Biophysical characterization of collimated and uncollimated fields in pencil beam scanning proton therapy.

Objective. The lateral dose fall-off in proton pencil beam scanning (PBS) technique remains the preferred choice for sparing adjacent organs at risk as opposed to the distal edge due to the proton range uncertainties and potentially high relative biological effectiveness. However, because of the substantial spot size along with the scattering in the air and in the patient, the lateral penumbra in PBS can be degraded. Combining PBS with an aperture can result in a sharper dose fall-off, particularly for shallow targets.Approach. The aim of this work was to characterize the radiation fields produced by collimated and uncollimated 100 and 140 MeV proton beams, using Monte Carlo simulations and measurements with a MiniPIX-Timepix detector. The dose and the linear energy transfer (LET) were then coupled with publishedin silicobiophysical models to elucidate the potential biological effects of collimated and uncollimated fields.Main results. Combining an aperture with PBS reduced the absorbed dose in the lateral fall-off and out-of-field by 60%. However, the results also showed that the absolute frequency-averaged LET (LETF) values increased by a maximum of 3.5 keVµm-1in collimated relative to uncollimated fields, while the dose-averaged LET (LETD) increased by a maximum of 7 keVµm-1. Despite the higher LET values produced by collimated fields, the predicted DNA damage yields remained lower, owing to the large dose reduction.Significance. This work demonstrated the dosimetric advantages of combining an aperture with PBS coupled with lower DNA damage induction. A methodology for calculating dose in water derived from measurements with a silicon-based detector was also presented. This work is the first to demonstrate experimentally the increase in LET caused by combining PBS with aperture, and to assess the potential DNA damage which is the initial step in the cascade of events leading to the majority of radiation-induced biological effects.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment. Materials and methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al. Results: Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 µSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 µSv (testes) and 48 µSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs. Conclusion: The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs.

Validation of a Monte Carlo Framework for Out-of-Field Dose Calculations in Proton Therapy.

Proton therapy enables to deliver highly conformed dose distributions owing to the characteristic Bragg peak and the finite range of protons. However, during proton therapy, secondary neutrons are created, which can travel long distances and deposit dose in out-of-field volumes. This out-of-field absorbed dose needs to be considered for radiation-induced secondary cancers, which are particularly relevant in the case of pediatric treatments. Unfortunately, no method exists in clinics for the computation of the out-of-field dose distributions in proton therapy. To help overcome this limitation, a computational tool has been developed based on the Monte Carlo code TOPAS. The purpose of this work is to evaluate the accuracy of this tool in comparison to experimental data obtained from an anthropomorphic phantom irradiation. An anthropomorphic phantom of a 5-year-old child (ATOM, CIRS) was irradiated for a brain tumor treatment in an IBA Proteus Plus facility using a pencil beam dedicated nozzle. The treatment consisted of three pencil beam scanning fields employing a lucite range shifter. Proton energies ranged from 100 to 165 MeV. A median dose of 50.4 Gy(RBE) with 1.8 Gy(RBE) per fraction was prescribed to the initial planning target volume (PTV), which was located in the cerebellum. Thermoluminescent detectors (TLDs), namely, Li-7-enriched LiF : Mg, Ti (MTS-7) type, were used to detect gamma radiation, which is produced by nuclear reactions, and secondary as well as recoil protons created out-of-field by secondary neutrons. Li-6-enriched LiF : Mg,Cu,P (MCP-6) was combined with Li-7-enriched MCP-7 to measure thermal neutrons. TLDs were calibrated in Co-60 and reported on absorbed dose in water per target dose (µGy/Gy) as well as thermal neutron dose equivalent per target dose (µSv/Gy). Additionally, bubble detectors for personal neutron dosimetry (BD-PND) were used for measuring neutrons (>50 keV), which were calibrated in a Cf-252 neutron beam to report on neutron dose equivalent dose data. The Monte Carlo code TOPAS (version 3.6) was run using a phase-space file containing 1010 histories reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1) on all voxels scoring more than 50% of the maximum dose. The primary beam was modeled following a Fermi-Eyges description of the spot envelope fitted to measurements. For the Monte Carlo simulation, the chemical composition of the tissues represented in ATOM was employed. The dose was tallied as dose-to-water, and data were normalized to the target dose (physical dose) to report on absorbed doses per target dose (mSv/Gy) or neutron dose equivalent per target dose (µSv/Gy), while also an estimate of the total organ dose was provided for a target dose of 50.4 Gy(RBE). Out-of-field doses showed absorbed doses that were 5 to 6 orders of magnitude lower than the target dose. The discrepancy between TLD data and the corresponding scored values in the Monte Carlo calculations involving proton and gamma contributions was on average 18%. The comparison between the neutron equivalent doses between the Monte Carlo simulation and the measured neutron doses was on average 8%. Organ dose calculations revealed the highest dose for the thyroid, which was 120 mSv, while other organ doses ranged from 18 mSv in the lungs to 0.6 mSv in the testes. The proposed computational method for routine calculation of the out-of-the-field dose in proton therapy produces results that are compatible with the experimental data and allow to calculate out-of-field organ doses during proton therapy.

Joint EURADOS WG9-WG11 rem-counter intercomparison in a Mevion S250i proton therapy facility with Hyperscan pulsed synchrocyclotron.

Objective Proton therapy is gaining popularity because of the improved dose delivery over conventional radiation therapy. The secondary dose to healthy tissues is dominated by secondary neutrons. Commercial rem-counters are valuable instruments for the on-line assessment of neutron ambient dose equivalent (H*(10)). In general, however, a priori knowledge of the type of facility and of the radiation field is required for the proper choice of any survey meter. The novel Mevion S250i Hyperscan synchrocyclotron mounts the accelerator directly on the gantry. It provides a scanned 227 MeV proton beam, delivered in pulses with a pulse width of 10 µs at 750 Hz frequency, which is afterwards degraded in energy by a range shifter modulator system. This environment is particularly challenging for commercial rem-counters; therefore, we tested the reliability of some of the most widespread rem-counters to understand their limits in the Mevion S250i stray neutron field. Approach This work, promoted by the European Radiation Dosimetry Group (EURADOS), describes a rem-counter intercomparison at the Maastro Proton Therapy centre in the Netherlands, which houses the novel Mevion S250i Hyperscan system. Several rem-counters were employed in the intercomparison (LUPIN, LINUS, WENDI-II, LB6411, NM2B-458, NM2B-495Pb), which included simulation of a patient treatment protocol employing a water tank phantom. The outcomes of the experiment were compared with models and data from the literature. Main results We found that only the LUPIN allowed for a correct assessment of H*(10) within a 20% uncertainty. All other rem-counters underestimated the reference H*(10) by factors from 2 to more than 10, depending on the detector model and on the neutron dose per pulse. In pulsed fields, the neutron dose per pulse is a fundamental parameter, while the average neutron dose rate is a secondary quantity. An average 150-200 µSv/GyRBE neutron H*(10) at various positions around the phantom and at distances between 186 cm and 300 cm from it was measured per unit therapeutic dose delivered to the target. Significance Our results are partially in line with results obtained at similar Mevion facilities employing passive energy modulation. Comparisons with facilities employing active energy modulation confirmed that the neutron H*(10) can increase up to more than a factor of 10 when passive energy modulation is employed. The challenging environment of the Mevion stray neutron field requires the use of specific rem-counters sensitive to high-energy neutrons (up to a few hundred MeV) and specifically designed to withstand pulsed neutron fields.

EURADOS REM-COUNTER INTERCOMPARISON AT MAASTRO PROTON THERAPY CENTRE: COMPARISON WITH LITERATURE DATA.

The Maastro Proton Therapy Centre is the first European facility housing the Mevion S250i Hyperscan synchrocyclotron. The proximity of the accelerator to the patient, the presence of an active pencil beam delivery system downstream of a passive energy degrader and the pulsed structure of the beam make the Mevion stray neutron field unique amongst proton therapy facilities. This paper reviews the results of a rem-counter intercomparison experiment promoted by the European Radiation Dosimetry Group at Maastro and compares them with those at other proton therapy facilities. The Maastro neutron H*(10) in the room (100-200 µSv/Gy at about 2 m from the isocentre) is in line with accelerators using purely passive or wobbling beam delivery modalities, even though Maastro shows a dose gradient peaked near the accelerator. Unlike synchrotron- and cyclotron-based facilities, the pulsed beam at Maastro requires the employment of rem-counters specifically designed to withstand pulsed neutron fields.