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Alanine pellets comparison using EPR dosimetry in the frame of quality assurance for a Gamma Knife system in Romania
Journal Pre-proof Alanine pellets comparison using EPR dosimetry in the frame of quality assurance for a Gamma Knife system in Romania C.S. Tuta, M.N. Amiot, L. Sommier, R.M. Ioan PII:
S0969-806X(19)30929-6
DOI:
https://doi.org/10.1016/j.radphyschem.2019.108653
Reference:
RPC 108653
To appear in:
Radiation Physics and Chemistry
Received Date: 31 July 2019 Revised Date:
5 November 2019
Accepted Date: 14 December 2019
Please cite this article as: Tuta, C.S., Amiot, M.N., Sommier, L., Ioan, R.M., Alanine pellets comparison using EPR dosimetry in the frame of quality assurance for a Gamma Knife system in Romania, Radiation Physics and Chemistry (2020), doi: https://doi.org/10.1016/j.radphyschem.2019.108653. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
Alanine Pellets Comparison using EPR dosimetry in the frame of Quality Assurance for a Gamma Knife System in Romania C.S. Tuta1, M.N. Amiot2, L. Sommier2 and R.M. Ioan1 Corresponding author: [email protected] Affiliation and complete address: 1
Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30
Reactorului Street, Magurele, RO-077125, Romania 2
CEA, LIST, Laboratoire National Henri Becquerel (LNE-LNHB), CEA-Saclay, 91191 Gif-Sur-
Yvette Cedex, France
Abstract In the last decade, the use of alanine/Electronic Paramagnetic Resonance (EPR) system was extended to radiotherapy doses. In stereotactic radiosurgery, doses up to 70 Gy are delivered to the brain tumor preserving healthy tissues. This type of treatment is delivered using dedicated equipment, like Cyberknife or Gamma Knife. Alanine dosimeters are characterized by their small size (5 mm diameter) and by similarity with tissue. They are well adapted for this wide dose range for which the dosimeter response is linear, independent of dose rate and energy for the range around few MeV. Therefore Alanine/EPR system is a suitable method for accurate and stable dose measurements as passive dosimeters for narrow treatment beams, which makes it an excellent candidate for end to end testing of radiosurgery treatments using Gamma Knife. The present work describes the development of the alanine/EPR method at Horia Hulubei National Institute for Physics and Nuclear Engeneering (IFIN-HH) in Romania including the optimization of system parameters for the radiosurgery dose range in the frame of an IFIN-HH and the French national metrology institute Laboratoire National Henri Becquerel federated by the Laboratoire National de métrologie et d’Essais (LNE-LNHB) collaboration. Romanian alanine dose measurements capability is presented regarding a comparison of calibration curves between both National Laboratories using Bruker and Synergy Health alanine pellets. Keywords:
Alanine,
Electron
Paramagnetic
Resonance
(EPR)
Spectrometry,
Stereotactic
Radiosurgery, Dosimetry, Quality Assurance.
1. Introduction The use of radiation in nuclear power plant, industry, hospitals necessitates consideration of the potential radiation exposure to workers in the course of carrying out their duties. Dosimetry is an essential component of all radiation safety and protection programs designed to monitor and achieve the safe use of radiation (Marrale et al. 2015a, Wieser and Darroudi 2014). In radiotherapy medical 1
centers which use high-energy photon beams, calibrations are made following international protocols (Almond et al. 1999, Andreo et al. 2000). In the last years the use of alanine/Electron Paramagnetic Resonance (EPR) dosimetry system was extended for small radiotherapy techniques such as: intensity modulated radiotherapy – IMRT (Schaeken et al. 2011), linear accelerator – LINAC (Gallo et al. 2017, Marrale et al. 2015b, Marrale et al. 2016), volumetric modulated arc therapy – VMAT (Wagner et al. 2017), light ion beam therapy – LIBT (Carlino et al. 2018), X-rays (Andon and Buermann 2015, Marrale et al. 2017) and radiosurgery fields. In stereotactic radiosurgery, doses up to 70 Gy are delivered to the brain tumor preserving healthy tissues. This type of treatment is delivered using dedicated equipment, like Cyberknife or Gamma Knife. The goal of radiosurgery is to kill the tumor cells and simultaneously achieve a high survival rate of the surrounding healthy tissue. A change in the delivered dose of 5 % can lead to a probability of 20 % - 30 % of significant damage of the healthy tissue (Helt-Hensen et al. 2009). However, the maximum uncertainty allowed on the dose delivered to tumors (2.5 % ICRU 24, 1976) is difficult to achieve due to the gap between the calibration conditions and the conditions used for new treatment modalities based on narrow and complex radiation fields. This requires (i) the metrological chain to be shortened and hence leads national laboratories to start providing dedicated calibration services to address the needs of the end users and to work in providing reliable quality assurance schemes in order to be able to control the dose delivery. Within a quality management system, Quality Assurance is a tool to provide highest accuracy, reliability and repeatability of all radiotherapy/radiosurgery procedures (Almond et al., 1999; Andreo et. al., 2000). A special attention is given to the performances of all equipment including the dosimetry system and treatment planning and to the skills of the personnel. Thus, assuring the accuracy, efficacy, and safety for the medical use of ionizing radiation is the major responsibility for the clinical medical physicist. EPR/alanine technique (Anton et al. 2006; Dolo and Garcia, 2006; Sharpe and Sephton 2006) has proven its relevance for radiotherapy (Budgell et al. 2011, De Angelis et al. 2005, Schaeken et al., 2011) and radiosurgery audits (Dimitriadis et al. 2017, Hornbeck et al. 2014, Massillon et al. 2013). Indeed this is a non-destructive, stable and reproducible method. The readout of an alanine dosimeter consists of measuring the number of the major free radicals created during irradiation, which is proportional to the absorbed dose. Alanine pellets presents the advantages for medical applications of being a water-equivalent material and having a small size. In particular, alanine dosimeters is suitable for the radiosurgery high dose range for absorbed dose measurements with high accuracy. Therefore Alanine/EPR system is an excellent candidate for end to end testing of radiotherapy/radiosurgery treatments using small field as passive dosimeters for reference dosimetry (Chen et al. 2005, Pantelis et al. 2010, Perichon et al. 2011, Gago-Arias 2012, 2013, Azangue et al. 2014, Baffa and Kinoshita 2014).
2
The present work describes the development of the alanine/EPR method at IFIN-HH in Romania including the optimization of EPR spectrometer parameters for the radiosurgery dose range in the frame of an IFIN-HH and LNE-LNHB collaboration. IFIN-HH’s alanine dose measurements capability is presented regarding to a bilateral comparison of calibration curves between LNE-LNHB and IFIN-HH using two different types of alanine pellets.
2. Materials and methods 2.1. Alanine dosimeters The pellets contain 96% L-Alanine and 4% of a binding substance and were provided by the two different commercial providers Bruker and Synergy health. The dimensions of the pellets are 4.8 mm diameter and 3 mm height. The mass of alanine pellets was (67.5 ± 0.1) mg for Synergy health and (64.5 ± 0.5) mg for Bruker. Stacks of 4 alanine pellets are sealed in dedicated cylindrical containers made of Delrin®. In the following, the container with alanine pellets is referred to as dosimeters.
2.2. Irradiation protocol Two sets of the two types of alanine pellets were irradiated at the DOSEO platform (2014) of LNELNHB using a Varian Truebeam® medical accelerator in compliance with the IAEA TRS-398 protocol. The LINAC X-rays was calibrated in terms of absorbed dose to water using the LNELNHB primary standard based on calorimetric measurements with an uncertainty equal to 0.5% (k = 1) (Delaunay et al. 2014). As the irradiation temperature has an influence on the alanine absorbed dose measurement, the temperature of the water of the phantom was recorded in order to determine the alanine EPR signal temperature correction. This correction is: = − ( − ),
where T and T0 (°C) are the irradiation and reference temperature respectively and CT the temperature coefficient equal to (0.14+/-0.02)%/°C-1 (Garcia et al. 2009, Nagy et al., 2000). The dose range of the irradiated dosimeters lies between 4 Gy and 88 Gy. In order to provide each laboratory with a set of 12 dosimeters irradiated at 4, 8, 16, 24, 32, 40, 48, 56, 62, 72 80 and 88 Gy of the two types of alanine pellets, 48 dosimeters were irradiated (one dosimeter per dose for each type of pellets). The dosimeters were irradiated in a standard water phantom (30 cm x 30 cm x 30 cm) at a 10 cm reference depth in a 10 cm x 10 cm 6 MV photon beam size with a detector-source distance (SDD) of 100 cm. The dose rate, which was calibrated using a NE 2571 ionization chamber, was equal to 3.6 Gy/min corresponding to 400 UM/min delivered by the Truebeam Varian medical system.
2.3. EPR measurements 3
EPR measurements were performed using A Bruker ELEXSYS E500 EPR spectrometer at LNELNHB and a MicroEMX EPR spectrometer at IFIN-HH. Both spectrometer operate in X-band in a controlled temperature (20 ± 2°C) and humidity (40 ± 10% HR) laboratory. Each alanine pellet was weighed with a microscale (Mettler-Toledo MX5) before EPR measurements. The readouts were made 15 days after the irradiation of the dosimeters for the two types of alanine pellets in each laboratory in order to allow alanine signal to stabilize (Dolo and Faugeas 2005). Tubes in Suprasil quartz with 5 mm internal diameter were used for maintaining the pellet in the centre of the magnet. Both laboratories work with an ER 4119 HS resonator readout cavity. The first derivative of the absorption curve is recorded in order to facilitate the reading and the spectral resolution. The EPR readout process consists in five measurements at three different angles (0, 120 and 240°), in order to average the EPR reading in case of variation of the response with angle due to the inhomogeneity of the pellets (Garcia et al. 2011). The pellet EPR signal is the average of the central peak amplitude of the EPR alanine spectrum (Regulla and Deffner 1982; Sharpe et al. 2006; Hornbeck et al. 2014) for the three above-mentioned angles. The background is the mean of the EPR signal of ten non irradiated alanine pellets of the same batch. The mean background EPR signal is substracted to each EPR pellet signal. The dosimeter EPR signal is the mean value of the 4 pellet EPR signals corrected from the background and divided by their respective mass and its associated composed uncertainty. All dosimeters were kept before and after irradiation in specific storage conditions, meaning a temperature of (20 ± 2) °C and a humidity of (40 ± 10) %, in order to avoid having significant fading effects. Indeed, the fading was estimated to be around 0.5% per year, which has no influence for this experiment. All uncertainties were determined using a coverage factor equal to one. The optimized parameters of the IFIN-HH EPR and LNE-LNHB spectrometers are presented in Table 1 and are in agreement with the previous work presented by Garcia et al. 2009. As the gain depends on the signal amplitude and on the EPR acquisition software and spectrometer, it differs from the two installations. The receiver gain is equal to 40 for the LNE-LNHB Elexsys spectrometer and is equal to 104 for the IFIN EMX spectrometer. Table 1: IFIN-HH and LNE-LNHB EPR measurements readout EPR Settings Attenuation (microwave power)
Value 20dB (2mW)
Amplitude Modulation Amplitude (AM)
0.3 mT
Time Constant (TC)
81.92ms
Conversion Time (CvT)
20.48ms
Sweep time (ST)
20.97s
Center Field
350 mT
4
Number of points Microwave Frequency Scan number
1024 9.87 9 GHz 5
3. Results and discussion Calibration curves are established for the two types of alanine pellets (Bruker and Synergy Health) using EPR spectrometers of each laboratory. The calibration curves in terms of absorbed dose to water are presented for the two types of pellets measure at LNE-LNHB in figure 1 and measure at IFIN-HH in figure 2. The results show that both dosimetry systems have linear dose/response relationship in the radiosurgery dose range. The x and y intercepts of the two regression lines for the two types to alanine pellets obtained at LNE-LNHB agree with zero point within the uncertainty. The residuals have a random distribution with the dose with an average value lower than 1mGy. The R2 values for each calibration curve show a very good linearity of the values obtained for the 4 Gy – 88 Gy doses range. The results obtained at LNE-LNHB are slightly less dispersed. This is due to the EPR spectrometer used. Indeed the Elexsys spectrometer electronics is more stable than the EMX one, which lead to a better stability and then to a lower uncertainty in the EPR signal measurement. Beyond this, the very good results obtained at IFIN-HH for the calibration curves validates the alanine/EPR system and the protocols established at IFIN-HH and also confirms that alanine/EPR dosimetry system could be a very good candidate for being used as a standard dosimetry system for Gamma Knife medical procedures.
5
Figure 1: (a) Calibration curves for Synergy Health (Sh) and Bruker (B) alanine pellets measured at LNE-LNHB presented by the EPR signal per unit of pellet mass as a function of absorbed dose to water. (b) Residuals between experimental data and best-fit values for both type of pellet. (c) Percentage standard deviation of the EPR signal.
6
Figure 2: (a) Calibration curves for Synergy Health (Sh) and Bruker (B) alanine pellets measured at IFIN-HH presented by the EPR signal per unit of pellet mass as a function of absorbed dose to water. (b) Residuals between experimental data and best-fit values for both type of pellet. (c) Percentage standard deviation of the EPR signal.
The slopes of the calibrations curves obtained for each type of pellets for the two laboratories are presented in table 3. The values of the slopes do agree within their uncertainty for the Bruker and Synergy Health pellets at IFIN-HH and at LNE-LNHB. Moreover no trend between the pellets can be detected for the two provider looking at the results obtained in each laboratory. Therefore, alanine pellets provided by Bruker and by Synergy Health can be used as dosimeters for absorbed dose to water without any differentiation, their behaviour is equivalent.
Table 2: Pellets provider comparison obtained at IFIN-HH and LNE-LNHB laboratories Laboratories
Type of pellets
Slope
Uncertainty
IFIN-HH
Bruker pellets
108.5
0.7
106.8
1.0
Synergy Health alanine pellets
7
LNE-LNHB
Bruker pellets
1,481
0.007
1,492
0.007
Synergy Health alanine pellets
4. Uncertainty budget for Alanine/EPR method Sources of uncertainty in EPR dosimetry are related to: (i) the spectrometer measurement, (ii) the analysed sample (mass) as well as (iii) the irradiation procedures. The uncertainty on the absorbed dose to water is equal to 0.465%. The latter is the combined uncertainties of all uncertainties related to ionization chamber measurements (among others recombination, polarity, anisotropy, hygrometry correction factors and calibration coefficient) and to alanine dosimeter positioning uncertainty (distance from the source and depth in water) which is equal to 0.157%. The methodology for the absorbed dose to water standardization is described elsewhere (Delaunay et al. 2014). The uncertainty budget for EPR measurements is presented in table 3. Spectrometer parameters settings have been studied in order to obtain a very good repeatability of measurement and the relative uncertainty for reproducibility, which includes the sample positioning in the spectrometer cavity, is equal to 0.3% at 20 Grays. The readout of the 4 pellets relative standard deviation is equal 0.3% for the same absorbed dose. The correction factor kT for the temperature of irradiation T taken into account was calculated following the relationship described at point 2.2. The relative uncertainty on the temperature coefficient is equal to 0.02%. The uncertainty on the absorbed dose to water and the uncertainty on the EPR measurements have been taken into account for each linear regression calculation and thus for each slope and its associated uncertainty. All uncertainties have been established according to the Guide of the Expression of Uncertainty in Measurement (1995) and are calculated with a coverage factor k equal to one.
Table 3: Typical uncertainty budget for EPR alanine signal measurements Uncertainty source
Type A (%) Type B (%)
Readout of the 4 pellets
0.3
Repeatability reproducibility
0.3
Pellet mass
0.01
System drift
0.4
Temperature correction
0.02
Combined in quadrature
0.58
5. Conclusions The slopes of the calibration curves obtained for the Bruker and Synergy Health alanine pellets are in an excellent agreement within their uncertainty at LNE-LNHB as well as at IFIN-HH. These results 8
confirm the equivalence between both types of alanine pellets when used for absorbed dose to water measurements. The results presented in this paper validate the alanine/EPR system and the protocols established at IFIN-HH and also show that alanine/EPR dosimetry system is a very good candidate for being used as a transfer dosimeter for Gamma Knife medical procedures.
Acknowledgements The IFIN-HH team would like to address special thanks to Marie-Noëlle Amiot, Jean-Marc Bordy and CEA Team for all the support and technical advices provided, and also to IFA-CEA for Financial support provided in the frame of C5-06 “Traceability of dosimetric measurements in stereotactic radiosurgery in Romania” Project.
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De Angelis, C., De Coste, V., Fattibene, P., Onori, S., Petetti, E., 2005. Use of alanine for dosimetry intercomparisons among Italian radiotherapy centers. Appl Radiat Isot. 62(2) 261-5. Delaunay, F., Gouriou, J., Daures, J., Le Roy, M., Ostrowsky, A., Rapp, B., and Sorel, S., 2014. New standards of absorbed dose to water under reference conditions by graphite calorimetry for Co-60 and high-energy x-rays at LNE-LNHB. Metrologia 51 552–562. Dimitriadis, A., Palmer, L. A., Thomas, R. A. S., Nisbet, A., and Clark, C.H., Adaptation and validation of a commercial head phantom for cranial radiosurgery dosimetry end-to-end audit. Dolo, J.M., Feaugas, V., 2005. Analysis of parameters that influence the amplitude of the ESR/alanine signal after irradiation. Appl. Rad. and Isot. 62 273–279 Dolo, J.M. and Garcia, T., 2006. Composition of alanine pellet dosimeters: background study for low doses applications, PTB reports no. PTB-Dos-51, Alanine Dosimetry for clinical applications. PTB reports no. PTB-Dos-51Braunschweig. 15-20. DOSEO platform 2014 http://www.plateformedoseo.com/ Gago-Arias, A., Rodríguez-Romero, R., Sánchez-Rubio, P., González-Castaño, D.M., Gómez, F., Núñez, L., Palmans, H., Sharpe, P., Pardo-Montero, J., 2012. Correction factors for A1SL ionization chamber dosimetry in TomoTherapy: Machinespecific, plan-class, and clinical fields. Med. Phys. 9(4) 1964-1970. Gago-Arias, A., Antolín, E., Fayos-Ferrer, F., Simón, R., González-Castaño, D.M., Palmans, H., Sharpe, P., Gómez, F., Pardo-Montero, J. 2013. Correction factors for ionization chamber dosimetry in CyberKnife: Machine-specific, plan-class, and clinical fields. Med. Phys.
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011721-10. Gallo, S., Iacoviello, G., Panzeca, S., Veronese, I., Brtolotta, A., Dondi, D., Gueli, A.M., Loi, G., Longo, A., Mones, E., Marrale, M., 2017. Characterization of phenolic pellets for ESR dosimetry in photon beam radiotherapy. Radiat. Environ. Biophys. 56 471-480. Garcia, T., Lacornerie, T., Popoff, R., Lourenco, V., Bordy, J.M., 2011. Dose verification and calibration of the Cyberknife by EPR/alanine dosimetry. Radiat. Meas. 46 952-957. Garcia, T., Lin, M., Pasquie, I., Lourenco, V., 2009. A methodology for choosing parameters for ESR readout of alanine dosimeters for radiotherapy. Radiat. Phys. Chem. 78 782-790. GUM, International Organization for Standardization, Guide to the Expression of Uncertainty in Measurements. 1995. Geneva, ISBN 92-67-10188-9. Helt-Hensen, J., Rosendal, F., Kofoed, I.M., Andersen, C.E., 2009. Medical reference dosimetry using EPR measurements of alanine: Development of an improved method for clinical dose levels. Acta Oncologica. 48 216-222. Hornbeck, A., Garcia, T., Cuttat, M., Jenny, C., 2014. Absolute calibration of the Gamma Knife Perfexion and delivered dose verification using EPR/alanine dosimetry. Med. Phys. 41 (6), 061708-1061708-10.
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ICRU 24 International Commission on Radiation Units and Measurements. “Determination of absorbed dose in a patient irradiated by beams of x or gamma rays in radiotherapy procedures” International Commission on Radiation Units and Measurements ICRU Report 24 (1976) Bethesda, Maryland. Marrale, M., Schmitz, T., Gallo, S., Hampel, G., Longo, A., Panzenca, S., Tanchina, L., 2015a. Comparison of EPR response of alanine and Gd2O3-alanine dosimeters exposed to TRIGA Mainz reactor. Appl. Rad. and Isot. 106 116–120. Marrale, M., Longo, A., Russo, G., Cassarino, C., Candiano, G., Gallo, S., Carlino, A., Brai, M., 2015b. Dosimetry for electron Intra-Operative RadioTherapy: Comparison of output factors obtained through alanine/EPR pellets, ionization chamber and Monte Carlo-GEANT4 simulations for IORT mobile dedicate accelerator. Nuclear Inst. and Methods in Physics Research B 358 52–58. Marrale, M., Carlino, A., Gallo, S., Longo, A., Panzeca, S., Bolsi, A., Hbracek. J., Lomax, T., 2016. EPR/alanine dosimetry for two therapeutic proton beams. Nuclear Inst. and Methods in Physics Research B 368 96–102. Marrale, M., Abbene, L., d’Errico, F., Gallo, S., Longo, A., Panzeca, S., Tana, L., Tranchina, L., Principato, F., 2017. Characterization of the ESR response of alanine dosimeters to low energy Cutarget X-tube photons. Radiat. Meas. 106 200-204. Massillon, G.J.L., Cueva-Procel, D., Diaz-Aguirre, P., Rodriguez-Ponce, M., Herrera-Martinez, F., 2013. Dosimetry for Small Fields in Stereotactic Radiosurgery Using Gafchromic MD-V2-55 Film, TLD-100 and Alanine Dosimeters. PLOS ONE 8(5), e63418. Nagy, V. Puhl, J.M., Desrosiers, M.F., 2000. Advancements in accuracy of the alanine dosimetry system. Part 2. The influence of the irradiation temperature. Radiat. Phys. and Chem. 57 1-9. Pantelis, E., Moutsatsos, A., Zourari, K., Kilby, W., Antypas, C., Papagiannis, P., Karaiskos, P., Georgiou, E., Sakelliou, L., 2010. On the implementation of a recently proposed dosimetric formalism to a robotic radiosurgery system. Med. Phys. 7(5) 2369-2379. Perichon, N., Garcia, T., François, P., Lourenço, V., Lesven, C., Bordy, J.M., 2011. Calibration of helical tomotherapy machine using EPR/alanine dosimetry. Med. Physics. 38 (3) 1168-1177. Regulla, D.F., Deffner, U., 1982. Dosimetry by ESR spectroscopy of alanine. Int. J. Appl. Radiat. Isot. 1101-1114. Schaeken, B., Cuypers, R., Lelie, S., Schroeyers, W., Schreurs, S., Janssens, H., Verellen, D., 2011. Implementation of alanine/EPR as transfer dosimetry system in a radiotherapy audit programme in Belgium. Radiother Oncol. 99, 94-96. Sharpe, P.H.G., and Sephton, J.P., 2006, Therapy level alanine dosimetry at the national physical laboratory Proc. of the PTB Workshop PTB-Dos-51 on Alanine Dosimetry for Clinical Applications (Braunschweig: Physikalisch-Technische Bundesanstalt). Wagner, D.M., Huttenrauch, P., Anton, M., von Voigts-Rhetz, P., Zink, K., Wolff, H.A., 2017. Feasibility study of entrance and exit dose measurements at the contra lateral breast with 11
alanine/electron spin resonance dosimetry in volumetric modulated radiotherapy of breast cancer. Phys. Med. Biol. 62 5462–5472. Wieser, A., Darroudi, F., 2014. EPRBioDose 2013: EPR applications and biological dosimetry. Radiat. Environ. Biophys. 53 217–220.
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Highlights
•
Relevance of Alanine/EPR dosimetry implementation in Gamma Knife Quality Assurance procedures;
•
Evaluation of the characteristics of two types of Alanine pellets;
•
Optimization of the setting parameters of the IFIN-HH’s EPR Spectrometer for radiosurgery specific dose range;
•
The advantages of using Alanine pellets in the radiosurgery-related dosimetry are highlighted: tissue equivalence, small size, easy to handle.
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Signed by all authors as follows: Author’s name
Affiliation
Dr. Catalin Stelian TUTA
IFIN – HH
Dr. Marie-Noëlle AMIOT
CEA Saclay
Mrs. Line SOMMIERE
CEA Saclay
Dr. Mihail Razvan IOAN
IFIN – HH
Signature
S0969-806X(19)30929-6
DOI:
https://doi.org/10.1016/j.radphyschem.2019.108653
Reference:
RPC 108653
To appear in:
Radiation Physics and Chemistry
Received Date: 31 July 2019 Revised Date:
5 November 2019
Accepted Date: 14 December 2019
Please cite this article as: Tuta, C.S., Amiot, M.N., Sommier, L., Ioan, R.M., Alanine pellets comparison using EPR dosimetry in the frame of quality assurance for a Gamma Knife system in Romania, Radiation Physics and Chemistry (2020), doi: https://doi.org/10.1016/j.radphyschem.2019.108653. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
Alanine Pellets Comparison using EPR dosimetry in the frame of Quality Assurance for a Gamma Knife System in Romania C.S. Tuta1, M.N. Amiot2, L. Sommier2 and R.M. Ioan1 Corresponding author: [email protected] Affiliation and complete address: 1
Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30
Reactorului Street, Magurele, RO-077125, Romania 2
CEA, LIST, Laboratoire National Henri Becquerel (LNE-LNHB), CEA-Saclay, 91191 Gif-Sur-
Yvette Cedex, France
Abstract In the last decade, the use of alanine/Electronic Paramagnetic Resonance (EPR) system was extended to radiotherapy doses. In stereotactic radiosurgery, doses up to 70 Gy are delivered to the brain tumor preserving healthy tissues. This type of treatment is delivered using dedicated equipment, like Cyberknife or Gamma Knife. Alanine dosimeters are characterized by their small size (5 mm diameter) and by similarity with tissue. They are well adapted for this wide dose range for which the dosimeter response is linear, independent of dose rate and energy for the range around few MeV. Therefore Alanine/EPR system is a suitable method for accurate and stable dose measurements as passive dosimeters for narrow treatment beams, which makes it an excellent candidate for end to end testing of radiosurgery treatments using Gamma Knife. The present work describes the development of the alanine/EPR method at Horia Hulubei National Institute for Physics and Nuclear Engeneering (IFIN-HH) in Romania including the optimization of system parameters for the radiosurgery dose range in the frame of an IFIN-HH and the French national metrology institute Laboratoire National Henri Becquerel federated by the Laboratoire National de métrologie et d’Essais (LNE-LNHB) collaboration. Romanian alanine dose measurements capability is presented regarding a comparison of calibration curves between both National Laboratories using Bruker and Synergy Health alanine pellets. Keywords:
Alanine,
Electron
Paramagnetic
Resonance
(EPR)
Spectrometry,
Stereotactic
Radiosurgery, Dosimetry, Quality Assurance.
1. Introduction The use of radiation in nuclear power plant, industry, hospitals necessitates consideration of the potential radiation exposure to workers in the course of carrying out their duties. Dosimetry is an essential component of all radiation safety and protection programs designed to monitor and achieve the safe use of radiation (Marrale et al. 2015a, Wieser and Darroudi 2014). In radiotherapy medical 1
centers which use high-energy photon beams, calibrations are made following international protocols (Almond et al. 1999, Andreo et al. 2000). In the last years the use of alanine/Electron Paramagnetic Resonance (EPR) dosimetry system was extended for small radiotherapy techniques such as: intensity modulated radiotherapy – IMRT (Schaeken et al. 2011), linear accelerator – LINAC (Gallo et al. 2017, Marrale et al. 2015b, Marrale et al. 2016), volumetric modulated arc therapy – VMAT (Wagner et al. 2017), light ion beam therapy – LIBT (Carlino et al. 2018), X-rays (Andon and Buermann 2015, Marrale et al. 2017) and radiosurgery fields. In stereotactic radiosurgery, doses up to 70 Gy are delivered to the brain tumor preserving healthy tissues. This type of treatment is delivered using dedicated equipment, like Cyberknife or Gamma Knife. The goal of radiosurgery is to kill the tumor cells and simultaneously achieve a high survival rate of the surrounding healthy tissue. A change in the delivered dose of 5 % can lead to a probability of 20 % - 30 % of significant damage of the healthy tissue (Helt-Hensen et al. 2009). However, the maximum uncertainty allowed on the dose delivered to tumors (2.5 % ICRU 24, 1976) is difficult to achieve due to the gap between the calibration conditions and the conditions used for new treatment modalities based on narrow and complex radiation fields. This requires (i) the metrological chain to be shortened and hence leads national laboratories to start providing dedicated calibration services to address the needs of the end users and to work in providing reliable quality assurance schemes in order to be able to control the dose delivery. Within a quality management system, Quality Assurance is a tool to provide highest accuracy, reliability and repeatability of all radiotherapy/radiosurgery procedures (Almond et al., 1999; Andreo et. al., 2000). A special attention is given to the performances of all equipment including the dosimetry system and treatment planning and to the skills of the personnel. Thus, assuring the accuracy, efficacy, and safety for the medical use of ionizing radiation is the major responsibility for the clinical medical physicist. EPR/alanine technique (Anton et al. 2006; Dolo and Garcia, 2006; Sharpe and Sephton 2006) has proven its relevance for radiotherapy (Budgell et al. 2011, De Angelis et al. 2005, Schaeken et al., 2011) and radiosurgery audits (Dimitriadis et al. 2017, Hornbeck et al. 2014, Massillon et al. 2013). Indeed this is a non-destructive, stable and reproducible method. The readout of an alanine dosimeter consists of measuring the number of the major free radicals created during irradiation, which is proportional to the absorbed dose. Alanine pellets presents the advantages for medical applications of being a water-equivalent material and having a small size. In particular, alanine dosimeters is suitable for the radiosurgery high dose range for absorbed dose measurements with high accuracy. Therefore Alanine/EPR system is an excellent candidate for end to end testing of radiotherapy/radiosurgery treatments using small field as passive dosimeters for reference dosimetry (Chen et al. 2005, Pantelis et al. 2010, Perichon et al. 2011, Gago-Arias 2012, 2013, Azangue et al. 2014, Baffa and Kinoshita 2014).
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The present work describes the development of the alanine/EPR method at IFIN-HH in Romania including the optimization of EPR spectrometer parameters for the radiosurgery dose range in the frame of an IFIN-HH and LNE-LNHB collaboration. IFIN-HH’s alanine dose measurements capability is presented regarding to a bilateral comparison of calibration curves between LNE-LNHB and IFIN-HH using two different types of alanine pellets.
2. Materials and methods 2.1. Alanine dosimeters The pellets contain 96% L-Alanine and 4% of a binding substance and were provided by the two different commercial providers Bruker and Synergy health. The dimensions of the pellets are 4.8 mm diameter and 3 mm height. The mass of alanine pellets was (67.5 ± 0.1) mg for Synergy health and (64.5 ± 0.5) mg for Bruker. Stacks of 4 alanine pellets are sealed in dedicated cylindrical containers made of Delrin®. In the following, the container with alanine pellets is referred to as dosimeters.
2.2. Irradiation protocol Two sets of the two types of alanine pellets were irradiated at the DOSEO platform (2014) of LNELNHB using a Varian Truebeam® medical accelerator in compliance with the IAEA TRS-398 protocol. The LINAC X-rays was calibrated in terms of absorbed dose to water using the LNELNHB primary standard based on calorimetric measurements with an uncertainty equal to 0.5% (k = 1) (Delaunay et al. 2014). As the irradiation temperature has an influence on the alanine absorbed dose measurement, the temperature of the water of the phantom was recorded in order to determine the alanine EPR signal temperature correction. This correction is: = − ( − ),
where T and T0 (°C) are the irradiation and reference temperature respectively and CT the temperature coefficient equal to (0.14+/-0.02)%/°C-1 (Garcia et al. 2009, Nagy et al., 2000). The dose range of the irradiated dosimeters lies between 4 Gy and 88 Gy. In order to provide each laboratory with a set of 12 dosimeters irradiated at 4, 8, 16, 24, 32, 40, 48, 56, 62, 72 80 and 88 Gy of the two types of alanine pellets, 48 dosimeters were irradiated (one dosimeter per dose for each type of pellets). The dosimeters were irradiated in a standard water phantom (30 cm x 30 cm x 30 cm) at a 10 cm reference depth in a 10 cm x 10 cm 6 MV photon beam size with a detector-source distance (SDD) of 100 cm. The dose rate, which was calibrated using a NE 2571 ionization chamber, was equal to 3.6 Gy/min corresponding to 400 UM/min delivered by the Truebeam Varian medical system.
2.3. EPR measurements 3
EPR measurements were performed using A Bruker ELEXSYS E500 EPR spectrometer at LNELNHB and a MicroEMX EPR spectrometer at IFIN-HH. Both spectrometer operate in X-band in a controlled temperature (20 ± 2°C) and humidity (40 ± 10% HR) laboratory. Each alanine pellet was weighed with a microscale (Mettler-Toledo MX5) before EPR measurements. The readouts were made 15 days after the irradiation of the dosimeters for the two types of alanine pellets in each laboratory in order to allow alanine signal to stabilize (Dolo and Faugeas 2005). Tubes in Suprasil quartz with 5 mm internal diameter were used for maintaining the pellet in the centre of the magnet. Both laboratories work with an ER 4119 HS resonator readout cavity. The first derivative of the absorption curve is recorded in order to facilitate the reading and the spectral resolution. The EPR readout process consists in five measurements at three different angles (0, 120 and 240°), in order to average the EPR reading in case of variation of the response with angle due to the inhomogeneity of the pellets (Garcia et al. 2011). The pellet EPR signal is the average of the central peak amplitude of the EPR alanine spectrum (Regulla and Deffner 1982; Sharpe et al. 2006; Hornbeck et al. 2014) for the three above-mentioned angles. The background is the mean of the EPR signal of ten non irradiated alanine pellets of the same batch. The mean background EPR signal is substracted to each EPR pellet signal. The dosimeter EPR signal is the mean value of the 4 pellet EPR signals corrected from the background and divided by their respective mass and its associated composed uncertainty. All dosimeters were kept before and after irradiation in specific storage conditions, meaning a temperature of (20 ± 2) °C and a humidity of (40 ± 10) %, in order to avoid having significant fading effects. Indeed, the fading was estimated to be around 0.5% per year, which has no influence for this experiment. All uncertainties were determined using a coverage factor equal to one. The optimized parameters of the IFIN-HH EPR and LNE-LNHB spectrometers are presented in Table 1 and are in agreement with the previous work presented by Garcia et al. 2009. As the gain depends on the signal amplitude and on the EPR acquisition software and spectrometer, it differs from the two installations. The receiver gain is equal to 40 for the LNE-LNHB Elexsys spectrometer and is equal to 104 for the IFIN EMX spectrometer. Table 1: IFIN-HH and LNE-LNHB EPR measurements readout EPR Settings Attenuation (microwave power)
Value 20dB (2mW)
Amplitude Modulation Amplitude (AM)
0.3 mT
Time Constant (TC)
81.92ms
Conversion Time (CvT)
20.48ms
Sweep time (ST)
20.97s
Center Field
350 mT
4
Number of points Microwave Frequency Scan number
1024 9.87 9 GHz 5
3. Results and discussion Calibration curves are established for the two types of alanine pellets (Bruker and Synergy Health) using EPR spectrometers of each laboratory. The calibration curves in terms of absorbed dose to water are presented for the two types of pellets measure at LNE-LNHB in figure 1 and measure at IFIN-HH in figure 2. The results show that both dosimetry systems have linear dose/response relationship in the radiosurgery dose range. The x and y intercepts of the two regression lines for the two types to alanine pellets obtained at LNE-LNHB agree with zero point within the uncertainty. The residuals have a random distribution with the dose with an average value lower than 1mGy. The R2 values for each calibration curve show a very good linearity of the values obtained for the 4 Gy – 88 Gy doses range. The results obtained at LNE-LNHB are slightly less dispersed. This is due to the EPR spectrometer used. Indeed the Elexsys spectrometer electronics is more stable than the EMX one, which lead to a better stability and then to a lower uncertainty in the EPR signal measurement. Beyond this, the very good results obtained at IFIN-HH for the calibration curves validates the alanine/EPR system and the protocols established at IFIN-HH and also confirms that alanine/EPR dosimetry system could be a very good candidate for being used as a standard dosimetry system for Gamma Knife medical procedures.
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Figure 1: (a) Calibration curves for Synergy Health (Sh) and Bruker (B) alanine pellets measured at LNE-LNHB presented by the EPR signal per unit of pellet mass as a function of absorbed dose to water. (b) Residuals between experimental data and best-fit values for both type of pellet. (c) Percentage standard deviation of the EPR signal.
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Figure 2: (a) Calibration curves for Synergy Health (Sh) and Bruker (B) alanine pellets measured at IFIN-HH presented by the EPR signal per unit of pellet mass as a function of absorbed dose to water. (b) Residuals between experimental data and best-fit values for both type of pellet. (c) Percentage standard deviation of the EPR signal.
The slopes of the calibrations curves obtained for each type of pellets for the two laboratories are presented in table 3. The values of the slopes do agree within their uncertainty for the Bruker and Synergy Health pellets at IFIN-HH and at LNE-LNHB. Moreover no trend between the pellets can be detected for the two provider looking at the results obtained in each laboratory. Therefore, alanine pellets provided by Bruker and by Synergy Health can be used as dosimeters for absorbed dose to water without any differentiation, their behaviour is equivalent.
Table 2: Pellets provider comparison obtained at IFIN-HH and LNE-LNHB laboratories Laboratories
Type of pellets
Slope
Uncertainty
IFIN-HH
Bruker pellets
108.5
0.7
106.8
1.0
Synergy Health alanine pellets
7
LNE-LNHB
Bruker pellets
1,481
0.007
1,492
0.007
Synergy Health alanine pellets
4. Uncertainty budget for Alanine/EPR method Sources of uncertainty in EPR dosimetry are related to: (i) the spectrometer measurement, (ii) the analysed sample (mass) as well as (iii) the irradiation procedures. The uncertainty on the absorbed dose to water is equal to 0.465%. The latter is the combined uncertainties of all uncertainties related to ionization chamber measurements (among others recombination, polarity, anisotropy, hygrometry correction factors and calibration coefficient) and to alanine dosimeter positioning uncertainty (distance from the source and depth in water) which is equal to 0.157%. The methodology for the absorbed dose to water standardization is described elsewhere (Delaunay et al. 2014). The uncertainty budget for EPR measurements is presented in table 3. Spectrometer parameters settings have been studied in order to obtain a very good repeatability of measurement and the relative uncertainty for reproducibility, which includes the sample positioning in the spectrometer cavity, is equal to 0.3% at 20 Grays. The readout of the 4 pellets relative standard deviation is equal 0.3% for the same absorbed dose. The correction factor kT for the temperature of irradiation T taken into account was calculated following the relationship described at point 2.2. The relative uncertainty on the temperature coefficient is equal to 0.02%. The uncertainty on the absorbed dose to water and the uncertainty on the EPR measurements have been taken into account for each linear regression calculation and thus for each slope and its associated uncertainty. All uncertainties have been established according to the Guide of the Expression of Uncertainty in Measurement (1995) and are calculated with a coverage factor k equal to one.
Table 3: Typical uncertainty budget for EPR alanine signal measurements Uncertainty source
Type A (%) Type B (%)
Readout of the 4 pellets
0.3
Repeatability reproducibility
0.3
Pellet mass
0.01
System drift
0.4
Temperature correction
0.02
Combined in quadrature
0.58
5. Conclusions The slopes of the calibration curves obtained for the Bruker and Synergy Health alanine pellets are in an excellent agreement within their uncertainty at LNE-LNHB as well as at IFIN-HH. These results 8
confirm the equivalence between both types of alanine pellets when used for absorbed dose to water measurements. The results presented in this paper validate the alanine/EPR system and the protocols established at IFIN-HH and also show that alanine/EPR dosimetry system is a very good candidate for being used as a transfer dosimeter for Gamma Knife medical procedures.
Acknowledgements The IFIN-HH team would like to address special thanks to Marie-Noëlle Amiot, Jean-Marc Bordy and CEA Team for all the support and technical advices provided, and also to IFA-CEA for Financial support provided in the frame of C5-06 “Traceability of dosimetric measurements in stereotactic radiosurgery in Romania” Project.
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ICRU 24 International Commission on Radiation Units and Measurements. “Determination of absorbed dose in a patient irradiated by beams of x or gamma rays in radiotherapy procedures” International Commission on Radiation Units and Measurements ICRU Report 24 (1976) Bethesda, Maryland. Marrale, M., Schmitz, T., Gallo, S., Hampel, G., Longo, A., Panzenca, S., Tanchina, L., 2015a. Comparison of EPR response of alanine and Gd2O3-alanine dosimeters exposed to TRIGA Mainz reactor. Appl. Rad. and Isot. 106 116–120. Marrale, M., Longo, A., Russo, G., Cassarino, C., Candiano, G., Gallo, S., Carlino, A., Brai, M., 2015b. Dosimetry for electron Intra-Operative RadioTherapy: Comparison of output factors obtained through alanine/EPR pellets, ionization chamber and Monte Carlo-GEANT4 simulations for IORT mobile dedicate accelerator. Nuclear Inst. and Methods in Physics Research B 358 52–58. Marrale, M., Carlino, A., Gallo, S., Longo, A., Panzeca, S., Bolsi, A., Hbracek. J., Lomax, T., 2016. EPR/alanine dosimetry for two therapeutic proton beams. Nuclear Inst. and Methods in Physics Research B 368 96–102. Marrale, M., Abbene, L., d’Errico, F., Gallo, S., Longo, A., Panzeca, S., Tana, L., Tranchina, L., Principato, F., 2017. Characterization of the ESR response of alanine dosimeters to low energy Cutarget X-tube photons. Radiat. Meas. 106 200-204. Massillon, G.J.L., Cueva-Procel, D., Diaz-Aguirre, P., Rodriguez-Ponce, M., Herrera-Martinez, F., 2013. Dosimetry for Small Fields in Stereotactic Radiosurgery Using Gafchromic MD-V2-55 Film, TLD-100 and Alanine Dosimeters. PLOS ONE 8(5), e63418. Nagy, V. Puhl, J.M., Desrosiers, M.F., 2000. Advancements in accuracy of the alanine dosimetry system. Part 2. The influence of the irradiation temperature. Radiat. Phys. and Chem. 57 1-9. Pantelis, E., Moutsatsos, A., Zourari, K., Kilby, W., Antypas, C., Papagiannis, P., Karaiskos, P., Georgiou, E., Sakelliou, L., 2010. On the implementation of a recently proposed dosimetric formalism to a robotic radiosurgery system. Med. Phys. 7(5) 2369-2379. Perichon, N., Garcia, T., François, P., Lourenço, V., Lesven, C., Bordy, J.M., 2011. Calibration of helical tomotherapy machine using EPR/alanine dosimetry. Med. Physics. 38 (3) 1168-1177. Regulla, D.F., Deffner, U., 1982. Dosimetry by ESR spectroscopy of alanine. Int. J. Appl. Radiat. Isot. 1101-1114. Schaeken, B., Cuypers, R., Lelie, S., Schroeyers, W., Schreurs, S., Janssens, H., Verellen, D., 2011. Implementation of alanine/EPR as transfer dosimetry system in a radiotherapy audit programme in Belgium. Radiother Oncol. 99, 94-96. Sharpe, P.H.G., and Sephton, J.P., 2006, Therapy level alanine dosimetry at the national physical laboratory Proc. of the PTB Workshop PTB-Dos-51 on Alanine Dosimetry for Clinical Applications (Braunschweig: Physikalisch-Technische Bundesanstalt). Wagner, D.M., Huttenrauch, P., Anton, M., von Voigts-Rhetz, P., Zink, K., Wolff, H.A., 2017. Feasibility study of entrance and exit dose measurements at the contra lateral breast with 11
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Highlights
•
Relevance of Alanine/EPR dosimetry implementation in Gamma Knife Quality Assurance procedures;
•
Evaluation of the characteristics of two types of Alanine pellets;
•
Optimization of the setting parameters of the IFIN-HH’s EPR Spectrometer for radiosurgery specific dose range;
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The advantages of using Alanine pellets in the radiosurgery-related dosimetry are highlighted: tissue equivalence, small size, easy to handle.
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Signed by all authors as follows: Author’s name
Affiliation
Dr. Catalin Stelian TUTA
IFIN – HH
Dr. Marie-Noëlle AMIOT
CEA Saclay
Mrs. Line SOMMIERE
CEA Saclay
Dr. Mihail Razvan IOAN
IFIN – HH
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