Characterization of passive dosimeters in proton pencil beam scanning - A EURADOS intercomparison for mailed dosimetry audits in proton therapy centres.

The lack of mailed dosimetry audits of proton therapy centres in Europe has encouraged researchers of EURADOS Working Group 9 (WG9) to compare response of several existing passive detector systems in therapeutic pencil beam scanning. Alanine Electron Paramagnetic Resonance dosimetry systems from 3 different institutes (ISS, Italy; UH, Belgium and IFJ PAN, Poland), natLiF:Mg, Ti (MTS-N) and natLiF:Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs), GD-352M radiophotoluminescent glass dosimeters (RPLGDs) and Al2O3:C optically stimulated dosimeters (OSLDs) were evaluate. Dosimeter repeatability, batch reproducibility and response in therapeutic Pencil Beam Scanning were verified for implementation as mail auditing system. Alanine detectors demonstrated the lowest linear energy transfer (LET) dependence with an agreement between measured and treatment planning system (TPS) dose below 1%. The OSLDs measured on average a 6.3% lower dose compared to TPS calculation, with no significant difference between varying modulations and ranges. Both GD-352M and MCP-N measured a lower dose than the TPS and luminescent response was dependent on the LET of the therapeutic proton beam. Thermoluminescent response of MTS-N was also found to be dependent on the LET and a higher dose than TPS was measured with the most pronounced increase of 11%. As alanine detectors are characterized by the lowest energy dependence for different parameters of therapeutic pencil beam scanning they are suitable candidates for mail auditing in proton therapy. The response of luminescence detector systems have shown promises even though more careful calibration and corrections are needed for its implementation as part of a mailed dosimetry audit system.

Out-of-field doses for scanning proton radiotherapy of shallowly located paediatric tumours-a comparison of range shifter and 3D printed compensator.

The lowest possible energy of proton scanning beam in cyclotron proton therapy facilities is typically between 60 and 100 MeV. Treatment of superficial lesions requires a pre-absorber to deliver doses to shallower volumes. In most of the cases a range shifter (RS) is used, but as an alternative solution, a patient-specific 3D printed proton beam compensator (BC) can be applied. A BC enables further reduction of the air gap and consequently reduction of beam scattering. Such pre-absorbers are additional sources of secondary radiation. The aim of this work was the comparison of RS and BC with respect to out-of-field doses for a simulated treatment of superficial paediatric brain tumours. EURADOS WG9 performed comparative measurements of scattered radiation in the Proteus C-235 IBA facility (Cyclotron Centre Bronowice at the Institute of Nuclear Physics, CCB IFJ PAN, Kraków, Poland) using two anthropomorphic phantoms-5 and 10 yr old-for a superficial target in the brain. Both active detectors located inside the therapy room, and passive detectors placed inside the phantoms were used. Measurements were supplemented by Monte Carlo simulation of the radiation transport. For the applied 3D printed pre-absorbers, out-of-field doses from both secondary photons and neutrons were lower than for RS. Measurements with active environmental dosimeters at five positions inside the therapy room indicated that the RS/BC ratio of the out-of-field dose was also higher than one, with a maximum of 1.7. Photon dose inside phantoms leads to higher out-of-field doses for RS than BC to almost all organs with the highest RS/BC ratio 12.5 and 13.2 for breasts for 5 and 10 yr old phantoms, respectively. For organs closest to the isocentre such as the thyroid, neutron doses were lower for BC than RS due to neutrons moderation in the target volume, but for more distant organs like bladder-conversely-lower doses for RS than BC were observed. The use of 3D printed BC as the pre-absorber placed in the near vicinity of patient in the treatment of superficial tumours does not result in the increase of secondary radiation compared to the treatment with RS, placed far from the patient.

Evaluation of the premature chromosome condensation scoring protocol after proton and X-ray irradiation of human peripheral blood lymphocytes at high doses range.

PURPOSE OF THE STUDY: One of the main difficulties in radiation dose assessment is cells inability to reach mitosis after exposure to acute radiation. Premature chromosome condensation (PCC) has become an important method used in biological dosimetry in case of exposure to high doses. Various ways to induce PCC including mitotic cells fusion, chemical stimulation with calyculin A or okadaic acid give wide spectrum of application. The main goal of this study was to evaluate the utility of drug-induced PCC scoring procedure by testing 2 experimental modes where 150 and 75 G2/M-PCC phase cells were analyzed after exposure to high dose proton and X-ray radiation. Another aim is to determine the differences in cellular response induced by proton and photon radiation using a HPBL in vitro model as a further extension of our previous studies involving doses up to 4.0 Gy. MATERIALS AND METHODS: Total body exposure was simulated by irradiating whole blood collected from a healthy donor. Whole blood samples were exposed to two radiation types: 60 MeV protons and 250 kVp X-rays in the dose range of 5.0-20.0 Gy, the dose rate for protons was 0.075 and 0.15 Gy/s for X-rays. Post 48 h of human peripheral blood lymphocytes (HPBL) culture, calyculin A was added. After Giemsa staining, chromosome spreads were photographed and manually analyzed by scorers in the G2/M-PCC phase. In order to check the consistency of obtained results all scorers followed identical scoring criteria. Additionally, PCC index kinetics was evaluated for first 500 cells scored. CONCLUSIONS: Here we provide a different method of results analysis. Presented dose-response curves were obtained by calculating the value of counted excess chromosome fragments. The results indicated that obtained dose estimates as adequate in the high dose range till 18.0 Gy for both studied radiation types, giving an opportunity to further improve PCC assay procedure and shorten the analysis time i.e. in case of partial-body exposure. Moreover, the study presents preliminary results of HPBL cellular response after proton irradiation at high doses range showing differences of PCC index kinetics for different cell classes and cell distribution.

Do protons and X-rays induce cell-killing in human peripheral blood lymphocytes by different mechanisms?

PURPOSE: Significant progress has been made in the technological and physical aspects of dose delivery and distribution in proton therapy. However, mode of cell killing induced by protons is less understood in comparison with X-rays. The purpose of this study is to see if there is any difference in the mode of cell-killing, induced by protons and X-rays in an ex vivo human peripheral blood lymphocyte (HPBL) model. MATERIALS AND METHODS: HPBL were irradiated with 60 MeV proton beam or 250-kVp X-rays in the dose range of 0.3-4.0 Gy. Frequency of apoptotic and necrotic cells was determined by the Fluorescein (FITC)-Annexin V labelling procedure, 1 and 4 h after irradiation. Chip-based DNA Ladder Assay was used to confirm radiation-induced apoptosis and necrosis. Chip-based DNA Ladder Assay was used to confirm radiation-induced apoptosis. RESULTS: Ex vivo irradiation of HPBL with proton beams of 60 MeV or 250 kVp X-rays resulted in apoptotic as well as necrotic modes of cell-killing, which were evident at both 1 and 4 h after irradiation in the whole dose and time range. Generally, our results indicated that protons cause relatively higher yields of cell death that appears to be necrosis compared to X-rays. The analysis also demonstrates that radiation type and dose play a critical role in mode of cell-killing. CONCLUSION: Obtained results suggest that X-rays and protons induce cell-killing by different modes. Such differences in cell-killing modes may have implications on the potential of a given therapeutic modality to cause immune modulation via programmed cell death (X-rays) or necrotic cell death (proton therapy). These studies point towards exploring for gene expression biomarkers related necrosis or apoptosis to predict immune response after proton therapy.

Evaluation of the relative TL efficiency of the thermoluminescent detectors to heavy charged particles.

The relative thermoluminescence efficiency, η, is in general not constant but depends on ionisation density. Evaluation of the η is therefore important especially for correct interpretation of measurements of densely ionising radiation doses in proton radiotherapy or in space dosimetry. The correct determination of the η is not always straightforward especially when more strongly ionising radiation is to be measured. In the present work, the process of calculation of the η based on two kinds of heavy charged particles was studied. Several factors which may influence the value of the η and their significance for the final result were discussed. These include for example non-uniform deposition of the dose within the detector volume, self-attenuation of thermoluminescent light, choice of the reference radiation, etc. The presented approach was applied to the experimental results of η of LiF:Mg,Ti detectors irradiated with two kinds of heavy charged particles, protons and alpha particles.

Relative TL and OSL efficiency to protons of various dosimetric materials.

Thermoluminescence (TL) and optically stimulated luminescence (OSL) are the well-known phenomena used for passive methods of dose measurements. TL and OSL detectors are frequently used in the dosimetry of cosmic radiation in space and of particle radiotherapy beams. However, the relative TL/OSL efficiency, which is defined as a ratio of the emitted light intensity per unit dose for a given radiation type, to the same quantity for the reference gamma radiation is not constant and depends on radiation type and energy. In the present work several types of TL and OSL dosimetric materials, including lithium fluoride (LiF), aluminium oxide, beryllium oxide and lithium aluminate, were tested with protons. The measurements were realised exploiting the 60-MeV proton beam of the AIC-144 cyclotron in the Proton Eye Radiotherapy Facility at Institute of Nuclear Physics (IFJ PAN). The influence of proton energy on the relative efficiency and other TL/OSL characteristics of the studied detector types was presented.

Two-dimensional dosimetry of radiotherapeutical proton beams using thermoluminescence foils.

In modern radiation therapy such as intensity modulated radiation therapy or proton therapy, one is able to cover the target volume with improved dose conformation and to spare surrounding tissue with help of modern measurement techniques. Novel thermoluminescence dosimetry (TLD) foils, developed from the hot-pressed mixture of LiF:Mg,Cu,P (MCP TL) powder and ethylene-tetrafluoroethylene (ETFE) copolymer, have been applied for 2-D dosimetry of radiotherapeutical proton beams at INFN Catania and IFJ Krakow. A TLD reader with 70 mm heating plate and CCD camera was used to read the 2-D emission pattern of irradiated foils. The absorbed dose profiles were evaluated, taking into account correction factors specific for TLD such as dose and energy response. TLD foils were applied for measuring of dose distributions within an eye phantom and compared with predictions obtained from the MCNPX code and Eclipse Ocular Proton Planning (Varian Medical Systems) clinical radiotherapy planning system. We demonstrate the possibility of measuring 2-D dose distributions with point resolution of about 0.5 x 0.5 mm(2).

Microdosimetric modelling of the response of thermoluminescence detectors to low- and high-LET ionising radiation.

The microdosimetric one hit detector model was applied to calculate the dose response, energy response and relative thermoluminescence (TL) efficiency, eta, of high sensitive LiF:Mg,Cu,P and Al(2)O(3):C detectors after their irradiations by X rays, gamma rays, beta electrons and heavy charged particles (HCP). Microdosimetric distributions in 60 nm targets for photons and beta rays were calculated using the TRION MC track structure code, for HCP using the analytical model of Xapsos with modified transport of secondary electrons and the model of Olko & Booz. The calculated values of eta compare favourably with a broad spectrum of experimental data, including ICHIBAN experiments with HCP. The model offers a method for calculating the thermoluminescence response of TL foils applied to 2-D dosimetry of radiotherapeutic proton beams.

Radon concentration in soil gas around local disjunctive tectonic zones in the Krakow area.

The purpose of this study was to investigate radon in the vicinity of geologic fault zones within the Krakow region of Poland, and to determine the influence of such formations on enhanced radon concentrations in soil. Radon ((222)Rn and (220)Rn) concentration measurements in soil gas (using ionization chamber AlphaGUARD PQ2000 PRO and diffusion chambers with CR-39 detectors), as well as radioactive natural isotopes of radium, thorium and potassium in soil samples (using gamma ray spectrometry with NaI(Tl) and HPGe detectors), were performed. Site selection was based on a geological map of Krakow. Geophysical methods (ground penetrating radar and shallow acoustic seismic) were applied to recognize the geological structure of the area and to locate the predicted courses of faults. Elevated levels of radon and thoron in soil gas were found in the study area when compared with those observed in an earlier survey covering Krakow agglomeration. For (222)Rn, the arithmetic mean of registered concentration values was 39 kBq/m(3) (median: 35.5 kBq/m(3)). For (220)Rn, the arithmetic mean was 10.8 kBq/m(3) and median 11.8 kBq/m(3).