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Minimal Benefit of an Endorectal Balloon for Prostate Immobilization as Verified by Daily Localization
Medical Dosimetry, Vol. 36, No. 2, pp. 195-199, 2011 Copyright © 2011 American Association of Medical Dosimetrists Printed in the USA. All rights reserved 0958-3947/11/$–see front matter
doi:10.1016/j.meddos.2010.03.003
MINIMAL BENEFIT OF AN ENDORECTAL BALLOON FOR PROSTATE IMMOBILIZATION AS VERIFIED BY DAILY LOCALIZATION ARTHUR Y. HUNG, M.D., MARK GARZOTTO, M.D., and DARRYL KAURIN, PH.D. Departments of Radiation Oncology and Surgery, Oregon Health & Science University, Portland, OR (Received 12 November 2008; Accepted 9 March 2010)
Abstract—We wanted to investigate whether using an endorectal balloon (ERB) in lieu of image guidance is reasonable. We compared daily prostate motion in 2 cohorts of patients with fiducial markers implanted in the prostate, one group with the ERB and the other without. Twenty-nine patients were treated using intensity-modulated radiation therapy: 14 with an ERB, and 15 without. All had fiducial markers placed in the prostate. We reviewed the daily displacements necessary to place the isocenter on the prostate as determined by portal imaging. In addition, we used the data to determine whether there is a change in prostate motion over the treatment course. The average prostate displacement for patients treated without an ERB was slightly greater than the average displacement for patients treated with the ERB. However, the difference observed with the ERB was not statistically significant (p > 0.05). The margins necessary to encompass the prostate 95% of the time for the patients treated without an ERB in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8, 12.1, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1, 10.4, and 11 mm, respectively. Prostate motion in the anteriorposterior direction actually increased over the course of treatment in patients without an ERB. This increase was prevented by use of the ERB. Day-to-day variability of the position of the prostate is reduced in all dimensions with the water-filled ERB, but not significantly statistically. Use of the water-filled ERB did not obviate performing some form of image guidance daily. © 2011 American Association of Medical Dosimetrists. Key Words: Prostate cancer, Prostate localization, Prostate image-guided radiation Therapy, Rectal balloon.
address these discrepancies, we studied two groups of patients: one treated with and one without an ERB. All patients had prostatic location verified on a daily basis by portal imaging of fiducial markers during IMRT. We undertook this study to evaluate the effect of an ERB on prostate motion.
INTRODUCTION The ability to accurately deliver a high dose of radiation to the target while minimizing radiation dose to the normal tissues is fundamental to the effective use of radiation as a treatment for cancer. In the treatment of prostate cancer, radiation dose to the rectal wall is responsible for much of the toxicity associated with the treatment. Intensity-modulated radiation therapy (IMRT) enables a concave distribution of dose, which improves the ability to deliver high doses of radiation to the prostate while avoiding the rectum. With this technology, motion of the prostate gland becomes a limiting factor in the ability to reduce treatment margins. Investigators have studied the use of an endorectal balloon (ERB) device for immobilization of the prostate gland during radiation treatment with IMRT for prostate cancer. Because prostate position depends largely on rectal filling, the balloon has been used to standardize the rectal volume, with the intent of decreasing the day-to-day variation in the position of the prostate and improve therapeutic targeting of the disease. Conflicting reports in the literature debate the effectiveness of an ERB for this purpose. Several authors have shown reduction of prostate motion using the balloon and suggested the feasibility of smaller margins with this device.1–3 Other recent reports, however, show no reduction in interfraction prostate motion with use of a balloon.4 To
MATERIALS AND METHODS Twenty-nine patients were identified who were treated definitively for prostate cancer with external beam radiation using IMRT. Patients with localized prostate cancer of all stages, Gleason grades, and prostate-specific antigen (PSA) levels were included in the analysis. Before treatment planning, all patients had three gold markers (Best Medical International, Inc., Springfield, VA) placed in the prostate under ultrasound guidance. Markers were placed bilaterally in the bases and singly in the apex. A planning pelvic computed tomography (CT) scan was then obtained using either 2.5 mm or 3.2 mm cuts. Before CT imaging, patients were asked to use an enema to evacuate the rectum. All patients were treated in the supine position with a MedTec (Orange City, IA) vacuum cradle fixing their leg, knee, and ankle position. All patients were scanned with and without an ERB. The decision regarding use of the balloon was nonrandomized and based on anatomical considerations from the planning CT. We elected to perform the treatment without the balloon in some patients because the balloon pushed the rectum closer to the prostate and seminal
Reprint requests to: Arthur Y. Hung, M.D., Department of Radiation Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mailcode: KPV4, Portland, OR 97239-3098. E-mail: [email protected] 195
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vesicles, making the organs more difficult to avoid. The clinical target volume (CTV) was the entire prostate. The planning target volume (PTV) was generated by expanding the CTV by 7 mm posteriorly, 7 mm inferiorly, and 12 mm around the remainder of the volume. Patients with high-risk features such as Gleason grade ⬎7, PSA ⬎15, or cT3 disease received concurrent hormonal ablation and were treated to 45 Gy to a pelvic field followed by an IMRT boost to the prostate 75.6 Gy. The data for high-risk patients is comprised only of adjustments made during the IMRT portion of their treatment (17 of the total 42 fractions). All other patients were treated with definitive IMRT to the CTV to 75.6 Gy. The rectal balloon is widely used in regional radiation treatment centers and was adopted from the technique described by the Loma Linda University Medical Center.5 The balloon is constructed with the following components: E-Z-Em Flexitip Infant Catheter Tip (E-Z-EM, Inc., New York, NY) (blue); Conmed 6-foot-long (Beaverton, OR), 3/16-in I.D. Suction Tubing (clear tube); nonlatex ultrasound probe covers (outer cover); female Luer Lock Connector (Dickinson Company, Franklin Lakes, NJ) (adapter for suction tubing and syringe); latex ultrasound probe cover (inner cover used with rubber band); Alliance Advantage Rubber Bands (Alliance Rubber Company, Hot Springs, AR); and 2 Luer Lock (Dickinson Company, Franklin Lakes, NJ) 60-mL syringes. To assemble the rectal balloon, a mark is made 9 cm from the top of the blue tip catheter. The catheter tip is then covered with the latex ultrasound probe cover and a rubber band is placed tightly around the cover at the 9-cm mark. The catheter tip is then inserted into the rectum until the rubber band reaches the anal verge. A volume of 120 mL of warm water is used to inflate the balloon after insertion. For daily treatments, the patient was lined up to isocenter based on external skin marks and orthogonal images obtained. A physician reviewed the images, and repositioning shifts were made in the lateral, anteriorposterior and cranial/caudal dimensions to within a 2-mm tolerance of where the fiducial markers were located on the digitally reconstructed radiographs of the treatment plan. These daily shifts from the original isocenter were recorded in the patient chart. To assess the effectiveness of the rectal balloon as an immobilization device, we reviewed the daily shifts necessary and compared the 2 patient cohorts. Mean shifts in each dimension were calculated for the entire treatment course for each cohort and this mean shift data was compared between the cohorts. We determined the range of prostate motion (defined as the sum of the greatest shift in the positive and negative direction) for each patient. The average range in each dimension was determined for each cohort. In addition, we used the data to determine whether there is a change in prostate mobility over the course of radiation treatment. Prostate motion over the treatment
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course was analyzed by dividing the 42 fractions into trimesters of 14 fractions each that were then compared with respect to prostate motion. The mean shift in each dimension for each patient cohort (balloon and no-balloon) was calculated for each 14-fraction trimester. Comparison between the trimesters was made within and across each cohort. The maximum prostate movement in any dimension for each treatment was identified for each patient. This data was used to evaluate differences in prostate movement between the groups and difference in movement over the treatment course. The range of prostate motion (defined as the sum of the greatest shift in the positive and negative direction) was calculated for each patient for each treatment day. Statistical analysis Analysis of variance tests (ANOVA) were applied to analyze the influence of different factors (presence of an ERB and elapsed treatment time) on shift magnitude in each dimension (anterior/posterior, right and left lateral, and superior/inferior). RESULTS Thirty patients treated definitively for prostate cancer using IMRT were identified. Fifteen patients were treated using a rectal balloon and 15 patients were treated without a balloon. One patient began treatment with a rectal balloon but, because of patient preference, use of the balloon was discontinued after two fractions. This patient was excluded from the analysis. Eleven patients in the series had high-risk disease; 4 of these patients were treated with a rectal balloon and 7 without a balloon (Table 1). The median number of shift measurements per patient in the no-balloon group for low-risk and high-risk patients was 39.5 and 16, respectively. The median number of shift measurements per patient in the ERB group for low- and high-risk patients was 39 and 14.5, respectively. Fewer data points were available in the high-risk patients because they received only the final 30.6 Gy boost (17 fractions) using IMRT. The average range in the lateral, cranial/caudal, and anterior/posterior directions for the cohort of patients treated without a balloon was 9.3 mm (2–29), 10.4 mm (2–25), and 13.4 mm (2–31), respectively, and for those treated with the balloon was 8.2 mm (2–13), 9.1 mm (2–21), and 9.6 mm (3–15), respectively. The data were compared using ANOVA tests and the differences were not statistically significant (p ⬎ 0.05). The average magnitude of prostate displacement over the entire course of treatment for patients treated without a balloon was 2.5 mm (SD 1.4), 4.6 mm (SD 2.9), and 7.3 mm (SD 4.8) in the lateral, cranial/caudal, and anterior/posterior dimension, respectively. For the cohort of patients treated with the balloon, the average
Endorectal balloon for prostate immobilization ● A. Y. HUNG et al.
Table 1. Clinical characteristics of 29 patients
Patient Characteristics Number of Patients Median Age Median Weight Karnofsky ⬍ 70 Median Karnofsky Median Prostate Volume (Range) Stage T1 T2 T3 T4 Gleason 6 7 8–10 PSA ⬍10 10–20 ⬎20 Treatment Hormones Pelvis Treated
197
12
Balloon
No Balloon
14 72 176 0 85 22.6 (17.1 – 72.4)
15 72 187 0 90 31.1 (8.8 – 131.4)
10 8 Balloon
6
No Balloon
4 2 0 1st Trimester
8 6 0 0
6 7 2 0
5 6 3
3 8 4
6 5 3
9 5 1
4 4
7 6
prostate displacement was 2.1 mm (SD 1.2), 4.1 mm (SD 3.6), and 5.4 mm (SD 3.4) in the lateral, cranial/caudal, and anterior/posterior dimension, respectively (Fig. 1). The difference in prostate motion with and without the rectal balloon was not statistically significant (p ⫽ 0.38, p ⫽ 0.27, and p ⫽ 0.22, respectively). We also analyzed the average prostate motion over the entire treatment course by dividing the 42 fractions into trimesters of 14 fractions each. The prostate motion in the lateral and superior-inferior dimensions did not change over the radiation treatment course. Surprisingly, prostate motion in the anterior-posterior dimension increased with treatment time in those patients treated without a balloon but not in patients treated with the balloon (p ⫽ 0.06). In the anterior/posterior direction for the cohort treated with no balloon, the mean shift nec-
2nd Trimester
3rd Trimester
Fig. 2. Mean prostate displacement in millimeters in the anterior/posterior dimension calculated for the first one-third (first trimester), second one-third, and final one-third of the treatment fractions. Comparison of patients treated with and without a rectal balloon (p ⫽ 0.06 for the trend). The error bars represent the standard error of the mean.
essary was 6.6 mm, 7.3 mm, and 8.3 mm in the first, second, and third trimester, respectively, whereas in the cohort treated with a balloon, the mean shift was 5.2 mm, 5.2 mm, and 5.5 mm in the first, second, and third trimester, respectively (Fig. 2). Another method of analyzing the data involved looking at the maximum displacement needed rather than the average displacement. We identified the maximum movement of the prostate in any dimension for each treatment. We analyzed whether this movement changed over time and discovered that the movement increased with each trimester to a statistically significant degree in the cohort of patients treated without a balloon. This increase was not seen in patients treated with a balloon (Fig. 3). In the cohort treated without a balloon, the mean value of the daily maximum shift in any direction was 7.6 mm, 9.0 mm, and 9.7 mm in the first, second, and third trimesters, respectively; in the cohort treated with a rectal balloon, the mean value of the daily maximum shift was 6.6 cm, 6.6 mm, and 7.1 mm in the first, second, and third trimesters, respectively. This trend for increased motion over time in patients treated without a balloon was significant with p ⫽ 0.006.
9
14
8 7
12
6 5
Balloon
4
No Balloon
3
10 8
Balloon No Balloon
6
2
4
1 0 Lateral Displacement
Cranio/caudal Displacement
Anterior/Posterior Displacement
2 0 1st Trimester
Fig. 1. Comparison of the mean prostate displacement in millimeters in each dimension over the entire radiation treatment course for patients treated with or without a rectal balloon (p ⫽ 0.38, p ⫽ 0.27, and p ⫽ 0.22 in the lateral, cranio/caudal, and anterior/posterior dimensions, respectively). The error bars represent the standard error of the mean.
2nd Trimester
3rd Trimester
Fig. 3. Maximum prostate displacement in any dimension averaged for each one-third (trimester) of the treatment fractions. Comparison of patients treated with and without a rectal balloon (p ⫽ 0.006 for the trend). The error bars represent the standard error of the mean.
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DISCUSSION To minimize treatment margins and maximize the therapeutic ratio, the prostate gland must be accurately targeted on a daily basis. To this end, radiation oncologists have used several strategies including daily insertion of an ERB as an immobilization device and daily tracking, via portal imaging, of fiducial markers placed in the prostate gland. Our data show that day-to-day variability of the position of the prostate is reduced in all dimensions with the use of a water-filled ERB. However, the absolute reduction in daily motion was small. The differences in prostate motion between the two groups of patients were not statistically different. Even with the balloon, daily variability of the prostate necessitated daily shifts to center the prostate on the isocenter throughout the treatment course. Use of the balloon did not obviate daily verification by portal imaging of fiducial markers. Based on our displacement data, the margins necessary to encompass the prostate 95% of the time for the no-balloon cohort in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8 mm, 12.1 mm, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1 mm, 10.4 mm, and 11 mm, respectively. The margins used in treating patients in this study were 7 mm posteriorly and 12 mm around the remainder of the volume. Therefore, if no adjustments were made to compensate for daily prostate displacement, even with an ERB the target volume would fall outside of the treatment margins in an unacceptably high percentage of the treatments. Some investigators have shown a decrease in prostate motion with use of an ERB.2,3,6,7 Wachter et al. prospectively studied 10 patients undergoing IMRT for prostate cancer.3 CT scans were performed with and without a rectal balloon at the beginning, middle, and end of treatment. Their rectal balloon was made from a 30-cm-long 2-way rectal tube with a Silkolatex RueschGold balloon with a pilot balloon. The dimensions of the balloon filled with 40 ml of air are 5.5 ⫻ 4.0 cm. A decrease in maximum prostate displacement was seen in patients treated with the balloon relative to those treated without the balloon (p ⫽ 0.008). A maximum displacement of ⬎5 mm was seen in 8 of 10 patients without the balloon and only 2 of 10 patients with the balloon. Another study that used CT scans to track prostate position also demonstrated reduced prostate motion with the rectal balloon. Teh et al. reported prostate displacement data from 10 patients treated with LDR brachytherapy followed by a 5-week course of IMRT using a rectal balloon.7 The device used in this study was a rectal catheter with an inflatable balloon (E-Z-EM, Westbury, NY) that is typically used for radiology studies. The balloon was inflated with 100 mL of air. Brachytherapy consisted of placement of 40 radioactive seeds in the prostate. CT scans were performed twice per week for all 5 weeks. Prostate motion in the AP and lateral dimension
Volume 36, Number 2, 2011
was on the order of uncertainty (approximately 1 mm). Mean and SD for SI displacements were 0.92 mm and 1.78 mm, respectively. A more recent report, authored by van Lin et al. of the University Medical Centre Nijmegen in the Netherlands, showed that there is not sufficient immobilization with a rectal balloon to allow for an off-line correction protocol to be safely executed in all patients. The authors used a rectal balloon designed as an endorectal coil for magnetic resonance imaging with a specific concave shape to conform to the prostate-rectal interface. It was inflated with 80 mL of air and had a length of 90 mm and diameter of 45 mm. Unlike the other studies, prostate displacement was measured daily in orthogonal directions with portal images. Implanted gold markers were used for prostate position verification and correction. Random day-to-day variation of prostate position was not reduced with a rectal balloon in this study. Offline correction protocols evaluated in this study did not adequately correct for the random (day-to-day) prostate displacements observed with use of their ERB. The authors speculate that the failure of the balloon to reduce random interfraction displacements in any direction relative to the treatment isocenter was a result of the presence of variable amounts of gas and stool beside the ERB.4 Several of these studies have demonstrated a reduction in prostate motion with the use of their ERBs, whereas our data and the study from The Netherlands clearly demonstrate very little advantage in internal immobilization for interfraction motion. A possible explanation is that only specific ERBs will be able to accomplish immobilization of the prostate. One problem complicating the use of the ERB, mentioned by van Lin et al., is the additional presence of gas or stool in the rectum varies sufficiently daily to displace the balloon and the prostate. The type of ERB may make a difference, and there have been no comparisons to date. The ERB we used was filled with 120 mL of water and should effectively displace stool and gas. To instill a larger balloon or more volume is unlikely to be feasible. Interestingly, the two studies that reported a benefit have been based on episodic CT imaging. Although CT scans reproduce the treatment position, imaging while in treatment position has obvious advantages. Daily CT imaging is difficult to justify, and few centers have the ability to image patients in treatment position. Our study and the study from the Netherlands utilized daily tracking of fiducial markers within the prostate with orthogonal portal imaging at the time of treatment. Furthermore, in addition to reporting more data per patient, our study and the study from The Netherlands include more patients, 2–3 times the number of patients included in the CT-based studies. A major limitation of all of these studies, including ours, is that the measured prostate motility is relative to the patients’ external skin marks. This positioning can be quite variable depending on how the therapists setup the
Endorectal balloon for prostate immobilization ● A. Y. HUNG et al.
patient on a particular day. In this way, setup variability is included with the prostate motion. A more complex investigation could measure the prostate displacement relative to the bony anatomy after the shifts have been made. Using bony anatomy to do so would require daily image guidance of some form. One of the goals of the rectal balloon is to avoid daily imaging of even the bony anatomy. Most practitioners who use the rectal balloon use it in lieu of daily image guidance. Our study demonstrates that the daily motion of the prostate with the rectal balloon, which does include setup variability, still requires daily image guidance to attain reliable accuracy. We compared the prostate motion during the first 14 fractions, our first “trimester,” with motion during fractions 15 through 28, the second trimester, and the third trimester, fractions 29 through 42. We hypothesized that rectal toxicity reduces tolerance to rectal distension causing the rectal volume to be more stable, and the prostate position, therefore, consistently posterior to its position at simulation. Data from a study by Crevoisier et al. regarding the effects of rectal distension at simulation supports this idea.8 In that study, patients with a distended rectum at simulation were significantly more likely to have a PSA failure. This may suggest that over the course of treatment the rectum was less likely to tolerate distention and the prostate position was, therefore, consistently posterior to its position on the planning CT. We were surprised to find that prostate motion increased significantly as the treatment progressed in patients treated without the ERB. This increase over the length of the treatment course was prevented by use of the ERB. We have no explanation for this finding but believe that this further supports the need for daily image guidance throughout the course of treatment. Our study is limited in its retrospective nature and its size. Our study numbers were limited to 29 because that was our accrual at the time we reviewed our data. If each patient is considered an independent subject, the small sample size of 29 patients is underpowered to detect a modest difference between the two groups. However, if each daily measurement is considered a sample unit, ignoring associations between the repeated measures, then the study has 100% power to detect differences of greater than 2 mm between the two groups. Another significant limitation of our study is the nonrandomized selection of patients for treatment with the ERB. The patients that were selected for the ERB may be predisposed to a more mobile prostate. And although we acknowledge the shortcomings of our comparison, to be effective, the ERB would have to stabilize the prostate in the vast majority of patients regardless of other factors. Regardless of the statistical comparisons between the two groups, our assessments that the margins necessary to completely encompass the prostate 95% of the time are based on ⬎400 repeated measures with the ERB.
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Without daily image guidance, the ERB does enable one to shrink the margins by a few millimeters vs. without a rectal balloon. However, the margins necessary in the lateral, cranio/caudal, and anterior/posterior dimensions are 4.1 mm, 10.4 mm, and 11 mm, respectively. To take full advantage of the conformality of IMRT or protons, daily image guidance needs to be performed. CONCLUSION Our data show that day-to-day variability of the position of the prostate is reduced in all dimensions with the use of our ERB. The differences we observed were not statistically significant. Even with the balloon, daily variability of the prostate necessitated daily shifts of the isocenter throughout the treatment course. Use of the balloon did not obviate daily verification by portal imaging of fiducial markers. The ERB did reduce the trend toward increased motion over the treatment course. This effect is dosimetrically insignificant and does not by itself indicate the use of the ERB. Highly conformal radiotherapy using close margins with IMRT or protons, therefore, cannot be delivered precisely using the ERB alone without daily imaging of fiducial markers. Dosimetric effects7 and decreased intrafraction motion1 with the balloon may still indicate an advantage for use of this device.
Acknowledgments—We would like to thank our therapy staff for their diligence in recording the data needed to evaluate the use of the rectal balloon.
REFERENCES 1. D’Amico, A.V.; Manola, J.; Loffredo, M.; et al. A practical method to achieve prostate gland immobilization and target verification for daily treatment. Int. J. Radiat. Oncol. Biol. Phys. 51:1431– 6; 2001. 2. McGary, J.E.; Teh, B.S.; Butler, E.B.; et al. Prostate immobilization using a rectal balloon. J. Appl. Clin. Med. Phys. 3:6 –11; 2002. 3. Wachter, S.; Gerstner, N.; Dorner, D.; et al. The influence of a rectal balloon tube as internal immobilization device on variations of volumes and dose-volume histograms during treatment course of conformal radiotherapy for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 52:91–100; 2002. 4. van Lin, E.N.; van der Vight, L.P.; Witjes, J.A.; et al. The effect of an endorectal balloon and off-line correction on the interfraction systematic and random prostate position variations: A comparative study. Int. J. Radiat. Oncol. Biol. Phys. 61:278 – 88; 2005. 5. Slater, J.D.; Rossi, C.J. Jr.; Yonemoto, L.T.; et al. Conformal proton therapy for early-stage prostate cancer. Urology. 53:978 – 84; 1999. 6. Gerstner, N.; Wachter, S.; Dorner, D.; et al. [Significance of a rectal balloon as internal immobilization device in conformal radiotherapy of prostatic carcinoma]. Strahlenther. Onkol. 175:232– 8; 1999. 7. Teh, B.S.; McGary, J.E.; Dong, L.; et al. The use of rectal balloon during the delivery of intensity modulated radiotherapy (IMRT) for prostate cancer: More than just a prostate gland immobilization device? Cancer. J. 8:476 – 83; 2002. 8. de Crevoisier, R.; Tucker, S.L.; Dong, L.; et al. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 62:965–73; 2005.
doi:10.1016/j.meddos.2010.03.003
MINIMAL BENEFIT OF AN ENDORECTAL BALLOON FOR PROSTATE IMMOBILIZATION AS VERIFIED BY DAILY LOCALIZATION ARTHUR Y. HUNG, M.D., MARK GARZOTTO, M.D., and DARRYL KAURIN, PH.D. Departments of Radiation Oncology and Surgery, Oregon Health & Science University, Portland, OR (Received 12 November 2008; Accepted 9 March 2010)
Abstract—We wanted to investigate whether using an endorectal balloon (ERB) in lieu of image guidance is reasonable. We compared daily prostate motion in 2 cohorts of patients with fiducial markers implanted in the prostate, one group with the ERB and the other without. Twenty-nine patients were treated using intensity-modulated radiation therapy: 14 with an ERB, and 15 without. All had fiducial markers placed in the prostate. We reviewed the daily displacements necessary to place the isocenter on the prostate as determined by portal imaging. In addition, we used the data to determine whether there is a change in prostate motion over the treatment course. The average prostate displacement for patients treated without an ERB was slightly greater than the average displacement for patients treated with the ERB. However, the difference observed with the ERB was not statistically significant (p > 0.05). The margins necessary to encompass the prostate 95% of the time for the patients treated without an ERB in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8, 12.1, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1, 10.4, and 11 mm, respectively. Prostate motion in the anteriorposterior direction actually increased over the course of treatment in patients without an ERB. This increase was prevented by use of the ERB. Day-to-day variability of the position of the prostate is reduced in all dimensions with the water-filled ERB, but not significantly statistically. Use of the water-filled ERB did not obviate performing some form of image guidance daily. © 2011 American Association of Medical Dosimetrists. Key Words: Prostate cancer, Prostate localization, Prostate image-guided radiation Therapy, Rectal balloon.
address these discrepancies, we studied two groups of patients: one treated with and one without an ERB. All patients had prostatic location verified on a daily basis by portal imaging of fiducial markers during IMRT. We undertook this study to evaluate the effect of an ERB on prostate motion.
INTRODUCTION The ability to accurately deliver a high dose of radiation to the target while minimizing radiation dose to the normal tissues is fundamental to the effective use of radiation as a treatment for cancer. In the treatment of prostate cancer, radiation dose to the rectal wall is responsible for much of the toxicity associated with the treatment. Intensity-modulated radiation therapy (IMRT) enables a concave distribution of dose, which improves the ability to deliver high doses of radiation to the prostate while avoiding the rectum. With this technology, motion of the prostate gland becomes a limiting factor in the ability to reduce treatment margins. Investigators have studied the use of an endorectal balloon (ERB) device for immobilization of the prostate gland during radiation treatment with IMRT for prostate cancer. Because prostate position depends largely on rectal filling, the balloon has been used to standardize the rectal volume, with the intent of decreasing the day-to-day variation in the position of the prostate and improve therapeutic targeting of the disease. Conflicting reports in the literature debate the effectiveness of an ERB for this purpose. Several authors have shown reduction of prostate motion using the balloon and suggested the feasibility of smaller margins with this device.1–3 Other recent reports, however, show no reduction in interfraction prostate motion with use of a balloon.4 To
MATERIALS AND METHODS Twenty-nine patients were identified who were treated definitively for prostate cancer with external beam radiation using IMRT. Patients with localized prostate cancer of all stages, Gleason grades, and prostate-specific antigen (PSA) levels were included in the analysis. Before treatment planning, all patients had three gold markers (Best Medical International, Inc., Springfield, VA) placed in the prostate under ultrasound guidance. Markers were placed bilaterally in the bases and singly in the apex. A planning pelvic computed tomography (CT) scan was then obtained using either 2.5 mm or 3.2 mm cuts. Before CT imaging, patients were asked to use an enema to evacuate the rectum. All patients were treated in the supine position with a MedTec (Orange City, IA) vacuum cradle fixing their leg, knee, and ankle position. All patients were scanned with and without an ERB. The decision regarding use of the balloon was nonrandomized and based on anatomical considerations from the planning CT. We elected to perform the treatment without the balloon in some patients because the balloon pushed the rectum closer to the prostate and seminal
Reprint requests to: Arthur Y. Hung, M.D., Department of Radiation Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mailcode: KPV4, Portland, OR 97239-3098. E-mail: [email protected] 195
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vesicles, making the organs more difficult to avoid. The clinical target volume (CTV) was the entire prostate. The planning target volume (PTV) was generated by expanding the CTV by 7 mm posteriorly, 7 mm inferiorly, and 12 mm around the remainder of the volume. Patients with high-risk features such as Gleason grade ⬎7, PSA ⬎15, or cT3 disease received concurrent hormonal ablation and were treated to 45 Gy to a pelvic field followed by an IMRT boost to the prostate 75.6 Gy. The data for high-risk patients is comprised only of adjustments made during the IMRT portion of their treatment (17 of the total 42 fractions). All other patients were treated with definitive IMRT to the CTV to 75.6 Gy. The rectal balloon is widely used in regional radiation treatment centers and was adopted from the technique described by the Loma Linda University Medical Center.5 The balloon is constructed with the following components: E-Z-Em Flexitip Infant Catheter Tip (E-Z-EM, Inc., New York, NY) (blue); Conmed 6-foot-long (Beaverton, OR), 3/16-in I.D. Suction Tubing (clear tube); nonlatex ultrasound probe covers (outer cover); female Luer Lock Connector (Dickinson Company, Franklin Lakes, NJ) (adapter for suction tubing and syringe); latex ultrasound probe cover (inner cover used with rubber band); Alliance Advantage Rubber Bands (Alliance Rubber Company, Hot Springs, AR); and 2 Luer Lock (Dickinson Company, Franklin Lakes, NJ) 60-mL syringes. To assemble the rectal balloon, a mark is made 9 cm from the top of the blue tip catheter. The catheter tip is then covered with the latex ultrasound probe cover and a rubber band is placed tightly around the cover at the 9-cm mark. The catheter tip is then inserted into the rectum until the rubber band reaches the anal verge. A volume of 120 mL of warm water is used to inflate the balloon after insertion. For daily treatments, the patient was lined up to isocenter based on external skin marks and orthogonal images obtained. A physician reviewed the images, and repositioning shifts were made in the lateral, anteriorposterior and cranial/caudal dimensions to within a 2-mm tolerance of where the fiducial markers were located on the digitally reconstructed radiographs of the treatment plan. These daily shifts from the original isocenter were recorded in the patient chart. To assess the effectiveness of the rectal balloon as an immobilization device, we reviewed the daily shifts necessary and compared the 2 patient cohorts. Mean shifts in each dimension were calculated for the entire treatment course for each cohort and this mean shift data was compared between the cohorts. We determined the range of prostate motion (defined as the sum of the greatest shift in the positive and negative direction) for each patient. The average range in each dimension was determined for each cohort. In addition, we used the data to determine whether there is a change in prostate mobility over the course of radiation treatment. Prostate motion over the treatment
Volume 36, Number 2, 2011
course was analyzed by dividing the 42 fractions into trimesters of 14 fractions each that were then compared with respect to prostate motion. The mean shift in each dimension for each patient cohort (balloon and no-balloon) was calculated for each 14-fraction trimester. Comparison between the trimesters was made within and across each cohort. The maximum prostate movement in any dimension for each treatment was identified for each patient. This data was used to evaluate differences in prostate movement between the groups and difference in movement over the treatment course. The range of prostate motion (defined as the sum of the greatest shift in the positive and negative direction) was calculated for each patient for each treatment day. Statistical analysis Analysis of variance tests (ANOVA) were applied to analyze the influence of different factors (presence of an ERB and elapsed treatment time) on shift magnitude in each dimension (anterior/posterior, right and left lateral, and superior/inferior). RESULTS Thirty patients treated definitively for prostate cancer using IMRT were identified. Fifteen patients were treated using a rectal balloon and 15 patients were treated without a balloon. One patient began treatment with a rectal balloon but, because of patient preference, use of the balloon was discontinued after two fractions. This patient was excluded from the analysis. Eleven patients in the series had high-risk disease; 4 of these patients were treated with a rectal balloon and 7 without a balloon (Table 1). The median number of shift measurements per patient in the no-balloon group for low-risk and high-risk patients was 39.5 and 16, respectively. The median number of shift measurements per patient in the ERB group for low- and high-risk patients was 39 and 14.5, respectively. Fewer data points were available in the high-risk patients because they received only the final 30.6 Gy boost (17 fractions) using IMRT. The average range in the lateral, cranial/caudal, and anterior/posterior directions for the cohort of patients treated without a balloon was 9.3 mm (2–29), 10.4 mm (2–25), and 13.4 mm (2–31), respectively, and for those treated with the balloon was 8.2 mm (2–13), 9.1 mm (2–21), and 9.6 mm (3–15), respectively. The data were compared using ANOVA tests and the differences were not statistically significant (p ⬎ 0.05). The average magnitude of prostate displacement over the entire course of treatment for patients treated without a balloon was 2.5 mm (SD 1.4), 4.6 mm (SD 2.9), and 7.3 mm (SD 4.8) in the lateral, cranial/caudal, and anterior/posterior dimension, respectively. For the cohort of patients treated with the balloon, the average
Endorectal balloon for prostate immobilization ● A. Y. HUNG et al.
Table 1. Clinical characteristics of 29 patients
Patient Characteristics Number of Patients Median Age Median Weight Karnofsky ⬍ 70 Median Karnofsky Median Prostate Volume (Range) Stage T1 T2 T3 T4 Gleason 6 7 8–10 PSA ⬍10 10–20 ⬎20 Treatment Hormones Pelvis Treated
197
12
Balloon
No Balloon
14 72 176 0 85 22.6 (17.1 – 72.4)
15 72 187 0 90 31.1 (8.8 – 131.4)
10 8 Balloon
6
No Balloon
4 2 0 1st Trimester
8 6 0 0
6 7 2 0
5 6 3
3 8 4
6 5 3
9 5 1
4 4
7 6
prostate displacement was 2.1 mm (SD 1.2), 4.1 mm (SD 3.6), and 5.4 mm (SD 3.4) in the lateral, cranial/caudal, and anterior/posterior dimension, respectively (Fig. 1). The difference in prostate motion with and without the rectal balloon was not statistically significant (p ⫽ 0.38, p ⫽ 0.27, and p ⫽ 0.22, respectively). We also analyzed the average prostate motion over the entire treatment course by dividing the 42 fractions into trimesters of 14 fractions each. The prostate motion in the lateral and superior-inferior dimensions did not change over the radiation treatment course. Surprisingly, prostate motion in the anterior-posterior dimension increased with treatment time in those patients treated without a balloon but not in patients treated with the balloon (p ⫽ 0.06). In the anterior/posterior direction for the cohort treated with no balloon, the mean shift nec-
2nd Trimester
3rd Trimester
Fig. 2. Mean prostate displacement in millimeters in the anterior/posterior dimension calculated for the first one-third (first trimester), second one-third, and final one-third of the treatment fractions. Comparison of patients treated with and without a rectal balloon (p ⫽ 0.06 for the trend). The error bars represent the standard error of the mean.
essary was 6.6 mm, 7.3 mm, and 8.3 mm in the first, second, and third trimester, respectively, whereas in the cohort treated with a balloon, the mean shift was 5.2 mm, 5.2 mm, and 5.5 mm in the first, second, and third trimester, respectively (Fig. 2). Another method of analyzing the data involved looking at the maximum displacement needed rather than the average displacement. We identified the maximum movement of the prostate in any dimension for each treatment. We analyzed whether this movement changed over time and discovered that the movement increased with each trimester to a statistically significant degree in the cohort of patients treated without a balloon. This increase was not seen in patients treated with a balloon (Fig. 3). In the cohort treated without a balloon, the mean value of the daily maximum shift in any direction was 7.6 mm, 9.0 mm, and 9.7 mm in the first, second, and third trimesters, respectively; in the cohort treated with a rectal balloon, the mean value of the daily maximum shift was 6.6 cm, 6.6 mm, and 7.1 mm in the first, second, and third trimesters, respectively. This trend for increased motion over time in patients treated without a balloon was significant with p ⫽ 0.006.
9
14
8 7
12
6 5
Balloon
4
No Balloon
3
10 8
Balloon No Balloon
6
2
4
1 0 Lateral Displacement
Cranio/caudal Displacement
Anterior/Posterior Displacement
2 0 1st Trimester
Fig. 1. Comparison of the mean prostate displacement in millimeters in each dimension over the entire radiation treatment course for patients treated with or without a rectal balloon (p ⫽ 0.38, p ⫽ 0.27, and p ⫽ 0.22 in the lateral, cranio/caudal, and anterior/posterior dimensions, respectively). The error bars represent the standard error of the mean.
2nd Trimester
3rd Trimester
Fig. 3. Maximum prostate displacement in any dimension averaged for each one-third (trimester) of the treatment fractions. Comparison of patients treated with and without a rectal balloon (p ⫽ 0.006 for the trend). The error bars represent the standard error of the mean.
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Medical Dosimetry
DISCUSSION To minimize treatment margins and maximize the therapeutic ratio, the prostate gland must be accurately targeted on a daily basis. To this end, radiation oncologists have used several strategies including daily insertion of an ERB as an immobilization device and daily tracking, via portal imaging, of fiducial markers placed in the prostate gland. Our data show that day-to-day variability of the position of the prostate is reduced in all dimensions with the use of a water-filled ERB. However, the absolute reduction in daily motion was small. The differences in prostate motion between the two groups of patients were not statistically different. Even with the balloon, daily variability of the prostate necessitated daily shifts to center the prostate on the isocenter throughout the treatment course. Use of the balloon did not obviate daily verification by portal imaging of fiducial markers. Based on our displacement data, the margins necessary to encompass the prostate 95% of the time for the no-balloon cohort in the lateral, cranio/caudal, and anterior/posterior dimensions would be 4.8 mm, 12.1 mm, and 15.2 mm, respectively. When using the ERB, the margins necessary would be 4.1 mm, 10.4 mm, and 11 mm, respectively. The margins used in treating patients in this study were 7 mm posteriorly and 12 mm around the remainder of the volume. Therefore, if no adjustments were made to compensate for daily prostate displacement, even with an ERB the target volume would fall outside of the treatment margins in an unacceptably high percentage of the treatments. Some investigators have shown a decrease in prostate motion with use of an ERB.2,3,6,7 Wachter et al. prospectively studied 10 patients undergoing IMRT for prostate cancer.3 CT scans were performed with and without a rectal balloon at the beginning, middle, and end of treatment. Their rectal balloon was made from a 30-cm-long 2-way rectal tube with a Silkolatex RueschGold balloon with a pilot balloon. The dimensions of the balloon filled with 40 ml of air are 5.5 ⫻ 4.0 cm. A decrease in maximum prostate displacement was seen in patients treated with the balloon relative to those treated without the balloon (p ⫽ 0.008). A maximum displacement of ⬎5 mm was seen in 8 of 10 patients without the balloon and only 2 of 10 patients with the balloon. Another study that used CT scans to track prostate position also demonstrated reduced prostate motion with the rectal balloon. Teh et al. reported prostate displacement data from 10 patients treated with LDR brachytherapy followed by a 5-week course of IMRT using a rectal balloon.7 The device used in this study was a rectal catheter with an inflatable balloon (E-Z-EM, Westbury, NY) that is typically used for radiology studies. The balloon was inflated with 100 mL of air. Brachytherapy consisted of placement of 40 radioactive seeds in the prostate. CT scans were performed twice per week for all 5 weeks. Prostate motion in the AP and lateral dimension
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was on the order of uncertainty (approximately 1 mm). Mean and SD for SI displacements were 0.92 mm and 1.78 mm, respectively. A more recent report, authored by van Lin et al. of the University Medical Centre Nijmegen in the Netherlands, showed that there is not sufficient immobilization with a rectal balloon to allow for an off-line correction protocol to be safely executed in all patients. The authors used a rectal balloon designed as an endorectal coil for magnetic resonance imaging with a specific concave shape to conform to the prostate-rectal interface. It was inflated with 80 mL of air and had a length of 90 mm and diameter of 45 mm. Unlike the other studies, prostate displacement was measured daily in orthogonal directions with portal images. Implanted gold markers were used for prostate position verification and correction. Random day-to-day variation of prostate position was not reduced with a rectal balloon in this study. Offline correction protocols evaluated in this study did not adequately correct for the random (day-to-day) prostate displacements observed with use of their ERB. The authors speculate that the failure of the balloon to reduce random interfraction displacements in any direction relative to the treatment isocenter was a result of the presence of variable amounts of gas and stool beside the ERB.4 Several of these studies have demonstrated a reduction in prostate motion with the use of their ERBs, whereas our data and the study from The Netherlands clearly demonstrate very little advantage in internal immobilization for interfraction motion. A possible explanation is that only specific ERBs will be able to accomplish immobilization of the prostate. One problem complicating the use of the ERB, mentioned by van Lin et al., is the additional presence of gas or stool in the rectum varies sufficiently daily to displace the balloon and the prostate. The type of ERB may make a difference, and there have been no comparisons to date. The ERB we used was filled with 120 mL of water and should effectively displace stool and gas. To instill a larger balloon or more volume is unlikely to be feasible. Interestingly, the two studies that reported a benefit have been based on episodic CT imaging. Although CT scans reproduce the treatment position, imaging while in treatment position has obvious advantages. Daily CT imaging is difficult to justify, and few centers have the ability to image patients in treatment position. Our study and the study from the Netherlands utilized daily tracking of fiducial markers within the prostate with orthogonal portal imaging at the time of treatment. Furthermore, in addition to reporting more data per patient, our study and the study from The Netherlands include more patients, 2–3 times the number of patients included in the CT-based studies. A major limitation of all of these studies, including ours, is that the measured prostate motility is relative to the patients’ external skin marks. This positioning can be quite variable depending on how the therapists setup the
Endorectal balloon for prostate immobilization ● A. Y. HUNG et al.
patient on a particular day. In this way, setup variability is included with the prostate motion. A more complex investigation could measure the prostate displacement relative to the bony anatomy after the shifts have been made. Using bony anatomy to do so would require daily image guidance of some form. One of the goals of the rectal balloon is to avoid daily imaging of even the bony anatomy. Most practitioners who use the rectal balloon use it in lieu of daily image guidance. Our study demonstrates that the daily motion of the prostate with the rectal balloon, which does include setup variability, still requires daily image guidance to attain reliable accuracy. We compared the prostate motion during the first 14 fractions, our first “trimester,” with motion during fractions 15 through 28, the second trimester, and the third trimester, fractions 29 through 42. We hypothesized that rectal toxicity reduces tolerance to rectal distension causing the rectal volume to be more stable, and the prostate position, therefore, consistently posterior to its position at simulation. Data from a study by Crevoisier et al. regarding the effects of rectal distension at simulation supports this idea.8 In that study, patients with a distended rectum at simulation were significantly more likely to have a PSA failure. This may suggest that over the course of treatment the rectum was less likely to tolerate distention and the prostate position was, therefore, consistently posterior to its position on the planning CT. We were surprised to find that prostate motion increased significantly as the treatment progressed in patients treated without the ERB. This increase over the length of the treatment course was prevented by use of the ERB. We have no explanation for this finding but believe that this further supports the need for daily image guidance throughout the course of treatment. Our study is limited in its retrospective nature and its size. Our study numbers were limited to 29 because that was our accrual at the time we reviewed our data. If each patient is considered an independent subject, the small sample size of 29 patients is underpowered to detect a modest difference between the two groups. However, if each daily measurement is considered a sample unit, ignoring associations between the repeated measures, then the study has 100% power to detect differences of greater than 2 mm between the two groups. Another significant limitation of our study is the nonrandomized selection of patients for treatment with the ERB. The patients that were selected for the ERB may be predisposed to a more mobile prostate. And although we acknowledge the shortcomings of our comparison, to be effective, the ERB would have to stabilize the prostate in the vast majority of patients regardless of other factors. Regardless of the statistical comparisons between the two groups, our assessments that the margins necessary to completely encompass the prostate 95% of the time are based on ⬎400 repeated measures with the ERB.
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Without daily image guidance, the ERB does enable one to shrink the margins by a few millimeters vs. without a rectal balloon. However, the margins necessary in the lateral, cranio/caudal, and anterior/posterior dimensions are 4.1 mm, 10.4 mm, and 11 mm, respectively. To take full advantage of the conformality of IMRT or protons, daily image guidance needs to be performed. CONCLUSION Our data show that day-to-day variability of the position of the prostate is reduced in all dimensions with the use of our ERB. The differences we observed were not statistically significant. Even with the balloon, daily variability of the prostate necessitated daily shifts of the isocenter throughout the treatment course. Use of the balloon did not obviate daily verification by portal imaging of fiducial markers. The ERB did reduce the trend toward increased motion over the treatment course. This effect is dosimetrically insignificant and does not by itself indicate the use of the ERB. Highly conformal radiotherapy using close margins with IMRT or protons, therefore, cannot be delivered precisely using the ERB alone without daily imaging of fiducial markers. Dosimetric effects7 and decreased intrafraction motion1 with the balloon may still indicate an advantage for use of this device.
Acknowledgments—We would like to thank our therapy staff for their diligence in recording the data needed to evaluate the use of the rectal balloon.
REFERENCES 1. D’Amico, A.V.; Manola, J.; Loffredo, M.; et al. A practical method to achieve prostate gland immobilization and target verification for daily treatment. Int. J. Radiat. Oncol. Biol. Phys. 51:1431– 6; 2001. 2. McGary, J.E.; Teh, B.S.; Butler, E.B.; et al. Prostate immobilization using a rectal balloon. J. Appl. Clin. Med. Phys. 3:6 –11; 2002. 3. Wachter, S.; Gerstner, N.; Dorner, D.; et al. The influence of a rectal balloon tube as internal immobilization device on variations of volumes and dose-volume histograms during treatment course of conformal radiotherapy for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 52:91–100; 2002. 4. van Lin, E.N.; van der Vight, L.P.; Witjes, J.A.; et al. The effect of an endorectal balloon and off-line correction on the interfraction systematic and random prostate position variations: A comparative study. Int. J. Radiat. Oncol. Biol. Phys. 61:278 – 88; 2005. 5. Slater, J.D.; Rossi, C.J. Jr.; Yonemoto, L.T.; et al. Conformal proton therapy for early-stage prostate cancer. Urology. 53:978 – 84; 1999. 6. Gerstner, N.; Wachter, S.; Dorner, D.; et al. [Significance of a rectal balloon as internal immobilization device in conformal radiotherapy of prostatic carcinoma]. Strahlenther. Onkol. 175:232– 8; 1999. 7. Teh, B.S.; McGary, J.E.; Dong, L.; et al. The use of rectal balloon during the delivery of intensity modulated radiotherapy (IMRT) for prostate cancer: More than just a prostate gland immobilization device? Cancer. J. 8:476 – 83; 2002. 8. de Crevoisier, R.; Tucker, S.L.; Dong, L.; et al. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 62:965–73; 2005.