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Register a new userUsing thymine-18 for enhancing dose delivery and localizing the Bragg peak in proton-beam therapy
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Therapeutic protons acting on O18-substituted thymidine increase cytotoxicity in radio-resistant human cancer cells. We consider here the physics behind the irradiation during proton beam therapy and diagnosis using O18-enriched thymine in DNA, with attention to the effect of the presence of thymine-18 on cancer cell death.
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Purpose: The purpose of this work was to provide a flexible platform for FLASH research with protons by adapting a former clinical pencil beam scanning gantry to irradiations with ultrahigh dose rates. Methods: PSI Gantry 1 treated patients until December 2018. We optimized the beamline parameters to transport the 250 MeV beam extracted from the PSI COMET accelerator to the treatment room, maximizing the transmission of beam intensity to the sample. We characterized a dose monitor on the gantry to ensure good control of the dose, delivered in spot-scanning mode. We characterized the beam for different dose rates and field sizes for transmission irradiations. We explored scanning possibilities in order to enable conformal irradiations or transmission irradiations of large targets (with transverse scanning). Results: We achieved a transmission of 86 % from the cyclotron to the treatment room. We reached a peak dose rate of 9000 Gy/s at 3 mm water equivalent depth, along the central axis of a single pencil beam. Field sizes of up to 5x5 mm$^{2}$ were achieved for single spot FLASH irradiations. Fast transverse scanning allowed to cover a field of 16x1.2 cm$^{2}$. With the use of a nozzle-mounted range shifter we are able to span depths in water ranging from 19.6 to 37.9 cm. Various dose levels were delivered with a precision within less than 1 %. Conclusions: We have realized a proton FLASH irradiation setup able to investigate continuously a wide dose rate spectrum, from 1 to 9000 Gy/s in a single spot irradiation as well as in the pencil beam scanning mode. As such, we have developed a versatile test bench for FLASH research.
This paper focuses on some dosimetry aspects of proton therapy and pencil beam scanning based on the experience accumulated at Paul Scherrer Institute(PSI). The basic formalism for absolute dosimetry in proton therapy is outlined and the two main techniques and equipment to perform the primary beam monitor chamber calibration are presented. Depth-dose curve and lateral beam width measurements are exposed and discussed in detail, with particular attention to the size of the ionization chamber and the characteristic of scintillating-CCD dosimetry systems, respectively. It is also explained how the angular-spatial distribution of individual pencil beams can be determined in practice. The equipment and the techniques for performing regularmachine-specific quality checks are focused on (i)output constancy checks, (ii)pencil beam position and size checks and (iii)beam energy checks. Finally, patient-specific verification is addressed.
Fast procedures for the beam quality assessment and for the monitoring of beam energy modulations during the irradiation are among the most urgent improvements in particle therapy. Indeed, the online measurement of the particle beam energy could allow assessing the range of penetration during treatments, encouraging the development of new dose delivery techniques for moving targets. Towards this end, the proof of concept of a new device, able to measure in a few seconds the energy of clinical proton beams (from 60 to 230 MeV) from the Time of Flight (ToF) of protons, is presented. The prototype consists of two Ultra Fast Silicon Detector (UFSD) pads, featuring an active thickness of 80 um and a sensitive area of 3 x 3 mm2, aligned along the beam direction in a telescope configuration, connected to a broadband amplifier and readout by a digitizer. Measurements were performed at the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy), at five different clinical beam energies and four distances between the sensors (from 7 to 97 cm) for each energy. In order to derive the beam energy from the measured average ToF, several systematic effects were considered, Monte Carlo simulations were developed to validate the method and a global fit approach was adopted to calibrate the system. The results were benchmarked against the energy values obtained from the water equivalent depths provided by CNAO. Deviations of few hundreds of keV have been achieved for all considered proton beam energies for both 67 and 97 cm distances between the sensors and few seconds of irradiation were necessary to collect the required statistics. These preliminary results indicate that a telescope of UFSDs could achieve in a few seconds the accuracy required for the clinical application and therefore encourage further investigations towards the improvement and the optimization of the present prototype.
PET imaging is a non-invasive technique for particle range verification in proton therapy. It is based on measuring the beta+ annihilations caused by nuclear interactions of the protons in the patient. In this work we present measurements for proton range verification in phantoms, performed at the CNAO particle therapy treatment center in Pavia, Italy, with our 10 x 10 cm^2 planar PET prototype DoPET. PMMA phantoms were irradiated with mono-energetic proton beams and clinical treatment plans, and PET data were acquired during and shortly after proton irradiation. We created 1-D profiles of the beta+ activity along the proton beam-axis, and evaluated the difference between the proximal rise and the distal fall-off position of the activity distribution. A good agreement with FLUKA Monte Carlo predictions was obtained. We also assessed the system response when the PMMA phantom contained an air cavity. The system was able to detect these cavities quickly after irradiation.
Purpose: To verify dose delivery and quality assurance of volumetric modulated arc therapy (VMAT) for head and neck cancer. Method: The Imaging and Radiation Oncology Core Houston (IROC-H) head and neck phantom with thermo- luminescent dosimeters (TLDs) and films, were imaged with computed tomography scan and the reconstructed image was transferred to pinnacle treatment planning system (TPS). On TPS the planning target volume (PTV), secondary target volume (STV) and organ at risk (OAR) were delineated manually and a treatment plan was made. The dose constraints were determined for the concerned organs according to IROC-H prescription. The treatment plan was optimized using adoptive convolution algorithm to improve dose homogeneity and conformity. The dose calculation was performed using C.C Convolution algorithm and a Varian True Beam linear accelerator was used to deliver the treatment plan to the head and neck phantom. The delivered radiation dose to the phantom was measured through TLDs and GafChromic EBT2 films. The dosimetric performance of the VMAT delivery was studied by analysing percent dose difference, iso-dose line profile and gamma analysis of the TPS computed dose and linac delivered doses. Result: the percent dose difference of 3.8% was observed between the planned and measured doses of TLDs and a 1.5mm distance to agreement (DTA) was observed by comparing iso-dose line profiles. Passed the gamma criteria of 3%/3 mm was with good percentages. Conclusion: The dosimetric performance of VMAT delivery for a challenging head and neck radiotherapy can be verified using TLDs and films imbedded in an anthropomorphic H&N phantom.
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