Extra-Cranial Radiosurgery For Prostate
Twyla Willoughby, M.S.
M.D. Anderson Cancer Center Orlando
Introduction:
Prostate ...
DOSES and FRACTIONACTION
Planning a course of radiotherapy includes dose and fractionation. The doses and
fractionation ar...
Epids
Historically, patients undergoing prostate
radiotherapy would be setup with skin marks and
then the position and fie...
For the ease of use and the non-invasive nature of this system it has been widely used to
increase accuracy of prostate tr...
7 were greater than 10mm. The maximum magnitude of shift in any direction was 15.66
mm vertical, 14.94 mm longitudinal, an...
2
Sannazzari GL, Ragona R, Ruo Redda MG, Giglioli FR, Isolato G, Guarneri A.. “CT-MRI image fusion for
delineation of volu...
2
Sannazzari GL, Ragona R, Ruo Redda MG, Giglioli FR, Isolato G, Guarneri A.. “CT-MRI image fusion for
delineation of volu...
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Extra-Cranial Radiosurgery For Prostate - Twyla Willoughby, M ...

  1. 1. Extra-Cranial Radiosurgery For Prostate Twyla Willoughby, M.S. M.D. Anderson Cancer Center Orlando Introduction: Prostate cancer has been treated with radiation therapy for many years. Traditionally these treatments would comprise of static gantry fields with slight blocking in order to spare some of the rectum and the bladder from getting full dose. Early prostate cancer treatment was designed to target the prostate, seminal vesicles and the pelvic lymphatic system. Today, with early screening, many of the patients who present with prostate cancer have localized disease in the prostate gland only. In these cases it is only necessary to try to target the prostate itself. This work has developed with the help of imaging and biopsy studies along with early screening programs to offer more options for prostate cancer patients. One of the problems with trying to target and treat only the prostate gland while sparing the surrounding structures is identifying the exact location of the prostate on a daily basis. It is known that the prostate gland will move with rectal and bladder filling and emptying. All of these considerations are taken into account when planning a course of treatment. The purpose of this paper is to survey the different techniques that are being developed for accurately targeting the prostate gland for localized prostate treatment. Target Delineation In order to apply stereotactic treatment to an area it is first necessary to be able to accurately delineate the target. In the case of stereotactic radiosurgery for brain the target is usually defined by contrast enhancing areas on MRI. The same level of accuracy in target delineation is required in order to perform radiosurgical procedures extracanially. In the prostate, it is still not possible to visualize the cancer cells within the prostate gland. Research is being done to try to determine the exact location of cancer within the prostate, but has not reached the level of accuracy necessary to be widely implemented. Research in the area of MR spectroscopy and nuclear medicine with prosticent may prove fruitful in the future. Since imaging is not yet specific enough to allow us to target only the cancerous area within the prostate, it is still the accepted practice to treat the entire prostate as the target. Some studies have indicated that the disease for prostate cancer is well contained within the capsule of the prostate and in most cases is within the prostate gland. Common radiotherapy practice is to define the prostate on CT images. The prostate gland may show differently on MRI and on CT than it does on ultrasound. The difference in the two different imaging modalities may show differences about 3-4mm between the two sets of images.1-3 It is very important to establish consistent criteria for drawing in the target for prostate at your institution, and for comparing studies between institutions.
  2. 2. DOSES and FRACTIONACTION Planning a course of radiotherapy includes dose and fractionation. The doses and fractionation are generally based on alpha-beta ratios so as to deliver safe doses to normal tissues and lethal doses to target tissues. The delivery method of most radiotherapy has changed dramatically within the last few years, which allows us to delivery radiation in a more conformal method. In doing so, we must evaluate the dose and fractionation schedule so that the best dose and fractionation is utilized for the technology and the disease. In the days of cobalt, the butterfly technique or arcs were quite common in order to spread the dose to the surrounding tissues as much as possible. In these cases a four- field technique or a six-field technique give a nice dose distribution of the prostate plus a margin around the prostate. More recently IMRT has become a treatment of choice in many cases for treating the prostate. These techniques include either arc therapy (peacock and Nomos) or MLC static gantry techniques. With this type of planning and delivery system it is possible to create dose distributions that are very complex and very conformal. With the ability to deliver tighter dose distributions, it was safer to attempt dose escalation studies. Studies by a number of publisher indicate the prostate cure rates have increase with increasing doses, however in order to increase the dose, it was necessary to decrease the field so as not to treat too much of the rectum. For the most part these studies have shown that doses about 76-78Gy are necessary to maximize the potential for cure of prostate cancer. Dose escalation studies continue to be evaluated and hopefully we’ll better understand the appropriate dose for prostate in the near future. Along with dose escalation becomes the issue of fractional doses. The standard of radiation therapy based on radiation biology suggested a fraction dose of 180cGy per day was the appropriate dose for cell kill and normal cell recovery. Studies in radiation biology indicate that there may be more cells specific dose fractionation schemes that may work better for prostate cancer. Some have looked at increased dose per fraction on the order or 250 cGy per fraction or 300 cGy per fraction.4-5 Image Guidance Therapy As treatments become more conformal, and the number of fractions is decreased it becomes increasingly important to accurately target the area of interest. As mentioned in the introduction, the prostate moves from day to day. In order to accurately deliver a high dose of radiation to a moving target without radiating too much normal tissue it is necessary to localize the prostate accurately and it might be necessary to track that motion throughout the treatment. Image-guided therapy has been continuing to develop and was featured in a recent Radiation Oncology journal. The AAPM has added this as an additional category of study, and it appears to be a growing area of research and concern. This section is a summary of techniques used in image guidance. This is not an attempt to include all possible modes of imaging, nor is it to highlight a particular mode of imaging as primary. This is an overview of the history of image-guidance for prostate as well as some current trends in research.
  3. 3. Epids Historically, patients undergoing prostate radiotherapy would be setup with skin marks and then the position and fields checked using portal images. With the advent of electronic portal imaging several years ago, the idea of verifying each fraction each treatment session became feasible. With most of these systems that included amorphous silicone and video imaging systems it was possible to visualize the pelvic bones, but not the prostate. . For these purposes various institutions have either looked at using a rectal balloon that will show up on the portal image to define the prostate rectal border, or they have looked at implanted markers as a means of determining prostate location. This allows one to more accurately position patients, but it does not give an indication of the prostate position within the field. In order to accurately see the prostate it is necessary to add some high contrast material such as marker seeds into the prostate. Many have investigated this approach including University of California San Francisco, University of Michigan, and Princess Margaret in Toronto. 6-8 The problem with this was that early generation electronic portal imaging devices it was necessary to use such large implantable marker seeds (>1.2 mm diameter) that this was a concern for urologists and oncologist who would have to implant these markers, but the results looked very promising.9-10 Within the next couple of years there will be much work presented in this area of research ULTRASOUND Another area of imaging that has been implemented in many facilities for the past five years or so has been the ability to localize the prostate using Ultrasound. The BAT™ system from Nomos is a self-contained system that can be added to any treatment machine or modality. It uses reconstructed contour information from the patient treatment plan to ensure the patients prostate is positioned in the same location relative to the isocenter on each day of treatment. Pictures below show an image of the BAT system and also of an ultrasound of the prostate with reconstructed contours. Because of the grayscale imaging that is obtained with ultrasound these images are subject to interpretation errors, but with training these can be minimized. Several have studied the accuracy of the BAT™ system and there continue to be papers and presentations about this technology. Most studies indicate similar results that allow one to align the prostate accurately to about 3 mm accuracy (or one slice thickness on CT).
  4. 4. For the ease of use and the non-invasive nature of this system it has been widely used to increase accuracy of prostate treatments.11 X-ray systems In order to overcome this problem some have developed KV x-ray systems that allow the user to take kV X-rays to identify either anatomical markers or implanted markers. This is the idea behind the system at the University of Michigan, the Cyberknife™ from Accuray, and the Novalis Body™ from Brainlab (pictured right). In addition to setting up patients with kV x-rays, the Cyberknife™ system can feedback the information to allow for tracking of a treatment area. Specifically at our institution we use the Novalis system from BrainLab™. This has with it an infrared detection system (Exactrac) along with a dual x-ray system (Novalis Body) with an amorphous silicone flatpanel. Included in the system is software to analyze the x- ray images for alignment. This software can use mutual information registration to the DRR’s or point by point matching between implanted marker seed location on CT and film. One study that was performed was designed to determine the prostate motion relative to the pelvic bones. Prior to treatment, patients are implanted with 3 gold marker seeds that were 0.8 mm diameter by 3 mm length. Treatment planning CTs are performed and planning completed as standard at our institution. The CT images are exported to the Exactrac computer where digitally reconstructed radiographs are created in the x-ray beam geometry. This configuration is a right, inferior-superior oblique and a left inferior – superior oblique. Each day of treatment, the patient was positioned at the isocenter using skin marks. Two different registrations were performed. The first registration used the automatic mutual information software and the DRRs. The second alignment used the marker locations on CT relative to the x-ray images. The expected shifts of each alignment were recorded. The difference in these shifts represents the difference between the bony anatomy and the intraprostatic markers. Data is presented on twenty patients who were aligned using three implanted marker seeds. An average of fourteen alignments were performed on each patient. A total of 287 different measurements were taken. The average and standard deviations of all displacements were -1.60 ± 3.40 mm posterior, -0.50 ± 2.72 mm inferior, and -1.25 ± 1.43 mm right. The overall difference averaged for all patients was 3.89 ± 2.85mm. Of the 287 different encounters, 75 of them had an overall difference greater than 5mm, and
  5. 5. 7 were greater than 10mm. The maximum magnitude of shift in any direction was 15.66 mm vertical, 14.94 mm longitudinal, and 9.07. The magnitude of the average of the difference between the prostate and the pelvis is on the order of 2 mm. The direction of the displacement of the intraprostatic markers relative to the pelvis is in the direction that is expected due to bladder and rectal filling. This difference is very small overall, but the maximum differences indicate that on occasion the prostate movement relative to the pelvis can be as much as a few cm. It is for this reason that it is important to be able to determine the prostate location and not just the bony anatomy location. If it is not possible to localize on the prostate then an additional 2-3 mm in margin may be required. These types of x-ray systems seem hopeful for the future. These systems, especially the Cyberknife could potentially be used to track and to monitor patient motion using x-ray during the course of treatment. This will be of particular use in treating lung tumors and liver tumors where motion is of concern, but will be of use in prostate treatments as well because patients can move or the prostate could potentially move during the treatment. CT, Cone-beam CT, & Tomotherapy Another method of imaging that is being investigated is the use of CT. Siemens Medical has developed a system that is a CT on rails that has a single couch for both the linear accelerator and the CT machine. This system (pictured right) can give accurate setup information of the patient in treatment position and then the table can be moved so the patient can be treated. This will give very accurate setup details, but may be a costly solution; it will also not be able to give feedback of the prostate location during treatment. Another form of CT for alignment is the Cone-beam CT with either megavoltage x-rays or with a secondary KV x-ray system.12-14 One other approach that uses the concept of CT is the tomotherapy machine that has inside of a CT gantry and MV x-ray system. While the patient is in treatment position, the machine can be rotated to acquire an MV CT image. These images are fairly high quality and allow the user to see the prostate gland and align to the soft tissues each treatment. Eventually it is the goal of tomotherapy to be able to reconstruct the prostate location during treatment and possibly even adjust the radiation field in order to account for motion within the patient.15-16 REFERENCES 1 Parker CC, Damyanovich A, Haycocks T, Haider M, Bayley A, Catton CN. “Magnetic resonance imaging in the radiation treatment planning of localized prostate cancer using intra-prostatic fiducial markers for computed tomography co-registration.” Radiother Oncol 2003 Feb;66(2):217-24.
  6. 6. 2 Sannazzari GL, Ragona R, Ruo Redda MG, Giglioli FR, Isolato G, Guarneri A.. “CT-MRI image fusion for delineation of volumes in three-dimensional conformal radiation therapy in the treatment of localized prostate cancer.” Br J Radiol 2002 Jul;75(895):603-7. 3 Teh BS, Bastasch MD, Wheeler TM, Mai WY, Frolov A, Uhl BM, Lu HH, Carpenter LS, Chiu JK, McGary J, Woo SY, Grant WH, Butler EB. “IMRT for prostate cancer: Defining target volume based on correlated pathologic volume of disease.” Int J Radiat Oncol Biol Phys 2003 May 1;56(1):184-91. 4 Yeoh EE, Fraser RJ, McGowan RE, Botten RJ, Di Matteo AC, Roos DE, Penniment MG, Borg MF. “Evidence for efficacy without increased toxicity of hypofractionated radiotherapy for prostate carcinoma: early results of a Phase III randomized. Int J Radiat Oncol Biol Phys 2003 Mar 15;55(4):943-55 . 5 Kupelian PA, Reddy CA, Klein EA, Willoughby TR. “Short-course intensity-modulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life.” Int J Radiat Oncol Biol Phys 2001 Nov 15;51(4):988-93. 6 Pang G, Beachey DJ, O'Brien PF, Rowlands JA. “Imaging of 1.0-mm-diameter radiopaque markers with megavoltage X-rays: an improved online imaging system.” Int J Radiat Oncol Biol Phys 2002 Feb 1;52(2):532-7. 7 Nederveen AJ, Lagendijk JJ, Hofman P. “Feasibility of automatic marker detection with an a-Si flat-panel imager.” Phys Med Biol 2001 Apr;46(4):1219-30 . 8 Alasti H, Petric MP, Catton CN, Warde PR . “Portal imaging for evaluation of daily on-line setup errors and off-line organ motion during conformal irradiation of carcinoma of the prostate.”. Int J Radiat Oncol Biol Phys 2001 Mar 1;49(3):869-84. 9 Litzenberg D, Dawson LA, Sandler H, Sanda MG, McShan DL, Ten Haken RK, Lam KL, Brock KK, Balter JM. “Daily prostate targeting using implanted radiopaque markers.” Int J Radiat Oncol Biol Phys 2002 Mar 1;52(3):699- 703. 10 Kitamura K, Shirato H, Shimizu S, Shinohara N, Harabayashi T, Shimizu T, Kodama Y, Endo H, Onimaru R, Nishioka S, Aoyama H, Tsuchiya K, Miyasaka K. “Registration accuracy and possible migration of internal fiducial gold marker implanted in prostate and liver treated with real-time tumor-tracking radiation therapy RTRT).” Radiother Oncol 2002 Mar;62(3):275-81. 11 Lattanzi J, McNeeley S, Donnelly S, Palacio E, Hanlon A, Schultheiss TE, Hanks GE. “Ultrasound-based stereotactic guidance in prostate cancer--quantification of organ motion and set-up errors in external beam radiation therapy.” Comput Aided Surg 2000;5(4):289-95. 12 Ford EC, Chang J, Mueller K, Sidhu K, Todor D, Mageras G, Yorke E, Ling CC, Amols H. “Cone-beam CT with megavoltage beams and an amorphous silicon electronic portal imaging device: potential for verification of radiotherapy of lung cancer.” Med Phys 2002 Dec;29(12):2913-24. 13 Groh BA, Siewerdsen JH, Drake DG, Wong JW, Jaffray DA. ”A performance comparison of flat-panel imager-based MV and kV cone-beam CT.” Med Phys 2002 Jun;29(6):967-75. 14 Jaffray DA, Siewerdsen JH, Wong JW, Martinez AA. “Flat-panel cone-beam computed tomography for image- guided radiation therapy.” Int J Radiat Oncol Biol Phys 2002 Aug 1;53(5):1337-49. 15 Mackie TR, Kapatoes J, Ruchala K, Lu W, Wu C, Olivera G, Forrest L, Tome W, Welsh J, Jeraj R, Harari P, Reckwerdt P, Paliwal B, Ritter M, Keller H, Fowler J, Mehta M. “Image guidance for precise conformal radiotherapy.” Int J Radiat Oncol Biol Phys 2003 May 1;56(1):89-105. 16 Welsh JS, Patel RR, Ritter MA, Harari PM, Mackie TR, Mehta MP. “Helical tomotherapy: an innovative technology and approach to radiation therapy.” Technol Cancer Res Treat 2002 Aug;1(4):311-6.
  7. 7. 2 Sannazzari GL, Ragona R, Ruo Redda MG, Giglioli FR, Isolato G, Guarneri A.. “CT-MRI image fusion for delineation of volumes in three-dimensional conformal radiation therapy in the treatment of localized prostate cancer.” Br J Radiol 2002 Jul;75(895):603-7. 3 Teh BS, Bastasch MD, Wheeler TM, Mai WY, Frolov A, Uhl BM, Lu HH, Carpenter LS, Chiu JK, McGary J, Woo SY, Grant WH, Butler EB. “IMRT for prostate cancer: Defining target volume based on correlated pathologic volume of disease.” Int J Radiat Oncol Biol Phys 2003 May 1;56(1):184-91. 4 Yeoh EE, Fraser RJ, McGowan RE, Botten RJ, Di Matteo AC, Roos DE, Penniment MG, Borg MF. “Evidence for efficacy without increased toxicity of hypofractionated radiotherapy for prostate carcinoma: early results of a Phase III randomized. Int J Radiat Oncol Biol Phys 2003 Mar 15;55(4):943-55 . 5 Kupelian PA, Reddy CA, Klein EA, Willoughby TR. “Short-course intensity-modulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life.” Int J Radiat Oncol Biol Phys 2001 Nov 15;51(4):988-93. 6 Pang G, Beachey DJ, O'Brien PF, Rowlands JA. “Imaging of 1.0-mm-diameter radiopaque markers with megavoltage X-rays: an improved online imaging system.” Int J Radiat Oncol Biol Phys 2002 Feb 1;52(2):532-7. 7 Nederveen AJ, Lagendijk JJ, Hofman P. “Feasibility of automatic marker detection with an a-Si flat-panel imager.” Phys Med Biol 2001 Apr;46(4):1219-30 . 8 Alasti H, Petric MP, Catton CN, Warde PR . “Portal imaging for evaluation of daily on-line setup errors and off-line organ motion during conformal irradiation of carcinoma of the prostate.”. Int J Radiat Oncol Biol Phys 2001 Mar 1;49(3):869-84. 9 Litzenberg D, Dawson LA, Sandler H, Sanda MG, McShan DL, Ten Haken RK, Lam KL, Brock KK, Balter JM. “Daily prostate targeting using implanted radiopaque markers.” Int J Radiat Oncol Biol Phys 2002 Mar 1;52(3):699- 703. 10 Kitamura K, Shirato H, Shimizu S, Shinohara N, Harabayashi T, Shimizu T, Kodama Y, Endo H, Onimaru R, Nishioka S, Aoyama H, Tsuchiya K, Miyasaka K. “Registration accuracy and possible migration of internal fiducial gold marker implanted in prostate and liver treated with real-time tumor-tracking radiation therapy RTRT).” Radiother Oncol 2002 Mar;62(3):275-81. 11 Lattanzi J, McNeeley S, Donnelly S, Palacio E, Hanlon A, Schultheiss TE, Hanks GE. “Ultrasound-based stereotactic guidance in prostate cancer--quantification of organ motion and set-up errors in external beam radiation therapy.” Comput Aided Surg 2000;5(4):289-95. 12 Ford EC, Chang J, Mueller K, Sidhu K, Todor D, Mageras G, Yorke E, Ling CC, Amols H. “Cone-beam CT with megavoltage beams and an amorphous silicon electronic portal imaging device: potential for verification of radiotherapy of lung cancer.” Med Phys 2002 Dec;29(12):2913-24. 13 Groh BA, Siewerdsen JH, Drake DG, Wong JW, Jaffray DA. ”A performance comparison of flat-panel imager-based MV and kV cone-beam CT.” Med Phys 2002 Jun;29(6):967-75. 14 Jaffray DA, Siewerdsen JH, Wong JW, Martinez AA. “Flat-panel cone-beam computed tomography for image- guided radiation therapy.” Int J Radiat Oncol Biol Phys 2002 Aug 1;53(5):1337-49. 15 Mackie TR, Kapatoes J, Ruchala K, Lu W, Wu C, Olivera G, Forrest L, Tome W, Welsh J, Jeraj R, Harari P, Reckwerdt P, Paliwal B, Ritter M, Keller H, Fowler J, Mehta M. “Image guidance for precise conformal radiotherapy.” Int J Radiat Oncol Biol Phys 2003 May 1;56(1):89-105. 16 Welsh JS, Patel RR, Ritter MA, Harari PM, Mackie TR, Mehta MP. “Helical tomotherapy: an innovative technology and approach to radiation therapy.” Technol Cancer Res Treat 2002 Aug;1(4):311-6.

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