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Thu, 01.01.1970
TREATMENT PLANNING AND DELIVERY FOR FLASH PROTON THERAPY WITH BRAGG PEAK
Abstract
Background and Aims
We developed a treatment delivery and planning approach to achieve a high dose rate while meeting the initial goals of an IMPT plan for dose conformity.
Methods
First, the proton fluence at the exit of the nozzle was maximized by transmitting beam at maximum energy through the beam line and using a range shifter to match the maximum proton range to the distal edge of the PTV. Spread-out Bragg peaks (SOBP) were obtained by modulating the range of the protons via a patient-specific ridge filter placed between the patient and the nozzle. To calculate the characteristics of this ridge filter, an IMPT plan was first computed to obtain the list of energies and associated weights that the filter should reproduce from beamlets at maximum energy. The filter was then optimized using an analytical model to allow a comparison in acceptable computational time with the reference dose. Finally, the scanning pattern was optimized with respect to local constraints on the dose rate.
Results
A patient-specific ridge filter is shown in Fig. 1. Corresponding SOBPs were simulated by Monte Carlo with the ridge filter inserted in the CT.
Conclusions
We proposed a treatment approach relying on the use of a patient-specific ridge filter to increase the dose rate without compromising the potential of the Bragg peak. The ridge filter and the spot scanning trajectory were optimized based on a standard IMPT plan by using an analytical algorithm inside MIROpt (http://openmiropt.org/), alongside the MCsquare dose engine (http://www.openmcsquare.org/).
PROTON-FLASH – RADIATION EFFECTS OF ULTRAHIGH DOSE-RATE IRRADIATION
Abstract
Background and Aims
The application of radiation with ultra-high dose-rates in radiotherapy shows a sparing effect on healthy tissue compared to cancerous tissue. This so-called FLASH-effect is mainly studied by using electrons or x-rays. Radiotherapy using protons already shows benefits in the low dose-rate application compared to conventional treatment. Therefore, a combination of both the particle-based sparing and the FLASH-effect could further widen the therapeutic window. Here, we investigated the FLASH-effect in proton treatment using an in-vivo mouse ear model.
Methods
For the experiment the right ears of 63 Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE at the 14 MV tandem accelerator in Garching near Munich by using three dose-rates (3.7 Gy/min, 558 Gy/min, and 55,800 Gy/min). Additionally, we compared the FLASH-effect at 23 Gy and 33 Gy. For quantification, we measured the ear thickness, desquamation, and erythema for 180 days.
Results
No difference in the 23 Gy group for the different dose-rates was visible, whereas for the 33 Gy group it was significant. For 558 Gy/min we received a 57 % reduction of ear swelling and a 40 % reduction for 55,800 Gy/min compared to the conventional dose-rate of 3.7 Gy/min. Desquamation and erythema were reduced by 68 % and 50 %.
Conclusions
By using FLASH-dose-rates for low LET proton irradiation a tissue-sparing effect can be achieved. This effect seems to be more significant with increased dose and was also observed at a dose-rate four times smaller than usually used FLASH-dose-rates (≥ 2400 Gy/min).
PROTON BEAM FLASH ONLINE MONITORING AT ARRONAX CYCLOTRON
Abstract
Background and Aims
The beam monitoring tools used in conventional irradiation may not be suitable in the case of irradiation using ultra-high dose rate > 40 Gy/sec (FLASH conditions). To monitor the beam, a fast detector coupled with a high dynamic range is needed. A photomultiplier tube measuring the nitrogen fluorescence produced by the beam-air interaction
can be a solution (figure below).
Methods
The ARRONAX facility has been used to deliver proton beams (68 MeV) ranging from low (0.25 Gy/s) to very high (30 kGy/s) dose rates. An in-house prototype consisting of a photomultiplier coupled to an air cavity was used. The signal intensity can be adjusted by changing the solid angle. To verify the measured beam charge, several aluminum targets were irradiated and the produced activities of the radioisotope 24Na were measured after the end of the beam. Several beam time structures with a high number of pulses were tested. In the case of a low doses, radiochromic films (for which we have shown a response independent of the dose rate) were used.
Results
The measured beam charge using the photomultiplier tube was found in good agreement with the produced activity (1.5 %) and with the film responses (< 5 %). A wide range of dose rates was successfully monitored in the linear response region of the photomultiplier using multiple detectors.
Conclusions
We have established a new robust noninvasive method to measure doses in Flash irradiations. The next step is to use the same technology to measure beam geometrical characteristics.
Treatment Planning And Dose-Rate Distributions For Conventionally Fractionated Head And Neck Cancer Using Uhdr Transmission Beam Proton Therapy
Abstract
Background and Aims
Transmission beam (TB) proton therapy (PT) uses single, high energy beams with Bragg-peak behind the target, sharp penumbras and simplified planning/delivery. TB facilitates ultra-high dose-rates (UHDRs, e.g. ≥40Gy/s), which is a requirement for the FLASH-effect. FLASH may also require a dose threshold, but this remains uncertain and UHDR-distribution investigation is of interest for head-and-neck cancer treatment.
Methods
We investigated (1) plan quality for conventionally-fractionated head-and-neck cancer treatment using spot-scanning proton TBs, intensity-modulated PT (IMPT) and photon volumetric-modulated arc therapy (VMAT); (2) UHDR-metrics. VMAT, 3-field IMPT and 10-field TB-plans, delivering 70/54.25Gy in 35 fractions to boost/elective volumes, were compared (n=10 patients). To increase spot peak dose-rates (SPDRs), TB-plans were split into three subplans, with varying spot monitor units and different gantry currents.
Results
Despite the lack of Bragg-peak advantages, average TB-plan OAR-sparing was comparable to IMPT: mean oral cavity/body dose were 4.1/2.5Gy higher than IMPT (9.3/2.0Gy lower than VMAT); most other OAR (salivary glands, larynx, pharynx) mean doses differed by <2Gy (2.0-12.1Gy lower than VMAT). Average percentage of dose delivered at UHDRs was 46%/12% for split/non-split TB-plans and mean dose-averaged dose-rate 46/21Gy/s. Average total beam-on irradiation time was 1.9/3.8s for split/non-split plans and overall time including scanning 8.9/7.6s.
Conclusions
Conventionally-fractionated proton TB-plans achieved comparable OAR-sparing to IMPT and better than VMAT, with total beam-on irradiation times <10s. Splitting TB-plans increased the UHDR, demonstrating the advantage of gantry current variation per spot. If a FLASH-effect can be demonstrated at conventional dose/fraction, this would further improve plan quality and TB-protons would be a suitable delivery system.
THE EFFECT OF PBS PROTON FLASH ON ACUTE SKIN TOXICITY AND TUMOR CONTROL IN A MOUSE MODEL
Abstract
Background and Aims
The aim of this study was to test the effect of proton FLASH delivered with a pencil beam scanning (PBS).
Methods
The right hind limb of CDF1 mice were irradiated in a single fraction in the entrance plateau of a scanning proton pencil beam using either conventional dose rate (0.4 Gy/s field dose rate, 244 MeV) or FLASH (69.7-88.7 Gy/s field dose rate, 250 MeV). The study included 292 non-tumor bearing mice and 80 mice with a C3H mouse mammary carcinoma implanted in the foot. The mice were irradiated with doses of 26-40Gy (non-tumor, conventional), 40-60Gy (non-tumor, FLASH) or 45-67Gy (tumor). The endpoints were the level of acute moist desquamation to the skin of the foot within 25 days post irradiation, and tumor control.
Results
Full dose response curves for acute damage to skin for both conventional and FLASH dose rate demonstrated a distinct normal tissue sparing effect in the FLASH arm of the study, with a mean value for the tissue sparing factor of 1.46. For tumor control, the pre-liminary dose response curves shows no difference between conventional and FLASH dose rates (follow up on tumor control is ongoing).
Conclusions
This study demonstrates a normal tissue sparing effect of proton FLASH delivered with pencil beam scanning, while no differences was found in tumor control rates. Compared to conventional dose rate, 41-55% higher dose were required to give the same biological toxicity in the normal tissue when using FLASH dose rates.
3D HIGH SPEED RF BEAM SCANNER FOR HADRON THERAPY OF CANCER
Abstract
Background and Aims
Treatment of cancer using actively scanned hadron pencil beams (protons and light ions) has major clinical advantages over treatments using photons. However, current methods used to adjust beam energies by degrading the beam are not compatible with the high dose rates needed for FLASH therapy. We are pursuing the demonstration of a compact accelerator technology to rapidly scan the energy and the trajectory of the hadron pencil beam to deposit the desired dose at FLASH dose rates.
Methods
We utilize RF energy modulation and deflection to enable a dose delivery of 50 Gy/L/s. Very fast irradiation presents many benefits to patients: (1) it solves the issue of patient motion and thus removes the need for tracking organ motion during irradiation (motion-adapted radiation therapy); it implies single- or hypofractionated treatments which will (2) increase dramatically patient throughput and (3) present biological benefits.
Results
We will present key innovations for energy modulation and lateral steering, including the design, optimization, and testing of critical components of an RF accelerator, RF deflector, and a PMQ. We have modeled dose deposition in phantoms with realistic beam parameters. We will also present our approach to integrating these technologies at a clinical beamline, monitoring dose deposition on a phantom target, and utilizing this information for treatment planning.
Conclusions
The scanner can be adjusted to cover the depth and lateral extent of the tumor while maintaining the quality of the pencil beam. Scanner operation in a clinical setting will provide definitive proof that the approach is viable and compatible with high dose rate FLASH.