Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation

Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary... Abstract A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 μGy.Gy−1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 μSv.Gy−1 for the paediatric patient and between 0.2 and 134 μSv.Gy−1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours. INTRODUCTION Proton therapy of malignant and benign brain tumours has become one of the most common proton applications due to the inherent potential of delivering high tumour doses while sparing surrounding healthy tissues(1–3). Previous generations of proton therapy facilities primarily employed the passive scattering technique for proton delivery, while new facilities more often use the pencil beam scanning (PBS) technique. One of the advantages with the PBS technique is the decrease in secondary radiation produced from proton–nuclear interactions with aperture and other beam line elements(4). The proton cross-section for non-elastic nuclear interactions is much higher for materials with high-atomic numbers than human tissue elements(5). Still, the nuclear interactions between incident protons and nuclei inside the patient give rise to secondary doses to remote organs(4, 6). The main concern regarding the secondary radiation is the high relative biological effectiveness (RBE) of the secondary neutrons and their ability to travel large distances from the point of interaction(3). Proton therapy is frequently employed for curative treatments of paediatric patients with long life expectancies for whom the risk of developing radiation-induced second malignancies (RISM) is higher than in elderly patients(7). From this perspective, the doses from secondary radiation for paediatric patients treated with proton therapy are highly relevant(6). Proton PBS of brain tumours is often delivered with one lateral field, one vertex field, or a multi-field combination between these orientations. The choice of field setup is routinely based on the tumour location relative to adjacently located organs at risk (OAR). For patients where a clinically acceptable tumour dose coverage can be achieved with different field setups without exceeding the dose thresholds to the OAR, the difference in dose to healthy tissues from secondary radiation and the associated risk of RISM could be used as a complementary criterion for plan selection in the decision process(8). The elevated risk of RISM in paediatric patients warrants the study of potential benefits of certain field arrangements with regard to secondary radiation production. Both the spatial distribution and the energy distribution of the secondary radiation produced within the patient vary with primary proton energy, field positioning, field size and patient size. The energy distribution of the secondary neutrons is of special importance due to the energy dependence of the neutron radiation weighting factor(9). Dose calculations in remote organs are often restricted by the limited anatomical coverage of the computed tomography (CT) used for treatment planning. The limitations in tracking secondary particles in most clinically employed treatment planning systems (TPS) also prevent the routine calculation of the doses from secondary radiation. In this work, organ doses from secondary radiation produced in patients treated with proton PBS therapy of a brain tumour were calculated and the influence of different field setup and patient size was studied. One lateral field setup and one vertex field setup were simulated using the Monte Carlo (MC) code MCNP6 (Los Alamos National Laboratory, Los Alamos, USA)(10). Out-of-field absorbed doses and neutron equivalent doses were calculated in one adult and one paediatric patient using whole-body CT data. The doses were compared and evaluated with regard to field setup. To allow for the analysis of equivalent doses, the neutron energy fluence spectra in different organs were also simulated. MATERIALS AND METHODS Treatment planning The treatment planning was performed at a dedicated proton PBS facility (Skandion Clinic, Uppsala, Sweden). Whole-body CT images of a 45-year-old female patient (adult) and one 6 year-old male patient (paediatric) were imported into the Eclipse TPS (Varian Medical Systems, Palo Alto, USA). A planning target volume (PTV) of 24 cm3 was delineated centrally in the brain, close to the brainstem, on both CT datasets. Two different treatment plans were created for each patient: one with a lateral field and one with a vertex field. The proton energies in the adult treatment plans ranged between 86 and 113 MeV (lateral field setup) and 96–126 MeV (vertex field setup), both distributed in 14 energy layers. The corresponding energies for the paediatric treatment plans were 80–110 MeV and 92–124 MeV in 15 energy layers. The calculated dose distributions from the two treatment plans in the adult patient are shown in Figure 1. All treatment plans were calculated with a prescribed absorbed dose of 49.2 Gy to the target delivered in 30 fractions corresponding to 54.1 Gy (RBE) under the assumption of a proton RBE of 1.1(11). Figure 1. View largeDownload slide Dose distributions in the adult patient from proton PBS treatments using either a lateral field setup (a) or a vertex field setup (b). Isodose lines correspond to percentage of the prescribed absorbed dose of 49.2 Gy. Figure 1. View largeDownload slide Dose distributions in the adult patient from proton PBS treatments using either a lateral field setup (a) or a vertex field setup (b). Isodose lines correspond to percentage of the prescribed absorbed dose of 49.2 Gy. Monte Carlo geometry The CT of both patients, with 15 delineated OAR and target volumes, was converted into MCNP6 lattice structures using an in-house Matlab script (Mathworks, Natick, USA). The CT data were sorted into 24 bins based on Hounsfield unit (HU) values and each bin was assigned a mass density derived from a stoichiometric calibration curve and a material composition derived from a HU-to-elemental-composition relationship(12). The dataset was rescaled from the original 512 × 512 matrix size to 128 × 128 using bi-cubic interpolation, with a resolution in slice thickness of 5 mm. The anatomy of the patients as represented by lattice structures in MCNP6 is presented in Figure 2. Figure 2. View largeDownload slide Patient anatomy with delineated organs as represented in MCNP6 of the adult patient (a) and the paediatric patient (b). Colour scale corresponds to materials. Figure 2. View largeDownload slide Patient anatomy with delineated organs as represented in MCNP6 of the adult patient (a) and the paediatric patient (b). Colour scale corresponds to materials. Dose calculations The treatment plans for both patients were exported from the TPS and MCNP6 input files were created for each energy layer. The energy layers were individually simulated using a beam model previously validated for the proton beam characteristics at the Skandion Clinic(13). The delineated organs were assigned energy deposition f6 tallies for scoring the absorbed dose from secondary neutrons, photons and scattered protons. Each organ was also assigned a neutron f6 tally with an energy card for scoring the absorbed dose in different energy intervals. The organ doses from secondary radiation, Dsec,i, were normalised with the relative weight, wi, of each energy layer i, and summed according to equation 1. The wi was calculated as the ratio of the number of monitor units delivered in energy layer i to the total number of monitor units. Dsec/DH=∑(Dsec,i×wi)/∑(DH,i×wi) (1) where Dsec/DH is the organ dose from secondary radiation for the entire treatment plan normalised to target dose and DH,i is the proton absorbed dose to the target volume for energy layer i, calculated from a proton energy deposition tally assigned to the PTV. The neutron equivalent dose, HT, was calculated from the absorbed doses to the organs using energy-specific radiation weighting factors, wR, adopted from the fitting equations in ICRP 103(9). Additionally, the neutron energy fluence spectra in all delineated organs were scored using f4 fluence tallies. The statistical uncertainty of each organ tally was calculated from the quadratic sum of the uncertainty in each energy layer weighted with wi. The statistical uncertainty of all organ tallies was within 0.02. All simulations were carried out with the ENDF/B-VII.1 library(14) and the Bertini intercascade model(15). RESULTS AND DISCUSSION Organ absorbed doses Simulated absorbed doses from secondary radiation from the lateral and vertex field setup are presented in Table 1. The doses from the vertex field were higher in all organs except for the right eye in both patients. The largest absolute difference in the adult patient was found in the dose to the right eye where the lateral field setup produced an increase in dose of 18.3 μGy.Gy-1. The corresponding increase in dose in the paediatric patient was found in the thyroid for the vertex field setup corresponding to 8.9 μGy.Gy−1. The relative difference between the vertex and lateral field irradiation was further increased in more remote organs by factors of 3–5. However, the difference between the two field setups in dose to remote organs decreased in absolute terms for both the adult and the paediatric patient with differences in the range of 0.2–3.9 μGy.Gy−1. The doses were higher in the paediatric patient with an average relative increase in dose of 1.8 and 1.7 for the lateral and vertex field setup respectively (excluding the eyes). For a prescribed tumour dose of 49.2 Gy, the highest cumulative absorbed doses were found in the eyes and the cervical region of the spinal cord corresponding to roughly 1–2 mGy for both patients. For remote organs, the cumulative doses were in the range of 3–173 μGy in the adult patient and 7–293 μGy in the paediatric patient. Table 1. Organ absorbed doses per prescribed dose (μGy.Gy−1) from secondary radiation produced from lateral and vertex field setups of a brain tumour proton PBS treatment. Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Spin cerv, spinal cord cervical region; Spin. thor, spinal cord thoracic region; Spin. lumb, Spinal cord lumbar region. Table 1. Organ absorbed doses per prescribed dose (μGy.Gy−1) from secondary radiation produced from lateral and vertex field setups of a brain tumour proton PBS treatment. Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Spin cerv, spinal cord cervical region; Spin. thor, spinal cord thoracic region; Spin. lumb, Spinal cord lumbar region. Studies on absorbed doses from secondary radiation from proton treatments of brain tumours delivered with modern PBS facilities are relatively scarce. Nevertheless, some publications have reported absorbed doses from similar treatments(16, 17). Thus, Newhauser et al(16). simulated organ absorbed doses from a craniospinal irradiation of an adult anthropomorphic phantom delivered with a scanned proton beam. The absorbed doses from a cranial field irradiation were 52 μGy.Gy−1 to the thyroid and 34 μGy.Gy−1 to the lungs, which are higher than the doses found in the present study. Studies on out-of-field doses from proton therapy delivered with the passive scattering technique have reported values ranging from the absorbed doses associated with PBS to much higher dose levels(6, 18). Thus, Farah et al.(18) reported on measurements and simulations in an anthropomorphic phantom irradiated with a lateral field for an intracranial target leading to doses of approximately 30–40 μGy.Gy−1 and 10–30 μGy.Gy−1 to the thyroid and the lungs respectively. Sayah et al.(6) simulated absorbed organ doses from a cranial treatment delivered with various field setups and reported averaged doses to a 5-year-old patient of 255 μGy.Gy−1 to the thyroid and 198 μGy.Gy−1 to the lungs. The corresponding doses in an adult patient were 231 μGy.Gy−1 and 120 μGy.Gy−1, respectively. These findings demonstrate both that the passive scattering technique is associated with higher doses from secondary radiation, and that comparisons between different studies are complex due to differences in treatment setup and beam characteristics associated with different proton facilities. Equivalent doses to organs Out-of-field equivalent doses from secondary neutrons to both patients are presented in Figure 3. The relative difference in dose for the two field setups increased with distance from isocenter as the vertex field produced a maximum relative increase of 4.5 in the bladder for the adult patient and 3.9 for the paediatric patient. The largest absolute differences were found in the cervical region of the spinal cord corresponding to 25 and 33 μSv.Gy−1 for the adult and paediatric patient respectively. As for the absorbed doses, the equivalent doses were higher in the paediatric patient for both field setups with an average relative increase of 2.0 and 1.9 for the lateral and vertex irradiation respectively (excluding the eyes). Figure 3. View largeDownload slide Equivalent doses to organs from secondary neutrons to the adult and paediatric patient from lateral and vertex fields. Figure 3. View largeDownload slide Equivalent doses to organs from secondary neutrons to the adult and paediatric patient from lateral and vertex fields. The maximum cumulative neutron equivalent dose to the eyes from an entire treatment was 6.6 mSv and 6.9 mSv for the adult and the paediatric patient, respectively. When adding the corresponding equivalent photon dose with wR = 1(9), the equivalent doses were 6.8 mSv and 7.2 mSv. These doses are comparable to the dose to the eyes from a cone-beam CT examination of the head-and-neck region(19, 20). The equivalent doses found in the present study are similar to previously reported data on cranial treatments delivered with PBS and lower than doses from passive scattering treatments. Thus, Geng et al.(21) reported neutron dose equivalents in the range of 1 μSv.Gy−1 and 100 μSv.Gy−1 in the bladder and thyroid of a 14-year-old patient from a brain tumour treatment with PBS. The doses to the bladder from the vertex field irradiation in the present study were 2 μSv.Gy−1 and 1 μSv.Gy−1 for the paediatric patient and the adult, respectively. Corresponding doses to the thyroid were 62 μSv.Gy−1 and 36 μSv.Gy−1. Sayah et al.(6) reported neutron equivalent doses from passive scattering of approximately 1.6 mSv.Gy-1 and 0.2 mSv.Gy−1 to the thyroid and bladder of an adult patient, averaged for different field setups. The small differences in equivalent doses between the adult and the paediatric patient in the present study could translate into larger differences in the associated risks of RISM due to the increased sensitivity of younger patients. As an example, the estimated lifetime risk of radiation-induced solid cancer death after an exposure of 100 mSv is 2.1% for an age at exposure of 10 years and 0.4% for an age at exposure of 50 years(7). The average relative increase in equivalent dose of 1.9–2.0 could consequently translate into an increased relative risk of 10 (1.95 × 2.1/0.4) for the paediatric patient. Nevertheless, the organ doses and consequently the absolute risk of RISM are low for both the adult and the paediatric patient. Consequently, differences in the risk of RISM between the adult and the paediatric patient are dominated by variations in risk coefficients, associated with large uncertainties, and should therefore be regarded as a relative measure. Radiation-induced tumours most often arise in regions close to the PTV receiving rather high doses(22). The risk of RISM for the patients included in the present study is therefore mostly influenced by the primary proton radiation and the corresponding dose distribution in adjacently located OAR. Still, when evaluating the risk of RISM for patients undergoing modern radiotherapy, it is essential that the total dose burden to the patient is considered(8). Consequently, the combined organ doses from primary radiation, secondary radiation and diagnostic imaging should be included for such calculations(23). Neutron spectra The small absolute differences in absorbed dose between the two field setups were also seen in the neutron equivalent doses. This indicates that the energy distribution of the secondary neutrons had limited impact on the neutron equivalent doses. This can be seen in Figure 4 where the neutron energy fluence in three different organs is presented for the paediatric patient (the results were similar for the adult patient). Indeed, there is an increase in fast neutrons for the vertex field setup due to the higher primary proton energies. Also, the forward-directed trajectories of the fast neutrons pass through the patient for the vertex irradiation instead of exiting as for the lateral field setup. The largest differences in neutron fluence between the two field setups were found in the energy range of approximately 10–100 MeV. In this region, the neutron wR falls from 10 to 5 reducing the influence on the calculated equivalent doses. In the energy region around 1 MeV, where wR ≥ 20, the difference in neutron fluence between the vertex and the lateral field irradiations was relatively small in the thyroid and increased with distance from the tumour. As the neutron fluence in these remote organs was relatively low, the difference in neutron fluence did not cause large variations in equivalent dose. Figure 4. View largeDownload slide Neutron energy fluence spectra in the thyroid, left lung and right kidney for the paediatric patient and neutron wR as function of energy. The solid lines correspond to the vertex field setup and dashed lines to the lateral field setup. Figure 4. View largeDownload slide Neutron energy fluence spectra in the thyroid, left lung and right kidney for the paediatric patient and neutron wR as function of energy. The solid lines correspond to the vertex field setup and dashed lines to the lateral field setup. CONCLUSIONS The results of this study showed that out-of-field absorbed doses and neutron equivalent doses produced inside patients treated with proton PBS for brain tumours are relatively low and in the order of mSv. The organ doses were higher in the paediatric patient in comparison to the adult, but all differences were low in absolute terms. Furthermore, the results indicate that changing the field setup does not lead to large variations in out-of-field doses in patients undergoing proton PBS of centrally located brain tumours. FUNDING This work was supported by the Swedish Radiation Safety Authority under the contract SSM2016-2425. REFERENCES 1 Yock , T. I. et al. . Quality of life outcomes in proton and photon treated pediatric brain tumor survivors . Radiother. Oncol. 113 ( 1 ), 89 – 94 ( 2014 ). Google Scholar CrossRef Search ADS PubMed 2 Newhauser , W. D. and Zhang , R. The physics of proton therapy . Phys. Med. Biol. 60 ( 8 ), R155 – R209 ( 2015 ). Google Scholar CrossRef Search ADS PubMed 3 Kaderka , R. , Schardt , D. , Durante , M. , Berger , T. , Ramm , U. , Licher , J. and La Tessa , C. Out-of-field dose measurements in a water phantom using different radiotherapy modalities . Phys. 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Report 13: solid cancer and noncancer disease mortality: 1950-1997 . Radiat. Res. 160 ( 4 ), 381 – 407 ( 2003 ). Google Scholar CrossRef Search ADS PubMed 8 Dasu , A. and Toma-Dasu , I. Long-term effects and secondary tumors. In: Comprehensive Biomedical Physics, Volume 9: Radiation Therapy Physics and Treatment Optimization ( Amsterdam, Netherlands : Elsevier B.V ) pp. 223 – 233 ( 2014 ) ISBN 978-0-444-53633-4. 9 International Commission on Radiological Protection . The 2007 Recommendations of International Commission on Radiological Protection. ICRP Publication 103 . Ann. ICRP 37 ( 2-4 ), 1 – 332 ( 2007 ). CrossRef Search ADS 10 Goorley , T. et al. . Features of MCNP6 . Ann. Nucl. Energy 87 , 772 – 783 ( 2016 ). Google Scholar CrossRef Search ADS 11 International Commission on Radiation Units and Measurements . . Prescribing, Recording, and Reporting Proton-Beam Therapy. ICRU Report 78. J. ICRU ( 2007 ). 12 Schneider , W. , Bortfeld , T. and Schlegel , W. Correlation between CT numbers and tissue parameters needed for Monte Carlo simulations of clinical dose distributions . Phys. Med. Biol. 45 ( 2 ), 459 – 478 ( 2000 ). Google Scholar CrossRef Search ADS PubMed 13 Ardenfors , O. , Dasu , A. , Kopeć , M. and Gudowska , I. Modelling of a proton spot scanning system using MCNP6 . J. Phys.: Conf. Ser. 860 , 012025 ( 2017 ). Google Scholar CrossRef Search ADS 14 Chadwick , M. B. et al. . ENDF/B-VII.1 nuclear data for science and technology: cross sections, covariances, fission product yields and decay data . Nucl. Data Sheets 112 ( 12 ), 2887 – 2996 ( 2011 ). Google Scholar CrossRef Search ADS 15 Bertini , H. W. Low-energy intranuclear cascade calculation . Phys. Rev. 131 , 1801 ( 1963 ). Google Scholar CrossRef Search ADS 16 Newhauser , W. D. et al. . The risk of developing a second cancer after receiving craniospinal proton irradiation . Phys. Med. Biol. 54 ( 8 ), 2277 – 2291 ( 2009 ). Google Scholar CrossRef Search ADS PubMed 17 Zhang , R. , Howell , R. M. , Taddei , P. J. , Giebeler , A. , Mahajan , A. and Newhauser , W. D. A comparative study on the risks of radiogenic second cancers and cardiac mortality in a set of pediatric medulloblastoma patients treated with photon or proton craniospinal irradiation . Radiother. Oncol. 113 ( 1 ), 84 – 88 ( 2014 ). Google Scholar CrossRef Search ADS PubMed 18 Farah , J. et al. . Monte Carlo modeling of proton therapy installations: a global experimental method to validate secondary neutron dose calculations . Phys. Med. Biol. 59 ( 11 ), 2747 – 2765 ( 2014 ). Google Scholar CrossRef Search ADS PubMed 19 Ding , G. X. and Coffey , C. W. Radiation dose from kilovoltage cone beam computed tomography in an image-guided radiotherapy procedure . Int. J. Radiat. Oncol. 73 ( 2 ), 610 – 617 ( 2009 ). Google Scholar CrossRef Search ADS 20 Gudowska , I. , Toma-Dasu , I. , Ardenfors , O. and Dasu , A. Radiation burden from secondary doses to patients undergoing radiation therapy with photons and light ions and radiation doses from imaging modalities . Radiat. Prot. Dosim. 161 ( 1-4 ), 357 – 362 ( 2014 ). Google Scholar CrossRef Search ADS 21 Geng , C. , Moteabbed , M. , Xie , Y. , Schuemann , J. , Yock , T. and Paganetti , H. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning . Phys. Med. Biol. 61 ( 1 ), 12 – 22 ( 2016 ). Google Scholar CrossRef Search ADS PubMed 22 Diallo , I. et al. . Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer . Int. J. Radiat. Oncol. 74 ( 3 ), 876 – 883 ( 2009 ). Google Scholar CrossRef Search ADS 23 Ardenfors , O. , Josefsson , D. and Dasu , A. Are IMRT treatments in the H&N region increasing the risk of secondary cancers? Acta Oncol. 53 ( 8 ), 1041 – 1047 ( 2014 ). Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Protection Dosimetry Oxford University Press

Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation

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Abstract

Abstract A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 μGy.Gy−1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 μSv.Gy−1 for the paediatric patient and between 0.2 and 134 μSv.Gy−1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours. INTRODUCTION Proton therapy of malignant and benign brain tumours has become one of the most common proton applications due to the inherent potential of delivering high tumour doses while sparing surrounding healthy tissues(1–3). Previous generations of proton therapy facilities primarily employed the passive scattering technique for proton delivery, while new facilities more often use the pencil beam scanning (PBS) technique. One of the advantages with the PBS technique is the decrease in secondary radiation produced from proton–nuclear interactions with aperture and other beam line elements(4). The proton cross-section for non-elastic nuclear interactions is much higher for materials with high-atomic numbers than human tissue elements(5). Still, the nuclear interactions between incident protons and nuclei inside the patient give rise to secondary doses to remote organs(4, 6). The main concern regarding the secondary radiation is the high relative biological effectiveness (RBE) of the secondary neutrons and their ability to travel large distances from the point of interaction(3). Proton therapy is frequently employed for curative treatments of paediatric patients with long life expectancies for whom the risk of developing radiation-induced second malignancies (RISM) is higher than in elderly patients(7). From this perspective, the doses from secondary radiation for paediatric patients treated with proton therapy are highly relevant(6). Proton PBS of brain tumours is often delivered with one lateral field, one vertex field, or a multi-field combination between these orientations. The choice of field setup is routinely based on the tumour location relative to adjacently located organs at risk (OAR). For patients where a clinically acceptable tumour dose coverage can be achieved with different field setups without exceeding the dose thresholds to the OAR, the difference in dose to healthy tissues from secondary radiation and the associated risk of RISM could be used as a complementary criterion for plan selection in the decision process(8). The elevated risk of RISM in paediatric patients warrants the study of potential benefits of certain field arrangements with regard to secondary radiation production. Both the spatial distribution and the energy distribution of the secondary radiation produced within the patient vary with primary proton energy, field positioning, field size and patient size. The energy distribution of the secondary neutrons is of special importance due to the energy dependence of the neutron radiation weighting factor(9). Dose calculations in remote organs are often restricted by the limited anatomical coverage of the computed tomography (CT) used for treatment planning. The limitations in tracking secondary particles in most clinically employed treatment planning systems (TPS) also prevent the routine calculation of the doses from secondary radiation. In this work, organ doses from secondary radiation produced in patients treated with proton PBS therapy of a brain tumour were calculated and the influence of different field setup and patient size was studied. One lateral field setup and one vertex field setup were simulated using the Monte Carlo (MC) code MCNP6 (Los Alamos National Laboratory, Los Alamos, USA)(10). Out-of-field absorbed doses and neutron equivalent doses were calculated in one adult and one paediatric patient using whole-body CT data. The doses were compared and evaluated with regard to field setup. To allow for the analysis of equivalent doses, the neutron energy fluence spectra in different organs were also simulated. MATERIALS AND METHODS Treatment planning The treatment planning was performed at a dedicated proton PBS facility (Skandion Clinic, Uppsala, Sweden). Whole-body CT images of a 45-year-old female patient (adult) and one 6 year-old male patient (paediatric) were imported into the Eclipse TPS (Varian Medical Systems, Palo Alto, USA). A planning target volume (PTV) of 24 cm3 was delineated centrally in the brain, close to the brainstem, on both CT datasets. Two different treatment plans were created for each patient: one with a lateral field and one with a vertex field. The proton energies in the adult treatment plans ranged between 86 and 113 MeV (lateral field setup) and 96–126 MeV (vertex field setup), both distributed in 14 energy layers. The corresponding energies for the paediatric treatment plans were 80–110 MeV and 92–124 MeV in 15 energy layers. The calculated dose distributions from the two treatment plans in the adult patient are shown in Figure 1. All treatment plans were calculated with a prescribed absorbed dose of 49.2 Gy to the target delivered in 30 fractions corresponding to 54.1 Gy (RBE) under the assumption of a proton RBE of 1.1(11). Figure 1. View largeDownload slide Dose distributions in the adult patient from proton PBS treatments using either a lateral field setup (a) or a vertex field setup (b). Isodose lines correspond to percentage of the prescribed absorbed dose of 49.2 Gy. Figure 1. View largeDownload slide Dose distributions in the adult patient from proton PBS treatments using either a lateral field setup (a) or a vertex field setup (b). Isodose lines correspond to percentage of the prescribed absorbed dose of 49.2 Gy. Monte Carlo geometry The CT of both patients, with 15 delineated OAR and target volumes, was converted into MCNP6 lattice structures using an in-house Matlab script (Mathworks, Natick, USA). The CT data were sorted into 24 bins based on Hounsfield unit (HU) values and each bin was assigned a mass density derived from a stoichiometric calibration curve and a material composition derived from a HU-to-elemental-composition relationship(12). The dataset was rescaled from the original 512 × 512 matrix size to 128 × 128 using bi-cubic interpolation, with a resolution in slice thickness of 5 mm. The anatomy of the patients as represented by lattice structures in MCNP6 is presented in Figure 2. Figure 2. View largeDownload slide Patient anatomy with delineated organs as represented in MCNP6 of the adult patient (a) and the paediatric patient (b). Colour scale corresponds to materials. Figure 2. View largeDownload slide Patient anatomy with delineated organs as represented in MCNP6 of the adult patient (a) and the paediatric patient (b). Colour scale corresponds to materials. Dose calculations The treatment plans for both patients were exported from the TPS and MCNP6 input files were created for each energy layer. The energy layers were individually simulated using a beam model previously validated for the proton beam characteristics at the Skandion Clinic(13). The delineated organs were assigned energy deposition f6 tallies for scoring the absorbed dose from secondary neutrons, photons and scattered protons. Each organ was also assigned a neutron f6 tally with an energy card for scoring the absorbed dose in different energy intervals. The organ doses from secondary radiation, Dsec,i, were normalised with the relative weight, wi, of each energy layer i, and summed according to equation 1. The wi was calculated as the ratio of the number of monitor units delivered in energy layer i to the total number of monitor units. Dsec/DH=∑(Dsec,i×wi)/∑(DH,i×wi) (1) where Dsec/DH is the organ dose from secondary radiation for the entire treatment plan normalised to target dose and DH,i is the proton absorbed dose to the target volume for energy layer i, calculated from a proton energy deposition tally assigned to the PTV. The neutron equivalent dose, HT, was calculated from the absorbed doses to the organs using energy-specific radiation weighting factors, wR, adopted from the fitting equations in ICRP 103(9). Additionally, the neutron energy fluence spectra in all delineated organs were scored using f4 fluence tallies. The statistical uncertainty of each organ tally was calculated from the quadratic sum of the uncertainty in each energy layer weighted with wi. The statistical uncertainty of all organ tallies was within 0.02. All simulations were carried out with the ENDF/B-VII.1 library(14) and the Bertini intercascade model(15). RESULTS AND DISCUSSION Organ absorbed doses Simulated absorbed doses from secondary radiation from the lateral and vertex field setup are presented in Table 1. The doses from the vertex field were higher in all organs except for the right eye in both patients. The largest absolute difference in the adult patient was found in the dose to the right eye where the lateral field setup produced an increase in dose of 18.3 μGy.Gy-1. The corresponding increase in dose in the paediatric patient was found in the thyroid for the vertex field setup corresponding to 8.9 μGy.Gy−1. The relative difference between the vertex and lateral field irradiation was further increased in more remote organs by factors of 3–5. However, the difference between the two field setups in dose to remote organs decreased in absolute terms for both the adult and the paediatric patient with differences in the range of 0.2–3.9 μGy.Gy−1. The doses were higher in the paediatric patient with an average relative increase in dose of 1.8 and 1.7 for the lateral and vertex field setup respectively (excluding the eyes). For a prescribed tumour dose of 49.2 Gy, the highest cumulative absorbed doses were found in the eyes and the cervical region of the spinal cord corresponding to roughly 1–2 mGy for both patients. For remote organs, the cumulative doses were in the range of 3–173 μGy in the adult patient and 7–293 μGy in the paediatric patient. Table 1. Organ absorbed doses per prescribed dose (μGy.Gy−1) from secondary radiation produced from lateral and vertex field setups of a brain tumour proton PBS treatment. Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Spin cerv, spinal cord cervical region; Spin. thor, spinal cord thoracic region; Spin. lumb, Spinal cord lumbar region. Table 1. Organ absorbed doses per prescribed dose (μGy.Gy−1) from secondary radiation produced from lateral and vertex field setups of a brain tumour proton PBS treatment. Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Adult Paediatric Organ Lat. Vert. Lat. Vert. Eye l. 19.5 21.5 18.2 23.3 Eye r. 43.1 24.8 30.8 25.3 Spin. cerv. 11.3 21.7 20.3 28.8 Thyroid 4.1 10.5 7.2 16.1 Lung l. 1.2 3.3 2.1 5.9 Lung r. 1.3 3.5 1.9 5.4 Spin. thor. 0.8 2.6 1.3 4.0 Breast l. 0.7 2.1 1.7 4.8 Breast r. 0.8 2.3 1.5 4.4 Liver 0.4 1.5 0.7 2.7 Kidney l. 0.2 1.0 0.5 1.9 Kidney r. 0.3 1.1 0.3 1.5 Spleen 0.4 1.5 0.6 2.4 Spin. lumb. 0.1 0.5 0.3 1.1 Bladder 0.1 0.3 0.1 0.7 Spin cerv, spinal cord cervical region; Spin. thor, spinal cord thoracic region; Spin. lumb, Spinal cord lumbar region. Studies on absorbed doses from secondary radiation from proton treatments of brain tumours delivered with modern PBS facilities are relatively scarce. Nevertheless, some publications have reported absorbed doses from similar treatments(16, 17). Thus, Newhauser et al(16). simulated organ absorbed doses from a craniospinal irradiation of an adult anthropomorphic phantom delivered with a scanned proton beam. The absorbed doses from a cranial field irradiation were 52 μGy.Gy−1 to the thyroid and 34 μGy.Gy−1 to the lungs, which are higher than the doses found in the present study. Studies on out-of-field doses from proton therapy delivered with the passive scattering technique have reported values ranging from the absorbed doses associated with PBS to much higher dose levels(6, 18). Thus, Farah et al.(18) reported on measurements and simulations in an anthropomorphic phantom irradiated with a lateral field for an intracranial target leading to doses of approximately 30–40 μGy.Gy−1 and 10–30 μGy.Gy−1 to the thyroid and the lungs respectively. Sayah et al.(6) simulated absorbed organ doses from a cranial treatment delivered with various field setups and reported averaged doses to a 5-year-old patient of 255 μGy.Gy−1 to the thyroid and 198 μGy.Gy−1 to the lungs. The corresponding doses in an adult patient were 231 μGy.Gy−1 and 120 μGy.Gy−1, respectively. These findings demonstrate both that the passive scattering technique is associated with higher doses from secondary radiation, and that comparisons between different studies are complex due to differences in treatment setup and beam characteristics associated with different proton facilities. Equivalent doses to organs Out-of-field equivalent doses from secondary neutrons to both patients are presented in Figure 3. The relative difference in dose for the two field setups increased with distance from isocenter as the vertex field produced a maximum relative increase of 4.5 in the bladder for the adult patient and 3.9 for the paediatric patient. The largest absolute differences were found in the cervical region of the spinal cord corresponding to 25 and 33 μSv.Gy−1 for the adult and paediatric patient respectively. As for the absorbed doses, the equivalent doses were higher in the paediatric patient for both field setups with an average relative increase of 2.0 and 1.9 for the lateral and vertex irradiation respectively (excluding the eyes). Figure 3. View largeDownload slide Equivalent doses to organs from secondary neutrons to the adult and paediatric patient from lateral and vertex fields. Figure 3. View largeDownload slide Equivalent doses to organs from secondary neutrons to the adult and paediatric patient from lateral and vertex fields. The maximum cumulative neutron equivalent dose to the eyes from an entire treatment was 6.6 mSv and 6.9 mSv for the adult and the paediatric patient, respectively. When adding the corresponding equivalent photon dose with wR = 1(9), the equivalent doses were 6.8 mSv and 7.2 mSv. These doses are comparable to the dose to the eyes from a cone-beam CT examination of the head-and-neck region(19, 20). The equivalent doses found in the present study are similar to previously reported data on cranial treatments delivered with PBS and lower than doses from passive scattering treatments. Thus, Geng et al.(21) reported neutron dose equivalents in the range of 1 μSv.Gy−1 and 100 μSv.Gy−1 in the bladder and thyroid of a 14-year-old patient from a brain tumour treatment with PBS. The doses to the bladder from the vertex field irradiation in the present study were 2 μSv.Gy−1 and 1 μSv.Gy−1 for the paediatric patient and the adult, respectively. Corresponding doses to the thyroid were 62 μSv.Gy−1 and 36 μSv.Gy−1. Sayah et al.(6) reported neutron equivalent doses from passive scattering of approximately 1.6 mSv.Gy-1 and 0.2 mSv.Gy−1 to the thyroid and bladder of an adult patient, averaged for different field setups. The small differences in equivalent doses between the adult and the paediatric patient in the present study could translate into larger differences in the associated risks of RISM due to the increased sensitivity of younger patients. As an example, the estimated lifetime risk of radiation-induced solid cancer death after an exposure of 100 mSv is 2.1% for an age at exposure of 10 years and 0.4% for an age at exposure of 50 years(7). The average relative increase in equivalent dose of 1.9–2.0 could consequently translate into an increased relative risk of 10 (1.95 × 2.1/0.4) for the paediatric patient. Nevertheless, the organ doses and consequently the absolute risk of RISM are low for both the adult and the paediatric patient. Consequently, differences in the risk of RISM between the adult and the paediatric patient are dominated by variations in risk coefficients, associated with large uncertainties, and should therefore be regarded as a relative measure. Radiation-induced tumours most often arise in regions close to the PTV receiving rather high doses(22). The risk of RISM for the patients included in the present study is therefore mostly influenced by the primary proton radiation and the corresponding dose distribution in adjacently located OAR. Still, when evaluating the risk of RISM for patients undergoing modern radiotherapy, it is essential that the total dose burden to the patient is considered(8). Consequently, the combined organ doses from primary radiation, secondary radiation and diagnostic imaging should be included for such calculations(23). Neutron spectra The small absolute differences in absorbed dose between the two field setups were also seen in the neutron equivalent doses. This indicates that the energy distribution of the secondary neutrons had limited impact on the neutron equivalent doses. This can be seen in Figure 4 where the neutron energy fluence in three different organs is presented for the paediatric patient (the results were similar for the adult patient). Indeed, there is an increase in fast neutrons for the vertex field setup due to the higher primary proton energies. Also, the forward-directed trajectories of the fast neutrons pass through the patient for the vertex irradiation instead of exiting as for the lateral field setup. The largest differences in neutron fluence between the two field setups were found in the energy range of approximately 10–100 MeV. In this region, the neutron wR falls from 10 to 5 reducing the influence on the calculated equivalent doses. In the energy region around 1 MeV, where wR ≥ 20, the difference in neutron fluence between the vertex and the lateral field irradiations was relatively small in the thyroid and increased with distance from the tumour. As the neutron fluence in these remote organs was relatively low, the difference in neutron fluence did not cause large variations in equivalent dose. Figure 4. View largeDownload slide Neutron energy fluence spectra in the thyroid, left lung and right kidney for the paediatric patient and neutron wR as function of energy. The solid lines correspond to the vertex field setup and dashed lines to the lateral field setup. Figure 4. View largeDownload slide Neutron energy fluence spectra in the thyroid, left lung and right kidney for the paediatric patient and neutron wR as function of energy. The solid lines correspond to the vertex field setup and dashed lines to the lateral field setup. CONCLUSIONS The results of this study showed that out-of-field absorbed doses and neutron equivalent doses produced inside patients treated with proton PBS for brain tumours are relatively low and in the order of mSv. The organ doses were higher in the paediatric patient in comparison to the adult, but all differences were low in absolute terms. Furthermore, the results indicate that changing the field setup does not lead to large variations in out-of-field doses in patients undergoing proton PBS of centrally located brain tumours. FUNDING This work was supported by the Swedish Radiation Safety Authority under the contract SSM2016-2425. REFERENCES 1 Yock , T. I. et al. . Quality of life outcomes in proton and photon treated pediatric brain tumor survivors . Radiother. Oncol. 113 ( 1 ), 89 – 94 ( 2014 ). Google Scholar CrossRef Search ADS PubMed 2 Newhauser , W. D. and Zhang , R. The physics of proton therapy . Phys. Med. Biol. 60 ( 8 ), R155 – R209 ( 2015 ). Google Scholar CrossRef Search ADS PubMed 3 Kaderka , R. , Schardt , D. , Durante , M. , Berger , T. , Ramm , U. , Licher , J. and La Tessa , C. Out-of-field dose measurements in a water phantom using different radiotherapy modalities . Phys. 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Correlation between CT numbers and tissue parameters needed for Monte Carlo simulations of clinical dose distributions . Phys. Med. Biol. 45 ( 2 ), 459 – 478 ( 2000 ). Google Scholar CrossRef Search ADS PubMed 13 Ardenfors , O. , Dasu , A. , Kopeć , M. and Gudowska , I. Modelling of a proton spot scanning system using MCNP6 . J. Phys.: Conf. Ser. 860 , 012025 ( 2017 ). Google Scholar CrossRef Search ADS 14 Chadwick , M. B. et al. . ENDF/B-VII.1 nuclear data for science and technology: cross sections, covariances, fission product yields and decay data . Nucl. Data Sheets 112 ( 12 ), 2887 – 2996 ( 2011 ). Google Scholar CrossRef Search ADS 15 Bertini , H. W. Low-energy intranuclear cascade calculation . Phys. Rev. 131 , 1801 ( 1963 ). Google Scholar CrossRef Search ADS 16 Newhauser , W. D. et al. . The risk of developing a second cancer after receiving craniospinal proton irradiation . Phys. Med. Biol. 54 ( 8 ), 2277 – 2291 ( 2009 ). 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Radiation burden from secondary doses to patients undergoing radiation therapy with photons and light ions and radiation doses from imaging modalities . Radiat. Prot. Dosim. 161 ( 1-4 ), 357 – 362 ( 2014 ). Google Scholar CrossRef Search ADS 21 Geng , C. , Moteabbed , M. , Xie , Y. , Schuemann , J. , Yock , T. and Paganetti , H. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning . Phys. Med. Biol. 61 ( 1 ), 12 – 22 ( 2016 ). Google Scholar CrossRef Search ADS PubMed 22 Diallo , I. et al. . Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer . Int. J. Radiat. Oncol. 74 ( 3 ), 876 – 883 ( 2009 ). Google Scholar CrossRef Search ADS 23 Ardenfors , O. , Josefsson , D. and Dasu , A. Are IMRT treatments in the H&N region increasing the risk of secondary cancers? Acta Oncol. 53 ( 8 ), 1041 – 1047 ( 2014 ). Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Radiation Protection DosimetryOxford University Press

Published: Mar 21, 2018

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