BERKELEY, CA (UroToday.com) - Stereotactic ablative body radiotherapy (SABR) is an external beam radiation modality that delivers therapeutic radiation to a target with enhanced precision and accuracy over other methods, including intensity modulated radiation therapy (IMRT). Recent advances in linear accelerator design and performance now permit the delivery of precisely shaped radiation dose distributions coupled with automated on/off control of the treatment beam in response to changes in the position of the prostate during a treatment session. As a result, curative radiation doses may now be safely and effectively delivered within a greatly compressed treatment schedule for selected patients: in the management of prostate cancer, a conventional IMRT treatment course of 8 to 9 weeks of daily radiotherapy may be reduced to 5 total stereotactic treatments delivered over 5 to 10 days.
Random movement of the prostate due to normal physiologic changes in bladder and rectal volumes has long been recognized as a source of targeting error in conventional external beam radiotherapy. In order to compensate for this movement, radiation oncologists apply a safety margin of 5 to 10 mm to the prostate, and this expanded volume then serves as the radiotherapy target intended to receive the prescribed dose. However, this expanded volume also encompasses portions of the anterior rectal wall and bladder neck, exposing these healthy tissues to potentially damaging radiation. Radiation oncologists mitigate this risk by limiting the daily radiation dose to relatively small amounts (e.g., 1.8 to 2.0 Gy per day) in order to allow for healthy tissue recovery. At these low dose levels, prostate cancer cells are killed at a rate greater than normal cells are permanently damaged, and the net therapeutic effect is therefore favorable. This strategy of limited daily doses has been successful in maintaining complication rates low while achieving excellent cure rates. However, this strategy also requires a large total number of treatments to attain cumulative radiation doses effective in sterilizing malignant disease. The resulting protracted treatment course may discourage patients from selecting radiotherapy on the basis of inconvenience and cost.
The research question that motivated our study was the following: if the prostate’s random movement could be monitored during treatment delivery and the treatment beam activated only when the prostate is present within a pre-determined narrow ‘window’, then could the safety margin be greatly reduced and allow for an expedited course using fewer treatments with much higher daily doses?
Our study investigated this question using Varian radiotherapy technology integrated with Varian’s Calypso® system for prostate tracking. The Calypso® system uses implanted transponders in place of standard gold fiducial markers. These transponders produce a signal when exposed to a low-energy electromagnetic field during a treatment session, and the system then receives this signal and calculates translational (x, y and z axes) and rotational (roll, pitch and yaw) positional information with submillimeter and subdegree accuracy continuously and in real-time.
According to our prostate SABR protocol, the treatment beam is synchronized to activate only when the Calypso® system informs the linear accelerator that the prostate’s position is within 2 mm of its intended treatment position. We selected a 2-mm threshold after discovering in earlier research work that this threshold achieves an acceptable balance between treatment delivery precision and patient time on the linear accelerator. By restricting beam-on time to this narrow window, the applied safety margin may then be safely reduced to 2 mm. This unusually tight margin in turn allows for greater exclusion of normal tissues from the treatment field, higher per-treatment radiation doses, and a shortened overall treatment course.
We recently reported our phase II experience of 102 patients with localized, low-risk prostate cancer treated with SABR to a total dose of 40.0 Gy in five 8.0-Gy treatment fractions. Treatment time for each fraction averaged less than 20 minutes, further adding to patient acceptance of the treatment. RapidArc®, a volumetric arc treatment technique, is a very efficient version of IMRT from Varian, which we are now using for treatment. Our assumptions concerning the feasibility of reduced safety margins when treatment beam activation and prostate position tracking are synchronized appear to have been validated, as serious long-term toxicities were absent, and disease control outcomes were excellent at a meaningfully long time point after therapy. Furthermore, quality-of-life assessments at 5 years demonstrated statistical equivalence to those assessments made immediately prior to the start of treatment. At present, research efforts involving prostate SABR are the investigation of its application in high-risk, localized cancer in conjunction with androgen suppression and conventional pelvic external beam radiotherapy.
Constantine A. Mantz, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Chief Medical Officer, 21st Century Oncology, Fort Myers, FL USA