Measurement of Dose to Critical Structures Surrounding the Prostate from Intensity-Modulated Radiation Therapy (IMRT) and Three Dimensional Conformal Radiation Therapy (3D-CRT); A Comparative Study Erik Frija M.A., Charles E. Poole B.S., R.T. (T), Chris Spicer R.T. (R)(T), C.M.D. Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX
Measurement of Dose to Critical Structures Surrounding the Prostate from Intensity-Modulated Radiation Therapy (IMRT) and Three Dimensional Conformal Radiation Therapy (3D-CRT); A Comparative Study - 1 -
ABSTRACT The purpose of this study is to confirm the improved dose distribution characteristics using intensity-modulated radiotherapy (IMRT) as opposed to conformal radiation therapy (3D-CRT) techniques in the treatment of prostate cancer. Additionally, dose to structures distant from the treatment area will be measured to discuss the possible long term effects of implementing the IMRT treatment modality. An axial computerized tomography scan will be performed on a Rando TM phantom and the prostate organ will be contoured to define a target volume. In addition, the nearby critical structures of the rectum, seminal vesicles, bladder, and both femoral heads will also be contoured throughout the area of interest. Treatment planning will be performed utilizing inverse-planning (IMRT) and forward planning (3D-CRT) to the target volume for 6 MV photon energy. Dose measurements to the target and critical structures and secondary scatter dose measurements to specified organs for this photon energy will be obtained from powder thermoluminescent dosimeters (TLD). These dosimeters will be placed throughout the irradiated volume of interest and at specified anatomical organ locations. Comparisons of the TLD readings for the target volume and critical structures will be made for 6 MV photon energy. This measured data will also demonstrate subtleties in dose distributions between the two treatment planning techniques. This study will evaluate and conclude not only a measured dose to target and critical structures but, how scattered dose to other organs may lead to secondary cancers. Keywords: IMRT, inverse-planning, conformal therapy, scatter dose - 2 -
INTRODUCTION For many types of cancer, the effectiveness of conventional, conformal radiation therapy (3D-CRT) is limited by the unsatisfactory targeting of tumors and by the insufficient doses of radiation delivered to these targets. Because the delivery of higher doses of radiation has clearly been shown to improve the outcome in patients with prostate cancer 1, these dose limitations are especially concerning. In attempting to compensate for these limitations, dosimetrists using 3D-CRT techniques will increase coverage and dose to the target while exposing a greater volume of healthy tissue to high doses of radiation. Because of these doses, critical structures such as the femoral heads, bladder, and rectum will show a greater number of acute treatment-induced side effects. 2 Therefore, dose escalation using 3D-CRT techniques may not be possible due to the high toxicity to normal tissues. Clinical outcome may be compromised in favor of limiting the severity of certain side effects. A solution to the paradox of delivering high doses of radiation to a target while limiting doses to adjacent critical structures has tentatively been found through the implementation of intensity-modulated radiation therapy (IMRT). With IMRT, an optimal dose of radiation can be delivered to the tumor while dose to surrounding healthy tissue is minimized. IMRT uses inverse-planning algorithms and fluence profiles based on pencil beam dose calculations to generate intensity-modulated beam profiles constrained by given treatment objectives. These profiles are used to generate dose intensity patterns that will best conform to the tumor shape. Modulation of the intensity of the radiation - 3 -
beams serves to focus radiation only on discrete sections of the target volume. Several combinations of intensity-modulated fields are examined from different beam angles in an attempt to maximize the dose to the tumor while minimizing the dose to adjacent critical structures. Because the ratio of normal tissue dose to tumor dose can be decreased using IMRT, higher doses of radiation can be delivered to tumors with fewer early side effects when compared to 3D-CRT. 3 Unfortunately, the apparent benefits of IMRT may come at a price. There are concerns that the precise conformal nature of the radiation fields will leave parts of the tumor untreated if the volume changes during the normal course of therapy. 4 In addition, since the monitor units delivered per fraction using IMRT may be 5-fold that of 3D-CRT, concerns surrounding greater whole-body dose, greater head leakage, and longer beam-on times resulting in a higher risk of second cancers are a growing concern. 5 The purpose of this study is to confirm the improved dose distribution characteristics using IMRT as opposed to 3D-CRT techniques in the treatment of prostate cancer. Additionally, dose to structures distant from the treatment area will be measured to discuss the possible long-term effects of implementing the IMRT treatment modality. METHODS Overview of research A computerized tomography (CT) scan was performed on the pelvis section of a Rando TM phantom. Using the CT data, volumes corresponding to the bladder, - 4 -
prostate, seminal vesicles, rectum, and femoral heads were contoured. Separate 3D-CRT and IMRT treatment plans were generated based on these contours. Identical beam arrangements and identical open field sizes were used for a fair evaluation of the disparate plans. Using thermoluminescent dosimeter (TLD) packs, actual dose from areas within the treatment field, as well as, secondary dose outside of the irradiated area was measured at specified anatomical locations during the execution of both external beam treatment plans. The results of these measurements were interpreted and compared to published data to evaluate the dose distribution variations between the 3D-CRT and IMRT techniques. The amount of scatter dose to areas outside of the irradiated field was also quantified and the effects of dose to these areas on the development of secondary cancers were evaluated. CT Simulation To obtain CT images for delineating volumes and for treatment planning, a Rando TM phantom was placed head first in the supine position onto a CT scanner (Philips Model PQ 5000). No immobilization devices were used in conjunction with setting up the phantom for simulation. Axial CT slices were taken throughout the lower pelvis. Using CT simulation software (AcQSim TM ), an isocenter was determined from the CT data. The isocenter coordinates were recorded in the lateral, longitudinal, and vertical planes and radio-opaque markers were placed on the phantom s pelvis to correspond with these coordinates. The phantom was scanned, producing 3 mm axial slices of the pelvis and abdomen - 5 -
with isocenter markers evident for verification and to help ensure setup reproducibility. Treatment Planning The treatment planning for the 3D-CRT technique and the IMRT technique utilized the Pinnacle 3 (ADAC/Philips Medical Systems) and the P 3 IMRT (ADAC/Philips Medical Systems) treatment planning systems respectively. Software version 6.2b was utilized in both instances. Since the Rando TM phantom contains no discernable organs other than bones, the position of the prostate, seminal vesicles, urinary bladder, and rectum were estimated using the bony landmarks in the Rando TM phantom s pelvis as a guideline. These contours were compared to anatomy on actual CT images and found to be appropriately sized and in good position anatomically. The target volume was identified, encompassing the prostate and seminal vesicles. This volume was expanded 0.7 cm in all directions to establish a planning treatment volume (PTV) for organ location differences and treatment setup uncertainty. In addition, a 0.5 cm expansion from the PTV to the block edge was utilized to allow ample coverage of the PTV without the volume s periphery losing dose in the penumbra region of the radiation beam. It is important to note, these expansions incorporated parts of the bladder and rectum into the target volume; therefore, excessively tight dose constraints on these critical structures were unable to be realized. - 6 -
A six-field beam configuration was used for both the 3D-CRT and IMRT plans. Beam arrangements were kept identical between the plans in order to minimize bias between the plans. For similar reasons, open field sizes were also identical for each plan s corresponding beam. The angles of the beams were chosen to be 235, 265, 325, 30, 100, and 125 degrees with 0 o representing the vertical gantry position. A final isocenter was placed in the center of the PTV and all beams were assigned to this isocenter. The dose prescription for the 3D- CRT and IMRT techniques were to deliver 7400 cgy in 37 fractions, at 200 cgy per fraction, proportional to the final isocenter point dose. 6 MV treatment energy was selected for both treatment techniques. 3D-CRT Plan Optimization The 3D-CRT plan was optimized by adjusting the percentage weighting of each beam to create a uniform dose distribution over the entire PTV volume. The prescription was adjusted to deliver 200 cgy to the 95% line to ensure adequate coverage. Dose to the bladder, rectum, and femoral heads were taken into consideration during optimization and efforts were taken to minimize dose to these structures. Since the expansion of the prostate and seminal vesicles to create the PTV also incorporated bladder and rectum, a certain percentage of each structure must receive 100% of the prescribed dose. Limitations of the Rando TM phantom and the estimated organ placement made it impossible to maintain clinical dose constraints for the critical structures. However, for the purpose of this comparative research, dose to the critical structures was minimized to as high - 7 -
a degree as possible while still maintaining coverage of 95% of the volume of the PTV with the prescribed dose. IMRT Plan Optimization In order to not introduce bias, inverse IMRT planning used identical beam orientations and open field sizes as the 3D-CRT plan. Dose objectives for the critical structures and treatment volume were chosen to preferentially deliver a lower dose to the rectum, while maintaining similar dose characteristics of the 3D-CRT plan for the bladder and femoral heads. Rectal dose objectives were targeted at: no more than 20% of the volume is to receive over 4500 cgy (80% of the volume must remain under 45 Gy) and no volume of the rectum will receive over 7500 cgy. Femoral head dose objectives were targeted at: no more than 25% of the volume is to receive over 5000 cgy (75% of the volume must remain under 50 Gy) and no volume of the femoral heads will receive over 6500 cgy. Urinary bladder dose objectives were targeted at: no more than 35% of the volume is to receive over 3500 cgy (65% of the volume must remain under 35 Gy) and no volume of the bladder will receive over 7500 cgy. The objective for the PTV was for a minimum 95% coverage with 7400 cgy and no volume of the PTV is to receive over 8200 cgy (representing a 10% hot-spot). The additional objective of a uniform dose of 7400 cgy over 85% of the PTV volume was also utilized. The treatment computer was allowed to develop an optimal solution to the dose objectives. This solution was computed using the same dose algorithm as - 8 -
the 3D-CRT plan. Furthermore, 200 cgy was prescribed to the 95% line for each fraction to be consistent with the 3D-CRT plan. Plan Comparison Figure 1 illustrates the isodose distribution achieved by each treatment planning technique. The white isodose curves represent 7400 cgy or the 100% isodose line on each technique. The IMRT plan shows marked improvement in the dose distribution surrounding the rectum and bladder. As expected, isodose curves for the IMRT plan show better conformality around the PTV and better avoidance of critical structures. Comparison of the dose volume histograms (DVH) for each technique demonstrates a marked decrease in dose delivered to the rectal volume (Figure 2). TLD Preparation and Placement TLD tubes and flat-packs were prepared for the measurement of dose during treatment. Lithium fluoride powder was loaded into one-centimeter by onecentimeter flat plastic packages. The flat packages were designed to measure the scatter dose from the treatment field to distant anatomical locations on the surface of the phantom. In addition to flat packages, dual loaded TLD tubes were prepared for measurement of internal dose. Lithium fluoride was loaded on either side of a hollow plastic tube with a 1 cm plug in the center. Plastic caps were placed on either end to seal the powder in the tube. The total length of each tube - 9 -
(with caps) was approximately 2.5 cm, with the center of each packing of powder around 1.5 cm apart. Flat TLD packs were placed on the surface of the Rando TM phantom to represent specific anatomical locations. Flat-packs were placed on the eyes of the phantom (to represent dose to the lens of the eye), on the neck (to represent dose to the thyroid), and on anatomical locations corresponding to the scrotum and anus. Several TLD tubes were placed inside the Rando TM phantom to measure dose to critical structures within the irradiated volume. Since each slice of the Rando TM phantom is approximately 2.5 cm thick, CT slices corresponding to the midpoint of specific Rando TM slices were chosen to represent organ location. As illustrated in Figure 3, measurement points were chosen on the left and right anterior surface of the bladder, left and right posterior surface of the bladder, as well as, the left and right anterior surface of the rectum, and left and right posterior surface of the rectum (points are illustrated as white circles and correspond to the midpoint of a TLD tube). Additional measurement points were placed in the phantom representing the most proximal location of the left and right kidneys to the treatment area (not illustrated). Treatment The treatments were delivered utilizing a Varian 2100 linear accelerator equipped with a 120 multi-leaf collimation (MLC) system capable of delivering both 3D- CRT and IMRT treatments. The Rando TM phantom was positioned so that the - 10 -
radio-opaque markers placed on the phantom s surface were aligned with the treatment room s optical laser localization system, assuring an accurate reproduction of the phantom s orientation during simulation. An isocenter shift was made to orient the beams to the final isocenter. Following the 3D-CRT plan, one fraction of therapy was delivered to the Rando TM phantom, representing 200 cgy to the treatment volume. TLD tubes and packs were collected from the phantom and were catalogued according to their anatomical location. Special care was taken to replace the irradiated TLDs with un-irradiated TLD packs and tubes, ensuring an accurate comparison of dose delivered between the two plans. The treatment process and TLD collection was repeated for the IMRT study. Several TLD standards were irradiated as a basis for comparison. For each standard, a TLD tube was placed inside a water phantom at a depth of d max, and exactly 200 cgy was delivered to each standard. TLD reading Approximately 48 hours after irradiation, the TLD tubes and packs were read. TLD powder was weighed and, using a TLD reader with a pre-anneal feature, values of Coulombs were obtained. These values were converted to cgy through comparison to the TLD standards, which were irradiated at the time of treatment. Since each of the TLD tubes was dual loaded with powder, each side of the tube was read separately. The values recorded for each TLD tube for this research reflect an average of the readings of the two sides of the tube. This average corresponds to the center of the TLD tube. Care was taken to ensure the center of - 11 -
each TLD tube matched the location of the measurement points representing organ location, chosen from CT scans. Flat-pack TLDs were read and values were recorded without any data manipulation. RESULTS The TLD packs, representing points around the bladder and rectum, were read and interpreted. As expected, IMRT treatment resulted in lower overall doses delivered to critical structures. As illustrated in Table 1, the anterior side of the bladder received no benefit from IMRT treatment, with a statistically negligible dose difference between the two plans. However, the posterior side of the bladder (nearest to the PTV) received approximately 20% less dose from the IMRT treatment. This represents a significant decrease in dose to the posterior side of the bladder over the entire treatment course. An average decrease of 23 cgy per fraction over 37 fractions would result in a total decrease of 850 cgy to the posterior side of the bladder for the completed treatment course. Results were equally as impressive when reviewing doses to the anterior side of the rectum. Illustrated in Table 1, while the posterior side of the rectum received relatively the same dose between the two plans, the anterior side (closest to the PTV) showed marked improvement in dose for the IMRT plan. The anterior of the rectum received approximately 43% less dose from the IMRT treatment, with an average decrease of 28 cgy per fraction. Over the course of therapy this IMRT treatment would result in a dose decrease of approximately 1040 cgy delivered to the anterior side of the rectum. - 12 -
The results of this research show IMRT can allow for an increased conformality around the target volume and decreased dose to surrounding critical structures, but at what cost? As illustrated in Table 2, dose to all distant structures measured showed marked increases when the IMRT treatment modality was implemented. These distant structures were chosen because of the extreme sensitivity of these organs to any dose of radiation. Of particular concern are the large increases in dose to the scrotum and anus, which were closest to the treatment area. While not clinically significant, this dose increase illustrates the potential for scatter dose to effect structures outside of the area of interest. DISCUSSION Quality of life is an important consideration in the treatment of prostate cancer. One solution to improve the quality of life is to lessen the severity of acute side effects associated with radiation therapy. Conformal therapy is limited with respect to field shaping near critical structures and often places nearby organs at great risk. With IMRT, it is now possible to greatly manipulate both the fluence and shape of the radiation beams. Targets can be divided into hundreds of sections, and discrete doses of radiation can be delivered to specific sections of the target. This results in enhanced targeting of volumes while protecting nearby critical structures. Moreover, IMRT has been found clinically to decrease treatment-related morbidity while enhancing tumor control. 6 However, IMRT s ability to decrease treatment-related side effects if often studied only from the acute vantage point. As illustrated in Table 3, the monitor - 13 -
units necessary to deliver the same 200 cgy fraction to the target volume using the IMRT technique is nearly five times that of 3D-CRT. With increased beamon times comes greater leakage and increased whole body doses; which are not accounted for in many normal tissue complication probability (NTCP) models. For these models to be useful for IMRT treatments, they must not only examine critical structures in the target area but also account for the risks of developing secondary cancer based on non-target structures as well. Examination of these factors outwardly predicts a significant increase in radiation-induced neoplasms resulting from the use of IMRT planning techniques. The move from 3D-CRT to IMRT involves implementation of plans with more beams, delivering higher numbers of monitor units. DVHs summarizing these plans show improved critical structure avoidance, but there is a price to pay for these improvements. The DVHs also show a larger volume of normal tissue exposed to low doses of radiation. Moreover, the number of monitor units is increased by a factor of 4 to 5, increasing the total body exposure. Both factors will tend to increase the risk of radiation-induced second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. 7 When planning for patient treatment, it is every dosimetrist s goal to deliver prescribed doses of radiation to the target volume while minimizing dose to critical structures. Every tool should be employed to best achieve this goal. - 14 -
With the increasing popularity of IMRT treatment techniques, in many instances, improved conformality and critical structure avoidance may be achieved. However, with these advances come surprisingly large increases in monitor units delivered, with corresponding increases in scatter dose to the patient. While not clinically significant in this research, the potential for complications should be assessed before choosing the IMRT treatment modality. - 15 -
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