OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS USING HYPOFRACTIONATED GAMMA KNIFE RADIOSURGERY AND INTENSITY-MODULATED RADIATION THERAPY

OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS USING... Abstract The purpose of this study was to measure out-of-field organ doses in two anthropomorphic child phantoms for the treatment of large brain arteriovenous malformations (AVMs) using hypofractionated gamma knife (GK) radiosurgery and to compare these with an alternative treatment using intensity-modulated radiation therapy (IMRT). Target volume was identical in size and shape in all cases. Radiophotoluminescent (RPL), thermoluminescent (TL) and optically stimulated luminescent (OSL) dosimeters were used for out-of-field dosimetry during GK treatment and a good agreement within 1–2% between results was shown. In addition, the use of multiple dosimetry systems strengthens the reliability of the findings. The number of GK isocentres was confirmed to be important for the magnitude of out-of-field doses. Measured GK doses for the same distance from the target, when expressed per target dose and isocentre, were comparable in both phantoms. GK out-of-field doses averaged for both phantoms were evaluated to be 120 mGy/Gy for eyes then sharply reduced to 20 mGy/Gy for mandible and slowly reduced up to 0.8 mGy/Gy for testes. Taking into account the fractionation regimen used to treat AVM patients, the total treatment organ doses to the out-of-field organs were calculated and compared with IMRT. The eyes were better spared with GK whilst for more distant organs doses were up to a factor of 2.8 and 4 times larger for GK compared to IMRT in 5-year and 10-year old phantoms, respectively. Presented out-of-field dose values are specific for the investigated AVM case, phantoms and treatment plans used for GK and IMRT, but provide useful information about out-of-field dose levels and emphasise their importance. INTRODUCTION The aim of the EURADOS (European Radiation Dosimetry Group) Working Group 9 (Radiation Dosimetry in Radiotherapy) is to assess undue, non-target patient doses in radiotherapy and related risks of secondary cancer. In particular, the group is concerned with paediatric radiotherapy patients who are, if irradiated on the same way as adults, subjected to higher organ doses because of their smaller body size. Moreover, paediatric patients are at potentially higher risk of developing secondary cancers because organs are more radiosensitive and children have longer life expectancy(1). A vulnerable group of patients are children having large size brain arteriovenous malformations (AVMs). These children have a high survival rate and because of their higher susceptibility to radiation they have a higher risk of developing radiation-induced cancer compared with adults. The out-of-field doses in these patients therefore raise an important radioprotection concern. During the last 10–20 years, research on out-of-field doses has gained much attention. A review of dosimetry studies on external-beam radiation treatment with respect to cancer induction can be found in the comprehensive paper(2) and recently, AAPM report regarding measurement and calculation of out-of-field doses has been published(3). However, it has to be noted that studies with paediatric anthropomorphic phantoms under clinical conditions are sparse and highly desirable. In general, doses measured under clinical conditions give more realistic information about organ doses for selected cases and also they are the most appropriate to test mathematical models of out-of-field doses. AVMs are commonly treated with stereotactic radiosurgery (SRS) such as Leksell Gamma Knife (GK) (Elekta Instruments, Stockholm, Sweden) radiosurgery and highly conformal radiotherapy techniques such as stereotactic radiotherapy (SRT), intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) depending on the size of the AVM(4–8). For AVMs having smaller size (diameter < 3 cm) GK radiosurgery delivered in a single fraction represents the optimal treatment modality due to an acceptable complication rate in adjacent brain tissue. For medium size AVMs (diameter 3–6 cm) and large AVMs (diameter > 6 cm)(9) due to the dose–volume relationship, the complication rate in surrounding brain tissue is high for single fraction treatment. Fractionation proves to be a good treatment alternative in these cases using hypofractionated SRS (HSRS) or highly conformal linear accelerator techniques such as SRT, IMRT and VMAT. For HSRS using GK it has been shown to be clinically feasible when a stereotactic frame is attached to the head of the patient during treatment from the first to the last fraction (up to 6 days)(10). To treat large AVMs, GK uses up to 5–6 fractions with the total dose up to 20–30 Gy depending on the size and position of the AVM, whilst conformal linear accelerator techniques use larger number of fractions (up to 10) resulting in higher total dose, but not exceeding 42 Gy(5–7, 9, 11). On the other hand, large tumour irradiations with GK result in increased duration and complexity of the GK procedure, raising a concern on the dose burden to the patient’s healthy tissue. Clinical treatment plans for GK radiosurgery of large target volumes are usually multi-isocentric (up to 50 isocentres) using a number of small spherical dose distributions to fill the large target volumes with a high dose of radiation(12). During the repositioning of the patient’s head from the previous to the next isocentre, while the shielding doors of GK are open, patient is exposed to the scatter radiation from the GK sources. This results in an additional, non-negligible dose contribution to the patient’s healthy tissue(13). Out-of-field organ doses for the IMRT treatment of the brain lesions using 3–9 cm field diameters have been studied using Monte Carlo simulations and several paediatric voxel phantoms by Athar et al.(14). Nevertheless, no data have been published studying out-of-field doses during GK treatment of such large AVM lesion. The aim of this study was to determine and compare the out-of-field doses for the treatment of the extremely large brain AVMs using two techniques: hypofractionated GK radiosurgery and IMRT. In this current study out-of-field doses were measured in the 5 and 10-year-old anthropomorphic phantoms treated with hypofractionated GK treatment while for IMRT out-of-field doses from previous study have been used(15). The total treatment organ doses to the out-of-field organs for both techniques were calculated and compared taking into account the fractionation regimen used to treat these patients. Doses were measured with three different techniques: thermoluminescence (TL), radiophotoluminescence (RPL) and optically stimulated luminescence (OSL) dosimetry. This allowed additional information to be gained on the performance of these dosimetry systems in measuring out-of-field doses in RT, one of the topics of interest in EURADOS WG9. MATERIALS AND METHODS Irradiation techniques and irradiation plans Measurements of the large AVMs in paediatric phantoms were performed at the University Hospital Centre Zagreb, Croatia using a Leksell Gamma Knife (GK) (Model 4 C, Elekta Instruments, Stockholm, Sweden). GK uses 201 fixed 60Co sources arranged on the surface of a hemisphere in the core of the unit. In total, 201 narrow photon beams intersect at a single point (the unit centre point), also called the isocentre. The dose rate of the GK unit ranged from 2.335 to 2.316 Gy/min for the reference 18 mm collimator during period of measurements in this study. The irradiation of each source is collimated both by a fixed primary collimator system and a secondary changeable collimator. For secondary collimation, four different collimator helmets can be used. Depending on the used collimator helmet, spherical dose distributions with diameters of 4, 8, 14 and 18 mm are produced around the isocentre. In order to achieve better conformity of the dose distribution to the tumour, clinical treatment plans usually employ more than one collimator helmet, each using many isocentres. A change of isocentre position is enabled by automatically repositioning the patient’s head into the required treatment position. Information given by treatment plan called ‘beam on time’ includes only the time during which patient is in the treatment position, i.e. in the position for tumour irradiation. ‘Total time’ includes ‘beam on time’ and time required for repositioning of the patient’s head from the previous to next isocentre as well as for movements of the couch with patient in and out the GK facility. Dose received during the repositioning time, when patient is not in the treatment position, is called ‘reposition dose’. For GK Model 4C, Tran et al.(13) defined ‘reposition dose’ for one reposition as ‘transit dose per reposition’ and reported contribution of the ‘reposition dose’ for the target if 18 mm collimator is used. In addition, the GK ‘leakage dose’ was considered in this work as another possible source of the dose contribution to the total out-of-field dose in GK treatment. Wu et al.(16) measured the GK ‘leakage dose’ as the dose arising from the transmitted radiation through the collimator helmet, i.e. the dose to the target when the patient is in the treatment position and all 201 photon beams are blocked. Treatment planning systems (TPS) do not calculate or report the ‘reposition dose’ and the ‘leakage dose’ and those dose contributions are never added to the patient dose file. In this study the dose calculation algorithm used in the TPS was a tissue-maximum ratio algorithm TMR10 (Elekta Instruments, Stockholm, Sweden). Details of the GK treatment plans for the AVM in the 5 and 10-year-old phantoms are presented in Table 1. Due to large tumour volume, for both phantoms, only the largest collimator (18 mm) was used with 25 and 31 isocentres for 5 and 10-year-old phantom, respectively. Measured doses were normalised to the mean target dose (4.1 Gy for both phantoms) and results are presented as (mGy/Gy). In both phantoms an AVM was represented by a sphere with a diameter of 6 cm (treatment volume ~113 cm3) located on the left-anterior side of the head with the centre in the middle of slice 3 of both phantoms. The total treatment doses chosen as an optimal prescription for large AVMs were 30 Gy in 5 fractions for hypofractionated GK treatment(8) and 37.6 Gy in 8 fractions for IMRT(17). The total treatment doses were not used for irradiations but served to calculate the total out-of-field organ doses (doses that would be absorbed in out-of-field organs during whole treatment). Treatment of the same tumour (sphere with a diameter of 6 cm located on the left-anterior side of the head) in both phantoms was simulated in a previous study using IMRT with 6 MV photon beams(15) and in this study results were compared with measured out-of-field doses for GK treatment. IMRT measurements were performed on a Varian Clinac 2300 in the Centre of Oncology, Krakow, Poland. Treatment plans were generated by an Eclipse External Beam Planning System (version 8.6 Varian Medical Systems, Palo Alto, CA). Details of the IMRT treatment plans are presented in Table 2. As shown, the IMRT plan included nine coplanar fields equally distributed in angle, irradiations of both phantoms were performed for a target dose of 2 Gy and all results are, after normalisation to target dose, presented as (mGy/Gy). Table 1. Details of the irradiation plans for Gamma Knife treatment of the 5-year-old and 10-year-old phantom. Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Table 1. Details of the irradiation plans for Gamma Knife treatment of the 5-year-old and 10-year-old phantom. Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Table 2. Details of the irradiation plans for IMRT treatment of the 5 and 10-year-old phantom (target dose 2 Gy)(11) Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Table 2. Details of the irradiation plans for IMRT treatment of the 5 and 10-year-old phantom (target dose 2 Gy)(11) Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Child anthropomorphic phantoms For this study anthropomorphic phantoms (ATOM, Computerised Imaging Reference Systems (CIRS), Inc, Norfolk, VA) representing a 10-year-old (type 706D) and 5-year-old child (type 705D) were used. The phantoms consist of 26 and 32 slices with 180 and 231 holes for dosimeters in 5 and 10-year-old phantoms, respectively. Slices of thickness 2.5 cm are made of tissue equivalent materials and dosimeters can be inserted into holes of diameter 5 mm located on positions of different organs/tissues and fixed with appropriate plugs. Using computed tomography (CT) images of the phantoms, distance from the middle of each dosimeter to the selected point in the phantom (centre of the spherical tumour) was evaluated. Dosimetry systems In the GK study, dose measurements were performed using radiophotoluminescent (RPL) dosimeters type GD-352M, optically stimulated luminescent (OSL) dosimeters type Luxel and two types of thermoluminescent (TL) dosimeters: MCP-n and MTS-7. For IMRT, out-of-field doses in both 5- and 10-year-old phantoms were performed with RPL dosimeters type GD-352M(15). Detailed characteristics of the dosimetry systems used can be found in previously published papers(18–21) and a short summary is given in Table 3. Information about dosimetry systems used for each irradiation can be found at the bottom of Table 3. Table 3. Characteristics and evaluation parameters of the used RPL, TL and OSL dosimetry systems. Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No NA: not applicable or not applied. aThickness of the polyester foils: 0.05 (top) and 0.08 (bottom). bExperimentally determined(22). cDetermined using the ratio of mass energy absorption coefficient for water to air for the energy of 60Co(23). d60 min heating on 400°C + 120 min heating on 100°C. Table 3. Characteristics and evaluation parameters of the used RPL, TL and OSL dosimetry systems. Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No NA: not applicable or not applied. aThickness of the polyester foils: 0.05 (top) and 0.08 (bottom). bExperimentally determined(22). cDetermined using the ratio of mass energy absorption coefficient for water to air for the energy of 60Co(23). d60 min heating on 400°C + 120 min heating on 100°C. Dual detector system for correction of OSL dosimeters type Luxel Since OSL (Luxel) dosimeter has a large over-response in the low energy range the Luxel data was corrected by calculating the ratio of TL (MCP-n) and OSL (Luxel) response measured simultaneously (referred to as Luxelc). This dual detector system, described in literature(24), combines values measured with TL and OSL dosimeters to approximate the photon energy and allows correction of OSL (Luxel) detectors. In the same way as described in literature(24), the response of both TL (MCP-n) and OSL (Luxel) dosimeters for eight different averaged energies (32, 63, 82, 99, 115, 160, 203 and 242 keV corresponding to ISO N-series: N40, N80, N100, N120, N150, N200, N250 and N300)(25) relative to 60Co was assessed using X-ray tube in the secondary standard laboratory in SCK-CEN. The relative response of TL (MCP-n) and OSL (Luxel) to 60Co as a function of energy was plotted together with the correction factor to be applied for Luxel energy correction (Figure 1). In the different positions in the phantom the ratio of Luxel/MCP-n was determined which allowed to approximate the photon energies and correction of OSL (Luxel) data (Luxelc). Figure 1. View largeDownload slide The relative response of TL dosimeters type MCP-n and OSL dosimeters type Luxel to 60Co as a function of energy in line plot and Luxel/MCP-n ratio and corresponding correction factor for Luxels energy dependence in scatter plot. Figure 1. View largeDownload slide The relative response of TL dosimeters type MCP-n and OSL dosimeters type Luxel to 60Co as a function of energy in line plot and Luxel/MCP-n ratio and corresponding correction factor for Luxels energy dependence in scatter plot. Every hole in the phantom was filled with one annealed dosimeter and each dosimeter was fixed so that its active volume was in the middle of the hole. Measured doses were in the range 1 mGy–1 Gy and that is within operational range for all dosimeters (lowest detectable limit for all dosimeters used in this study is below 0.1 mGy, while upper limit of a useful dose range is above 10 Gy). In addition, for dose range 1 mGy–1 Gy all used dosimeters show linear dose response(18, 21, 26, 27). The measured doses for all dosimeters were expressed as absorbed dose to water, Dw (mGy), and normalised to the mean target dose (mGy/Gy). Relative standard uncertainty of the determined dose for RPLs (GD 352-M), OSLs (Luxel) and TLDs (MCP-n and MTS-7) were 2.1, 4.5, 3.3 and 2.9%(20), respectively. For MTS-7 and Luxel, uncertainties include repeatability and calibration while for RPL and MCP-n, uncertainties include repeatability, calibration and angular correction. The mean organ doses in the phantoms measured with selected type of dosimeters were calculated as an average value of all dosimeters of that type placed in the particular organs. Number of dosimeters for each organ in both phantoms are shown in Table 4. For all organs (with exception of prostate) doses were measured in, at least, two different points within the organ. The spread of the average dose measured in each organ was higher than uncertainty on the dose measurement (between 2 and 4%). This is especially true for large organs. Depending on the total treatment dose (stated in Irradiation techniques and irradiation plans section), total out-of-field organ doses were calculated by multiplying mean out-of-field organ dose (in mGy/Gy) with total treatment dose (in Gy). Table 4. Number of dosimeters in each organ of the 5- and 10-year-old phantom. Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 Table 4. Number of dosimeters in each organ of the 5- and 10-year-old phantom. Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 RESULTS AND DISCUSSION Comparison of dosimetry systems For each GK irradiation performed in this study, the dosimetry systems used can be found at the bottom of Table 3. The use of three types of detectors (RPL (GD-352M), TL (MCP-n) and OSL (Luxel)) in the 5-year-old phantom allowed to compare the response of the different dosimetry systems and to evaluate their use in the application of out-of-field dosimetry in radiotherapy. For each position inside the phantoms, ratios of measured values with different dosimeters have been calculated. In Table 5, average values of those ratios for each phantom and each pair of compared dosimeters are shown. The average response ratios demonstrate a close correspondence between RPLs (GD-352M) and TLDs (MCP-n). However, for the OSL (Luxels) a large overestimation was observed. After the correction of OSL Luxels (Luxelc), using the dual detector technique for the over-response to low energy photons, a close correspondence with RPL (GD-352M) was observed. The dual dosimetry analysis revealed Luxel/MCP-n ratios between 1.3 and 1.7 corresponding to approximate photon energies inside the phantom which ranged between 200 and 900 keV for the plugs outside the brain region of the 5-year-old phantom treated with GK (Figure 1). This is a result of patient scattering as well as different sources of leakage and scatter inside the collimator of the GK head. As shown in Table 5 a good correspondence was observed between the RPL (GD-352M) and TLD (MTS-7) data as measured in the 10-year-old phantom. Table 5. Average response ratios to compare correspondence between RPL GD-352M, TL (MCP-n and MTS-7) and OSL Luxel dosimeters, studied in the 5 and 10-year-old phantoms during GK irradiations. Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 aLuxelc represents Luxel result after correction for enmergy dependence. Table 5. Average response ratios to compare correspondence between RPL GD-352M, TL (MCP-n and MTS-7) and OSL Luxel dosimeters, studied in the 5 and 10-year-old phantoms during GK irradiations. Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 aLuxelc represents Luxel result after correction for enmergy dependence. In summary, GK data show that RPL (GD-352-M) and both types of TL dosimeters (MCP-n and MTS-7) could be used in this particular application while OSL (Luxel) dosimeters need to be corrected for increased response with decreasing energies, which is feasible using the dual dosimetry analysis. Because RPLs (GD-352M) were used to measure doses in both phantoms, the final data in the following sections on the out-of-field organ doses will be shown based only on the RPL results. Out-of-field organ doses for GK treatment Out-of-field organ doses per target dose in both phantoms for GK treatment of the large AVM measured with RPL detectors are shown in Figure 2. Organs are ordered according to their average distance from the target. For double organs (such as eyes), averaged dose values for both parts are shown in Figure 2. Because tumour was located above left eye, for all irradiations dose to left eye was higher than dose to right eye (average left to right eye dose ratio was 1.3 and 1.45 for GK and IMRT, respectively). In all figures, the doses to eyes represents the average dose received by both eyes. The average out-of-field doses in the 5 and 10-year-old phantoms treated with GK were comparable. Organs in the 5-year-old phantom are closer to the target than in the 10-year-old phantom and from that point of view higher organ doses were expected for the smaller phantom. On the other hand, due to the geometrical differences between the phantoms (positions of the head in the stereotactic frame), the treatment planning resulted in a different number of isocentres (Table 1) and that influenced on the dose distribution, as shown in Figure 3. Figure 2. View largeDownload slide Out-of-field organ doses per target dose (mGy/Gy) for AVM treated with Gamma Knife (GK) measured in the 5 and 10-year-old phantom. Figure 2. View largeDownload slide Out-of-field organ doses per target dose (mGy/Gy) for AVM treated with Gamma Knife (GK) measured in the 5 and 10-year-old phantom. Figure 3. View largeDownload slide (Top) Dose per target dose as a function of the distances from the target. The best fitting functions for the pairs of values shown on x-axis (distance) and y-axis (dose per target dose) are shown as y = f(x). (Bottom) Dose per target dose per isocentre as a function of the distance from the centre of the target. Eyes were not included in this figure. Both figures are for GK treatment. Figure 3. View largeDownload slide (Top) Dose per target dose as a function of the distances from the target. The best fitting functions for the pairs of values shown on x-axis (distance) and y-axis (dose per target dose) are shown as y = f(x). (Bottom) Dose per target dose per isocentre as a function of the distance from the centre of the target. Eyes were not included in this figure. Both figures are for GK treatment. The dose per target dose for each dosimeter as a function of dosimeter’s distance from the target for both phantoms is shown in Figure 3 (Top). This revealed a slightly higher dose burden in the 10-year-old phantom compared to the 5-year-old phantom for the same distance from the target. This can be explained by the higher number of isocentres for the treatment plan of the 10-year-old phantom resulting in larger number of head movements, with associated ‘reposition dose’, as well as longer ‘beam on time’ as shown in Table 1. For the target, Tran et al.(13) reported ‘reposition dose’ with amount of 23.7 mGy for the 18 mm collimator at the GK unit dose rate of 2.254 Gy/min. Since in our study the GK unit dose rate ranged from 2.335 to 2.316 Gy/min, and taking into account that the repositioning time is the same for all GK units, ‘reposition dose’ for the target per one repositioning of the phantom, calculated by using value from Tran et al.(13) study, was up to 24.6 mGy. For the whole hypofractionated treatment (25 and 31 isocentres per irradiation/fraction, i.e. in total 125 and 155 isocentres for five fractions), total calculated ‘reposition dose’ for the target was 3075.0 and 3813.0 mGy, respectively, which is a significant (10–13% of the target dose) dose contribution to the target volume that will give additional rise to the GK out-of-field doses. The GK ‘leakage dose’ contribution to the target was reported by Wu et al.(16) to be 0.35% of the dose with all 201 photon beams not blocked. Compared to the ‘reposition dose’ the GK ‘leakage dose’ represents practically negligible contribution to the GK out-of-field doses. In Figure 3 (Bottom), dose per target dose per isocentre is shown for both phantoms and a much closer agreement of the data for the 5 and 10-year-old phantoms is achieved. This clearly indicates an important contribution of the ‘reposition dose’ to the GK out-of-field doses and an increased dose burden for higher number of isocentres. From radioprotection point of view, it is suggested that treatment planning strategy should aim to reduce the number of isocentres as much as possible during large AVM treatments using GK in hypofractionated regime. In Figure 3 (top), fitting functions for the experimental data for both phantoms were shown confirming inverse square distance dependence of the measured dose. In Figure 3 (bottom) dose per target dose per isocentre is shown for both phantoms and a much closer agreement of the data for 5 and 10-year-old phantom is achieved suggesting that both data, when expressed as dose per target dose per isocentre, can be modelled with essentially the same function. The generation of simple analytical models to allow assessment of out-of-field organ doses in clinical routine has been initiated by a number of research groups(28, 29). Authors of such studies aim to generalise these models and request measured data as an input to validate their models. The dose versus distance plot shown in Figure 3 could serve as input for these analytical modelling approaches. Comparison of GK and IMRT out-of-field organ doses Comparison of out-of-field doses for GK and IMRT treatment of the large AVM is shown in Figure 4 (both comparison of mGy/Gy and comparison of total doses are shown). As shown in Figure 4, the eye doses per target dose were a factor of two higher for IMRT compared to GK treatment. Reduction of eye doses is important because children exposed to a lenticular dose of 1 Gy have a 50% increased risk of developing a posterior subcapsular opacity and the risk of developing cortical cataract is increased by ~35% with a follow-up observation period of at least 40 years(30). The total treatment doses chosen as an optimal prescription for large AVMs in this study were 30 Gy in 5 fractions for hypofractionated GK treatment(8) and 37.6 Gy in 8 fractions for IMRT(18). Therefore eye doses, calculated for the total IMRT treatment, were 9 and 12 Gy for 10 and 5-year-old phantom, respectively, while for both phantoms the total eye doses for GK treatment were ~4 Gy. This suggests that the eyes (normal tissue close to the target) were more spared during GK than during IMRT treatment which can be explained by the known steeper dose gradient for target to neighbouring tissue transition in GK compared to IMRT. In addition, IMRT uses a larger number of monitor units to deliver the dose through small field segments achieved by multileaf collimators (MLC) and that results in higher overall MLC leakage dose in the proximity of the target and therefore larger doses for the organs close to the target volume during IMRT. Scatter or leakage radiation during IMRT for particular linear accelerator and MLC/beam configuration is not easy to assess but from the literature, for Varian machines, it can be roughly assessed to be up to 10% of the maximum in-field dose(31). Compared to the GK ‘leakage dose’, leakage radiation of IMRT gives much higher contribution to the out-of-field doses. Figure 4. View largeDownload slide (Top) Organ dose per target dose [mGy/Gy] and total organ dose [mGy] in bar plot and line plot, respectively for GK and IMRT as measured in the 5-year-old phantom. For the total treatment 30 Gy in 5 fractions was assumed for GK and 37.6 Gy in 8 fractions for IMRT. (Bottom) As for (Top) but for the 10-year-old phantom. Figure 4. View largeDownload slide (Top) Organ dose per target dose [mGy/Gy] and total organ dose [mGy] in bar plot and line plot, respectively for GK and IMRT as measured in the 5-year-old phantom. For the total treatment 30 Gy in 5 fractions was assumed for GK and 37.6 Gy in 8 fractions for IMRT. (Bottom) As for (Top) but for the 10-year-old phantom. The rest of the out-of-field organs shown in Figure 4 received higher doses with the GK treatment compared to IMRT. These organs are more distant from the target than eyes and for them ratios of GK to IMRT organ doses per target dose ranged from 2 to 3.5 and 2.9 to 5 in 5 and 10-year-old phantoms, respectively (Table 6). For the more appropriate comparison of the GK and IMRT, different treatment regimens have to be taken into account. Namely, irradiations are performed in several fractions but in relatively short time period and it can be assumed that cancer risk is proportional to the total accumulated dose(32). The fraction dose and total dose were calculated from the most conservative treatment regimen which was assumed to be 30 Gy in 5 fractions (6 Gy per fraction) for GK(8) and 37.6 Gy in 8 fractions (4.7 Gy per fraction) for IMRT(17) treatment. Higher dose per fraction for GK treatment than for IMRT was chosen due to the fact that GK dose distribution provides better dose conformity and better sparing of the normal tissue close to the target. As shown in Table 6, taking into account treatment regimens, calculated GK to IMRT organ ratios were, compared to ratios for dose per target dose, increased for fraction dose and decreased for total treatment dose. The fraction doses result in higher GK to IMRT ratios up to a factor of 6.4 in the 10-year-old phantom. Because of the lower total treatment dose in GK, the total organ doses were 1.5–2.8 and 2.3–4 times higher than the IMRT total organ doses as shown in Table 6. The markedly higher out-of-field doses in this study for GK compared to IMRT can be explained as coming mainly from the difference in the treatment techniques. For the GK technique, ‘reposition dose’ gives important contribution to the out-of-field doses. ‘Reposition dose’ is absorbed during repositioning of the patient’s head from the previous to the next isocentre, i.e. while patient is not in the treatment position and the shielding doors of GK are open. Therefore, out-of-field doses increase with the number of repositioning (i.e. number of isocentres) during GK procedures. For IMRT technique, the treatment beam is turned off during the repositioning of the linear accelerator gantry from one to another treatment field and additional dose is not present. Table 6. Gamma Knife (GK) to IMRT ratios depicted as minimum and maximum ratios measured in the out-of-field organs (except the eyes) as observed for dose per target dose, fraction dose and total dose of each treatment regimen and for both 5-year-old and 10-year-old phantoms. GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 Table 6. Gamma Knife (GK) to IMRT ratios depicted as minimum and maximum ratios measured in the out-of-field organs (except the eyes) as observed for dose per target dose, fraction dose and total dose of each treatment regimen and for both 5-year-old and 10-year-old phantoms. GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 CONCLUSION RPL, TL and OSL dosimeters have proven to be reliable dosimeters for scattered photons during different clinical situations and radiotherapy treatment protocols(15, 18, 19, 33). In this study, all three systems showed good agreement within 1–2% and they are proved to be suitable for out-of-field dose measurements during GK radiosurgery treatment. In addition to previous studies, for TLD and RPL used in this study no correction was required, while for OSL energy correction was necessary: by means of a dual detector system, as demonstrated in the current study, or by Monte Carlo simulations as shown in previous work(33). For each phantom in this study clinically relevant GK treatment plan was applied. Number of isocentres was confirmed to be important for the level of out-of-field dose. For both phantoms GK out-of-field doses for the same distance to target, when divided with target dose and number of isocentres, were comparable. GK out-of-field organ doses were increased by number of isocentres but decreased with organ to target distance and as a result, out-of-field organ doses were also comparable in both phantoms. On average, both phantom treatments with GK show an out-of-field dose of 120 mGy/Gy for eyes which sharply reduced to 20 mGy/Gy for mandible and further reduced up to 0.8 mGy/Gy for testes. Finally, the current study showed that children with large size brain AVMs treated with hypofractionated GK radiosurgery experience smaller eyes doses but higher other out-of-field organs doses compared to the highly conformal IMRT technique. The presented out-of-field dose values are specific for the investigated AVM case, phantoms and treatment plans used, but they provide useful information about out-of-field dose levels and emphasise the importance of out-of-field dosimetry. The use of multiple dosimetry systems strengthens the reliability of the findings. FUNDING This work was partly supported by the European Radiation Dosimetry Group (EURADOS, WG9, Radiation dosimetry in radiotherapy, Postfach 11 29, D-85758, Neuherberg). REFERENCES 1 Oeffinger , K. C. et al. . Chronic health conditions in adult survivors of childhood cancer . New Engl. J Med. 355 ( 15 ), 1572 – 1582 ( 2006 ). Google Scholar Crossref Search ADS 2 Xu , X. , Bednarz , B. J. and Paganatti , H. 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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/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Radiation Protection Dosimetry Oxford University Press

OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS USING HYPOFRACTIONATED GAMMA KNIFE RADIOSURGERY AND INTENSITY-MODULATED RADIATION THERAPY

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Abstract

Abstract The purpose of this study was to measure out-of-field organ doses in two anthropomorphic child phantoms for the treatment of large brain arteriovenous malformations (AVMs) using hypofractionated gamma knife (GK) radiosurgery and to compare these with an alternative treatment using intensity-modulated radiation therapy (IMRT). Target volume was identical in size and shape in all cases. Radiophotoluminescent (RPL), thermoluminescent (TL) and optically stimulated luminescent (OSL) dosimeters were used for out-of-field dosimetry during GK treatment and a good agreement within 1–2% between results was shown. In addition, the use of multiple dosimetry systems strengthens the reliability of the findings. The number of GK isocentres was confirmed to be important for the magnitude of out-of-field doses. Measured GK doses for the same distance from the target, when expressed per target dose and isocentre, were comparable in both phantoms. GK out-of-field doses averaged for both phantoms were evaluated to be 120 mGy/Gy for eyes then sharply reduced to 20 mGy/Gy for mandible and slowly reduced up to 0.8 mGy/Gy for testes. Taking into account the fractionation regimen used to treat AVM patients, the total treatment organ doses to the out-of-field organs were calculated and compared with IMRT. The eyes were better spared with GK whilst for more distant organs doses were up to a factor of 2.8 and 4 times larger for GK compared to IMRT in 5-year and 10-year old phantoms, respectively. Presented out-of-field dose values are specific for the investigated AVM case, phantoms and treatment plans used for GK and IMRT, but provide useful information about out-of-field dose levels and emphasise their importance. INTRODUCTION The aim of the EURADOS (European Radiation Dosimetry Group) Working Group 9 (Radiation Dosimetry in Radiotherapy) is to assess undue, non-target patient doses in radiotherapy and related risks of secondary cancer. In particular, the group is concerned with paediatric radiotherapy patients who are, if irradiated on the same way as adults, subjected to higher organ doses because of their smaller body size. Moreover, paediatric patients are at potentially higher risk of developing secondary cancers because organs are more radiosensitive and children have longer life expectancy(1). A vulnerable group of patients are children having large size brain arteriovenous malformations (AVMs). These children have a high survival rate and because of their higher susceptibility to radiation they have a higher risk of developing radiation-induced cancer compared with adults. The out-of-field doses in these patients therefore raise an important radioprotection concern. During the last 10–20 years, research on out-of-field doses has gained much attention. A review of dosimetry studies on external-beam radiation treatment with respect to cancer induction can be found in the comprehensive paper(2) and recently, AAPM report regarding measurement and calculation of out-of-field doses has been published(3). However, it has to be noted that studies with paediatric anthropomorphic phantoms under clinical conditions are sparse and highly desirable. In general, doses measured under clinical conditions give more realistic information about organ doses for selected cases and also they are the most appropriate to test mathematical models of out-of-field doses. AVMs are commonly treated with stereotactic radiosurgery (SRS) such as Leksell Gamma Knife (GK) (Elekta Instruments, Stockholm, Sweden) radiosurgery and highly conformal radiotherapy techniques such as stereotactic radiotherapy (SRT), intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) depending on the size of the AVM(4–8). For AVMs having smaller size (diameter < 3 cm) GK radiosurgery delivered in a single fraction represents the optimal treatment modality due to an acceptable complication rate in adjacent brain tissue. For medium size AVMs (diameter 3–6 cm) and large AVMs (diameter > 6 cm)(9) due to the dose–volume relationship, the complication rate in surrounding brain tissue is high for single fraction treatment. Fractionation proves to be a good treatment alternative in these cases using hypofractionated SRS (HSRS) or highly conformal linear accelerator techniques such as SRT, IMRT and VMAT. For HSRS using GK it has been shown to be clinically feasible when a stereotactic frame is attached to the head of the patient during treatment from the first to the last fraction (up to 6 days)(10). To treat large AVMs, GK uses up to 5–6 fractions with the total dose up to 20–30 Gy depending on the size and position of the AVM, whilst conformal linear accelerator techniques use larger number of fractions (up to 10) resulting in higher total dose, but not exceeding 42 Gy(5–7, 9, 11). On the other hand, large tumour irradiations with GK result in increased duration and complexity of the GK procedure, raising a concern on the dose burden to the patient’s healthy tissue. Clinical treatment plans for GK radiosurgery of large target volumes are usually multi-isocentric (up to 50 isocentres) using a number of small spherical dose distributions to fill the large target volumes with a high dose of radiation(12). During the repositioning of the patient’s head from the previous to the next isocentre, while the shielding doors of GK are open, patient is exposed to the scatter radiation from the GK sources. This results in an additional, non-negligible dose contribution to the patient’s healthy tissue(13). Out-of-field organ doses for the IMRT treatment of the brain lesions using 3–9 cm field diameters have been studied using Monte Carlo simulations and several paediatric voxel phantoms by Athar et al.(14). Nevertheless, no data have been published studying out-of-field doses during GK treatment of such large AVM lesion. The aim of this study was to determine and compare the out-of-field doses for the treatment of the extremely large brain AVMs using two techniques: hypofractionated GK radiosurgery and IMRT. In this current study out-of-field doses were measured in the 5 and 10-year-old anthropomorphic phantoms treated with hypofractionated GK treatment while for IMRT out-of-field doses from previous study have been used(15). The total treatment organ doses to the out-of-field organs for both techniques were calculated and compared taking into account the fractionation regimen used to treat these patients. Doses were measured with three different techniques: thermoluminescence (TL), radiophotoluminescence (RPL) and optically stimulated luminescence (OSL) dosimetry. This allowed additional information to be gained on the performance of these dosimetry systems in measuring out-of-field doses in RT, one of the topics of interest in EURADOS WG9. MATERIALS AND METHODS Irradiation techniques and irradiation plans Measurements of the large AVMs in paediatric phantoms were performed at the University Hospital Centre Zagreb, Croatia using a Leksell Gamma Knife (GK) (Model 4 C, Elekta Instruments, Stockholm, Sweden). GK uses 201 fixed 60Co sources arranged on the surface of a hemisphere in the core of the unit. In total, 201 narrow photon beams intersect at a single point (the unit centre point), also called the isocentre. The dose rate of the GK unit ranged from 2.335 to 2.316 Gy/min for the reference 18 mm collimator during period of measurements in this study. The irradiation of each source is collimated both by a fixed primary collimator system and a secondary changeable collimator. For secondary collimation, four different collimator helmets can be used. Depending on the used collimator helmet, spherical dose distributions with diameters of 4, 8, 14 and 18 mm are produced around the isocentre. In order to achieve better conformity of the dose distribution to the tumour, clinical treatment plans usually employ more than one collimator helmet, each using many isocentres. A change of isocentre position is enabled by automatically repositioning the patient’s head into the required treatment position. Information given by treatment plan called ‘beam on time’ includes only the time during which patient is in the treatment position, i.e. in the position for tumour irradiation. ‘Total time’ includes ‘beam on time’ and time required for repositioning of the patient’s head from the previous to next isocentre as well as for movements of the couch with patient in and out the GK facility. Dose received during the repositioning time, when patient is not in the treatment position, is called ‘reposition dose’. For GK Model 4C, Tran et al.(13) defined ‘reposition dose’ for one reposition as ‘transit dose per reposition’ and reported contribution of the ‘reposition dose’ for the target if 18 mm collimator is used. In addition, the GK ‘leakage dose’ was considered in this work as another possible source of the dose contribution to the total out-of-field dose in GK treatment. Wu et al.(16) measured the GK ‘leakage dose’ as the dose arising from the transmitted radiation through the collimator helmet, i.e. the dose to the target when the patient is in the treatment position and all 201 photon beams are blocked. Treatment planning systems (TPS) do not calculate or report the ‘reposition dose’ and the ‘leakage dose’ and those dose contributions are never added to the patient dose file. In this study the dose calculation algorithm used in the TPS was a tissue-maximum ratio algorithm TMR10 (Elekta Instruments, Stockholm, Sweden). Details of the GK treatment plans for the AVM in the 5 and 10-year-old phantoms are presented in Table 1. Due to large tumour volume, for both phantoms, only the largest collimator (18 mm) was used with 25 and 31 isocentres for 5 and 10-year-old phantom, respectively. Measured doses were normalised to the mean target dose (4.1 Gy for both phantoms) and results are presented as (mGy/Gy). In both phantoms an AVM was represented by a sphere with a diameter of 6 cm (treatment volume ~113 cm3) located on the left-anterior side of the head with the centre in the middle of slice 3 of both phantoms. The total treatment doses chosen as an optimal prescription for large AVMs were 30 Gy in 5 fractions for hypofractionated GK treatment(8) and 37.6 Gy in 8 fractions for IMRT(17). The total treatment doses were not used for irradiations but served to calculate the total out-of-field organ doses (doses that would be absorbed in out-of-field organs during whole treatment). Treatment of the same tumour (sphere with a diameter of 6 cm located on the left-anterior side of the head) in both phantoms was simulated in a previous study using IMRT with 6 MV photon beams(15) and in this study results were compared with measured out-of-field doses for GK treatment. IMRT measurements were performed on a Varian Clinac 2300 in the Centre of Oncology, Krakow, Poland. Treatment plans were generated by an Eclipse External Beam Planning System (version 8.6 Varian Medical Systems, Palo Alto, CA). Details of the IMRT treatment plans are presented in Table 2. As shown, the IMRT plan included nine coplanar fields equally distributed in angle, irradiations of both phantoms were performed for a target dose of 2 Gy and all results are, after normalisation to target dose, presented as (mGy/Gy). Table 1. Details of the irradiation plans for Gamma Knife treatment of the 5-year-old and 10-year-old phantom. Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Table 1. Details of the irradiation plans for Gamma Knife treatment of the 5-year-old and 10-year-old phantom. Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Phantom 5-year-old 10-year-old Collimator (mm) 18 18 Number of isocentres 25 31 Beam on time (min) 12.2 13.1 Total time (min) 32 43 Mean target dose (Gy) 4.1 ± 0.8 4.1 ± 0.8 Table 2. Details of the irradiation plans for IMRT treatment of the 5 and 10-year-old phantom (target dose 2 Gy)(11) Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Table 2. Details of the irradiation plans for IMRT treatment of the 5 and 10-year-old phantom (target dose 2 Gy)(11) Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Phantom Angles MU Phantom Angles MU Gantry Collimator Table Gantry Collimator Table 5-year-old 0 0 0 51 10-year-old 0 0 0 49 40 0 0 40 40 90 0 42 80 0 0 49 80 90 0 54 120 0 0 54 120 0 0 42 160 0 0 44 160 0 0 54 200 0 0 57 200 0 0 51 240 0 0 48 240 0 0 52 280 0 0 55 280 0 0 55 320 0 0 45 320 0 0 51 Total MU 443 Total MU 450 Child anthropomorphic phantoms For this study anthropomorphic phantoms (ATOM, Computerised Imaging Reference Systems (CIRS), Inc, Norfolk, VA) representing a 10-year-old (type 706D) and 5-year-old child (type 705D) were used. The phantoms consist of 26 and 32 slices with 180 and 231 holes for dosimeters in 5 and 10-year-old phantoms, respectively. Slices of thickness 2.5 cm are made of tissue equivalent materials and dosimeters can be inserted into holes of diameter 5 mm located on positions of different organs/tissues and fixed with appropriate plugs. Using computed tomography (CT) images of the phantoms, distance from the middle of each dosimeter to the selected point in the phantom (centre of the spherical tumour) was evaluated. Dosimetry systems In the GK study, dose measurements were performed using radiophotoluminescent (RPL) dosimeters type GD-352M, optically stimulated luminescent (OSL) dosimeters type Luxel and two types of thermoluminescent (TL) dosimeters: MCP-n and MTS-7. For IMRT, out-of-field doses in both 5- and 10-year-old phantoms were performed with RPL dosimeters type GD-352M(15). Detailed characteristics of the dosimetry systems used can be found in previously published papers(18–21) and a short summary is given in Table 3. Information about dosimetry systems used for each irradiation can be found at the bottom of Table 3. Table 3. Characteristics and evaluation parameters of the used RPL, TL and OSL dosimetry systems. Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No NA: not applicable or not applied. aThickness of the polyester foils: 0.05 (top) and 0.08 (bottom). bExperimentally determined(22). cDetermined using the ratio of mass energy absorption coefficient for water to air for the energy of 60Co(23). d60 min heating on 400°C + 120 min heating on 100°C. Table 3. Characteristics and evaluation parameters of the used RPL, TL and OSL dosimetry systems. Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No Dosimeter RPL TLD TLD OSL GD-352M MCP-n MTS-7 Luxel Manufacturer ATCG IFJ PAN, Poland IFJ PAN, Poland Landauer Inc. Material Ag activated phosphate glass natLiF:Mg,Cu,P 7LiF:Mg,Ti Al2O3:C Dimensions (mm) ϕ1.5 × 12 (rod) ϕ4.5 × 0.9 ϕ4.5 × 0.9 ϕ4.5 × 0.13a ϕ1.5 × 14.5 (holder) Reader Dose Ace FGD-1000 Harshaw model 5500 Harshaw model 3500 TL/OSL-DA-20 reader system Calibration/Quantity 60Co/Kair 60Co/Kair 60Co/Dw 60Co/Kair Conversion factor Kair to Dw 1.12b 1.112c — 1.112c Pre-radiation annealing/bleaching  Temperature (°C)/bleaching condition 400 240°C 400 + 100d White light using UV filter  Time (min) 20 12 60 + 120d Overnight Preheat  Temperature (°C) 70 NA 100 NA  Time (min) 30 NA 10 NA Readout  Temperature (°C) UV excitation 250 360 NA  Time(min) 0.5 1 NA  Heating rate (°C/s) 15 5 NA Used for GK irradiation 5-year-old phantom Yes Yes No Yes 10-year-old phantom Yes No Yes No NA: not applicable or not applied. aThickness of the polyester foils: 0.05 (top) and 0.08 (bottom). bExperimentally determined(22). cDetermined using the ratio of mass energy absorption coefficient for water to air for the energy of 60Co(23). d60 min heating on 400°C + 120 min heating on 100°C. Dual detector system for correction of OSL dosimeters type Luxel Since OSL (Luxel) dosimeter has a large over-response in the low energy range the Luxel data was corrected by calculating the ratio of TL (MCP-n) and OSL (Luxel) response measured simultaneously (referred to as Luxelc). This dual detector system, described in literature(24), combines values measured with TL and OSL dosimeters to approximate the photon energy and allows correction of OSL (Luxel) detectors. In the same way as described in literature(24), the response of both TL (MCP-n) and OSL (Luxel) dosimeters for eight different averaged energies (32, 63, 82, 99, 115, 160, 203 and 242 keV corresponding to ISO N-series: N40, N80, N100, N120, N150, N200, N250 and N300)(25) relative to 60Co was assessed using X-ray tube in the secondary standard laboratory in SCK-CEN. The relative response of TL (MCP-n) and OSL (Luxel) to 60Co as a function of energy was plotted together with the correction factor to be applied for Luxel energy correction (Figure 1). In the different positions in the phantom the ratio of Luxel/MCP-n was determined which allowed to approximate the photon energies and correction of OSL (Luxel) data (Luxelc). Figure 1. View largeDownload slide The relative response of TL dosimeters type MCP-n and OSL dosimeters type Luxel to 60Co as a function of energy in line plot and Luxel/MCP-n ratio and corresponding correction factor for Luxels energy dependence in scatter plot. Figure 1. View largeDownload slide The relative response of TL dosimeters type MCP-n and OSL dosimeters type Luxel to 60Co as a function of energy in line plot and Luxel/MCP-n ratio and corresponding correction factor for Luxels energy dependence in scatter plot. Every hole in the phantom was filled with one annealed dosimeter and each dosimeter was fixed so that its active volume was in the middle of the hole. Measured doses were in the range 1 mGy–1 Gy and that is within operational range for all dosimeters (lowest detectable limit for all dosimeters used in this study is below 0.1 mGy, while upper limit of a useful dose range is above 10 Gy). In addition, for dose range 1 mGy–1 Gy all used dosimeters show linear dose response(18, 21, 26, 27). The measured doses for all dosimeters were expressed as absorbed dose to water, Dw (mGy), and normalised to the mean target dose (mGy/Gy). Relative standard uncertainty of the determined dose for RPLs (GD 352-M), OSLs (Luxel) and TLDs (MCP-n and MTS-7) were 2.1, 4.5, 3.3 and 2.9%(20), respectively. For MTS-7 and Luxel, uncertainties include repeatability and calibration while for RPL and MCP-n, uncertainties include repeatability, calibration and angular correction. The mean organ doses in the phantoms measured with selected type of dosimeters were calculated as an average value of all dosimeters of that type placed in the particular organs. Number of dosimeters for each organ in both phantoms are shown in Table 4. For all organs (with exception of prostate) doses were measured in, at least, two different points within the organ. The spread of the average dose measured in each organ was higher than uncertainty on the dose measurement (between 2 and 4%). This is especially true for large organs. Depending on the total treatment dose (stated in Irradiation techniques and irradiation plans section), total out-of-field organ doses were calculated by multiplying mean out-of-field organ dose (in mGy/Gy) with total treatment dose (in Gy). Table 4. Number of dosimeters in each organ of the 5- and 10-year-old phantom. Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 Table 4. Number of dosimeters in each organ of the 5- and 10-year-old phantom. Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 Organ 5-year-old 10-year-old Eyes 2 2 Mandible 3 3 Thyroid 4 4 Clavicle 2 4 Scapulas 6 11 Oesophagus 3 5 Thymus 3 3 Lungs 28 24 Sternum 2 3 Ribs 17 15 Breasts 2 2 T/L Spine 6 7 Adrenals 2 2 Spleen 4 6 Kidneys 8 8 Liver 18 22 Pancreas 3 3 Stomach 10 10 Gall blader 2 3 Interstine 10 11 Pelvis 8 16 Ovaries 2 2 Bladder 6 6 Uterus 2 2 Prostate 1 1 Testes 2 2 Femura 2 6 RESULTS AND DISCUSSION Comparison of dosimetry systems For each GK irradiation performed in this study, the dosimetry systems used can be found at the bottom of Table 3. The use of three types of detectors (RPL (GD-352M), TL (MCP-n) and OSL (Luxel)) in the 5-year-old phantom allowed to compare the response of the different dosimetry systems and to evaluate their use in the application of out-of-field dosimetry in radiotherapy. For each position inside the phantoms, ratios of measured values with different dosimeters have been calculated. In Table 5, average values of those ratios for each phantom and each pair of compared dosimeters are shown. The average response ratios demonstrate a close correspondence between RPLs (GD-352M) and TLDs (MCP-n). However, for the OSL (Luxels) a large overestimation was observed. After the correction of OSL Luxels (Luxelc), using the dual detector technique for the over-response to low energy photons, a close correspondence with RPL (GD-352M) was observed. The dual dosimetry analysis revealed Luxel/MCP-n ratios between 1.3 and 1.7 corresponding to approximate photon energies inside the phantom which ranged between 200 and 900 keV for the plugs outside the brain region of the 5-year-old phantom treated with GK (Figure 1). This is a result of patient scattering as well as different sources of leakage and scatter inside the collimator of the GK head. As shown in Table 5 a good correspondence was observed between the RPL (GD-352M) and TLD (MTS-7) data as measured in the 10-year-old phantom. Table 5. Average response ratios to compare correspondence between RPL GD-352M, TL (MCP-n and MTS-7) and OSL Luxel dosimeters, studied in the 5 and 10-year-old phantoms during GK irradiations. Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 aLuxelc represents Luxel result after correction for enmergy dependence. Table 5. Average response ratios to compare correspondence between RPL GD-352M, TL (MCP-n and MTS-7) and OSL Luxel dosimeters, studied in the 5 and 10-year-old phantoms during GK irradiations. Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 Dosimetry systems 5-year-old phantom RPL/MCP-n 0.98 ± 0.09 RPL/Luxel 0.69 ± 0.08 MCP-n/Luxel 0.70 ± 0.09 RPL/Luxelca 0.99 ± 0.09 MCP-n/Luxelca 1.01 ± 0.01 10-year-old phantom RPL/MTS-7 0.99 ± 0.09 aLuxelc represents Luxel result after correction for enmergy dependence. In summary, GK data show that RPL (GD-352-M) and both types of TL dosimeters (MCP-n and MTS-7) could be used in this particular application while OSL (Luxel) dosimeters need to be corrected for increased response with decreasing energies, which is feasible using the dual dosimetry analysis. Because RPLs (GD-352M) were used to measure doses in both phantoms, the final data in the following sections on the out-of-field organ doses will be shown based only on the RPL results. Out-of-field organ doses for GK treatment Out-of-field organ doses per target dose in both phantoms for GK treatment of the large AVM measured with RPL detectors are shown in Figure 2. Organs are ordered according to their average distance from the target. For double organs (such as eyes), averaged dose values for both parts are shown in Figure 2. Because tumour was located above left eye, for all irradiations dose to left eye was higher than dose to right eye (average left to right eye dose ratio was 1.3 and 1.45 for GK and IMRT, respectively). In all figures, the doses to eyes represents the average dose received by both eyes. The average out-of-field doses in the 5 and 10-year-old phantoms treated with GK were comparable. Organs in the 5-year-old phantom are closer to the target than in the 10-year-old phantom and from that point of view higher organ doses were expected for the smaller phantom. On the other hand, due to the geometrical differences between the phantoms (positions of the head in the stereotactic frame), the treatment planning resulted in a different number of isocentres (Table 1) and that influenced on the dose distribution, as shown in Figure 3. Figure 2. View largeDownload slide Out-of-field organ doses per target dose (mGy/Gy) for AVM treated with Gamma Knife (GK) measured in the 5 and 10-year-old phantom. Figure 2. View largeDownload slide Out-of-field organ doses per target dose (mGy/Gy) for AVM treated with Gamma Knife (GK) measured in the 5 and 10-year-old phantom. Figure 3. View largeDownload slide (Top) Dose per target dose as a function of the distances from the target. The best fitting functions for the pairs of values shown on x-axis (distance) and y-axis (dose per target dose) are shown as y = f(x). (Bottom) Dose per target dose per isocentre as a function of the distance from the centre of the target. Eyes were not included in this figure. Both figures are for GK treatment. Figure 3. View largeDownload slide (Top) Dose per target dose as a function of the distances from the target. The best fitting functions for the pairs of values shown on x-axis (distance) and y-axis (dose per target dose) are shown as y = f(x). (Bottom) Dose per target dose per isocentre as a function of the distance from the centre of the target. Eyes were not included in this figure. Both figures are for GK treatment. The dose per target dose for each dosimeter as a function of dosimeter’s distance from the target for both phantoms is shown in Figure 3 (Top). This revealed a slightly higher dose burden in the 10-year-old phantom compared to the 5-year-old phantom for the same distance from the target. This can be explained by the higher number of isocentres for the treatment plan of the 10-year-old phantom resulting in larger number of head movements, with associated ‘reposition dose’, as well as longer ‘beam on time’ as shown in Table 1. For the target, Tran et al.(13) reported ‘reposition dose’ with amount of 23.7 mGy for the 18 mm collimator at the GK unit dose rate of 2.254 Gy/min. Since in our study the GK unit dose rate ranged from 2.335 to 2.316 Gy/min, and taking into account that the repositioning time is the same for all GK units, ‘reposition dose’ for the target per one repositioning of the phantom, calculated by using value from Tran et al.(13) study, was up to 24.6 mGy. For the whole hypofractionated treatment (25 and 31 isocentres per irradiation/fraction, i.e. in total 125 and 155 isocentres for five fractions), total calculated ‘reposition dose’ for the target was 3075.0 and 3813.0 mGy, respectively, which is a significant (10–13% of the target dose) dose contribution to the target volume that will give additional rise to the GK out-of-field doses. The GK ‘leakage dose’ contribution to the target was reported by Wu et al.(16) to be 0.35% of the dose with all 201 photon beams not blocked. Compared to the ‘reposition dose’ the GK ‘leakage dose’ represents practically negligible contribution to the GK out-of-field doses. In Figure 3 (Bottom), dose per target dose per isocentre is shown for both phantoms and a much closer agreement of the data for the 5 and 10-year-old phantoms is achieved. This clearly indicates an important contribution of the ‘reposition dose’ to the GK out-of-field doses and an increased dose burden for higher number of isocentres. From radioprotection point of view, it is suggested that treatment planning strategy should aim to reduce the number of isocentres as much as possible during large AVM treatments using GK in hypofractionated regime. In Figure 3 (top), fitting functions for the experimental data for both phantoms were shown confirming inverse square distance dependence of the measured dose. In Figure 3 (bottom) dose per target dose per isocentre is shown for both phantoms and a much closer agreement of the data for 5 and 10-year-old phantom is achieved suggesting that both data, when expressed as dose per target dose per isocentre, can be modelled with essentially the same function. The generation of simple analytical models to allow assessment of out-of-field organ doses in clinical routine has been initiated by a number of research groups(28, 29). Authors of such studies aim to generalise these models and request measured data as an input to validate their models. The dose versus distance plot shown in Figure 3 could serve as input for these analytical modelling approaches. Comparison of GK and IMRT out-of-field organ doses Comparison of out-of-field doses for GK and IMRT treatment of the large AVM is shown in Figure 4 (both comparison of mGy/Gy and comparison of total doses are shown). As shown in Figure 4, the eye doses per target dose were a factor of two higher for IMRT compared to GK treatment. Reduction of eye doses is important because children exposed to a lenticular dose of 1 Gy have a 50% increased risk of developing a posterior subcapsular opacity and the risk of developing cortical cataract is increased by ~35% with a follow-up observation period of at least 40 years(30). The total treatment doses chosen as an optimal prescription for large AVMs in this study were 30 Gy in 5 fractions for hypofractionated GK treatment(8) and 37.6 Gy in 8 fractions for IMRT(18). Therefore eye doses, calculated for the total IMRT treatment, were 9 and 12 Gy for 10 and 5-year-old phantom, respectively, while for both phantoms the total eye doses for GK treatment were ~4 Gy. This suggests that the eyes (normal tissue close to the target) were more spared during GK than during IMRT treatment which can be explained by the known steeper dose gradient for target to neighbouring tissue transition in GK compared to IMRT. In addition, IMRT uses a larger number of monitor units to deliver the dose through small field segments achieved by multileaf collimators (MLC) and that results in higher overall MLC leakage dose in the proximity of the target and therefore larger doses for the organs close to the target volume during IMRT. Scatter or leakage radiation during IMRT for particular linear accelerator and MLC/beam configuration is not easy to assess but from the literature, for Varian machines, it can be roughly assessed to be up to 10% of the maximum in-field dose(31). Compared to the GK ‘leakage dose’, leakage radiation of IMRT gives much higher contribution to the out-of-field doses. Figure 4. View largeDownload slide (Top) Organ dose per target dose [mGy/Gy] and total organ dose [mGy] in bar plot and line plot, respectively for GK and IMRT as measured in the 5-year-old phantom. For the total treatment 30 Gy in 5 fractions was assumed for GK and 37.6 Gy in 8 fractions for IMRT. (Bottom) As for (Top) but for the 10-year-old phantom. Figure 4. View largeDownload slide (Top) Organ dose per target dose [mGy/Gy] and total organ dose [mGy] in bar plot and line plot, respectively for GK and IMRT as measured in the 5-year-old phantom. For the total treatment 30 Gy in 5 fractions was assumed for GK and 37.6 Gy in 8 fractions for IMRT. (Bottom) As for (Top) but for the 10-year-old phantom. The rest of the out-of-field organs shown in Figure 4 received higher doses with the GK treatment compared to IMRT. These organs are more distant from the target than eyes and for them ratios of GK to IMRT organ doses per target dose ranged from 2 to 3.5 and 2.9 to 5 in 5 and 10-year-old phantoms, respectively (Table 6). For the more appropriate comparison of the GK and IMRT, different treatment regimens have to be taken into account. Namely, irradiations are performed in several fractions but in relatively short time period and it can be assumed that cancer risk is proportional to the total accumulated dose(32). The fraction dose and total dose were calculated from the most conservative treatment regimen which was assumed to be 30 Gy in 5 fractions (6 Gy per fraction) for GK(8) and 37.6 Gy in 8 fractions (4.7 Gy per fraction) for IMRT(17) treatment. Higher dose per fraction for GK treatment than for IMRT was chosen due to the fact that GK dose distribution provides better dose conformity and better sparing of the normal tissue close to the target. As shown in Table 6, taking into account treatment regimens, calculated GK to IMRT organ ratios were, compared to ratios for dose per target dose, increased for fraction dose and decreased for total treatment dose. The fraction doses result in higher GK to IMRT ratios up to a factor of 6.4 in the 10-year-old phantom. Because of the lower total treatment dose in GK, the total organ doses were 1.5–2.8 and 2.3–4 times higher than the IMRT total organ doses as shown in Table 6. The markedly higher out-of-field doses in this study for GK compared to IMRT can be explained as coming mainly from the difference in the treatment techniques. For the GK technique, ‘reposition dose’ gives important contribution to the out-of-field doses. ‘Reposition dose’ is absorbed during repositioning of the patient’s head from the previous to the next isocentre, i.e. while patient is not in the treatment position and the shielding doors of GK are open. Therefore, out-of-field doses increase with the number of repositioning (i.e. number of isocentres) during GK procedures. For IMRT technique, the treatment beam is turned off during the repositioning of the linear accelerator gantry from one to another treatment field and additional dose is not present. Table 6. Gamma Knife (GK) to IMRT ratios depicted as minimum and maximum ratios measured in the out-of-field organs (except the eyes) as observed for dose per target dose, fraction dose and total dose of each treatment regimen and for both 5-year-old and 10-year-old phantoms. GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 Table 6. Gamma Knife (GK) to IMRT ratios depicted as minimum and maximum ratios measured in the out-of-field organs (except the eyes) as observed for dose per target dose, fraction dose and total dose of each treatment regimen and for both 5-year-old and 10-year-old phantoms. GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 GK to IMRT ratio 5-year-old phantom 10-year-old phantom Dose per target dose (mGy/Gy) 2.0–3.5 2.9–5.0 Fraction dose (mGy) 2.4–4.4 3.8–6.4 Total dose (mGy) 1.5–2.8 2.3–4.0 CONCLUSION RPL, TL and OSL dosimeters have proven to be reliable dosimeters for scattered photons during different clinical situations and radiotherapy treatment protocols(15, 18, 19, 33). In this study, all three systems showed good agreement within 1–2% and they are proved to be suitable for out-of-field dose measurements during GK radiosurgery treatment. In addition to previous studies, for TLD and RPL used in this study no correction was required, while for OSL energy correction was necessary: by means of a dual detector system, as demonstrated in the current study, or by Monte Carlo simulations as shown in previous work(33). For each phantom in this study clinically relevant GK treatment plan was applied. Number of isocentres was confirmed to be important for the level of out-of-field dose. For both phantoms GK out-of-field doses for the same distance to target, when divided with target dose and number of isocentres, were comparable. GK out-of-field organ doses were increased by number of isocentres but decreased with organ to target distance and as a result, out-of-field organ doses were also comparable in both phantoms. On average, both phantom treatments with GK show an out-of-field dose of 120 mGy/Gy for eyes which sharply reduced to 20 mGy/Gy for mandible and further reduced up to 0.8 mGy/Gy for testes. 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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/open_access/funder_policies/chorus/standard_publication_model)

Journal

Radiation Protection DosimetryOxford University Press

Published: Oct 1, 2018

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