Dosimetric verification of a high dose rate brachytherapy treatment planning system in homogeneous and heterogeneous media

Physica Medica (2013) 29, 171e177

Available online at www.sciencedirect.com

journal homepage: http://intl.elsevierhealth.com/journals/ejmp

ORIGINAL PAPER

Dosimetric verification of a high dose rate brachytherapy treatment planning system in homogeneous and heterogeneous media S.C. Uniyal a,*, S.D. Sharma b, U.C. Naithani c a Department of Radiology, Himalayan Institute of Medical Sciences, HIHT University, C-I-5, HIHT Campus, Swami Ram Nagar, P.O. Doiwala, Jolly Grant, Dehradun, Uttarakhand 248140, India b Radiological Physics & Advisory Division, Bhabha Atomic Research Centre, CT & CRS Building, Anushaktinagar, Mumbai 400094, India c Department of Physics, HNB Garhwal Central University, Campus Pauri, Pauri (Garhwal), Uttarakhand 246001, India

Received 19 August 2011; received in revised form 2 December 2011; accepted 17 January 2012 Available online 18 February 2012

KEYWORDS HDR; TPS; Film dosimetry; Tissue heterogeneity

Abstract Objectives: To verify the dosimetric accuracy of treatment plans in high dose rate (HDR) brachytherapy by using Gafchromic EBT2 film and to demonstrate the adequacy of dose calculations of a commercial treatment planning system (TPS) in a heterogeneous medium. Methods: Absorbed doses at chosen points in anatomically different tissue equivalent phantoms were measured using Gafchromic EBT2 film. In one case, tandem ovoid brachytherapy was performed in a homogeneous cervix phantom, whereas in the other, organ heterogeneities were introduced in a phantom to replicate the upper thorax for esophageal brachytherapy treatment. A commercially available TPS was used to perform treatment planning in each case and the EBT2 films were irradiated with the HDR Ir-192 brachytherapy source. Results: Film measurements in the cervix phantom were found to agree with the TPS calculated values within 3% in the clinically relevant volume. In the thorax phantom, the presence of surrounding heterogeneities was not seen to affect the dose distribution in the volume being treated, whereas, a little dose perturbation was observed at the lung surface. Doses to the spinal cord and to the sternum bone were overestimated and underestimated by 14.6% and 16.5% respectively by the TPS relative to the film measurements. At the trachea wall facing the esophagus, a dose reduction of 10% was noticed in the measurements. Conclusions: The dose calculation accuracy of the TPS was confirmed in homogeneous medium, whereas, it was proved inadequate to produce correct dosimetric results in conditions of tissue heterogeneity. ª 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

* Corresponding author. Tel.: þ91 9412916008. E-mail address: [email protected] (S.C. Uniyal). 1120-1797/$ - see front matter ª 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejmp.2012.01.004

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Introduction Brachytherapy is aimed to treat malignancies by placing radionuclides near the tumor volume in order to maximize the dose delivered to the tumor and minimize the dose delivered to the surrounding healthy tissues. High dose rate (HDR) brachytherapy offers the advantage of highly conformal and precise dose delivery to the malignant tissues as it can directly irradiate the tumor and minimize damage to normal surrounding tissues [1]. Prior to the patient treatment, precise dose calculation is of vital importance because the administered dose per fraction is very high and inaccuracies in dose distribution may lead to critical damage to normal tissues and inappropriate target dosage. The modern HDR brachytherapy treatment planning systems (TPS) rely heavily on dose optimization software which can tailor doses to specific clinical needs without knowing the composition of the tissue through which radiation transport is taking place in actual treatment conditions. In the process of optimization, the dwell times for a number of dwell positions are computed to deliver a prescribed dose to the target or dose constraint points and the corresponding three dimensional dose distributions are presented. With the advancement in imaging and communication technology, the dependency on TPS calculated dose distribution has increased. Due to the complex and variable nature of the treatment planning process, the dosimetric verification of HDR treatment planning system (TPS) is necessary rather than simply relying on the computed results. The verification of the TPS calculated doses by experimental and Monte Carlo simulation methods have been reported in the literature [2e5]. Also, the current TPS dosimetry algorithms are based on the superposition of single source dose distributions in homogeneous water medium, so they do not fully exploit the information available from patient images. Many investigators [6e12] have recognized that significant dose calculation errors are introduced due to the effect of inherent patient heterogeneities. This work presents the dosimetric verifications of treatment plans in HDR brachytherapy by using Gafchromic EBT2 films and also demonstrates the TPS inability to accurately account for material heterogeneities. For this purpose, two anatomically different cases were considered, in which the first case of tandem ovoid brachytherapy of carcinoma cervix assumed a homogeneous tissue equivalent medium for dose measurement while the second case of esophageal brachytherapy included the presence of heterogeneous structures around the source.

Materials and methods HDR treatment unit and the TPS A microSelectron HDR v2 remote afterloading brachytherapy unit (Nucletron International B. V., The Netherlands) along with a computed tomography (CT) based brachytherapy TPS, Oncentra MasterPlan version 3.3 was used for HDR treatments. The TPS uses the AAPM Task Group-43 (TG43) formalism [13,14] for dose calculation and includes

S.C. Uniyal et al. various methods of optimization of the treatment dose distribution such as geometrical optimization, graphical optimization, manual adjustment of dwell weights/times and IPSA (inverse planning by simulated annealing) [15]. The source strength was verified using a well type ionization chamber (HDR 1000 Plus, Standard Imaging, US) which was calibrated at the University of Wisconsin Accredited Dosimetry Calibration Laboratory. The local measured and the vendor quoted source strengths were found in excellent agreement within 1%.

Radiochromic film dosimetry system The Gafchromic EBT2 film (ISP Technologies, Lot Number F020609) used in this study is an improved uniformity, high resolution and high sensitivity radiochromic film which can be used in the dose range of 0.01e40 Gy. Further details about the composition and dimensional aspects of the film are available elsewhere [16]. The EBT2 film is a favorable 2D dosimeter due to its radiological tissue equivalency, real time development, ease of use, and low cost. The film is a practical dosimeter for phantom studies because it can be cut in any shape and size for placing in a specially designed or custom made dosimetry phantom. The read-out of the films irradiated during the calibration and experiment was carried out using a flatbed scanner (Epson Expression 10000 XL) and the film images were analyzed using Image J software. The exposed film samples were scanned 48 h after irradiation following a constant scan set-up to ensure optimum growth of optical density and consistency in the evaluation purpose [17,18]. As the EBT2 film response is nearly energy independent in the range of photon energy from 6 MV down to 22 keV [19,20], the dose response calibration of the film was carried out in a 6 MV photon beam produced by a medical linear accelerator (Siemens Primus M) in the dose range of 25e700 cGy. For this purpose, film samples of size 2.0  2.0 cm2 were irradiated in a 10  10 cm2 field of the accelerator by positioning them at 10 cm depth in a PMMA phantom of size 30  30  30 cm3. A set of un-irradiated film samples (background film samples) was also stored along with the irradiated film samples to account for the effect of variation in environmental conditions on the films. The OD of the background film samples was subtracted from the OD of the irradiated film to determine the net OD. Each film sample was scanned in landscape orientation and in red color channel mode of the Epson scanner. The optical density (OD) of each pixel in the central 1.0  1.0 cm2 region of the film was measured and the mean optical density (MOD) was then calculated for each calibration film. A calibration curve between MOD and corresponding dose for the EBT2 film was plotted and a fit equation was obtained for subsequent determination of the absorbed dose from the measured OD.

Experimental set-up To facilitate the comparison of TPS calculated and experimentally measured dose distributions, two anatomic phantoms were designed and fabricated locally by using a tissue equivalent alloy of wax and paraffin mixture. The

Dosimetric verification of an HDR brachytherapy TPS two HDR brachytherapy treatments considered were: the carcinoma cervix and the carcinoma esophagus. The reason for choosing these two different cases was that they were anatomically different regarding their organ densities and treatment techniques used. The cervix phantom was composed of different parts which were connected to create a homogeneous cuboid of dimensions 25  25  20 cm3. The central part was a cuboid (3.0  3.0  9.0 cm3) molded with a gynecological brachytherapy applicator set (Fletcher suit, Nucletron BV, The Netherlands) into it for source insertion. The tip of the tandem applicator was extended up to the front 3.0  3.0 cm2 plane of the central cuboid. Remaining parts of the phantom were also cuboids in exact contact with the central cuboid to provide a scattering medium. In the experimental arrangement, one sample of EBT2 film was

173 sandwiched between each of the five surfaces [as depicted in Fig. 1 (A) by T (top), B (bottom), L (left), R (right), F (front)] of the central cuboid and the adjacent cuboid. A total of 10 dosimetric points at regular distances of 0.5 cm were considered from the tip of the tandem along the longitudinal bisectors of the four films of size 3.0  9.0 cm2, while in case of front square film 4 dosimetric points at a regular gap of 0.5 cm along its bisector were chosen for dose measurements. Care was exercised to make proper contact between each pair of surfaces in order to avoid any air gap between them. In the second case, a phantom equivalent to upper thorax was constructed to simulate HDR brachytherapy of carcinoma esophagus. The esophagus, though a hollow structure, was observed as a collapsed organ in CT images and therefore considered as homogeneous tissue equivalent

Figure 1 Schematic diagrams of the experimental arrangements simulating the HDR brachytherapy treatments of (A) carcinoma cervix and (B) carcinoma esophagus.

174 in the phantom with a groove to introduce a plastic applicator for subsequent source insertion. The diameter esophagus was considered to be 2 cm in the present work and provision was made in the phantom to put a parallel film at 1 cm distance from the longitudinal axis of the esophageal applicator to measure dose at the esophageal wall. The locations and dimensions of the heterogeneities surrounding the esophagus such as the spinal cord, the sternum bone, the trachea and the lungs were derived by the average value of the corresponding measurements on the CT images of ten randomly selected patients of carcinoma esophagus. The trachea was considered as an air pipe of diameter 2 cm, whereas, equivalent thicknesses of aluminum and cork were used as substitutes for bones and lungs, respectively [21,22]. Density of the cork used for this purpose was measured to be 0.32 g/cc while the density of healthy lung may be within 0.2e0.5 g/cc. All parts were connected to compose a cuboid of dimensions 25  25  20 cm3 [Fig. 1 (B)]. The longitudinal alignment of source dwell positions in the esophageal applicator was considered along the z-axis and dosimetric points at the following organs were chosen in the transverse plane passing through the central dwell position: wall of the esophagus (E), surface of the lung (L), wall of the trachea [two points T1 (facing the esophagus) and T2 (facing the sternum)], the sternum bone (S) and the spinal cord (C).

Phantom and TPS dosimetry In order to illustrate the dosimetric accuracy of the EBT2 film when irradiated by an Ir-192 source, doses in a phantom of wax-paraffin were measured at various distances along the transverse axis of the source. The film samples were placed into the phantom parallel to the longitudinal axis of the source with 1 cm distance between any two consecutive films. The measurements were done over a range of 1e5 cm distance from the Ir-192 source and relative depth dose (RDD) at each distance was then calculated from the ratio of the dose rate at a given radial distance (r) to the dose rate at the reference distance (r0 Z 1 cm). The depth dose responses of the film were then compared to the corresponding TPS calculated doses. For treatment planning, CT scans were acquired from the cervix and the thorax phantoms with the required applicators in place into the phantoms. During CT scanning, external fiducial marks were used to avoid any mismatch between the planned and the treated phantom set-ups. For the cervix phantom, CT scans with 3.0 mm slices were acquired at all the regions except the region near applicator tips (tandem and colpostats) where 1.5 mm slices were acquired to improve image resolution. All CT slices were transferred into the treatment planning computer. Consecutive dwell positions at 2.5 mm spaces were determined inside the uterine tandem and colpostats, identified on CT images of the phantom. The dose values at the previously chosen dosimetric points were calculated by prescribing a dose of 5 Gy to point A. For experimental determination of the dose distribution around the applicator in the cervix phantom, four film samples of size 3.0  9.0 cm2 were placed on four long sides of the central cuboid and one film sample of size 3.0  3.0 cm2 at its front

S.C. Uniyal et al. plane. The irradiation was performed by the HDR source as per the TPS generated treatment plan. The CT images of the thorax phantom with a single plastic esophageal applicator were obtained and transferred to the TPS. The treatment plan was executed with a dose of 3 Gy prescribed at the surface of the esophagus and doses were calculated at the previously chosen points in the phantom. To find out maximum dose received by the lung, rectangular film samples were rolled onto the cylindrically shaped lungs facing towards the source applicator. A rectangular film strip was rolled in shape of a hollow cylinder to get exactly fitted inside the pipe simulating the trachea. Films were placed around the esophageal wall, at the sternum bone and the spinal cord into the phantom. Film samples in required positions into the phantom were irradiated by the HDR source as per the previously completed treatment plans. Each irradiated film was scanned in the way as described in the calibration method and their images were acquired. The dosimetric points were located on the images and pixel values of each dosimetric point and of four pixels in its closest neighborhood (along and across) were obtained. Corresponding to each pixel value, the optical density (OD) was calculated by using the pixel values of interest and the mean background pixel value. An average of optical densities at and the four points around each of the dosimetric point was calculated and was further converted into absorbed dose by using the previously obtained fit equation. The final value of dose was taken from an average of five measurements at each dosimetric point.

Results and discussion Film calibration and RDD The calibration curve for EBT2 film plotted between MOD and corresponding dose is shown in Fig. 2. Due to its nonlinearity a polynomial fit equation (Equation (1)) of second order was obtained for determination of the dose from the measured optical density in the subsequent experiment.

Figure 2 Dose response calibration curve of Gafchromic EBT2 film in 6 MV x-rays.

Dosimetric verification of an HDR brachytherapy TPS D ðcGyÞZ2753 ðMODÞ2 þ451:4 ðMODÞ

175 ð1Þ

Where, D is absorbed dose in cGy and MOD is the mean optical density of the film. Various factors contributed towards uncertainty in dose response calibration of the film. The overall uncertainty in film calibration was obtained by combining type A and type B uncertainties of the concerned parameters. This was contributed by uncertainties in the dose rate calibration of the 6 MV x-rays (0.8%), film non-uniformity (1.5%) and the scanner reproducibility (0.5%). The combined standard uncertainty in the dose response calibration of the film is estimated to be 1.8% (k Z 1) which was obtained by summing the individual components in quadrature. Accordingly, the expanded standard uncertainty in the film calibration is estimated to be 3.6% (coverage factor, k Z 2). The values of relative depth dose measured with the EBT2 film and those calculated using brachytherapy TPS were found to be in good agreement with each other at distances up to 2 cm from the source, which are of greater clinical concern with regards to dose to the structures surrounding the source in the present work (Table 1). At 3 cm, the RDD measured with the EBT2 film was around 5.3% less than the TPS calculated RDD. The deviation further noticed to be increasing with depth. At higher depths, the observed higher discrepancy could be due to much reduced dose values at greater depths and limited response of the film against these doses. The expanded standard uncertainty in determining dose to a point in the PMMA phantom by EBT2 film was estimated to be 3.8% (coverage factor, k Z 2). This includes uncertainty in dose calibration of the film (3.6% at k Z 2), uncertainty in depth scaling in PMMA phantom (0.5% at k Z 2) and uncertainty in OD measurement (1.0% at k Z 2) including variation in OD with time after irradiation. The expanded standard uncertainty in TPS dose calculation at a point is 6.0% (coverage factor, k Z 2). This includes the uncertainty in air kerma strength measurement of HDR 192Ir source (1.2% at k Z 1), uncertainty in dose estimated using Monte Carlo calculated dosimetry data of the source (1.3% at k Z 1), uncertainty in interpolation of dosimetry data by the TPS (2.4% at k Z 1).

Measurement in cervix phantom The EBT2 film samples precisely accommodated in the required positions in the cervix phantom were irradiated and dose values at the specified dosimetric points on each film sample were calculated. As described earlier, no inhomogeneity was considered in the cervix equivalent phantom, so the experimental results could directly be correlated with the corresponding TPS calculated values. Figure 3 presents the percentage difference between the TPS calculated results and the film measured values of absorbed dose at the given dosimetric points. Of the five film samples used in the phantom, L & R film samples were used to check the positional symmetry of the applicator set into the phantom. The doses on corresponding points on L & R film samples were found in agreement with one another thereby indicating the central position of the applicator set and so, the dose results of only one film sample (R) are included in Fig. 3. The film measured doses were found to deviate with the TPS calculated doses by up to 3% for points in the vicinity of source dwell positions [points from 1 to 5] as anticipated according to the RDD measurements. On moving away, the deviation was seen to increase up to a maximum of 8%, which was essentially beyond the clinically relevant pear shaped dose distribution obtained by the TPS. The experimental results of this work were found to exhibit the trend of values reported by Lipinska et al. [5] in a similar but methodologically different work in which small thermoluminescent dosimeters were used to quantify point doses around the brachytherapy applicator set. Some discrepancies, however, existed due to different parameters used in the works such as dosimetric methods employed, dose prescription points, number of dwell positions.

Measurement in thorax phantom In Fig. 4 the percentage differences of the film measured dose values from the corresponding TPS calculated results

Table 1 Experimentally measured and TPS calculated values of relative depth dose (RDD) for the HDR Ir-192 brachytherapy source. The RDD was measured in a paraffin wax phantom while TPS calculation was done in water. Also shown in the table is the ratio of EBT film measured and TPS calculated RDD values along with uncertainty associated with the EBT2 film measurement. Radial RDD measured RDD Ratio of EBT2 distance using EBT2 film calculated measured and TPS r (cm) using TPS calculated RDD and the associated uncertainty of EBT2 1.0 2.0 3.0 4.0 5.0

1.000 0.242 0.108 0.055 0.033

1.000 0.252 0.114 0.061 0.038

1.00 0.96 0.95 0.90 0.87

    

0.037 0.035 0.035 0.033 0.032

Figure 3 Percentage difference between the TPS calculated results and the film measured values of absorbed dose at dosimetric points on top (T), bottom (B), right (R), and front (F) surfaces of the central cuboid in the cervix phantom.

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Figure 4 Percentage differences between the TPS calculated and the film measured doses for the lung (L), the esophagus (E), trachea point facing the esophagus (T1), trachea point facing the sternum (T2), the spinal cord (C), and the sternum bone (S).

S.C. Uniyal et al. doses discriminate significantly at the spinal cord, the sternum and the trachea. However, the doses remained at the spinal cord and the sternum bone were observed to be below 10% and 5% of the prescribed dose respectively, which would essentially be within the tolerance dose limits of these organs. Hence, dose variations found at these organs were not of major concern. Being closest to the esophagus, the front wall of the trachea receives much high dose as per the TPS calculations. The presence of air, which was neglected by the TPS, produces a more favorable dose distribution with reduced dose to point T1 of the front wall. The experimental values found in this work exist close to the theoretical results reported by Anagnostopoulos et al. [6], in which the effect of organ inhomogeneities on dose distribution around the esophagus was quantified by using the Monte Carlo and analytic calculations in a mathematical phantom equivalent to the upper thorax.

Conclusions are presented in the form of columns projected away from the zero level. It shows that the film measured dose to wall of the esophagus (which is the organ being treated in this case) is in agreement with the planned dose and is not affected by the heterogeneities present around it. For other structures, however, considerable differences between the TPS calculated and film measured results were noticed. Major dose discrepancies were observed at trachea (points T1 and T2), spinal cord (point C) and sternum bone (points S). At point T1 on the trachea wall facing the esophagus, the film measured dose value is around 10% less than the TPS calculated value, while at point T2 on the opposite trachea wall, the measured dose is higher than the calculated one by about 16%. The dose discrepancy between the calculated and measured values is attributed to the presence of air in the trachea, which neither scatters nor attenuates photons and which is not accounted for by the TPS. In case of point T1, due to lack of back scatter, the TPS overestimates dose, while at T2, the effect is reversed due to lack of attenuation of photons in the trachea. The effect of inhomogeneity caused due to organ air has been demonstrated in some previous studies [23,24]. At point S on the sternum bone, the TPS calculated dose is less than the film measured value by 16.5%. This deviation is due to the reduced attenuation posed by trachea air, which lies between the esophagus and the sternum bone and which is not assumed by the TPS. Though, the attenuation is more in the sternum bone with respect to water, the consequent dose reduction is compensated by the dose increase due to scatter dose built up within the distance between the esophagus and the sternum bone. At point C of the spinal cord, the dose is overestimated by the TPS relative to the film reading by 14.6%. This is an obvious outcome due to the fact that the increased attenuation within the bone material is not accounted for by the TPS. In case of lungs, the dose to each lung surface measured by the film is observed to be slightly different (around 4.5% less) from the TPS results. The reason for this difference could be the change in back scatter from lungs due to the varied composition of lungs relative to water. The TPS calculated and film measured

The doses were experimentally measured by using Gafchromic EBT2 film in homogeneous and heterogeneous organ geometries. In case of homogeneous cervix phantom, the film measured results were in good agreement with the TPS calculations, thereby verifying the correct performance of the treatment planning system. For the second case of thorax phantom for esophageal brachytherapy, the observed mismatch between calculated and measured doses shows the inability of the TPS to produce correct results due to the inherent heterogeneities present in the anatomy. However, the measured dose in the treated region (esophageal wall) was found to be in excellent agreement with the calculated dose, which reassured the correct TPS calculations. On the basis of the calculated and measured dose distributions in the twin cases presented here, it is inferred that while the calculation algorithm used by the planning system gives reliable results in homogeneous patient medium, it may not detect the dose perturbations caused by the presence of patient heterogeneities. Despite the observed dose discrepancies in case of esophageal brachytherapy treatment, it can be noticed from the results that actual doses to the organs at risk essentially remain within their tolerance limits for clinical dose prescriptions. However, in general, the wrong estimation of doses by the TPS for patient heterogeneities may result in erroneous treatment associated with high doses to normal tissues and consequent patient complications.

Acknowledgments The authors would like to express sincere gratitude to Dr. Samuel D., Head, Department of Radiology and Dr. Sunil Saini, Director, Cancer Research Institute, HIHT University, Jolly Grant, Dehradun for their valuable support in this work. Special thanks and appreciation to Mr. Anoop Srivastava and Mr. Ravi Kant, Department of Medical Physics, Cancer Research Institute, HIHT University, Jolly Grant, Dehradun for their help and assistance in this work.

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