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In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer
Brachytherapy 10 (2011) 498e502
In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer Ashraf H. Hassouna1,2,4,*, Yasir A. Bahadur3, Camelia Constantinescu1, Mohamed E. El Sayed1,2, Hussain Naseem1, Adly F. Naga1,2 1
Department of Oncology, King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia 2 Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt 3 Department of Radiology, King Abdul Aziz University, Jeddah, Saudi Arabia
ABSTRACT
PURPOSE: To investigate the correlation between the dose predicted by the treatment planning system using digitally reconstructed radiographs or three-dimensional (3D)ereconstructed CT images and the dose measured by semiconductor detectors, under clinical conditions of high-dose-rate brachytherapy of the cervix uteri. PATIENTS AND METHODS: Thirty-two intracavitary brachytherapy applications were performed for 12 patients with cancer of the cervix uteri. The prescribed dose to Point A was 7 Gy. Dose was calculated for both International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal points based on digitally reconstructed radiographs and for 3D CT imagesebased volumetric calculation of the bladder and rectum. In vivo diode dosimetry was performed for the bladder and rectum. RESULTS: The ICRU reference point and the volumes of 1, 2, and 5 cm3 received 3.6 0.9, 5.6 2.0, 5.1 1.7, 4.3 1.4 and 5.0 1.2, 5.3 1.3, 4.9 1.1, and 4.2 0.9 Gy for the bladder and rectum, respectively. The ratio of the 1 cm3 and the ICRU reference point dose to the diode dose was 1.8 0.7 and 1.2 0.5 for the bladder and 1.9 0.6 and 1.7 0.5 for the rectum, respectively. CONCLUSIONS: 3D imageebased dose calculation is the most accurate and reliable method to evaluate the dose given to critical organs. In vivo diode dosimetry is an important method of quality assurance, but clinical decisions should be made based on 3D-reconstructed CT image calculations. Ó 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Cervical cancer; HDR brachytherapy; In vivo dosimetry; Diodes
Introduction One of the main difficulties in the brachytherapy for the cancer of the cervix uteri is to define parameters related to the organs at risk that are relevant to predict the side effects Received 5 November 2010; received in revised form 22 March 2011; accepted 24 March 2011. Conflict of interest: The authors disclose that there is no conflict of interest. * Corresponding author. Department of Radiation Oncology, National Cancer Institute, PO Box 11796, Cairo University, Cairo, Egypt. Tel.: þ20160331928 (mobile). E-mail address: [email protected] (A.H. Hassouna). 4 Current address: Department of Oncology, Radiation Oncology Unit, King Faisal Specialist Hospital & Research Center, PO Box 40047, Jeddah, Saudi Arabia. Tel.: þ966-559895880 (mobile); fax: þ966-26408047.
and to which the dose should be referred. The dose to the anterior rectal wall and posterior bladder wall is clinically relevant, and International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal reference points were proposed in 1985 to improve uniformity in dose reporting (1). When changing from a radiographic-based dose planning procedure to sectional imagingebased dose planning procedure, it is possible to improve the dose to the target without compromising the dose to the critical organs (2). This development has been further advanced by published recommendations of target definition (3) and doseevolume parameters in three-dimensional (3D) imageebased treatment planning of brachytherapy (4). In the new 3D approach, the dose distribution is optimized according to the individual
1538-4721/$ - see front matter Ó 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.brachy.2011.03.004
A.H. Hassouna et al. / Brachytherapy 10 (2011) 498e502
anatomy as visualized on 3D images obtained for dose planning. In 2005, the Gynaecology - Groupe Europeen de Curietherapie - European Society for Therapeutic Radiology and Oncology (GYN-GEC ESTRO) Working Group (4) recommended the use of 3D approach in cervix brachytherapy and proposed volumes of 1, 2, and 5 cm3 of organs at risk to be selected for reporting treatments. In our opinion, the volume of 1 cm3 of organs at risk is small enough such that its dose is a good estimate for late side effects. For the delivered dose to be equal to the planned dose, the treatment planning system (TPS) should correctly calculate the dose distribution, and the patient’s anatomy should remain stable during the whole treatment. In intracavitary brachytherapy of the cervix, in vivo dosimetry is commonly applied to check dose delivery to the critical organs, that is, rectum and bladder. In vivo dosimetry can be performed with semiconductor diodes (5e7) or thermoluminescent dosimeters (TLDs) (8e10). The aim of the present study was to 1. Compare the three methods of assessing the critical organ dose in the high-dose-rate (HDR) brachytherapy for cancer of the cervix uteri. This involved the dose predicted by the TPS using orthogonal digitally reconstructed radiographs, 3D CT imagesebased volumetric calculation, and the dose measured by semiconductor detectors. 2. Evaluate to what extent the measured doses can provide a reliable estimation of the dose at the ICRU reference points or with the recommended volumes of organs at risk.
499
given in three fractions, with a prescribed dose per fraction of 7 Gy to Point A. The bladder probe (type 9111, PTW Freiburg, Germany) had one diode, with an outer diameter of 4.75 mm. The bladder dose was measured for each application. A Foley catheter was used. The bladder probe was subsequently positioned in the bladder, adjacent to the bladder wall and Foley catheter balloon. A rectal probe (type 9112, PTW Freiburg, Germany) with five identical diodes (with outer diameters of 7 mm, placed 15 mm apart in a flexible tube) was used for measurement of rectal doses. The rectal dose was measured for each application and reported for each of the five diodes of the rectal probe. All the probes were connected to a computerized controlling system (adapter, personal computer, software). A CT scan was taken and used for the reconstruction of the applicators, points of interest (the in vivo probes and the ICRU rectum and bladder reference points), volumes of interest (rectum and bladder volumes), and dose distribution with doseevolume histogram calculation. The dose calculations were performed using a Varian TPS Brachyvision 8.6.15. The calculation algorithm used in this study was based on the formalism (Task Group-43) currently recommended by the American Association of Physicists in Medicine (11), which is well documented and commonly accepted (12). The organs at risk (rectum and bladder) can be defined accurately on axial CT images (Fig. 1); the diodes and applicators were defined on orthogonal digitally reconstructed radiographs derived from CT images. The study was approved by the institutional review board, and the written informed consent obtained from every patient.
Patients and methods A total of 12 patients with cancer of the cervix uteri, Stages IB2eIIB, were prospectively treated with a combination of external beam radiotherapy (EBRT) and chemotherapy, followed by brachytherapy. The prescribed dose for EBRT was 45 Gy in 25 fractions, given to the pelvis by four-field box technique, using high-energy photons. In total, 32 brachytherapy applications were performed for the 12 patients. After EBRT, pelvic MRI was performed to evaluate the patients before brachytherapy. For bowel preparation, an enema was given to the patient the day before the brachytherapy procedure. On the day of application, examination under general anesthesia was performed followed by cervical dilatation and placement of the applicators. The vagina was packed with gauze to displace the bladder and rectum and stabilize the position of ovoids. CT/MRIecompatible Fletcher-Suit-Delclos applicator system (tandem and ovoids) together with the VariSource 200 HDR afterloading unit (Varian Medical Systems, Palo Alto, CA), with a 5-mm iridium-192 step source was used for brachytherapy treatments. Brachytherapy was
Results The prescribed dose to Point A was 7 Gy for all applications. The bladder probe had a single detector located near its tip, and efforts were made to place this tip close to the bladder neck, which was demarcated by the Foley catheter balloon. The calculated dose at the bladder ICRU reference point was very close to the measured dose by bladder diode (ratio of 1.2 0.5). Contouring of the bladder on serial axial CT cuts demonstrated that the bladder neck (and also the tip of the bladder diode) was not located in the bladder high-dose region. Therefore, the calculated dose at 1 and 2 cm3 of the bladder was much higher than the calculated dose at ICRU point and the measured dose (ratio of 1.8 0.7 and 1.7 0.7) (Table 1). The rectal probe had five detectors located in a serial configuration starting from its tip. Efforts were made to place the middle diode opposite to the posterior tip of the ovoids in sagittal CT cuts. This position was supposed to be the rectal high-dose region, which also contained the rectal ICRU point. In spite of this, the calculated dose at
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1.7 0.5) (Table 1). Analysis of these data using linear regression curves (Fig. 2) did not show any linear correlation between the measured and calculated doses at points or volumes of interest. Calibration and evaluation of physical uncertainties of in vivo dosimetry system was carried out. The mean uncertainty of calibration factors was 1.9% (range, 0.4e4.3%), which was obtained by comparing repeated measurements to calculated values provided by the TPS in the afterloading calibration phantom. The reproducibility of the diodes was better than 0.5% over 1 week.
Discussion
Fig. 1. (a) Axial and (b) sagittal CT images used for treatment planning. ICRU 5 International Commissioning on Radiation Units and Measurements.
the rectal ICRU reference point was much higher than the measured dose by rectal diode (ratio of 1.7 0.5). CT rectal contouring demonstrated that the rectal ICRU reference point was located in the rectal high-dose region (the middle rectal diode was away from this region). Therefore, the calculated dose at 1 and 2 cm3 of the rectum was much higher than the measured dose (ratio of 1.9 0.6 and Table 1 Comparison of in vivo measured doses to calculated doses at ICRU reference points and the volumes of 1, 2, and 5 cm3 of organs at risk Organs at risk
Average calculated dose (Gy)
Average ratio of calculated dose to measured dose
Bladder ICRU point 1 cm3 2 cm3 5 cm3
3.6 5.6 5.1 4.3
0.9 2 1.7 1.4
1.2 1.8 1.7 1.4
0.5 0.7 0.7 0.6
Rectum ICRU point 1 cm3 2 cm3 5 cm3
5.0 5.3 4.9 4.2
1.2 1.3 1.1 0.9
1.7 1.9 1.7 1.4
0.5 0.6 0.5 0.4
ICRU 5 International Commissioning on Radiation Units Measurements.
and
The characteristics of different types of semiconductors used for in vivo dosimetry in the clinical practice of EBRT are well documented. However, only a few studies are available for brachytherapy applications. The present study has analyzed in detail the clinical brachytherapy applications based on the physical characteristics of the diodes used for intracavitary in vivo dose measurement. Furthermore, it compared in vivo measurements with calculated patient-related data. The in vivo measured doses were, in general, lower than the calculated doses at the ICRU reference points (Fig. 2). This can be explained to a large extent with the steep dose gradients and that the in vivo probes were not positioned exactly at the ICRU reference points. The same observation could be noticed regarding the volumes of 1, 2, and 5 cm3 of organs at risk. However, there was no correlation between measured and calculated doses of these volumes. For the rectum, the ICRU point is defined as a point 5 mm behind the anterior rectal wall. Assuming a dose of 5.0 1.2 Gy (average dose to the ICRU rectum reference point standard deviation) a shift of 8.5 mm (3.5 mm radius of the probe þ 5 mm from the rectal wall) could result in a dose reduction of 43% (measured dose of 2.9 0.5 Gy) corresponding to the dose falloff between the ICRU rectal point and the diode, as observed during the present study. For the bladder, the probe is placed at the surface of the posterior bladder wall (the probe has a radius of 2.4 mm). Assuming a dose of 3.6 0.9 Gy (average dose to the ICRU bladder reference point standard deviation) a shift of 2.4 mm could result in a dose reduction of 12% (measured dose of 3.2 0.8 Gy) corresponding to the dose falloff between the ICRU bladder point and the diode. The recent literature is scarce in coherent studies on in vivo dosimetry for HDR brachytherapy of the cervix. The published reports in the literature reveal a wide variety of methods and technology used; therefore, a systematic comparison to our study is difficult. The dosimetric equipment of choice was either diodes (7, 13e16) or TLDs (8, 10). Almost similar data have been reported by Clark et al. (7) and Waldh€ausl et al. (13). These results compared doses to ICRU 38 reference points to in vivo measurements
A.H. Hassouna et al. / Brachytherapy 10 (2011) 498e502
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Fig. 2. (a and b) Clinically relevant calculated and measured doses. Linear regression curves were calculated, and the slope, intercept, and correlation coefficient are specified. The reference curve shows equal measured and calculated doses. ICRU 5 International Commissioning on Radiation Units and Measurements.
with diodes. The previous studies showed that the rectal and bladder doses measured in vivo tended to be lower than the doses indicated by the ICRU rectum and bladder reference points. The present study confirms this (Table 2). Eich et al. (14) reported data of rectal in vivo dosimetry in HDR brachytherapy of the cervix using diodes and localization radiographs. The measured actual rectum dosage was analyzed retrospectively in 75 applications and prospectively in another 11 applications. Their results showed a deviation between measured and calculated values of 30% and 40% in retrospective and prospective data, respectively. Factors causing errors were incorrect assessment of the applicator’s positioning, nonorthogonal radiographs, incorrect calibration of the diode, and movement of probe in the time between radiograph and application. In another study done by Eich et al. (15), the in vivo measurements using rectum diodes were out by a factor of 1.5 below the doses determined for the ICRU rectum reference point (4.05 0.68 vs. 6.11 1.63 Gy). Contrary to our data that did not show any linear correlation between the measured and the calculated doses, Kapp et al. (8) showed a good correlation of rectal doses from orthogonal films, with in vivo readings using TLDs (with a correlation coefficient factor of 0.9556). In another study (10), TLDs were used for in vivo dosimetry in 71 cases, and the maximum deviation between measured
and calculated doses was 20% (with a correlation coefficient factor of 0.9694). The present study adds to the accumulating data confirming that the ICRU reference points are no longer suitable for reporting the highest doses delivered to critical pelvic organs or predicting the long-term brachytherapy complications. 3D data calculation from CT and/or MRI images demonstrated that these reference points were not located in the high-dose region of the corresponding critical organ. These high-dose regions are better evaluated using the doseevolume histogram (17). Quality assurance programs for HDR brachytherapy are still deficient with respect to reliable methods to assure the accurate and safe delivery of the prescribed dose to target volumes and to prevent overdoses of nearby critical organs. It is clear that in vivo diode dosimetry is beneficial in measuring the actual dose delivered to the organs at risk. Although we could not accurately place the diode in the high-dose region of the critical organs, its reading can help prevent large errors from occurring during dose delivery. Huh et al. (16) have used TLDs for rectal dose measurements and CT-assisted HDR brachytherapy in a total of 136 cervical cancer patients and correlated the rectal dose values with late rectal complications. The calculated rectal doses did not differ in patients with rectal bleeding and those without, but the measured rectal doses were
Table 2 Comparison of ratios of calculated (at bladder and rectum ICRU reference points) and measured (by in vivo diode dosimetry) doses to Point A dose, as presented in the literature Bladder
Rectum
Reference
Calculated dose to Point A dose (%)
Measured dose to Point A dose (%)
Calculated dose to Point A dose (%)
Measured dose to Point A dose (%)
Clark et al. (7) Waldh€ausl et al. (13) Present study
80 78 50.7 12.5
37 48 45.5 11.2
81 76 70.4 17.0
28 56 41.7 7.4
ICRU 5 International Commissioning on Radiation Units and Measurements.
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A.H. Hassouna et al. / Brachytherapy 10 (2011) 498e502
[2]
[3]
[4]
[5] Fig. 3. Axial CT image shows artifacts caused by diodes. ICRU 5 International Commissioning on Radiation Units and Measurements.
higher in affected patients. Therefore, they concluded that in vivo dosimetry using TLD was a good predictor of late rectal complications. Increasing artifacts in CT image was one of the drawbacks of using diodes for in vivo dosimetry (Fig. 3). If rectal wall discrimination was difficult, we referred to CT images taken in-between diodes to help rectal contouring (Fig. 1a). We estimated the uncertainty for diode measurements to be 5% in the afterloading calibration phantom, in agreement with the manufacturer’s technical specifications. We could not find significant differences of measurement performances among individual diodes, as checked in the afterloading calibration phantom. To optimize the calibration, we have performed weekly measurement series. Our results showed that weekly calibration does not increase accuracy and that monthly calibration seems to be sufficient for clinical use. It was reported that accumulated dose influences dose response and calibration factors (18). However, we did not observe such a dependency for the rather low accumulated doses (e.g., for the rectal probes: 32 applications with an average dose of 4 Gy per application results in about 128 Gy). Conclusion The in vivo dosimetry using diodes can be performed in addition to, and not instead of, 3D dose calculation. Brachytherapy in vivo dosimetry using diodes can be an important method for a quality assurance program. However, the clinical decisions based on 3D imageebased dose calculation remained the most available accurate and safe method for cervix brachytherapy application. References [1] Chassagne D, Dutreix A, Almond P, et al. ICRU report no. 38: Dose and volume specification for reporting intracavitary therapy in
[6] [7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
gynecology. Bethesda, MD: International Commissioning on Radiation Units and Measurements; 1985. Wachter-Gerstner N, Wachter S, Reinstadler E, et al. The impact of sectional imaging on dose escalation in endocavitary HDRbrachytherapy of cervical cancer: Results of a prospective comparative trial. Radiother Oncol 2003;68:51e59. Haie-Meder C, P€otter R, Van Limbergen E, et al., Gynecological (GYN) GEC-ESTRO Working Group. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): Concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235e245. P€otter R, Haie-Meder C, Van Limbergen E, et al., GEC ESTRO Working Group. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D imagebased treatment planning in cervix cancer brachytherapyd3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006;78:67e77. Alecu R, Alecu M. In-vivo rectal dose measurements with diodes to avoid misadministrations during intracavitary high dose rate brachytherapy for carcinoma of the cervix. Med Phys 1999;26:768e770. Chow H, Lane RG, Rosen II. Uncertainty in dose estimation for gynecological implants. Int J Radiat Oncol Biol Phys 1990;19:1555e1559. Clark BG, Souhami L, Roman TN, et al. Rectal complications in patients with carcinoma of the cervix treated with concomitant cisplatin and external beam irradiation with high dose rate brachytherapy: A dosimetric analysis. Int J Radiat Oncol Biol Phys 1994; 28:1243e1250. Kapp KS, Stuecklschweiger GF, Kapp DS, et al. Dosimetry of intracavitary placements for uterine and cervical carcinoma: Results of orthogonal film, TLD, and CT-assisted techniques. Radiother Oncol 1992;24:137e146. Lahtinen T, Tenhunen M, V€ayrynen M. ICRU reference points and maximum doses of rectum and bladder in intracavitary radiotherapy. Radiother Oncol 1993;28:174e176. Stuecklschweiger GF, Arian-Schad KS, Poier E, et al. Bladder and rectal dose of gynecologic high-dose-rate implants: Comparison of orthogonal radiographic measurements with in vivo and CT-assisted measurements. Radiology 1991;181:889e894. Nath R, Anderson LL, Luxton G, et al. Dosimetry of interstitial brachytherapy sources: Recommendations of the AAPM Radiation Therapy Committee Task Group No. 43. American Association of Physicists in Medicine. Med Phys 1995;22:209e234. Thomadsen B, Shahabi S, Stitt J, et al. Treatment planning and optimization in high dose rate brachytherapy: A textbook. Armonk, NY: Futura Publishing Company, Inc.; 1994. pp. 79e145. Waldh€ausl C, Wambersie A, P€otter R, et al. In-vivo dosimetry for gynecological brachytherapy: Physical and clinical considerations. Radiother Oncol 2005;77:310e317. Eich HT, Haverkamp U, Micke O, et al. Dosimetry methods in determining radiation dosage of the rectum in HDR-brachytherapy of cervix carcinoma. Strahlenther Onkol 1998;174:375e380. Eich HT, Haverkamp U, Micke O, et al. Dosimetric analysis at ICRU reference points in HDR-brachytherapy of cervical carcinoma. Rontgenpraxis 2000;53:62e66. Huh SJ, Lim DH, Ahn YC, et al. Comparison between in vivo dosimetry and barium contrast technique for prediction of rectal complications in high-dose-rate intracavitary radiotherapy in cervix cancer patients. Strahlenther Onkol 2003;179:191e196. Bahadur YA, El-Sayed ME, El-Taher ZH, et al. Using the computed tomography in comparison to the orthogonal radiography based treatment planning in high dose rate (HDR) brachytherapy in cervical uteri cancer patients; a single institution feasibility study. J Egypt Natl Canc Inst 2008;20:1e9. Van Dam J, Leunes G, Dutreix A. Correlation between temperature and dose rate dependence of semiconductor response; influence of accumulated dose. Radiother Oncol 1990;19:345e351.
In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer Ashraf H. Hassouna1,2,4,*, Yasir A. Bahadur3, Camelia Constantinescu1, Mohamed E. El Sayed1,2, Hussain Naseem1, Adly F. Naga1,2 1
Department of Oncology, King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia 2 Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt 3 Department of Radiology, King Abdul Aziz University, Jeddah, Saudi Arabia
ABSTRACT
PURPOSE: To investigate the correlation between the dose predicted by the treatment planning system using digitally reconstructed radiographs or three-dimensional (3D)ereconstructed CT images and the dose measured by semiconductor detectors, under clinical conditions of high-dose-rate brachytherapy of the cervix uteri. PATIENTS AND METHODS: Thirty-two intracavitary brachytherapy applications were performed for 12 patients with cancer of the cervix uteri. The prescribed dose to Point A was 7 Gy. Dose was calculated for both International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal points based on digitally reconstructed radiographs and for 3D CT imagesebased volumetric calculation of the bladder and rectum. In vivo diode dosimetry was performed for the bladder and rectum. RESULTS: The ICRU reference point and the volumes of 1, 2, and 5 cm3 received 3.6 0.9, 5.6 2.0, 5.1 1.7, 4.3 1.4 and 5.0 1.2, 5.3 1.3, 4.9 1.1, and 4.2 0.9 Gy for the bladder and rectum, respectively. The ratio of the 1 cm3 and the ICRU reference point dose to the diode dose was 1.8 0.7 and 1.2 0.5 for the bladder and 1.9 0.6 and 1.7 0.5 for the rectum, respectively. CONCLUSIONS: 3D imageebased dose calculation is the most accurate and reliable method to evaluate the dose given to critical organs. In vivo diode dosimetry is an important method of quality assurance, but clinical decisions should be made based on 3D-reconstructed CT image calculations. Ó 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Cervical cancer; HDR brachytherapy; In vivo dosimetry; Diodes
Introduction One of the main difficulties in the brachytherapy for the cancer of the cervix uteri is to define parameters related to the organs at risk that are relevant to predict the side effects Received 5 November 2010; received in revised form 22 March 2011; accepted 24 March 2011. Conflict of interest: The authors disclose that there is no conflict of interest. * Corresponding author. Department of Radiation Oncology, National Cancer Institute, PO Box 11796, Cairo University, Cairo, Egypt. Tel.: þ20160331928 (mobile). E-mail address: [email protected] (A.H. Hassouna). 4 Current address: Department of Oncology, Radiation Oncology Unit, King Faisal Specialist Hospital & Research Center, PO Box 40047, Jeddah, Saudi Arabia. Tel.: þ966-559895880 (mobile); fax: þ966-26408047.
and to which the dose should be referred. The dose to the anterior rectal wall and posterior bladder wall is clinically relevant, and International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal reference points were proposed in 1985 to improve uniformity in dose reporting (1). When changing from a radiographic-based dose planning procedure to sectional imagingebased dose planning procedure, it is possible to improve the dose to the target without compromising the dose to the critical organs (2). This development has been further advanced by published recommendations of target definition (3) and doseevolume parameters in three-dimensional (3D) imageebased treatment planning of brachytherapy (4). In the new 3D approach, the dose distribution is optimized according to the individual
1538-4721/$ - see front matter Ó 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.brachy.2011.03.004
A.H. Hassouna et al. / Brachytherapy 10 (2011) 498e502
anatomy as visualized on 3D images obtained for dose planning. In 2005, the Gynaecology - Groupe Europeen de Curietherapie - European Society for Therapeutic Radiology and Oncology (GYN-GEC ESTRO) Working Group (4) recommended the use of 3D approach in cervix brachytherapy and proposed volumes of 1, 2, and 5 cm3 of organs at risk to be selected for reporting treatments. In our opinion, the volume of 1 cm3 of organs at risk is small enough such that its dose is a good estimate for late side effects. For the delivered dose to be equal to the planned dose, the treatment planning system (TPS) should correctly calculate the dose distribution, and the patient’s anatomy should remain stable during the whole treatment. In intracavitary brachytherapy of the cervix, in vivo dosimetry is commonly applied to check dose delivery to the critical organs, that is, rectum and bladder. In vivo dosimetry can be performed with semiconductor diodes (5e7) or thermoluminescent dosimeters (TLDs) (8e10). The aim of the present study was to 1. Compare the three methods of assessing the critical organ dose in the high-dose-rate (HDR) brachytherapy for cancer of the cervix uteri. This involved the dose predicted by the TPS using orthogonal digitally reconstructed radiographs, 3D CT imagesebased volumetric calculation, and the dose measured by semiconductor detectors. 2. Evaluate to what extent the measured doses can provide a reliable estimation of the dose at the ICRU reference points or with the recommended volumes of organs at risk.
499
given in three fractions, with a prescribed dose per fraction of 7 Gy to Point A. The bladder probe (type 9111, PTW Freiburg, Germany) had one diode, with an outer diameter of 4.75 mm. The bladder dose was measured for each application. A Foley catheter was used. The bladder probe was subsequently positioned in the bladder, adjacent to the bladder wall and Foley catheter balloon. A rectal probe (type 9112, PTW Freiburg, Germany) with five identical diodes (with outer diameters of 7 mm, placed 15 mm apart in a flexible tube) was used for measurement of rectal doses. The rectal dose was measured for each application and reported for each of the five diodes of the rectal probe. All the probes were connected to a computerized controlling system (adapter, personal computer, software). A CT scan was taken and used for the reconstruction of the applicators, points of interest (the in vivo probes and the ICRU rectum and bladder reference points), volumes of interest (rectum and bladder volumes), and dose distribution with doseevolume histogram calculation. The dose calculations were performed using a Varian TPS Brachyvision 8.6.15. The calculation algorithm used in this study was based on the formalism (Task Group-43) currently recommended by the American Association of Physicists in Medicine (11), which is well documented and commonly accepted (12). The organs at risk (rectum and bladder) can be defined accurately on axial CT images (Fig. 1); the diodes and applicators were defined on orthogonal digitally reconstructed radiographs derived from CT images. The study was approved by the institutional review board, and the written informed consent obtained from every patient.
Patients and methods A total of 12 patients with cancer of the cervix uteri, Stages IB2eIIB, were prospectively treated with a combination of external beam radiotherapy (EBRT) and chemotherapy, followed by brachytherapy. The prescribed dose for EBRT was 45 Gy in 25 fractions, given to the pelvis by four-field box technique, using high-energy photons. In total, 32 brachytherapy applications were performed for the 12 patients. After EBRT, pelvic MRI was performed to evaluate the patients before brachytherapy. For bowel preparation, an enema was given to the patient the day before the brachytherapy procedure. On the day of application, examination under general anesthesia was performed followed by cervical dilatation and placement of the applicators. The vagina was packed with gauze to displace the bladder and rectum and stabilize the position of ovoids. CT/MRIecompatible Fletcher-Suit-Delclos applicator system (tandem and ovoids) together with the VariSource 200 HDR afterloading unit (Varian Medical Systems, Palo Alto, CA), with a 5-mm iridium-192 step source was used for brachytherapy treatments. Brachytherapy was
Results The prescribed dose to Point A was 7 Gy for all applications. The bladder probe had a single detector located near its tip, and efforts were made to place this tip close to the bladder neck, which was demarcated by the Foley catheter balloon. The calculated dose at the bladder ICRU reference point was very close to the measured dose by bladder diode (ratio of 1.2 0.5). Contouring of the bladder on serial axial CT cuts demonstrated that the bladder neck (and also the tip of the bladder diode) was not located in the bladder high-dose region. Therefore, the calculated dose at 1 and 2 cm3 of the bladder was much higher than the calculated dose at ICRU point and the measured dose (ratio of 1.8 0.7 and 1.7 0.7) (Table 1). The rectal probe had five detectors located in a serial configuration starting from its tip. Efforts were made to place the middle diode opposite to the posterior tip of the ovoids in sagittal CT cuts. This position was supposed to be the rectal high-dose region, which also contained the rectal ICRU point. In spite of this, the calculated dose at
500
A.H. Hassouna et al. / Brachytherapy 10 (2011) 498e502
1.7 0.5) (Table 1). Analysis of these data using linear regression curves (Fig. 2) did not show any linear correlation between the measured and calculated doses at points or volumes of interest. Calibration and evaluation of physical uncertainties of in vivo dosimetry system was carried out. The mean uncertainty of calibration factors was 1.9% (range, 0.4e4.3%), which was obtained by comparing repeated measurements to calculated values provided by the TPS in the afterloading calibration phantom. The reproducibility of the diodes was better than 0.5% over 1 week.
Discussion
Fig. 1. (a) Axial and (b) sagittal CT images used for treatment planning. ICRU 5 International Commissioning on Radiation Units and Measurements.
the rectal ICRU reference point was much higher than the measured dose by rectal diode (ratio of 1.7 0.5). CT rectal contouring demonstrated that the rectal ICRU reference point was located in the rectal high-dose region (the middle rectal diode was away from this region). Therefore, the calculated dose at 1 and 2 cm3 of the rectum was much higher than the measured dose (ratio of 1.9 0.6 and Table 1 Comparison of in vivo measured doses to calculated doses at ICRU reference points and the volumes of 1, 2, and 5 cm3 of organs at risk Organs at risk
Average calculated dose (Gy)
Average ratio of calculated dose to measured dose
Bladder ICRU point 1 cm3 2 cm3 5 cm3
3.6 5.6 5.1 4.3
0.9 2 1.7 1.4
1.2 1.8 1.7 1.4
0.5 0.7 0.7 0.6
Rectum ICRU point 1 cm3 2 cm3 5 cm3
5.0 5.3 4.9 4.2
1.2 1.3 1.1 0.9
1.7 1.9 1.7 1.4
0.5 0.6 0.5 0.4
ICRU 5 International Commissioning on Radiation Units Measurements.
and
The characteristics of different types of semiconductors used for in vivo dosimetry in the clinical practice of EBRT are well documented. However, only a few studies are available for brachytherapy applications. The present study has analyzed in detail the clinical brachytherapy applications based on the physical characteristics of the diodes used for intracavitary in vivo dose measurement. Furthermore, it compared in vivo measurements with calculated patient-related data. The in vivo measured doses were, in general, lower than the calculated doses at the ICRU reference points (Fig. 2). This can be explained to a large extent with the steep dose gradients and that the in vivo probes were not positioned exactly at the ICRU reference points. The same observation could be noticed regarding the volumes of 1, 2, and 5 cm3 of organs at risk. However, there was no correlation between measured and calculated doses of these volumes. For the rectum, the ICRU point is defined as a point 5 mm behind the anterior rectal wall. Assuming a dose of 5.0 1.2 Gy (average dose to the ICRU rectum reference point standard deviation) a shift of 8.5 mm (3.5 mm radius of the probe þ 5 mm from the rectal wall) could result in a dose reduction of 43% (measured dose of 2.9 0.5 Gy) corresponding to the dose falloff between the ICRU rectal point and the diode, as observed during the present study. For the bladder, the probe is placed at the surface of the posterior bladder wall (the probe has a radius of 2.4 mm). Assuming a dose of 3.6 0.9 Gy (average dose to the ICRU bladder reference point standard deviation) a shift of 2.4 mm could result in a dose reduction of 12% (measured dose of 3.2 0.8 Gy) corresponding to the dose falloff between the ICRU bladder point and the diode. The recent literature is scarce in coherent studies on in vivo dosimetry for HDR brachytherapy of the cervix. The published reports in the literature reveal a wide variety of methods and technology used; therefore, a systematic comparison to our study is difficult. The dosimetric equipment of choice was either diodes (7, 13e16) or TLDs (8, 10). Almost similar data have been reported by Clark et al. (7) and Waldh€ausl et al. (13). These results compared doses to ICRU 38 reference points to in vivo measurements
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Fig. 2. (a and b) Clinically relevant calculated and measured doses. Linear regression curves were calculated, and the slope, intercept, and correlation coefficient are specified. The reference curve shows equal measured and calculated doses. ICRU 5 International Commissioning on Radiation Units and Measurements.
with diodes. The previous studies showed that the rectal and bladder doses measured in vivo tended to be lower than the doses indicated by the ICRU rectum and bladder reference points. The present study confirms this (Table 2). Eich et al. (14) reported data of rectal in vivo dosimetry in HDR brachytherapy of the cervix using diodes and localization radiographs. The measured actual rectum dosage was analyzed retrospectively in 75 applications and prospectively in another 11 applications. Their results showed a deviation between measured and calculated values of 30% and 40% in retrospective and prospective data, respectively. Factors causing errors were incorrect assessment of the applicator’s positioning, nonorthogonal radiographs, incorrect calibration of the diode, and movement of probe in the time between radiograph and application. In another study done by Eich et al. (15), the in vivo measurements using rectum diodes were out by a factor of 1.5 below the doses determined for the ICRU rectum reference point (4.05 0.68 vs. 6.11 1.63 Gy). Contrary to our data that did not show any linear correlation between the measured and the calculated doses, Kapp et al. (8) showed a good correlation of rectal doses from orthogonal films, with in vivo readings using TLDs (with a correlation coefficient factor of 0.9556). In another study (10), TLDs were used for in vivo dosimetry in 71 cases, and the maximum deviation between measured
and calculated doses was 20% (with a correlation coefficient factor of 0.9694). The present study adds to the accumulating data confirming that the ICRU reference points are no longer suitable for reporting the highest doses delivered to critical pelvic organs or predicting the long-term brachytherapy complications. 3D data calculation from CT and/or MRI images demonstrated that these reference points were not located in the high-dose region of the corresponding critical organ. These high-dose regions are better evaluated using the doseevolume histogram (17). Quality assurance programs for HDR brachytherapy are still deficient with respect to reliable methods to assure the accurate and safe delivery of the prescribed dose to target volumes and to prevent overdoses of nearby critical organs. It is clear that in vivo diode dosimetry is beneficial in measuring the actual dose delivered to the organs at risk. Although we could not accurately place the diode in the high-dose region of the critical organs, its reading can help prevent large errors from occurring during dose delivery. Huh et al. (16) have used TLDs for rectal dose measurements and CT-assisted HDR brachytherapy in a total of 136 cervical cancer patients and correlated the rectal dose values with late rectal complications. The calculated rectal doses did not differ in patients with rectal bleeding and those without, but the measured rectal doses were
Table 2 Comparison of ratios of calculated (at bladder and rectum ICRU reference points) and measured (by in vivo diode dosimetry) doses to Point A dose, as presented in the literature Bladder
Rectum
Reference
Calculated dose to Point A dose (%)
Measured dose to Point A dose (%)
Calculated dose to Point A dose (%)
Measured dose to Point A dose (%)
Clark et al. (7) Waldh€ausl et al. (13) Present study
80 78 50.7 12.5
37 48 45.5 11.2
81 76 70.4 17.0
28 56 41.7 7.4
ICRU 5 International Commissioning on Radiation Units and Measurements.
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[2]
[3]
[4]
[5] Fig. 3. Axial CT image shows artifacts caused by diodes. ICRU 5 International Commissioning on Radiation Units and Measurements.
higher in affected patients. Therefore, they concluded that in vivo dosimetry using TLD was a good predictor of late rectal complications. Increasing artifacts in CT image was one of the drawbacks of using diodes for in vivo dosimetry (Fig. 3). If rectal wall discrimination was difficult, we referred to CT images taken in-between diodes to help rectal contouring (Fig. 1a). We estimated the uncertainty for diode measurements to be 5% in the afterloading calibration phantom, in agreement with the manufacturer’s technical specifications. We could not find significant differences of measurement performances among individual diodes, as checked in the afterloading calibration phantom. To optimize the calibration, we have performed weekly measurement series. Our results showed that weekly calibration does not increase accuracy and that monthly calibration seems to be sufficient for clinical use. It was reported that accumulated dose influences dose response and calibration factors (18). However, we did not observe such a dependency for the rather low accumulated doses (e.g., for the rectal probes: 32 applications with an average dose of 4 Gy per application results in about 128 Gy). Conclusion The in vivo dosimetry using diodes can be performed in addition to, and not instead of, 3D dose calculation. Brachytherapy in vivo dosimetry using diodes can be an important method for a quality assurance program. However, the clinical decisions based on 3D imageebased dose calculation remained the most available accurate and safe method for cervix brachytherapy application. References [1] Chassagne D, Dutreix A, Almond P, et al. ICRU report no. 38: Dose and volume specification for reporting intracavitary therapy in
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