Dose Homogeneity of the Total Body Irradiation in vivo and in vitro confirmed with Thermoluminescent Dosimeter

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1 Dose Homogeneity of the Total Body Irradiation in vivo and in vitro confirmed with Thermoluminescent Dosimeter E.K. Chie M.D. 1, S.W. Park M.D. 1, W.S. Kang PhD. 1,2, I.H. Kim M.D. 1,2, S.W. Ha M.D. 1,2, and C.I. Park M.D. 1,2 1 Department of Therapeutic Radiology, Seoul National University College of Medicine Seoul, Korea 2 Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea INTRODUCTION Although radiotherapy is generally used as a local modality, it also can be used as systemic modality in number of occasions. Indications of total body irradiation (TBI) or whole body irradiation are immune suppression prior to bone marrow transplantation (immunologic diseases, aplastic anemia), eradication of malignant cells (leukemia, lymphoma and some solid tumor), and eradication of genetic diseases (Fanconi s anemia, thalasemia major). Though low single dose irradiation of 2-3 Gy has been used for immune suppression of immune diseases and in combination with chemotherapetic agents, such as cyclophosphamides for aplastic anemia, higher doses of fractionated irradiation is required to eradicate malignant cells as well as to overcome graft injection in allogenic bone marrow transplantation. TBI also plays role in providing grafting space in bone marrow, which heightens successful transplantation rate. Single high dose therapy of 9- Gy was initially which was later replaced with fractionated and/or low dose rate therapy to lessen the treatment limiting complications, such as radiation pneumonitis. In cases of fractionated regimen, adjustments could be done in following fraction for more homogenous dose delivery by accurately estimating the exposed dose to organ of interest (1,2). Methods of TBI can be divided into parallel-opposed lateral technique and parallel opposed anteroposterior/posteroranterior (AP/PA) technique, although there are many other different methods. Advantages of parallel-opposed lateral technique are natural lung compensation with arms and more comfortable patient position. Although parallel opposed anteroposterior/posteroranterior (AP/PA) technique does not require additional compensator as patient thickness along long axis is minimized, additional lung block to reduce lung dose and additional irradiation to increase the doses to chest wall are necessary and also requires long source-to patient distance (1). TBI setup represents a very irregular and extended field. It is essential to deliver homogenous radiation dose over whole body, which requires careful setup design to minimize the possible errors. Verification of total body irradiation dosimetry techniques at many institutions in United States revealed that quality control and assurance is essential for corresponding institute, facility, and treatment setup (3). Reported range of error of dose homogeneity with methods incorporating water phantom and entrance dose was ±7%, and with methods using humanoid phantom was ±% (4-6). American Association of Physicists in Medicine (AAPM) recommended error range of ~ +5% for dose homogeneity in case of total body irradiation in the report 17 (7). Frequently used in vivo dosimeters are thermoluminescent dosimeter (TLD) and diode. TLD was used more frequently in multiple dosimetry due to low cost, but with development of multi-channel diode electrometer, use of diodes is increasing (4). Small water phantom was frequently used in confirmation of dose distribution. But, as systemic error in range of ±4% was reported in case of TBI, use of humanoid phantom is recommended (3). Dose distribution and homogeneity for Co- teletherapy has been reported previously from this department (8). But, dose homogeneity and quality assurance program using linear accelerator has not been settled. Recently, some institution in Korea have reported dose profiles in TBI setup (9-11). The objective of this study was to analyze and confirm the accuracy and the homogeneity of the treatment setup, the parallel opposed lateral technique, currently used in Seoul National University Hospital. METHODS and MATERIALS 1. Patient Dosimetry Surface dose data, measured with a thermoluminescent dosimeter in 8 patients among patients, who were given total body irradiation with the parallel-opposed lateral technique between September 1996 to August 1998, at Seoul National University Hospital was analyzed. Age distribution was from 15 to years old with median value of 21. Five patients were male and three patients were female. Six patients had acute leukemia, one had aplastic anemia, and the other had high-grade non-hodgkin s lymphoma. MV x-rays from Clinac 2C (Varian Associates, USA) were used. Seven patients were irradiated with daily 3Gy/fraction for 4 fractions totaling 12Gy, while one patient was treated with daily 3.5Gy/fraction for 3 fractions totaling.5gy. Lowest output rate of MU/min from Clinac 2C was chosen to keep dose rate under.1gy/min (.95+/-.57 Gy/min). Source-to-isocenter distance was 274cm, resulting in field size of 9.6*9.6cm 2 with collimator opening of *cm 2. Parallel-opposed lateral technique was used with patient in knee-chest position. Acrylic plate with thickness of 1cm was placed cm in front of treatment couch to 1

2 function as a beam spoiler. Thickness of head, neck, shoulder, axilla, abdomen (umbilicus plane), hip, thigh, and ankle level was measured. Tissue deficit compensator was constructed to compensate for the missing tissue enabling more homogenous dose distribution. Thickness of the compensator was calculated from equation below. T Pb = (T R T M )*.7/ 2, where T Pb is thickness of tissue deficit compensator made of lead; T R is the thickness of the prescribed point (umbilicus plane for the patient); T M is the thickness of plane of interest; and.7 is compensatory ratio of lead to soft tissue for MV x-rays from Clinac 2C used at Department of Therapeutic Radiology, Seoul National University Hospital. Dose was prescribed to the umbilicus level, which was calculated from monitor unit conversion table (12). TLD was placed parallel to skin surface on both sides of head, neck, axilla, thigh, and ankle level for each treatment session to measure both entrance and exit dose. 2. Phantom Dosimetry Humanoid phantom (Huestis, USA) was used to simulate the patient set-up. Identical method was used to construct tissue deficit compensator for the phantom. Surface and midline doses of head, neck, axilla, abdomen, and hip level were similarly measured. Contrary to patient setup, Humanoid phantom was in erect position as knee-chest position was not possible. Cylinder shaped water phantom with diameter of 8cm and length of 32cm was used to simulate the upper arm. X-ray output used was MU/min resulting in dose rate of.48gy/min. Measurement was repeated for eight times. 3. TLD Dosimetry Chip shaped TLD- (Harshaw Chemie BV, the Netherlands) containing 7.5% Li-6 and 92.5% Li-7 and 28mg of LiF with the dimension of 3.1*3.1*.89 mm 3 and maximum thermoluminescent temperature of 195 C was used. TLD s with reproduction range within 3% was chosen for the experiment. TLD s were heated at C for one hour and at C for another one hour with TLD oven (PTW-Freiberg, Germany) before every use. TLD reading was done with Harshaw/QS TLD system reader (Solon Technologies, USA) at temperature range of ~ C for seconds after preheating at C for seconds. 4. Data Analysis Mean value of measured surface dose and ratio to prescribed dose was calculated from the patient data. Relative dose for points of interest and ratio of surface dose to mid-depth dose as well as mean value of measured surface dose and mid-depth dose were calculated from the phantom data. SAS program (The SAS program for Windows version 6.12, SAS Institute Inc., USA) was used for the statistical analysis. RESULTS 1. Measured Surface Dose in Patient 2

3 Patient Fig.1 Radiation doses measured with TLD chips on the surface of the patients relative to mid-depth dose prescribed to umbilicus level in 3 measurements for case #7 or 4 measurements for all others per treatment (Mean±S.D.). Distribution of surface doses and standard deviations relative to prescribed dose for individual patient is shown in Fig. 1. Mean measured surface dose and standard deviation relative to prescribed dose from every points of every patient was 95.7±7.2%. Measured surface doses and standard deviations relative to prescribed dose for the head, neck, axilla, thigh, and ankle level were 91.3±7.8%, 98.3±7.5%, 95.1±6.3%, 98.3±5.5%, and 95.3±6.3%, respectively in patients (Fig. 2). 2. Measured Dose in Phantom 1) Measured Surface Dose Measured surface doses and standard deviations relative to prescribed dose for the head, neck, axilla, abdomen, and thigh level were 85.±4.%, 86.6±5.8%, 83.9±4.9%, 94.8±2.8%, respectively (Fig. 3). 2) Measured Mid-depth Dose Measured mid-depth doses and standard deviations relative to prescribed dose for the head, neck, axilla, abdomen, and thigh level were 96.6±2.2%, 95.3±3.2%,.4±1.9%,.±3.1%,.5±2.2%, respectively (Fig. 4). Head Neck Axilla Thigh Ankle Fig.2 Radiation doses measured with TLD chips for different levels on the surface of the patients relative to midline dose prescribed to umbilicus level in 8 patients (Mean±S.D.). Head Neck Axilla Umbilicus Hip Fig.3 Radiation doses measured with TLD chips for different levels on the surface of the Humanoid phantom relative to mid-depth dose prescribed to umbilicus level of 8 different measurements (Mean±S.D.). 3) Measured Dose to Mid-depth Dose Ratio The surface to mid-depth dose conversion ratios and standard deviations obtained from the phantom 3 Head Neck Axilla Umbilicus Hip Fig.4 Radiation doses measured with TLD chips for different levels in the mid-depth of the Humanoid phantom relative to mid-depth dose prescribed to umbilicus level of 8 different measurements (Mean±S.D.).

4 study were 1.14±.6, 1.±.9,.96±.5, 1.6±.6,.95±.2 for head, neck, axilla, abdomen, and hip level, respectively. 3. Converted Mid-depth Dose in Patient The mid-depth doses and standard deviations of the head, neck, axilla, thigh, and ankle in patients estimated from the surface to mid-depth dose conversion ratios were 3.4±9.%, 7.8±.5%, 91.1±6.1%, 93.8±4.5%, and 4.5±9.3%, respectively (Fig. 5). DISCUSSION Many different treatment setups have been devised to deliver homogenous dose to whole body including skin surface for respective institution with different therapeutic facilities and treatment conditions. The effects of scattered radiation and inhomogeneity of lateral radiation quality, morphological difference and thickness difference of patient, inhomogeneity and surface irregularity of tissue, and tissue deficit present special problem. Different types of compensation and quality assurance measures had been devised to overcome these problems and deliver homogenous dose to the patient. Despite necessity of tissue deficit compensator and beam spoiler, the parallel-opposed lateral technique, currently used in Seoul National University Hospital, has an advantage of homogenous lung dose delivery without additional compensator due to natural compensation with arms (1,2). As treatment settings of TBI differ from institute to institute, customized methods of quality assurance is mandatory. It has been reported that dose inhomogeneity of over % could result from omitting regular quality assurance (3). Some of the institutions in Korea have reported on the dose distribution with TBI. Most used dose analysis from phantom, omitting the actual patient data analysis, with dose range of ±8% (9-11). 4

5 Head Neck Axilla Thigh Ankle Fig.5 Estimated mid-depth doses of patients from the surface to mid-depth ratio obtained from the Humanoid phantom (Mean±S.D.). Surface dose range of 8.7~-1.7% for the patients from this study was within satisfactory range, but converted mid-depth dose distribution showed error range of 8.9~+7.8%, which failed to fall in recommended dose range. This difference is much bigger, taking the dose range of 1.2~+3.% obtained from water phantom dosimetry to acquire monitor unit conversion table, which is expected dose range, into account. However, middepth dose conversion ratio should be modified and better fitted, considering the thickness difference between the patient and the phantom. Additionally, repetition limitation of 3% of TLD s, allocation error of TLD placement, and output of linear accelerator could, although should be minute, attribute to the widening of the dose range. Allocation error could be a cause of wider dose range for surface dose distribution than mid-depth dose distribution. Table 1. Comparison of Thickness for the Patients and the Humanoid Phantom Patient Humanoid phantom Site Thickness (cm) Ratio* (Mean±S.D.) (Mean±S.D.) Thickness (cm) Ratio Head 16.1±.6.61± Neck.6±1.7.39± Shoulder 43.± ± Axilla 28.9± ± Umbilicus 27.3± Hip 34.1± ± * ratio of the thickness relative to the reference level 5

6 Deviation of dose range from the expected value for points of interest could be attributed to following causes. First, more than % decrease of relative mid-depth dose for axilla to prescribed dose could result from thickness difference between patients and the phantom. As shown in table 1, relative thickness difference for the axilla region to prescribed umbilicus is quite significant. This is largely due to the fact that shape of the phantom follows that of Caucasian. While difference of thickness of head and neck region could be compensated using tissue-deficit compensators, use of this type of compensator is not possible for shoulder and axilla region. This directly leads to difference in absorbed dose. Converting the thickness difference to relative rate to that of prescribed umbilicus level results in % increase in thickness for the phantom. By plotting into the percent depth dose profile for TBI used at this institution, this thickness difference of % could cause dose difference of % (Fig 6). This in turn results in % dose difference in mid-depth dose relative to the prescribed dose. Surface dose used in this study is sum of the entrance dose and the exit dose. The impact on the entrance dose is minimal with thickness difference, while the exit dose is more readily influenced by the difference. This could lead to less decrease of surface dose than the mid-depth dose. It has been reported that calculating the mid-depth dose from the entrance dose and the exit dose could also result in % decrease. Some have attributed lower incidence of radiation pneumonitis with parallel-opposed lateral technique to this decrease in radiation dose (4). For more accurate mid-depth dose calculation, construction of humanoid phantom with skeletal composition of corresponding trait, which in this case would be Korean, seems necessary. Improving the dose estimates by measuring percent depth dose (PDD) or tissue maximum ratio (TMR) profiles for individual thickness and offaxis ratio (OAR) for corresponding points of interest have been reported. But, the resulted range of dose estimates tend to be narrower then those obtained from actual measurement (3-6). Percent depth dose (PDD) Depth(cm) Fig.6 Beam data for TBI setup at Seoul National University Hospital using MV x-ray from Clinac 2C (Varian Associates, USA) with phantom size 25*25* cm 3, SSD 274cm, and field size 4.9*4.9 cm 2, measured with Farmer type chamber Secondly, decrease in surface dose of neck region could not be attributed to overcompensation of tissue-deficit compensator, as mid-depth dose was not decreased. Shank have reported that thickness of more than 2cm is required to obtain adequate scattering effect for 6~18 MV x-rays (13). Decrease in thickness of neck region relative to umbilicus region could lessen the scattering effect of the scattering acrylic plate. This decrease in surface dose could be emphasized in the patients, as relative thickness is smaller than that of the phantom. Furthermore, there was 5% increase in mid-depth dose of neck region, estimated from the ratio of surface dose to mid-depth dose obtained from the phantom data. Penetrating power of high energy x-rays above 6~8 MV from the linear accelerator decreases as the distance from the isocenter to point of interest is lengthened. Erect position of the phantom has longer isocenter-to-point distance for the neck region than the knee-chest position of the patient. This increase in distance could be a cause of decrease in surface to mid-depth dose ratio for the phantom. Thirdly, decrease in surface dose for the head region could be attributed to the identical causes as the neck region. Lastly, as for the ankle region, conversion ratio of the neck region was adopted due to similarity in depth ratio, which results in identical deviation of dose profile. As mentioned in the introduction, AAPM recommended dose variation range of ~+5% to the prescribed point, which is mid-depth dose of umbilicus region, for the TBI treatment setup in their report number 17 (7). Measured surface dose range of 8.7~-1.7% and converted mid-depth dose range of 8.9~+7.8% for the 6

7 patients is somewhat superior to reported dose range of ±% from other institutions (4-6). Further more, accounting the possible increase in surface to mid-depth conversion ratio of the head and neck region, current TBI setup utilized at this institution should be superior to the experiment derived dose range values. Due to factors such as scattered irradiation, simple calculation methods could not derive at actual delivered dose to the points of interest or homogeneity of dose distribution. Due to the difference in the treatment facilities and treatment setups, simple adaptation of calculation methods devised from the literature should be avoided. Current method of TLD measurement for each and every session of TBI employed at this department enables possible dose modification in the following sessions. This result in more accurate and homogenous treatment, which in turn heightens the treatment effect and decrease possible complications. REFERENCES 1. H.Lin and R.E.Drzymala, Total body and hemibody irradiation. In C.A.Perez and L.W.Brady eds. Principles and practices of radiation oncology, 3rd ed. Lippincott-Raven Publishers, Philadelphia (1997) 2. B.Shank, Total body irradiation. In S.A.Leibel and T.L.Phillips TL eds. Textbook of radiation oncology. WB Saunders Company, Philadelphia (1998) 3. T.H.Kirby, W.F.Hanson, and D.A.Cates, Verification of total body photon irradiation dosimetry techniques. Med Phys 15, (1988) 4. J.R.Greig, R.W.Miller, and P.Okunieff, An approach to dose measurement for total body irradiation. Int J Radiat Oncol Biol Phys 36, (1996) 5. P.C.Lee, J.M.Sawicka, and G.P.Glasgow, Patient dosimetry quality assurance program with a commercial diode system. Int J Radiat Oncol Biol Phys 29, (1994) 6. E.B.Podgorsak, C.Pla, M.Evans, and M.Pla, The influence of phantom size on output factor, peak scatter factor, and percentage depth dose in large-field photon irradiation. Med Phys 12, (1985) 7. J.Van Dyk, J.M.Galvin, G.P.Glasgow, et al, The physical aspect of total and half body photon irradiation. A report of Task Group 29 Radiation Therapy Committee, American Association of Physicists in Medicine. AAPM Report No. 17 (1986) 8. W.S.Kang, Dose distribution of total body irradiation with Co-. Korean J Med Phys 2, 9- (1991) 9. D.R.Choi, I.B.Choi, K.M.Kang, K.S.Shin, and C.C.Kim, Total body irradiation technique: basic data measurements and in vivo dosimetry. J Korean Soc Ther Radiol 12, (1994). S.J.Ahn, W.S.Kang, S.J.Park, T.K.Nam, W.K.Chung, and B.S.Nah, The dosimetric data of MV linear accelerator photon beam for total body irradiation. J Korean Soc Ther Radiol 12, (1994) 11. S.J.Park, W.K.Chung, S.J.Ahn, T.K.Nam, and B.S.Nah, Utilization of tissue compensator for uniform dose distribution in total body irradiation. J Korean Soc Ther Radiol 12, (1994) 12. Dept. of Therapeutic Radiology. Seoul National University Hospital. Dosimetric databook for TBI, SRS, and FSRT (unpublished) 13. B. Shank B, Techniques of magna-field irradiation. Int J Radiat Oncol Biol Phys 9, (1983) 7