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).

A practical cyberattack contingency plan for radiation oncology.

PURPOSE: This article presents a solution for continuing radiation therapy without interruption in the event of a cyberattack to the radiation oncology information systems (ROIS). This process could be easily deployed to any radiation oncology practice, with little clinical overhead or burden. METHODS AND MATERIALS: The solution automatically retrieves all essential information from the clinical ROIS for each under-treatment patient and periodically (e.g., daily) saves these data to a dedicated secure server for recovery. In the event that the clinical ROIS is not functioning as a result of a cyberattack, this essential information is used to build a new secondary ROIS server to continue radiotherapy treatments until the main ROIS is recovered. Once the cyberattack threat is cleared, the clinical ROIS server is rebuilt from the institution's enterprise backup. The newly accumulated treatment information for each patient is then exported from the secondary ROIS to bring the clinical ROIS up to date. RESULTS: The Department of Radiation Oncology at the University of Maryland Medical System implemented this solution for clinical use with the Varian ARIA ROIS in the management of ~250 daily radiotherapy treatments, inclusive of a proton center. This solution was determined to be a feasible and affordable business continuity plan for the radiation oncology practice by minimizing radiation treatment downtime to a couple of hours in a simulated cyberattack drill. CONCLUSIONS: The proposed solution can achieve continuation of radiation therapy treatment without treatment breaks in the event of a cyberattack. It also provides cushion time for radiation oncology departments to rebuild their clinical ROIS systems from the enterprise data backup.

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.

Action Levels on Dose and Anatomic Variation for Adaptive Radiation Therapy Using Daily Offline Plan Evaluation: Preliminary Results.

PURPOSE: This study aimed to develop action levels for replanning to accommodate dosimetric variations resulting from anatomic changes during the course of treatments, using daily cone beam computed tomography (CBCT). METHODS AND MATERIALS: Daily or weekly CBCT images of 20 patients (10 head and neck, 5 lung, and 5 prostate cancers) who underwent resimulation per physicians' clinical decisions, mainly from the comparison of CBCT scans, were used to determine action levels. The first CBCT image acquired before the first treatment was used as the reference image to rule out effects of dose inaccuracy from the CBCT. The Pearson correlation of clinical target volume (CTV) was used as a parameter of anatomic variation. Parameters for action levels on dose and anatomic variation were deduced by comparing the parameters and clinical decisions made for replanning. A software tool was developed to automatically perform all procedures, including dose calculations, using the CBCT and plan evaluations. RESULTS: Replans were clinically decided based on either significant dose or anatomic changes in 13 cases. The 7 cases that did not require replanning showed dose differences <5%, and the Pearson correlation of the CTV was >75% for all fractions. A difference in planning target volume dose >5% or a difference in the image correlation coefficient of the CTV <0.75 proved to be indicators for replanning. Once the results of the CBCT plan met the replanning criteria, the software tool automatically alerted the attending physician and physicist by both e-mail and pager so that the case could be examined closely. CONCLUSIONS: Our study shows that a dose difference of 5% and/or anatomy variation at 0.75 Pearson correlations are practical action levels on dose and anatomic variation for replanning for the given data sets.

Efficacy of Neulasta or Neupogen on H-ARS and GI-ARS Mortality and Hematopoietic Recovery in Nonhuman Primates After 10-Gy Irradiation With 2.5% Bone Marrow Sparing.

A nonhuman primate model of acute, partial-body, high-dose irradiation with minimal (2.5%) bone marrow sparing was used to assess endogenous gastrointestinal and hematopoietic recovery and the ability of Neulasta (pegylated granulocyte colony-stimulating factor) or Neupogen (granulocyte colony-stimulating factor) to enhance recovery from myelosuppression when administered at an increased interval between exposure and initiation of treatment. A secondary objective was to assess the effect of Neulasta or Neupogen on mortality and morbidity due to the hematopoietic acute radiation syndrome and concomitant gastrointestinal acute radiation syndrome. Nonhuman primates were exposed to 10.0 Gy, 6 MV, linear accelerator-derived photons delivered at 0.80 Gy min. All nonhuman primates received subject-based medical management. Nonhuman primates were dosed daily with control article (5% dextrose in water), initiated on day 1 postexposure; Neulasta (300 µg kg), administered on days 1, 8, and 15 or days 3, 10, and 17 postexposure; or Neupogen (10 µg kg), administered daily postexposure following its initiation on day 1 or day 3 until neutrophil recovery (absolute neutrophil count ≥1,000 cells µL for 3 consecutive days). Mortality in the irradiated cohorts suggested that administration of Neulasta or Neupogen on either schedule did not affect mortality due to gastrointestinal acute radiation syndrome or mitigate mortality due to hematopoietic acute radiation syndrome (plus gastrointestinal damage). Following 10.0 Gy partial-body irradiation with 2.5% bone marrow sparing, the mean duration of neutropenia (absolute neutrophil count <500 cells µL) was 22.4 d in the control cohort vs. 13.0 and 15.3 d in the Neulasta day 1, 8, 15 and day 3, 10, 17 cohorts, relative to 16.2 and 17.4 d in the Neupogen cohorts initiated on day 1 and day 3, respectively. The absolute neutrophil count nadirs were 48 cells µL in the controls; 117 cells µL and 40 cells µL in the Neulasta days 1, 8, and 15 or days 3, 10, and 17 cohorts, respectively; and 75 cells µL and 37 cells µL in the Neupogen day 1 and day 3 cohorts, respectively. Therefore, the earlier administration of Neulasta or Neupogen was more effective in this model of marginal 2.5% bone marrow sparing. The approximate 2.5% bone marrow sparing may approach the threshold for efficacy of the lineage-specific medical countermeasure. The partial-body irradiation with 2.5% bone marrow sparing model can be used to assess medical countermeasure efficacy in the context of the concomitant gastrointestinal and hematopoietic acute radiation syndrome sequelae.

Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density curve to determine time of replanning.

PURPOSE: (a) To investigate the accuracy of cone-beam computed tomography (CBCT)-derived dose distributions relative to fanbeam-based simulation CT-derived dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the appropriateness of replanning. METHODS AND MATERIALS: Image data corresponding to 40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were randomly selected. Each patient had both intensity-modulated radiation therapy and volumetric-modulated arc therapy plans; these 80 plans were subsequently recomputed on the CBCT images using a patient-specific stepwise curve (Hounsfield units-to-density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation-CT-derived treatment plans and CBCT-based plans. Gamma analyses were performed using criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT-derived doses were then used to evaluate the appropriateness of replanning decisions in 12 additional HN patients whose plans were previously revised during radiation therapy because of anatomic changes; replanning in these cases was guided by the conventional observed source-to-skin-distance change-derived approach. RESULTS: For all disease sites, the difference in PTV mean dose was 0.1% ± 1.1%, D2% was 0.7% ± 0.1%, D95% was 0.2% ± 1.1%, D98% was 0.2% ± 1.0%, and V95% was 0.3% ± 0.8%; For 3D dose comparison, 99.0% ± 1.9%, 97.6% ± 4.4%, and 95.3% ± 6.0% of points passed the 3%/3 mm criterion of gamma analysis in high-, medium-, and low-dose zones, respectively. The CBCT images achieved comparable dose distributions. In the 12 previously replanned 12 HN patients, CBCT-based dose predicted well changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the replanning criteria, 7/12 patients could avoid replanning. CONCLUSIONS: CBCT-based dose calculations produced accuracy comparable to that of simulation CT. CBCT-based dosimetry can guide the decision to replan during the course of treatment.

AEOL 10150 Mitigates Radiation-Induced Lung Injury in the Nonhuman Primate: Morbidity and Mortality are Administration Schedule-Dependent.

Pneumonitis and fibrosis are potentially lethal, delayed effects of acute radiation exposure. In this study, male rhesus macaques received whole-thorax lung irradiation (WTLI) with a target dose of 10.74 Gy prescribed to midplane at a dose rate of 0.80 ± 0.05 Gy/min using 6 MV linear accelerator-derived photons. The study design was comprised of four animal cohorts: one control and three treated with AEOL 10150 (n = 20 animals per cohort). AEOL 10150, a metalloporphyrin antioxidant, superoxide dismutase mimetic was administered by daily subcutaneous injection at 5 mg/kg in each of three schedules, beginning 24 ± 2 h postirradiation: from day 1 to day 28, day 1 to day 60 or a divided regimen from day 1 to day 28 plus day 60 to day 88. Control animals received 0.9% saline injections from day 1 to day 28. All animals received medical management and were followed for 180 days. Computed tomography (CT) scan and baseline hematology values were assessed prior to WTLI. Postirradiation monthly CT scans were collected, and images were analyzed for evidence of lung injury (pneumonitis, fibrosis, pleural and pericardial effusion) based on differences in radiodensity characteristics of the normal versus damaged lung. The primary end point was survival to 180 days based on all-cause mortality. The latency, incidence and severity of lung injury were assessed through clinical, radiographic and histological parameters. A clear survival relationship was observed with the AEOL 10150 treatment schedule and time after lethal WTLI. The day 1-60 administration schedule increased survival from 25 to 50%, mean survival time of decedents and the latency to nonsedated respiratory rate to >60 or >80 breaths/min and diminished quantitative radiographic lung injury as determined by CT scans. It did not affect incidence or severity of pneumonitis/fibrosis as determined by histological evaluation, pleural effusion or pericardial effusion as determined by CT scans. Analysis of the Kaplan-Meier survival curves suggested that treatment efficacy could be increased by extending the treatment schedule to 90 days or longer after WTLI. No survival improvement was noted in the AEOL 10150 cohorts treated from day 1-28 or using the divided schedule of day 1-28 plus day 60-88. These results suggest that AEOL 10150 may be an effective medical countermeasure against severe and lethal radiation-induced lung injury.

Clinical implementation of an electron monitor unit dosimetry system based on task group 71 report and a commercial calculation program.

Many clinics still use monitor unit (MU) calculations for electron treatment planning and/or quality assurance (QA). This work (1) investigates the clinical implementation of a dosimetry system including a modified American Association of Physicists in Medicine-task group-71 (TG-71)-based electron MU calculation protocol (modified TG-71 electron [mTG-71E] and an independent commercial calculation program and (2) provides the practice recommendations for clinical usage. Following the recently published TG-71 guidance, an organized mTG-71E databook was developed to facilitate data access and subsequent MU computation according to our clinical need. A recently released commercial secondary calculation program - Mobius3D (version 1.5.1) Electron Quick Calc (EQC) (Mobius Medical System, LP, Houston, TX, USA), with inherent pencil beam algorithm and independent beam data, was used to corroborate the calculation results. For various setups, the calculation consistency and accuracy of mTG-71E and EQC were validated by their cross-comparison and the ion chamber measurements in a solid water phantom. Our results show good agreement between mTG-71E and EQC calculations, with average 2% difference. Both mTG-71E and EQC calculations match with measurements within 3%. In general, these differences increase with decreased cutout size, increased extended source to surface distance, and lower energy. It is feasible to use TG71 and Mobius3D clinically as primary and secondary electron MU calculations or vice versa. We recommend a practice that only requires patient-specific measurements in rare cases when mTG-71E and EQC calculations differ by 5% or more.

Optimizing the MLC model parameters for IMRT in the RayStation treatment planning system.

Unlike other commercial treatment planning systems (TPS) which model the rounded leaf end differently (such as the MLC dosimetric leaf gap (DLG) or rounded leaf-tip radius), the RayStation TPS (RaySearch Laboratories, Stockholm, Sweden) models transmission through the rounded leaf end of the MLC with a step function, in which the radiation transmission through the leaf end is the square root of the average MLC transmission factor. We report on the optimization of MLC model parameters for the RayStation planning system. This (TPS) models the rounded leaf end of the MLC with the following parameters: eaf-tip offset, leaf-tip width, average transmission factor, and tongue and groove. We optimized the MLC model parameters for IMRT in the RayStation v. 4.0 planning system and for a Varian C-series linac with a 120-leaf Millennium MLC, and validated the model using measured data. The leaf-tip offset is the geometric offset due to the rounded leaf-end design and resulting divergence of the light/radiation field. The offset value is a function of the leaf-tip position, and tabulated data are available from the vendor. The leaf-tip width was iteratively evaluated by comparing computed and measured transverse dose profiles of MLC defined fields at dmax in water. In-water profile comparisons were also used to verify the MLC leaf position (leaf-tip offset). The average transmission factor and leaf tongue-and-groove width were derived iteratively by maximizing the agreement between measurements and RayStation TPS calculations for five clinical IMRT QA plans. Plan verifications were performed by comparing MapCHECK2 measurements and Monte Carlo calculations. The MLC model was validated using five test IMRT cases from the AAPM Task Group 119 report. Absolute gamma analyses (3 mm/3% and 2 mm/2%) were applied. In addition, computed output factors for MLC-defined small fields (2 × 2, 3 × 3, 4 × 4, 6× 6cm2) of both 6 MV and 18 MV photons were compared to those independently measured by the Imaging and Radiation Oncology Core (IROC), Houston, TX. 6MV and 18 MV models were both determined to have the same MLC parameters: leaf-tip offset = 0.3 cm, 2.5% transmission, and leaf tongue-and-groove width = 0.05 cm. IMRT QA analysis for five test cases in TG-119 resulted in a 100% passing rate with 3 mm/3% gamma analysis for 6 MV, and > 97.5% for 18 MV. The passing rate was > 94.6% for 6 MV and > 90.9% for 18 MV when the 2 mm/2% gamma analysis criteria was applied. These results compared favorably with those published in AAPM Task Group 119. The reported MLC model parameters serve as a reference for other users.

Mean Organ Doses Resulting From Non-Human Primate Whole Thorax Lung Irradiation Prescribed to Mid-Line Tissue.

Multi-organ dose evaluations and the effects of heterogeneous tissue dose calculations have been retrospectively evaluated following irradiation to the whole thorax and lung in non-human primates (NHP). A clinical-based approach was established to evaluate actual doses received in the heart and lungs during whole thorax lung irradiation. Anatomical structure and organ densities have been introduced in the calculations to show the effects of dose distribution through heterogeneous tissue. Mean organ doses received by non-human primates undergoing whole thorax lung irradiations were calculated using a treatment planning system that is routinely used in clinical radiation oncology. The doses received by non-human primates irradiated following conventional dose calculations have been retrospectively reconstructed using computerized tomography-based, heterogeneity-corrected dose calculations. The use of dose volume descriptors for irradiation to organs at risk and tissue exposed to radiation is introduced. Mean and partial-volume doses to lung and heart are presented and contrasted. The importance of exact dose definitions is highlighted, and the relevance of precise dosimetry to establish organ-specific dose response relationships in NHP models of acute and delayed effects of acute radiation exposure is emphasized.

The Effect of Radiation Dose and Variation in Neupogen® Initiation Schedule on the Mitigation of Myelosuppression during the Concomitant GI-ARS and H-ARS in a Nonhuman Primate Model of High-dose Exposure with Marrow Sparing.

A nonhuman primate (NHP) model of acute high-dose, partial-body irradiation with 5% bone marrow (PBI/BM5) sparing was used to assess the effect of Neupogen® [granulocyte colony stimulating factor (G-CSF)] to mitigate the associated myelosuppression when administered at an increasing interval between exposure and initiation of treatment. A secondary objective was to assess the effect of Neupogen® on the mortality or morbidity of the hematopoietic (H)- acute radiation syndrome (ARS) and concurrent acute gastrointestinal radiation syndrome (GI-ARS). NHP were exposed to 10.0 or 11.0 Gy with 6 MV LINAC-derived photons at approximately 0.80 Gy min. All NHP received medical management. NHP were dosed daily with control article (5% dextrose in water) initiated on day 1 post-exposure or Neupogen® (10 µg kg) initiated on day 1, day 3, or day 5 until recovery [absolute neutrophil count (ANC) ≥ 1,000 cells µL for three consecutive days]. Mortality in both the 10.0 Gy and 11.0 Gy cohorts suggested that early administration of Neupogen® at day 1 post exposure may affect acute GI-ARS mortality, while Neupogen® appeared to mitigate mortality due to the H-ARS. However, the study was not powered to detect statistically significant differences in survival. The ability of Neupogen® to stimulate granulopoiesis was assessed by evaluating key parameters for ANC recovery: the depth of nadir, duration of neutropenia (ANC < 500 cells µL) and recovery time to ANC ≥ 1,000 cells µL. Following 10.0 Gy PBI/BM5, the mean duration of neutropenia was 11.6 d in the control cohort vs. 3.5 d and 4.6 d in the day 1 and day 3 Neupogen® cohorts, respectively. The respective ANC nadirs were 94 cells µL, 220 cells µL, and 243 cells µL for the control and day 1 and day 3 Neupogen® cohorts. Following 11.0 Gy PBI/BM5, the duration of neutropenia was 10.9 d in the control cohort vs. 2.8 d, 3.8 d, and 4.5 d in the day 1, day 3, and day 5 Neupogen® cohorts, respectively. The respective ANC nadirs for the control and day 1, day 3, and day 5 Neupogen® cohorts were 131 cells µL, 292 cells µL, 236 cells µL, and 217 cells µL, respectively. Therefore, the acceleration of granulopoiesis by Neupogen® in this model is independent of the time interval between radiation exposure and treatment initiation up to 5 d post-exposure. The PBI/BM5 model can be used to assess medical countermeasure efficacy in the context of the concurrent GI- and H-ARS.

Automated compromised right lung segmentation method using a robust atlas-based active volume model with sparse shape composition prior in CT.

To resolve challenges in image segmentation in oncologic patients with severely compromised lung, we propose an automated right lung segmentation framework that uses a robust, atlas-based active volume model with a sparse shape composition prior. The robust atlas is achieved by combining the atlas with the output of sparse shape composition. Thoracic computed tomography images (n=38) from patients with lung tumors were collected. The right lung in each scan was manually segmented to build a reference training dataset against which the performance of the automated segmentation method was assessed. The quantitative results of this proposed segmentation method with sparse shape composition achieved mean Dice similarity coefficient (DSC) of (0.72, 0.81) with 95% CI, mean accuracy (ACC) of (0.97, 0.98) with 95% CI, and mean relative error (RE) of (0.46, 0.74) with 95% CI. Both qualitative and quantitative comparisons suggest that this proposed method can achieve better segmentation accuracy with less variance than other atlas-based segmentation methods in the compromised lung segmentation.

Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 µg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/µL, ANC ≥1,000/µL and platelet (PLT) count ≥20,000/µL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data demonstrate that pegfilgrastim is an additional medical countermeasure capable of increasing survival and neutrophil-related parameters when administered in an abbreviated schedule to a NHP model of lethal H-ARS.

A six-year review of more than 13,000 patient-specific IMRT QA results from 13 different treatment sites.

Due to a lack of information regarding the current clinical experience of IMRT QA for a large and varied plan population, we reviewed our patient-specific IMRT quality assurance (QA) results for 13,003 treatment plans from 13 distinct treatment sites from a six-year period. QA records were reviewed for dose difference (single point with ion chamber measurement; ± 3% agreement criteria) and percentage of pixels passing relative dose gamma analysis (film measurement; 90% passing 5%(global)/3 mm agreement criteria) from 2005 through 2011. Plan records were analyzed for trends with measurement date and treatment site. Plans failing to meet QA tolerance criteria were evaluated for follow-up clinical action (i.e., if repeat measurements were performed). The mean difference (± SD) between ion chamber point measurements and calculated doses was -0.29% ± 1.64% (calculated values being slightly higher) and, regarding planar dose evaluations, the mean percentage of pixels passing the gamma criteria of 5%(global)/3 mm was 97.7% (lower 95th percentile: 92.2%). 97.7% and 99.3% of plans passed the point dose and planar dose verification, respectively. We observed statistically significant differences (p< 0.05) in both point dose and planar dose verification measurements as a function of treatment site (particularly for stereotactic spine and mesothelioma sites) and measurement date (average agreement improved with time). However, despite improved dosimetric agreement, the percentage of failing plans has remained nearly constant at 2.3%.

An analytical formalism to calculate phantom scatter factors for flattening filter free (FFF) mode photon beams.

Phantom Scatter Factors, Sp in the Khan formalism (Khan et al 1980 J. Radiat. Oncol. Biol. Phys. 6 745-51) describe medium-induced changes in photon-beam intensity as a function of size of the beam. According to the British Journal of Radiology, Supplement 25, megavoltage phantom scatter factors are invariant as a function of photon-beam energy. However, during the commissioning of an accelerator with flattening filter free (FFF) photon beams (Varian TrueBeam(TM) 6-MV FFF and 10-MV FFF), differences were noted in phantom scatter between the filtered beams and FFF-mode beams. The purpose of this work was to evaluate this difference and provide an analytical formalism to explain the phantom scatter differences between FFF-mode and the filtered mode. An analytical formalism was devised to demonstrate the source of phantom scatter differences between the filtered and the FFF-mode beams. The reason for the differences in the phantom scatter factors between the filtered and the FFF-mode beams is hypothesized to be the non-uniform beam profiles of the FFF-mode beams. The analytical formalism proposed here is based on this idea, taking the product of the filtered phantom scatter factors and the ratio of the off-axis ratio between the FFF-mode and the filtered beams. All measurements were performed using a Varian TrueBeam(TM) linear accelerator with photon energies of 6-MV and 10-MV in both filtered and FFF-modes. For all measurements, a PTW Farmer type chamber and a Scanditronix CC04 cylindrical ionization were used. The in-water measurements were made at depth dose maximum and 100 cm source-to-axis distance. The in-air measurements were done at 100 cm source-to-axis distance with appropriate build-up cap. From these measurements, the phantom scatter factors were derived for the filtered beams and the FFF-mode beams for both energies to be evaluated against the phantoms scatter factors calculated using the proposed algorithm. For 6-MV, the difference between the measured and the calculated FFF-mode phantom scatter factors ranged from -0.34% to 0.73%. The average per cent difference was -0.17% (1σ = 0.25%). For 10-MV, the difference ranged from -0.19% to 0.24%. The average per cent difference was -0.17% (1σ = 0.13%). An analytical formalism was presented to calculate the phantom scatter factors for FFF-mode beams using filtered phantom scatter factors as a basis. The overall differences between measurements and calculations were within ± 0.5% for 6-MV and ± 0.25% for 10-MV.

The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 µg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells µL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage.

The objective of this pilot study was to explore whether administration of a catalytic antioxidant, AEOL 10150 (C48H56C15MnN12), could reduce radiation-induced lung injury and improve overall survival when administered after 11.5 Gy of whole thorax lung irradiation in a non-human primate model. Thirteen animals were irradiated with a single exposure of 11.5 Gy, prescribed to midplane, and delivered with 6 MV photons at a dose rate of 0.8 Gy min. Beginning at 24 h post irradiation, the AEOL 10150 cohort (n = 7) received daily subcutaneous injections of the catalytic antioxidant at a concentration of 5 mg kg for a total of 4 wk. All animals received medical management, including dexamethasone, based on clinical signs during the planned 180-d in-life phase of the study. All decedent study animals were euthanized for failure to maintain saturation of peripheral oxygen > 88% on room air. Exposure of the whole thorax to 11.5 Gy resulted in radiation-induced lung injury in all animals. AEOL 10150, as administered in this pilot study, demonstrated potential efficacy as a mitigator against fatal radiation-induced lung injury. Treatment with the drug resulted in 28.6% survival following exposure to a radiation dose that proved to be 100% fatal in the control cohort (n = 6). Computed tomography scans demonstrated less quantitative radiographic injury (pneumonitis, fibrosis, effusions) in the AEOL 10150-treated cohort at day 60 post-exposure, and AEOL 10150-treated animals required less dexamethasone support during the in-life phase of the study. Analysis of serial plasma samples suggested that AEOL 10150 treatment led to lower relative transforming growth factor-Beta-1 levels when compared with the control animals. The results of this pilot study demonstrate that treatment with AEOL 10150 results in reduced clinical, radiographic, anatomic, and molecular evidence of radiation-induced lung injury and merits further study as a medical countermeasure against radiation-induced pulmonary injury.

The MCART radiation physics core: the quest for radiation dosimetry standardization.

Dose-related radiobiological research results can only be compared meaningfully when radiation dosimetry is standardized. To this purpose, the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Medical Countermeasures Against Radiological Threats (MCART) consortium recently created a Radiation Physics Core (RPC) as an entity to assume responsibility of standardizing radiation dosimetry practices among its member laboratories. The animal research activities in these laboratories use a variety of ionizing photon beams from several irradiators such as 250-320 kVp x-ray generators, Cs irradiators, Co teletherapy machines, and medical linear accelerators (LINACs). In addition to this variety of sources, these centers use a range of irradiation techniques and make use of different dose calculation schemes to conduct their experiments. An extremely important objective in these research activities is to obtain a Dose Response Relationship (DRR) appropriate to their respective organ-specific models of acute and delayed radiation effects. A clear and unambiguous definition of the DRR is essential for the development of medical countermeasures. It is imperative that these DRRs are transparent between centers. The MCART RPC has initiated the establishment of standard dosimetry practices among member centers and is introducing a Remote Dosimetry Monitoring Service (RDMS) to ascertain ongoing quality assurance. This paper will describe the initial activities of the MCART RPC toward implementing these standardization goals. It is appropriate to report a summary of initial activities with the intent of reporting the full implementation at a later date.

Dosimetric and geometric evaluation of a novel stereotactic radiotherapy device for breast cancer: the GammaPod™.

PURPOSE: A dedicated stereotactic gamma irradiation device, the GammaPod™ from Xcision Medical Systems, was developed specifically to treat small breast cancers. This study presents the first evaluation of dosimetric and geometric characteristics from the initial prototype installed at University of Maryland Radiation Oncology Department. METHODS: The GammaPod™ stereotactic radiotherapy device is an assembly of a hemi-spherical source carrier containing 36 (60)Co sources, a tungsten collimator, a dynamically controlled patient support table, and the breast immobilization system which also functions as a stereotactic frame. The source carrier contains the sources in six columns spaced longitudinally at 60° intervals and it rotates together with the variable-size collimator to form 36 noncoplanar, concentric arcs focused at the isocenter. The patient support table enables motion in three dimensions to position the patient tumor at the focal point of the irradiation. The table moves continuously in three cardinal dimensions during treatment to provide dynamic shaping of the dose distribution. The breast is immobilized using a breast cup applying a small negative pressure, where the immobilization cup is embedded with fiducials also functioning as the stereotactic frame for the breast. Geometric and dosimetric evaluations of the system as well as a protocol for absorbed dose calibration are provided. Dosimetric verifications of dynamically delivered patient plans are performed for seven patients using radiochromic films in hypothetical preop, postop, and target-in-target treatment scenarios. RESULTS: Loaded with 36 (60)Co sources with cumulative activity of 4320 Ci, the prototype GammaPod™ unit delivers 5.31 Gy/min at the isocenter using the largest 2.5 cm diameter collimator. Due to the noncoplanar beam arrangement and dynamic dose shaping features, the GammaPod™ device is found to deliver uniform doses to targets with good conformity. The spatial accuracy of the device to locate the radiation isocenter is determined to be less than 1 mm. Single shot profiles with 2.5 cm collimator are measured with radiochromic film and found to be in good agreement with respect to the Monte Carlo based calculations (congruence of FWHM less than 1 mm). Dosimetric verifications corresponding to all hypothetical treatment plans corresponding to three target scenarios for each of the seven patients demonstrated good agreement with gamma index pass rates of better than 97% (99.0% ± 0.7%). CONCLUSIONS: Dosimetric evaluation of the first GammaPod™ stereotactic breast radiotherapy unit was performed and the dosimetric and spatial accuracy of this novel technology is found to be feasible with respect to clinical radiotherapy standards. The observed level of agreement between the treatment planning system calculations and dosimetric measurements has confirmed that the system can deliver highly complex treatment plans with remarkable geometric and dosimetric accuracy.