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doi:10.1016/j.meddos.2004.10.
IMPACT OF SETUP UNCERTAINTY IN THE DOSIMETRY OF
PROSTATE AND SURROUNDING TISSUES IN PROSTATE CANCER
PATIENTS TREATED WITH PEACOCK/IMRT
Presented at the 87th Scientific Assembly and Annual Meeting of Radiological Society of North America, Chicago, IL, November 25–30, 2001.
S ALAHUDDIN A HMAD, P H.D., M ARIA T. V LACHAKI, M.D., P H.D., T ERRANCE N. T ESLOW, P H.D.,
C HAD M. AMOSSON, M.D., JOHN M CG ARY, P H.D., B IN S. T EH, M.D., S HIAO Y. W OO, M.D.,
E. B RIAN B UTLER, M.D., and W ALTER H. G RANT, III, P H.D.
Department of Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX
( Accepted 13 October 2004)
Abstract—The purpose of this paper was to assess the effect of setup uncertainty on dosimetry of prostate, seminal vesicles,
bladder, rectum, and colon in prostate cancer patients treated with Peacock intensity-modulated radiation therapy (IMRT).
Ten patients underwent computed tomography (CT) scans using the “prostate box” for external, and an “endorectal balloon”
for target immobilization devices, and treatment plans were generated (T1). A maximum of 5-mm setup error was chosen
to model dosimetric effects. Isodose lines from the T1 treatment plan were then superimposed on each patient’s CT anatomy
shifted by 5 mm toward the cephalad and caudal direction, generating 2 more dosimetric plans (H1 and H2, respectively).
Average mean doses ranged from 74.5 to 74.92 Gy for prostate and 73.65 to 74.94 Gy for seminal vesicles. Average percent
target volume below 70 Gy increased significantly for seminal vesicles, from 0.53% to 6.26%, but minimally for prostate, from
2.08% to 4.4%. Dose statistics adhered to prescription limits for normal tissues. Setup uncertainty had minimum impact on
target dose escalation and normal tissue dosing. The impact of target dose inhomogeneity is currently evaluated in clinical
studies. © 2005 American Association of Medical Dosimetrists.
Key Words: Prostate cancer, IMRT, Setup error.
INTRODUCTION
Radiation therapy is a standard therapeutic technique for
early and locally-advanced prostate cancer. Conventional
techniques have been associated with high failure rates,
as they do not allow the delivery of higher curative tumor
doses without overdosing the surrounding normal tis-
sues. Dose escalation to tumor is necessary to overcome
tumor clone resistance and intracellular repair of radia-
tion-induced damage.^1 The limitations of conventional
therapy have been overcome with the development of
three-dimensional conformal radiotherapy
2–
and, espe-
cially, with intensity modulated radiation therapy
(IMRT).6,7^ IMRT conforms radiation to the shape of the
target while minimizing exposure of surrounding critical
structures.8 –11^ Such approach allows for safer tumor
dose escalation and promises to widen the therapeutic
window of the treatment by improving tumor control and
decreasing treatment-related complications.
At Baylor College of Medicine and at the Houston
Veterans Affairs Medical Center (VAMC), prostate im-
mobilization is achieved by an endorectal balloon
12–
inflated with 100 cc of air. The balloon pushes the
prostate toward the pubic symphysis and the posterior
rectal wall away from the prostate and, therefore, from
the area targeted by high radiation doses.
16 –
Our group
has previously reported that the maximum prostate dis-
placement in the presence of an endorectal balloon dur-
ing radiotherapy occurs in the superior-inferior direction
with a standard deviation of 1.78 mm.12,13^ By using a
special external immobilization device, our group has
also reported that the standard deviation of setup errors is
3.5 mm and from daily portal films, most of the setup
errors observed were closer to 5 mm.^19 Dosimetric data
resulting from setup variations are lacking.^19
The present study was undertaken to assess the
effect of setup uncertainty on the dosimetry of the pros-
tate, seminal vesicles, and surrounding normal tissues. It
focuses on modeling the range of dosimetric variations,
based on a maximum setup uncertainty of 5 mm. The
objective of this study is to report the impact of these
variations on target dose escalation and on normal tissue
avoidance, as these may greatly influence tumor control
and normal tissue complication probability.
METHODS AND MATERIALS
Ten prostate cancer patients treated with IMRT at
the Houston VAMC were included in the present study.
The treatment planning was performed with the Peacock
NOMOS system consisting of the multileaf intensity-
modulating collimator (MIMiC™) and the Corvus™
(version 3.0 rev. 1) treatment planning system.12,20 –
Reprint requests to: Salahuddin Ahmad, Ph.D., Department of Radiation Oncology, University of Oklahoma HSC, Everett Tower, 1200 North Everett Drive, Room B603, Oklahoma City, OK 73104
Medical Dosimetry, Vol. 30, No. 1, pp. 1-7, 2005 Copyright © 2005 American Association of Medical Dosimetrists Printed in the USA. All rights reserved 0958-3947/05/$–see front matter
External immobilization
The external immobilization with the Peacock/
IMRT system is achieved with a device called the “pros-
tate box.” Details about this technique have been pub-
lished elsewhere.12,13,19^ In summary, it consists of a
wooden box-like frame that supports the fiducial plates
for target alignment and a beanbag that molds over the
shape of the patient (Fig. 1). The beanbag is a commer-
cially available vinyl bag (Soule) filled with 55 liters of
Styrofoam beads. By sequentially introducing and evac-
uating air with a vacuum pump, the beads move and the
bag molds and solidifies, providing a rigid impression of
the patient’s body. Treatment planning is performed with
the patient in the prone position and the fiducial plates
are used to ensure that the central axis of the beam is
tangential to the top of the pubic symphysis.
Organ immobilization
Prostate immobilization is achieved with the use of
an inflated endorectal balloon. A nonlatex endorectal
catheter (Flexi-Cuff™, EZEM) covered by a condom is
inserted into the rectum before each treatment and the
inflatable balloon is then filled with 100 cc of air (Fig. 2).
CT scan technique
All 10 patients underwent computerized tomogra-
phy (CT) planning in the prone position. CT scans were
taken from just above the top of the bladder to the level
of the anal verge with the endorectal balloon in the
rectum. Anteroposterior and lateral scout films were ob-
tained to ensure that the pubic symphysis was aligned
with the central axis, defined by the wired center axis of
the fiducial plates (Fig. 3).
During the course of treatment, the patient’s exter-
nal treatment position was secured by 3 horizontal lines
marked on the beanbag, and on the patient’s lower legs
(Fig.1). For patient position verification throughout the
treatment, daily lateral port films were obtained for the
first week, followed by weekly lateral port films for all patients. Comparisons between portal and scout films demonstrated maximum patient setup deviations of 4. mm in the superior and 3.9 mm in the inferior axis (data not shown). For the purposes of this study, a setup error of 5 mm was thus chosen to model dosimetric effects resulting from setup uncertainties.
Computerized treatment planning The plan (T1) used for patient treatment was per- formed using the delineated anatomy from CT and dose- volume histograms (DVHs) and isodose lines were gen- erated for this plan. Two hybrid plans (H1 and H2) were then generated by superimposing each patient’s isodose lines from treatment plan T1 on CT anatomy shifted by 5 mm superiorly and inferiorly, respectively, to the setup
Fig. 1. The “prostate box” is the external immobilization device
used for patient treatments with the Peacock/IMRT technique.
It supports the moldable beanbag and affixes to the fiducial
alignment system.
Fig. 2. Inflated endorectal balloon for prostate immobilization.
Fig. 3. Sagittal CT scout film depicting the endorectal balloon
as well as the alignment of the center of beam axis with the top
of the pubic symphysis.
2 Medical Dosimetry Volume 30, Number 1, 2005
prostate, it ranged from 65.62 to 73.86 Gy (Table 4). These target EUD changes were observed with shifts in the superior direction only. A regression method was used to evaluate the possible correlation between target EUD values for all 30 plans (3 plans per patient, 10 patients) and their mean and minimum doses as well as the percent target volumes below goal. It was observed that EUD doses correlated highly only with the minimum doses for both the prostate and seminal vesicles, with coefficients of determination (squared value of correla- tion coefficient R) of 0.932 and 0.704, respectively. Notably, EUD doses below 72.5 Gy corresponded to minimum doses below 61 Gy for prostate and below 65 Gy for seminal vesicles (Fig.4).
DISCUSSION
This study assesses the dosimetric effect of both external and organ immobilization uncertainties on tar- gets and normal tissues in prostate cancer patients treated with Peacock/IMRT using an endorectal balloon for prostate immobilization. It was designed to model and describe the range of dosimetric variations resulting from a maximum clinically acceptable setup error of 5 mm. Measurement and understanding of these dosimetric
variations may prove useful in optimizing inhomoge- neous plans and in developing data-evidenced guidelines for the evaluation and selection of IMRT plans, espe- cially in view of our efforts to deliver higher curative radiation doses while minimizing radiation reactions. In this report, mean target doses remained escalated above 70 Gy, despite excessive dosimetric variations introduced by study design. Higher escalated average mean doses above 74 Gy were observed for the prostate, while average mean seminal vesicle doses also remained escalated above 73.6 Gy, with the exception of one plan (71.8 Gy). However, setup uncertainties increased target dose inhomogeneity, as evidenced by the significant changes in the target minimum doses and EUDs. Specifically, mean EUD decreases of 11% for prostate and 4% for seminal vesicles were observed as a result of a 5-mm shift in the superior direction only. A similar shift in the inferior direction did not decrease target EUD values. Correlations between target minimum doses and EUDs revealed that minimum doses of at least 61 Gy for the prostate and 66 Gy for the seminal vesicles are necessary to achieve EUDs higher than 72.5 Gy, which have been reported to be associated with better outcomes.
24
Table 3. Percent volumes of normal tissues receiving doses greater than prescription limit* of all 10 studied patients
Rectum Colon Bladder
Patient T1 H1 H2 T1 H1 H2 T1 H1 H
1 13.1 17.2 10.6 12.0 13.3 8.2 9.6 3.0 17. 2 14.9 15.5 13.6 4.8 4.7 4.9 10.8 4.9 19. 3 15.3 15.6 15.5 15.4 12.1 20.3 7.0 3.2 11. 4 13.5 13.6 13.2 15.2 14.1 13.5 9.4 3.7 15. 5 12.2 13.2 12.9 11.1 9.8 13.5 4.7 2.0 8. 6 17.7 18.6 16.6 13.5 11.0 9.6 8.2 2.0 16. 7 13.0 14.3 12.1 15.4 17.8 12.5 5.8 1.4 11. 8 12.6 12.1 12.4 3.4 3.0 2.8 9.3 5.5 13. 9 14.8 14.5 14.4 7.8 2.3 11.6 6.9 3.2 11. 10 15.4 17.8 13.1 20.1 20.8 16.1 5.6 2.2 9. Mean 14.3 15.2 13.4 11.9 10.9 11.3 7.73 3.11 13.
*Prescription limit: 15% rectum and colon volume to exceed 68 Gy; 33% bladder volume to exceed 65 Gy.
Table 4. The equivalent uniform dose (EUD) for prostate and seminal vesicles for each of the 10 studied patients
using all dosimetric plans
Prostate Seminal Vesicles
Patient T1 H1 H2 T1 H1 H
1 73.76 73.87 74.96 75.14 74.47 73. 2 73.62 61.59 73.67 74.42 72.42 74. 3 75.39 73.96 75.81 77.29 62.92 77. 4 73.76 73.72 73.51 74.75 73.35 74. 5 73.87 67.58 74.02 72.74 72.38 71. 6 74.14 59.74 75.09 73.28 71.27 69. 7 71.10 45.33 71.67 73.42 71.36 73. 8 73.52 73.96 72.31 75.84 73.42 76. 9 74.36 68.57 73.99 76.40 74.86 75. 10 72.82 57.90 73.59 73.89 71.53 72. Mean 73.63 65.62 73.86 74.72 71.80 73.
4 Medical Dosimetry Volume 30, Number 1, 2005
The observed prostate dose inhomogeneity may be
attributed to the PTV size of 5 mm for prostate and 3 mm
for seminal vesicles used in this study, compared to
PTVs of 0.6 –1.5 cm reported by others.2,3^ However, in
those studies, organ immobilization devices were not
used in treatment planning or delivery, in order to limit
inter- and intra-fraction organ movement.24 –33^ Our
group has already reported that the endorectal balloon
limits prostate motion to less that 2 mm^12 and that, with
the use of “prostate box” for external immobilization, the
standard deviation of the setup error is 3.5 mm.^19 In
addition, our group has already shown that CT prostate
volumes, as delineated by radiation oncologists, are 35–
126% larger compared to prostatectomy specimens, and
that the PTVs overestimate prostate volumes by 233–
404%.^35 These data indicate that our current PTV of 5
mm is adequate and accounts for average variations in
the organ position and patient setup. In addition, enlarg-
ing the PTV in IMRT plans enhances target dose inho-
mogeneity, and increases the size and the radiation doses delivered in hot spots, therefore, placing the surrounding normal tissues at risk of overdosing in cases when organ movement or errors in patient external immobilization occur. Among the targets, seminal vesicles were mostly affected by dose inhomogeneities, as evidenced by the changes in the EUDs and percent organ volume receiv- ing a dose below 70 Gy. The clinical impact of these findings is unclear especially for the seminal vesicles, as the indications, dose, and volume of treatment is a field of investigation and controversy. Some clinicians prefer to administer subclinical radiation doses to uninvolved seminal vesicles, or deliver higher doses only when they are at high risk of involvement with disease. Even in cases with clinical and/or radiographic evidence of in- volvement, some radiotherapists prefer to deliver an in- termediate seminal vesicle boost dose of 56 Gy, as fur- ther dose escalation may increase the risk of rectal toxicity.^36 Therefore, the demonstrated minimum semi- nal vesicle EUD values of 62.92 Gy in our study may prove satisfactory both for patients at low and high risk for disease dissemination to the seminal vesicles. It is also notable in this study that a 5-mm variation in patient setup does not significantly change normal tissue dosimetry, as average normal tissue vol- umes above tolerance adhered to prescription guidelines. However, review of individual plans demonstrated per- cent rectum and colon volumes above prescription limits in excess of 18% in 3 of 10 patients. These data indicate that the choice of larger PTV margins may result in normal tissue overdosing in view of target dose escala- tion and patient and organ position uncertainties. These dosimetric observations are supported by published clinical data on 100 patients treated with this technique, demonstrating its very favorable acute toxic- ity profile^14 Specifically, escalated mean prostate and seminal vesicle doses of 75.8 and 73.9 Gy resulted in RTOG (Radiation Therapy Oncology Group) grade 1 and 2 acute genitourinary toxicities in 38% and 35% of patients, respectively, and in grade 1 and 2 gastrointes- tinal toxicities in 11% and 6% of patients, respectively.^37 In addition, late toxicity was reported to be favorable as well, as grade 1, 2, and 3 toxicity scores were 10.3%, 6.9%, and 1.7% for GI and 10.3%, 16.4%, and 2.6% for GU-related complications, respectively.^38 No statisti- cally significant correlation was found between acute or late GI/GU toxicity and mean bladder/rectal dose or bladder/rectal volumes receiving above 65, 70, or 75 Gy. It was concluded that more work with larger cohorts of patients is warranted to investigate predictors of acute and late toxicities in prostate cancer patients treated with the Peacock/IMRT technique. The authors recognize the limitations of the present study. Although our study attempted to simulate the range of dosimetric variations during therapy as they may be introduced by our maximally clinically accept-
Fig. 4. Target EUD for all 60 plans correlate highly only with
the minimum doses.
Setup uncertainty in prostate cancer treated with IMRT ● S. A HMAD et al. 5
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- Padhani, A.R.; Khoo, V.S.; Suckling, J.; et al. Evaluating the effect of rectal distension and rectal movement on prostate gland position using cine MRI. Int. J. Radiat. Oncol. Biol. Phys. 44: 525–33;
- Langen, K.M.; Jones, D.T.L. Organ motion and its management. Int. J. Radiat. Oncol. Biol. Phys. 50: 265–78; 2001.
- Uhl, B.M.; Teh, B.S.; Wheeler, T.; et al. Intensity-modulated radiation therapy (IMRT) for localized prostate cancer: A compar- ison of Peacock conformal treatment volumes and pathologic rad- ical prostatectomy specimens. Int. J. Radiat. Oncol. Biol. Phys. 42 (Suppl):292; 1998.
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Setup uncertainty in prostate cancer treated with IMRT ● S. A HMAD et al. 7
