Gdansk, Poland Gdansk, Poland

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1 Radiation Protection Dosimetry (2006), Vol. 120, No. 1 4, pp doi: /rpd/nci528 Advance Access published on March 24, 2006 EPR/ALANINE DOSIMETRY IN LDR BRACHYTHERAPY A FEASIBILITY STUDY Katarzyna Schultka 1,, Bartlomiej Ciesielski 1, Krystyna Serkies 2, Tomasz Sawicki 2, Zofia Tarnawska 2 and Jacek Jassem 2 1 Department of Physics and Biophysics, Medical University of Gdansk, Debinki 1, Gdansk, Poland 2 Department of Oncology and Radiotherapy, Medical University of Gdansk, Debinki 1, Gdansk, Poland In this study, we present the results of in vivo dosimetry, using electron paramagnetic resonance in L-alanine, performed on 13 patients treated for gynaecological cancers. The doses from 137 Cs (12 samples) and 192 Ir (one sample) brachytherapy sources were determined inside vagina. The detectors had a form of small cellulose capsules tightly filled with crystalline alanine. The positions of the detectors were reconstructed from two orthogonal radiographs. The planned doses were calculated with a computer planning system (PLATO, Nucletron). The relative deviations between planned and measured doses ranged from 23 to þ14%. The mean deviation from the prescribed dose was relatively low ( 5%) with SD of 10%. The main sources of differences between the measured and calculated doses were attributed to uncertainty in the determination of the detector position inside the patient s body and to uncontrolled changes in the detector position during the treatment. INTRODUCTION In radiotherapy there is a constant need for the quantitative determination of the absorbed radiation dose. Electron paramagnetic resonance (EPR)/ alanine dosimetry was proved to be a reliable in vivo dosimetric method in teletherapy (1 3), even for the measurement of single fraction doses. Recently, an application of the dosimetric technique in phantom and in vivo high-dose rate (HDR) and low-dose rate (LDR) brachytherapy were reported (4 8). Schaeken and Scalliet (6) used encapsulated detectors (85% alanine and 15% paraffin, sealed in 0.15 mm thick plastic) glued to the patient s mould. The alanine detectors were positioned at locations relevant to the treatment at the anterior side of the mould to check the dose in the direction of the bladder and at the posterior side to monitor the dose in the direction of the rectum wall. They obtained results from 14 to þ8% for HDR brachytherapy and from 4 to þ13% for LDR brachytherapy for Gy and Gy range doses, respectively. Kuntz et al. (7) used alanine pellets (95% alanine, 3% binding material and 2% lubricant) placed into small orifices made in a square polyethylene holder. They measured doses on the surface of a vaginal applicator during HDR treatment of the vaginal stump. They obtained approximately 20% difference between the measured and the planned doses. In this work alanine dosemeters were used during LDR gynaecological brachytherapy, which often results in high doses to various pelvic structures, especially to the rectum and the urinary bladder. Corresponding author: kschult@amg.gda.pl Late complications from these two organs may lower the therapeutic ratio and significantly decrease patient quality of life (9). The aim of this study was to compare the doses measured in vivo and those calculated by treatment planning system. MATERIALS AND METHODS The detectors were applied in 13 gynaecological cancer patients: 10 cervical cancer (6 postoperatively) and 3 endometrial cancer, treated with LDR brachytherapy in the Department of Oncology and Radiotherapy, Medical University of Gdansk. In four cervical cancer patients treated with definitive irradiation the application included both ovoids and an intrauterine tube. In the remaining nine cervical or endometrial cancer patients treated postoperatively, only standard Selectron vaginal ovoids were employed. The Selectron LDR/MDR (Nucletron, The Netherlands) afterloading radiation system containing 137 Cs sources in 12 cases and 192 Ir source in one case were used. The dose distribution in the pelvic region was calculated using radiotherapy treatment planning (RTP) system PLATO (Nucletron) after applicator insertion. The RTP calculated doses are doses absorbed in water medium. The positions of detectors placed in the vagina were determined using anterior-posterior (AP) and lateral orthogonal radiographs. The detectors had a form of small cellulose capsules (exterior diameter 5 mm and length 15 mm) filled with 0.5 g of polycrystalline alanine powder (SIGMA Chemical Company). The capsules were sealed in waterproof Parafilm pockets. In order to visualise the detectors on radiographs, the capsules were bordered by an oval frame made of 1 mm cupronickel wire (Figure 1). The capsules with Ó The Author Published by Oxford University Press. All rights reserved. For Permissions, please journals.permissions@oupjournals.org

2 the cupronickel frame were sealed in waterproof foil and placed in the vagina after the ovoid application. At the beginning of this study (the first seven samples in Table 1) the planned doses were calculated by RTP at the centre of the dosemeter, as shown in Figure 1. This method resulted in relatively low precision of the calculated doses and, consequently, relatively Figure 1. Visualisation of a detector on radiograph used for treatment planning. The cross marks the central point of the detector in which the dose was calculated by RTP. K. SCHULTKA ET AL. large differences between the planned and measured doses (see Results and Discussion section). The uncertainty of the calculated doses was mainly owing to the impossibility of determining the position of effective point of measurement, i.e. the point in which the local dose is equal to the dose averaged over the whole detector volume. Its actual position is dependent on detector orientation in the dose gradient, and therefore should be determined individually for each detector this effect was neglected in this preliminary study and the point of measurement was arbitrarily set at the detector centre. Therefore, in order to reduce uncertainty in calculated doses, in further measurements the dose inside a detector (the planned dose ) was calculated as the mean of the doses computed in four points at opposite edges of the detector (the points marked as A 1,A 2,A 3 and A 4 in Figure 2). Such an approach allowed for the reduction of uncertainty in the planned doses by averaging out the unavoidable dose fluctuations, resulting from limited accuracy of determination of the detector position in radiographs. The EPR measurements were performed using Varian E-4 spectrometer. After the irradiation, the alanine powder was transferred into EPR quartz tube (4 or 3 mm inner diameter) and the dosimetric signal was measured at 5 mw microwave power and 1.25 mt modulation amplitude. The tubes were continuously tapped, which assured a uniform and consistent filling. Similarly as in our previous works (3), the tubes were filled 2 3 cm high, enough to cover the whole active region of the EPR cavity. Therefore, the measured EPR signal amplitude was proportional to the linear packing density of the detector material in the tube. Linear packing density was defined as a ratio of alanine mass and its packing Table 1. The results of in vivo dosimetry in gynaecological brachytherapy comparison of the measured and planned doses. Radiation source Sample no. Method of dose determination Planned dose (Gy) Deviation of measured dose from planned dose (%) Mean deviation (%) 137 Cs 1 Capsule centre Average from þ0.1 points A 1,A 2,A 3 and A Ir

3 EPR/ALANINE DOSIMETRY IN LDR BRACHYTHERAPY Figure 2. Exemplary dose distribution from treatment planning with alanine detector and 137 Cs applicators (marked 1 and 2 ). A 1,A 2,A 3 and A 4 show points where the dose calculations were performed. height in the tube; it was or g cm 1, for the thicker or thinner tube, respectively, and was reproducible within 1% (1 SD). The readings of EPR signal amplitude were normalised to spectrometer gain and linear packing density. Under these conditions the measurement uncertainty was shown to be <3% for doses >2 Gy (3). In addition, because the temperature of detectors located inside body cavities differed from their temperature during calibration procedure (performed at 23 C), a temperature correction factor k(t ) ¼ 0.166% K 1 (Nagy et al. (10) ) was introduced. The temperature corrected intensities of the EPR signals were converted to dose using a reference alanine sample irradiated with 60 Co photons (Theratron 780C, AECL) to the dose of 300 Gy (in terms of dose to water); accuracy of the calibration dose was 1% (1 SD). RESULTS AND DISCUSSION The results of in vivo dosimetry are presented in Table 1. For the first seven samples (sample nos 1 7) the planned doses were calculated by the planning system at the centre of capsules. For sample nos 8 13 the planned dose was obtained by averaging four doses calculated at opposite points of the detector border (see Figure 1). The relative maximum deviations of measured from the planned doses varied from 23 to þ14% (Table 1). The mean deviation from prescribed dose, averaged over all measurements, was relatively low ( 5%) with SD ¼ 10%. For the first seven cases the mean deviation is 10% with a data scatter of 12% (SD). For sample nos 8 13 the mean deviation is significantly lower: þ0.1% with a data scatter of 4% (SD). There seems to be a systematic difference between the first group (nos 1 7) and the second group (nos 8 13) in agreement with the measured and the planned doses. However, owing to the low number of data points and their large scattering in the two groups, justification of such a conclusion requires further research and analysis based on larger population of experimental data. In our previous studies using EPR/ alanine dosimetry in external beam radiotherapy (3) it was shown that uncertainty of the EPR signal measurements was 3% for doses >2 Gy. Therefore, the much larger differences demonstrated here cannot be attributed to the uncertainty of EPR measurements. The main sources of differences between the measured and the calculated doses rather can be attributed to the following factors: (1) uncertainty in determination of the initial detector position on radiograph images, (2) displacement of the detector s point of measurement from the detector centre in strong dose gradients a change in calculated dose due to a 1 mm shift in position of that point is within 0 15%, (3) averaging of the dose over the whole detector volume in radiation fields with steep dose gradient and (4) uncontrolled changes in the detector position during the treatment. The influence of factors (1) and (2) was reduced when for the reference or planned dose the average of doses calculated by RTP at four opposite points at the detectors border was applied (compare data point nos 1 7 with the data nos 8 13 in Table 1). Such an approach, apparently, partially eliminates the position-related uncertainties by the process of averaging. However, owing to the exponential character of dose variations in 173

4 space, the linear averaging of doses applied here for points A 1 A 4 introduces a systematic overestimation of the actual mean dose in the detector. Estimations based on treatment plan data show that the value of this overestimation may reach 4 5% for detectors oriented in parallel to the dose gradient. Accurate accounting for those effects would require an integration of the dose over the whole volume for each detector, based on its 3-D orientation in isodose distribution. This is a time-consuming procedure and was neglected in this preliminary study. For detectors perpendicular to the dose gradient, the errors resulting from linear averaging are of much lower value (<0.5%) and were ignored in this feasibility study. For the detectors placed in strong dose gradients a change in calculated dose due to a 1 mm shift in position of the detector centre was shown to be within 0 15%, for typical brachytherapy dose distributions studied here. Considering all effects that influence determination of the planned doses in a dosemeter, i.e. the steep dose gradient within the detector, the uncertainty in the determination of the capsule position and its unavoidable shifts in patient s body during the brachytherapy session, the relatively low value ( 5%) of average difference between the measured and the planned does not indicate any statistically relevant discrepancy between the treatment plan and the real doses. The observed difference in mean deviation between sample nos 1 7 and nos 8 13 indicate that the detector s geometrical centre (1) does not represent correctly the effective point of measurement for the dosemeter and (2) cannot be determined accurately from radiographs. However, the number of samples in the two groups differing with respect to dose calculation is low and, therefore, the difference between those two groups cannot be considered as generally representative for those two methods of dose calculations. To estimate the effect of detector motion, a second set of radiographs should be made at the end of each therapy session. However, this would require additional exposure of the patient and would affect the routine clinical procedure. Therefore, it was not applied in this study. It has to be emphasised that the position-related and motionrelated effects are among the largest sources of uncertainty in in vivo verification of RTP doses. The largest differences detected in this study ( 23% and þ14%) were approximately equivalent to only 2 mm and 1 mm shifts of detector positions. At present, no measures are available to prevent the movement of detectors inside the patient s body during several hours of LDR treatment sessions, with the exception of fixing them to the applicators surface or a patient s mould, however, even in such cases (6,7) the percentage difference between the planned and the measured doses were similar to those reported here. A reduction in detector size would be one of possible K. SCHULTKA ET AL. 174 measures to overcome the effects related to the dose gradient. However, the size reduction would enhance problems with visualisation and motion of the detectors in the patient s body. CONCLUSIONS The proposed method of in vivo EPR/alanine dosimetry allows the verification of the planned doses in gynaecological brachytherapy. The accuracy of determination of the planned doses in the detectors is the most important factor affecting the results of comparison of the measured and planned doses. Calculation of doses at the centre of the detector image on radiographs results in larger scatter of the data than when dose in the detector was obtained as an average dose from four points at the detector border. In order to verify agreement between the measured and the planned dose of a single brachytherapy session with accuracy better than 10 15%, the planned, average dose in a detector should be calculated by integration of dose distribution over the whole volume of the detector. ACKNOWLEDGEMENTS The authors would like to thank Dr Krzysztof Cal from the Department of Pharmaceutical Technology and Dr Michał Penkowski from the Department of Physics and Biophysics, MUG for their help in manufacturing the alanine detectors. REFERENCES 1. Chu, S., Wieser, A., Feist, H. and Regulla, D. F. ESR/ alanine dosimetry of high-energy electrons in radiotherapy. Appl. Radiat. Isot. 40(10 12), (1989). 2. Kudyński, R., Kudyńska, J. and Buckmaster, H. E. The application of EPR dosimetry for radiotherapy and radiation protection. Appl. Radiat. Isot. 44(6), (1993). 3. Ciesielski, B., Schultka, K., Kobierska, A., Nowak, R. and Peimel-Stuglik, Z. In vivo alanine/epr dosimetry in daily clinical practice: a feasibility study. Int. J. Radiat. Oncol. Biol. Phys. 56, (2003). 4. De Angelis, C., Onori, S., Petetti, E., Piermattei, A. and Azario, L. Alanine/EPR dosimetry in brachytherapy. Phys. Med. Biol. 44, (1999). 5. Olsson, S., Bergstrand, E. S., Carlsson, Å. K., Hole, E. O. and Lund, A. Radiation dose measurements with alanine/agarose gel and thin alanine films around a 192 Ir brachytherapy source, using ESR spectroscopy. Phys. Med. Biol. 47, (2002). 6. Schaeken, B. and Scalliet, P. One year of experience with alanine dosimetry in radiotherapy. Appl. Radiat. Isot. 47, (1996). 7. Kuntz, F., Pabst, J. Y., Delpech, J. P., Wagner, J. P. and Marchioni, E. Alanine-ESR in vivo dosimetry: a feasibility study and possible applications. Appl. Radiat. Isot. 47, (1996).

5 EPR/ALANINE DOSIMETRY IN LDR BRACHYTHERAPY 8. Schultka, K., Ciesielski, B., Serkies, K., Wysocka, B., Sawicki, T., Tarnawska, Z. and Jassem, J. In vivo dosimetry using electron paramagnetic resonance in L-alanine in gynecological low dose rate brachytherapy. Nowotwory J. Oncol. 6, (2004). 9. Serkies, K., Badzio, A., Jereczek-Fossa, B., Tarnawska, Z., Nowak, R., Szewczyk, P. and Jassem, J. Rectal doses in intracavitary brachytherapy of gynecological malignancies: comparison of two dosimetric methods. Radiother. Oncol. 58, (2001). 10. Nagy, V., Puhl, J. P. and Desrosiers, M. F. Advencements in accuracy of the alanine dosimetry system: Part 2. The influence of irradiation temperature. Radiat. Phys. Chem. 57, 1 9 (2000). 175