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BACKGROUND: Pencil Beam Scanning proton therapy has many advantages from a therapeutic point of view, but raises technical constraints in terms of treatment verification. The treatment relies on a large number of planned pencil beams (PB) (up to thousands), whose delivery is divided in several low-intensity pulses delivered a high frequency (1 kHz in this study). PURPOSE: The purpose of this study was to develop a three-dimensional quality assurance system allowing to verify all the PBs' characteristics (position, energy, intensity in terms of delivered monitor unit-MU) of patient treatment plans on a pulse-by-pulse or a PB-by-PB basis. METHODS: A system named SCICOPRO has been developed. It is based on a 10 × 10 × 10 cm3 scintillator cube and a fast camera, synchronized with beam delivery, recording two views (direct and using a mirror) of the scintillation distribution generated by the pulses. A specific calibration and analysis process allowed to extract the characteristics of all the pulses delivered during the treatment, and consequently of all the PBs. The system uncertainties, defined here as average value + standard deviation, were characterized with a customized irradiation plan at different PB intensities (0.02, 0.1, and 1 MU) and with two patient's treatment plans of three beams each. The system's ability to detect potential treatment delivery problems, such as positioning errors of the treatment table in this work (1° rotations and a 2 mm translation), was assessed by calculating the confidence intervals (CI) for the different characteristics and evaluating the proportion of PBs within these intervals. RESULTS: The performances of SCICOPRO were evaluated on a pulse-by-pulse basis. They showed a very good signal-to-noise ratio for all the pulse intensities (between 2 × 10-3 MU and 150 × 10-3 MU) allowing uncertainties smaller than 580 µm for the position, 180 keV for the energy and 3% for the intensity on patients treatment plans. The position and energy uncertainties were found to be little dependent from the pulse intensities whereas the intensity uncertainty depends on the pulses number and intensity distribution. Finally, treatment plans evaluations showed that 98% of the PBs were within the CIs with a nominal positioning against 83% or less with the table positioning errors, thus proving the ability of SCICOPRO to detect this kind of errors. CONCLUSION: The high acquisition rate and the very high sensitivity of the system developed in this work allowed to record pulses of intensities as low as 2 × 10-3 MU. SCICOPRO was thus able to measure all the characteristics of the spots of a treatment (position, energy, intensity) in a single measurement, making it possible to verify their compliance with the treatment plan. SCICOPRO thus proved to be a fast and accurate tool that would be useful for patient-specific quality assurance (PSQA) on a pulse-by-pulse or PB-by-PB verification basis.
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Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE-/- mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-αVCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE-/- mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p < 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p < 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE-/-, but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions.
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Brain metastases (BM) are frequently detected during the follow-up of patients with malignant tumors, particularly in those with advanced disease. Despite a major progress in systemic anti-cancer treatments, the average overall survival of these patients remains limited (6 months from diagnosis). Also, cognitive decline is regularly reported especially in patients treated with whole brain external beam radiotherapy (WBRT), due to the absorbed radiation dose in healthy brain tissue. New targeted therapies, for an earlier and/or more specific treatment of the tumor and its microenvironment, are needed. Radioimmunotherapy (RIT), a combination of a radionuclide to a specific antibody, appears to be a promising tool. Inflammation, which is involved in multiple steps, including the early phase, of BM development is attractive as a relevant target for RIT. This review will focus on the (1) early biomarkers of inflammation in BM pertinent for RIT, (2) state of the art studies on RIT for BM, and (3) the importance of dosimetry to RIT in BM. These two last points will be addressed in comparison to the conventional EBRT treatment, particularly with respect to the balance between tumor control and healthy tissue complications. Finally, because new diagnostic imaging techniques show a potential for the detection of BM at an early stage of the disease, we focus particularly on this therapeutic window.