Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

BACKGROUND: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. METHODS: In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. FINDINGS: In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. CONCLUSIONS: These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. FUNDING: NIH, ASTRO, AHA, Longer Life Foundation.

Technical Note: Dosimetric characterization of the dynamic beam flattening MLC sequence on a ring shaped, Jawless Linear Accelerator with double stacked MLC.

PURPOSE: To characterize the dosimetric features and limitations of the dynamic beam flattening (DBF) on the Halcyon 2.0 linear accelerator (Varian Medical Systems). METHODS: A predefined multi-leaf collimator (MLC) sequence was introduced and used to flatten the 6 MV flattening filter free (FFF) beam on the Halcyon 2.0. Dosimetric characterizations of the flattened beams, including beam flatness, symmetry, percent depth dose (PDD), output factor and MU linearity, were investigated. Flatness and symmetry were obtained from profile measurements with both radiographic films (EDR2) and a two dimensional ion-chamber array (IC Profiler, Sun Nuclear Corporation). MU linearity, output factors, and PDDs were measured in a water tank with a CC13 ion chamber (Scanditronix Wellhöfer, Nuremburg, Germany). In addition, the effect of the DBF sequence on 3D plan quality was evaluated by creating DBF plans for a 4-field box rectum and an AP/PA spine plan. Patient specific QA was performed on these plans. RESULTS: At 100 cm SSD and 10 cm depth, a flatness of <3% was observed on both transversal and radial profiles for all square field sizes ≥10 cm with DBF. For both larger and smaller field sizes the flatness showed a tendency to increase as the fields got bigger or smaller, respectively. Similar trends in flatness were observed at all depths measured. All measured output factors for square field sizes ≥5 cm were within 1% of the TPS prediction. Linearity was ≤2.02% for all measurements. For both treatment sites, the MD judged the plans created for the Halcyon without the use of DBF not to be clinically acceptable, however considered both the TrueBeam plan and the Halcyon plan with the DBF sequence to be clinically acceptable. CONCLUSIONS: The DBF sequence on the Halcyon and its characteristics were investigated. The analysis indicates that the DBF sequence can be used on the Halcyon to generate clinically acceptable 3D treatment plans.

Feasibility study of surface motion tracking with millimeter wave technology during radiotherapy.

PURPOSE: Continuous monitoring of patient movement is crucial to administering safe radiation therapy (RT). Conventional optical approaches often cannot be used when the patient's surface is blocked by immobilization devices. Millimeter waves (mmWaves) are capable of penetrating nonconductive objects. In this study, we investigated using mmWave technology to monitor patient surface displacements, as well as breathing and cardiac phases, through clothing and body fixtures. METHODS: A mmWave device was mounted inside the bore of a ring-based radiotherapy linear accelerator and pointed at a reflective surface on top of the couch. Measurements were obtained at displacements of 10, 7.5, 5.0, 2.5, and 1.0 mm at heights 100, 150, and 200 mm below isocenter. Submillimeter displacements were performed at a height of 200 mm. Additionally, millimeter and submillimeter displacements were measured with and without a gown and body mold placed between the surface and the sensor. The device was programmed to transmit chirp signals at 77-81 GHz. The subject's surface was detected by fast Fourier transform (FFT) of the reflected chirp signal within a rough range bin. Fine displacements within that range bin were calculated through phase extraction and phase demodulation. The displacement data were sent through two separate bandpass filters with passbands of 0.1-0.6 and 0.8-2.0 Hz to obtain the subject's breathing and cardiac waveforms, respectively. The breathing and cardiac measurements were compared to those of a Vernier Respiration Monitor Belt and an electrocardiogram (EKG), respectively, to assess validity. RESULTS: The device was able to detect millimeter and submillimeter displacements as small as 0.1 mm, as well as monitor displacement with an accuracy within 1 mm in the presence of an obstructive object. The device's breathing and cardiac waveforms exhibited a strong phase correlation between the respiration monitor belt (ρ = 0.9156) and EKG (ρ = 0.7895), respectively. CONCLUSIONS: The mmWave device can monitor surface displacements with an accuracy better than 0.1 mm without obstructions and better than 1 mm with obstructions. It can also provide real-time monitoring of breathing and cardiac waveforms simultaneously with high correlation with traditional respiratory and cardiac monitoring devices. Overall, mmWave technology demonstrates potential for motion monitoring in the field of radiation oncology.

Dosimetric parameters for three low-energy brachytherapy sources using the Monte Carlo N-particle code.

Monte Carlo calculations have been performed for the purpose of characterizing the dosimetric properties of three brachytherapy sources. The three sources are manufactured by Syncor Pharmaceuticals Inc. and consist of two 125I seeds (BT-125-1 and BT-125-2) and one 103Pd seed (BT-103-3). The BT-125-1 and BT-125-2 seed consists of a solid palladium and silver core, respectively. A thin layer (0.5 microm) of 125I is adsorbed onto the solid core for each seed and encased within a titanium housing. The BT-103-3 seed consists of a central gold marker and four resin balls encased within a titanium housing. A thin layer of 103Pd is bonded onto each resin ball. The dosimetric properties, including the dose rate constant, radial dose function, and anisotropy were calculated in water according to the TG-43 protocol using the Monte Carlo N-Particle code. The dose rate constant was calculated to be 0.955+/-0.005 and 0.967+/-0.005 cGyh(-1) U(-1) for the BT-125-1 and BT- 125-2 seeds, respectively. A dose rate constant of 0.659+/-0.005 cGy h(-1) U(-1) was calculated for the BT-103-3 seed. Radial dose function, g(r), calculated to a distance of 10 cm, and an isotropy function, F(r, theta), calculated for radii from 0.5 to 7.0 cm, were found to be in close agreement with previously published data.