coronary intervention, increasing lesion length, and increasing body mass index; antegrade vascular access, critical limb ischemia, and increasing age predicted decreased DAP. CONCLUSIONS: Radiation dosage with the potential for tissue injury occurs in 1 of every 14 patients undergoing lower extremity endovascular interventions, and all such patients are exposed to the potential for subsequent malignancy. Pre-procedural assessment of patients' risk for elevated radiation dosage may allow targeted use of radiation mitigation strategies in patients at increased risk for elevated exposure.

Direct and indirect measurement of patient radiation exposure during endovascular aortic aneurysm repair.

With the increasing complexity of endovascular procedures, concern has grown regarding patient radiation exposure. Abdominal aortic aneurysm (AAA) repair represents the most common complex endovascular procedure currently performed by vascular specialists. Our study evaluates the patient radiation dose received during endovascular AAA repair. Over a 3-month period we prospectively monitored the radiation dose in a series of consecutive patients undergoing endovascular AAA repair. All patients underwent standard endovascular AAA repair with one of two commercially available grafts using the GE OEC 9800 unit. Direct measurement of maximum radiation dose at skin level (peak skin dose, PSD) was recorded using GAFCHROMIC radiographic dosimetry film. Indirect measurements of radiation dose (fluoroscopy time and dose-area-product [DAP]) were recorded with the C-arm dosimeter. A total of 12 consecutive patients undergoing standard endovascular AAA repair were evaluated. Mean PSD was 0.75 Gy (range 0.27-1.25). Mean total fluoroscopy time was 20.6 min (range 12.6-34.2) with an average of 92% spent in standard fluoroscopy and 8% spent in cinefluoroscopy. Regarding total fluoroscopy time, 49% was spent in normal field of view and 51% in magnified view. Mean DAP was 15,166 cGy x cm(2) (range 5,207-24,536). PSD correlated with DAP (r = 0.9, p < 0.05) but not total fluoroscopy time (r = 0.18, p > 0.05). PSD also correlated with body mass index (BMI; r = 0.82, p < 0.05). Obese patients had a mean PSD of 1.1 Gy compared to 0.5 Gy in nonobese patients. PSD of all patients was well below the accepted 2.0 Gy threshold for skin injury. PSD correlated with DAP but not total fluoroscopy time. PSD also correlated with BMI, and the mean PSD was significantly increased in obese compared to nonobese patients. Despite the complexity and duration of endovascular AAA repair, the procedure can be performed safely without excessive radiation exposure.

Establishing an institutional model for the administration of tositumomab and iodine I 131 tositumomab.

Radioimmunotherapy with radiolabeled anti-CD20 antibodies is a promising new treatment approach for low-grade non-Hodgkin's lymphoma. However, the administration of radiolabeled antibodies presents some added complexity. At the University of Nebraska Medical Center (Omaha, NE), an institutional model has been developed that ensures the efficient and safe delivery of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA and GlaxoSmithKline, Philadelphia, PA). An integrated, multidisciplinary treatment team is responsible for managing all aspects of treatment. Using this model, it is possible to administer tositumomab and iodine I 131 tositumomab safely and effectively in the outpatient setting. Patients can usually be released immediately after treatment. Guidelines and instructions for patient release have been developed and validated and are provided herein. These instructions ensure that radiation exposure of family members and caregivers who are exposed to the patient is maintained as low as reasonably achievable and well within regulatory limits.

Combination therapy for non-Hodgkin's lymphoma: an opportunity for pharmaceutical care in a specialty practice.

OBJECTIVE: To describe the application of pharmaceutical care practices in the administration of new therapeutic radiopharmaceuticals used in the treatment of non-Hodgkin's lymphoma (NHL). PRACTICE DESCRIPTION: At the Antibody Labeling Facility at the University of Nebraska Medical Center, the nuclear pharmacist provides support in the formulation, preparation, and quality testing of radiopharmaceuticals. The nuclear pharmacist also provides direct patient care by assisting in the administration of radiopharmaceuticals, monitoring patients during their infusions, and counseling patients on radioimmunotherapy and radiation safety. PRACTICE INNOVATION: Expanding the role of the nuclear pharmacist in treating patients with NHL using radiolabeled monoclonal antibodies (MABs). INTERVENTIONS: The nuclear pharmacist provides specialized pharmaceutical care by being involved in planning patient care, administering diagnostic and therapeutic radiopharmaceuticals, performing individualized patient dose calculations, monitoring patients, and counseling patients. MAIN OUTCOME MEASURES: Number of patients treated with radiolabeled MABs. RESULTS: Since January 1996, 85 patients with NHL have been treated using 131I-tositumomab (Corixa, GlaxoSmithKline), an anti-B1 MAB, under various clinical research protocols requiring specialized pharmaceutical care. The nuclear pharmacist on the team provided direct patient care, assisting with the administration of diagnostic and therapeutic radiopharmaceuticals under a collaborative agreement with a nuclear medicine physician or a radiation oncologist. Other pharmaceutical care activities performed include calculating individual patient doses, obtaining medication histories, counseling patients on their therapy and on radiation safety after early release, and monitoring patients for adverse effects during medication infusion. Patients have responded favorably to nontraditional nuclear pharmacy activities. CONCLUSION: The nuclear pharmacist has become an important member of the health care team that provides a new and unique therapy for patients with NHL. To date, the nuclear pharmacist, in collaboration with the nuclear medicine physician or the radiation oncologist, has successfully administered the tositumomab and 131I-tositumomab combination therapy without significant incident.