First published online November 22, 2006
British Journal of Radiology (2007) 80, 279-283
© 2007 British Institute of Radiology
doi: 10.1259/bjr/54321311
A feasibility study of using gold seeds as fiducial markers for bladder localization during radical radiotherapy
S Mangar, MRCP, FRCR
1
A Thompson, FRCS
1
E Miles, MRCP, FRCR, PhD
2
R Huddart, MRCP, FRCR, PhD
1
A Horwich, FRCP, FRCR, PhD
1 and
V Khoo, FRACR, FRCR, PhD
1
1 Academic Department of Urology, 2 Radiotherapy Department, Royal Marsden Hospital and Institute of Cancer Research, London, UK
Correspondence: Dr Vincent Khoo, Consultant Clinical Oncologist, Academic Urology Unit, The Royal Marsden NHS Trust, Fulham Road, London SW3 6JJ, UK. E-mail: Vincent.Khoo{at}rmh.nhs.uk
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Abstract
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Target localization and verification of the treatment position is important for the accurate delivery of conformal radiotherapy. The bladder in particular is a deformable structure whose shape and position continually varies throughout a course of radiation treatment as a result of bladder filling. We report a novel technique of organ localization using gold seeds as fiducial markers that are implanted into the bladder using a specially adapted applicator that is passed through a rigid cystoscope. The seeds are readily apparent on electronic portal imaging taken at the time of radiotherapy and can thus act as a surrogate for bladder position. The feasibility and technical aspects of performing such a procedure on eight patients were assessed. In all of the patients, some of the seeds were visible on the planning CT scan and remained within the bladder wall throughout the course of radiotherapy treatment. The drop-out rate was minimized by the use of cystodiathermy at the site of seed insertion. It was possible to place the seeds in both areas of normal and diseased bladder tissue. The procedure was associated with minimal toxicity. This technique will form the basis for planning further studies on bladder localization.
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Introduction
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The treatment of bladder cancer using radiotherapy presents a technical challenge to the oncologist. The bladder is a mobile deformable structure whose shape and position is continually changing due to urinary filling. There are likely to be significant differences in bladder shape during radiotherapy compared with the planning scan resulting in a substantial systematic error [1–4]. Treatment set-up and verification is usually undertaken using electronic portal imaging and this method is only able to image bony landmarks and does not provide any soft tissue cross-sectional information.
To compensate for these circumstances relatively large safety margins need to be incorporated into the treatment plan to avoid geographical miss due to either a change in bladder position or shape.
The necessary use of conformal techniques allows us to shape the field more closely to the contour of the bladder, necessitating a greater need for improved bladder and tumour localization [5, 6]. Improving the localization of the bladder will result in more accurate treatment set-up and may allow for a reduction in the safety margin needed. The subsequent reduction in treatment volume could potentially lead to less treatment related toxicity and thus improve the effectiveness of bladder radiotherapy given alone or in combination with chemotherapy.
This report describes a novel approach to bladder localization using implanted gold seeds to act as fiducial markers. Gold seeds have been used in various ways for pelvic malignancies [7, 8]. In prostate cancer the seeds are introduced via an applicator attached to a transrectal ultrasound probe and can then be detected reliably using portal imaging [7, 9]. Although interstitial implantation has been used to treat localized bladder cancer, this technique involved the placement of rigid caesium needles, and more recently iridium wires via an afterloading technique [10, 11]. Both of these methods required direct visualization of the tumour by opening the bladder via a Pfannenstiel incision with the catheters exiting via a cystostomy.
This aim of this study was to determine whether cystoscopic seed implantation into a thin mobile wall such as the bladder is technically feasible and also whether they would remain in position during a course of radiotherapy to allow visualization.
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Materials and methods
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The procedure was performed in eight patients who were selected to have radiotherapy for their bladder cancer. All patients provided informed consent. The study was approved by both the scientific and local ethics committee at the Royal Marsden Hospital.
We developed a technique of implantation using a specifically adapted needle applicator that can be passed through a rigid cystoscope allowing the seeds to be inserted under direct visualization (Figure 1
). A rigid cystoscopy was performed under a short general anaesthetic prior to the patient's treatment planning scan. The needle applicator was of 0.8 mm bore; this size was chosen to allow free passage through the cystocope. The gold seeds were commercially available and chosen because the high density of gold (99.9% purity) facilitates optimum imaging on electronic portal imaging. Each seed after sterilization was manually pre-loaded into the needle using an aseptic technique before the applicator was passed through the cystoscope. The needle of the applicator was inserted into the bladder wall under direct visualization and the seeds implanted via the use of a guidewire operated manually. Five seeds were chosen initially, with three implanted around the original site of the tumour and the remaining in the contralateral wall. Seed lengths of 1 cm and 0.8 cm were used. These lengths were chosen as there is evidence that lengths of this magnitude give the best visualization on electronic portal imaging [12]. Toxicity was assessed by a patient questionnaire completed 48 h after the procedure. The seed drop-out rate was assessed at the time of the planning CT scan approximately 1 week later and then subsequently via regular electronic portal imaging taken at the time of radiotherapy.
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Results
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Initial experience
There was no additional toxicity over and beyond that associated with having a cystoscopy. In the first patient only one seed remained at the site of previous disease with the remaining four having fallen out (two right lateral wall, two left lateral wall) before the planning CT scan that was performed 1 week later. The seed was visible on the CT scan, simulator posteroanterior radiograph and the subsequent portal images for the duration of the radiotherapy. There was no evidence of seed migration into the abdomen or pelvis. All five seeds used were of 1 cm length (NB. This single seed has remained in situ at 1 year follow up).
Subsequent modifications
On the basis of these results we elected on the second and third patients to use a smaller seed and needle length as it was felt that the 1 cm seeds were too long to allow full implantation into the bladder wall. Also it was decided to use diathermy to seal the entrance site of the seed within the bladder wall. Again toxicity was limited to mild dysuria in two patients that settled spontaneously within 24 h. Using such modifications on the second patient, five out of six seeds were successfully implanted (six seeds were placed as we were unsure as to the placement of one seed at the time of the procedure). Similarly in the third patient four out of the five seeds were visible on both the planning CT and simulator radiograph (one right lateral wall, one left lateral wall and two in the perivesical fat). The seeds remained in place for the duration of radiotherapy treatment as evidenced by weekly portal imaging (Figure 3).
Our experience with the fourth patient who had placement of three seeds at the dome of the bladder (the site of disease) and one in each lateral wall was disappointing. All three seeds were displaced from the dome (including one from the lateral wall). Our data for the fifth patient were incomplete in that there was a persistently large amount of bowel within the treatment field, and dose tolerances could not be met. As a result this patient proceeded to radical cystectomy. Nevertheless, the feasibility of implanting at the dome and the durability of the procedure was re-affirmed in the sixth and subsequent patients. Table 1 provides a summary for all eight patients.
Of the 11 seeds in total that were displaced eight (73%) were from the site of original disease. The seed drop-out rate was two out of three for the disease affected lateral bladder walls compared with one out of three for the non-diseased lateral walls. It was not possible to place any seeds at the dome when affected by disease. The overall procedure time for all patients did not exceed 20 min. The seeds were visible on the CT, simulator and portal images (Figures 2 and 3
).
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Discussion
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Unlike implantation of gold seed fiducials into the prostate, several different factors need to be taken into account when considering bladder wall implantation. The bladder wall is relatively thin and is subject to continual distension from urine and to a lesser extent from rectal changes. Thus perforation of the wall and drop-out rate are likely to be much higher than in prostate implantation where the seeds are being placed within the substance of the gland. Although seeds have been placed in the bladder wall as markers for helping with brachytherapy regimens, these have required insertion with the bladder wall open under direct visualization and few data are available as to how durable these were.
Our initial experience with gold seed implantation into the bladder via a needle applicator passed through a cystoscope and under direct visualization has shown this to be a feasible approach. This procedure is associated with minimal toxicity and seed drop-out rate is reduced by the use of cystodiathermy. The technique of implanting the seeds appears to be durable in that if the seeds are present at the time of radiotherapy planning scan they are likely to remain in place for the duration of the treatment.
It is possible to implant the seeds around the tumour site and our initial experience suggests that this area is likely to be associated with a higher chance of seed drop-out. This may be explained by the fact that the involved bladder wall is somehow altered at the site of the tumour bed possibly being thinner as a result of previous transurethral resection. Also the fragility of the mucosa of the resected area made it more difficult to insert the needle adequately into the bladder wall. This was especially apparent in the second patient where one of the seeds could not be anchored within the wall satisfactorily and fell out during the procedure. In addition the length of the needle may have been too long such that it pierced the bladder wall. Although the needle length was shortened after the first patient, there was still evidence that seeds were being deposited within the perivesical fat in subsequent patients. It is planned in the future to further shorten the needle length by 1 mm. We were unable to successfully implant the seeds where the tumour site was located at the dome of the bladder and this may be because of the predominant superior wall motion as the bladder fills [13–15]. It is most likely that seed drop-out was as a result of a combination of these factors.
Not all of the seeds visible were placed successfully in the bladder wall itself. 21% of the seeds were placed outside the bladder wall within the perivesical fat and these did not seem to migrate. As such these can still serve as a useful surrogate marker as they lie adjacent to the bladder wall. Given the increased propensity for seeds to be displaced from the tumour bed we suggest that at least three seeds should be inserted into the affected bladder wall and two seeds into non-affected walls. Although our experiences from patient 8 suggest that it is possible to place seeds at the site of disease within the bladder dome, further clarification will be required to establish the durability of implanting this wall when affected by tumour.
We plan to continue to develop this procedure especially in the context of image guided regimens. If the site of the bladder tumour can be accurately localized by placement of these markers, then it may be possible to incorporate this technique in the planning of boost treatments for partial bladder irradiation for which accurate tumour localization is mandatory. In the next cohort of patients we will seek to explore whether any seed movement occurs during radiotherapy and define more closely the optimal number of seeds required and seed drop-out rate.
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Acknowledgments
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This work was undertaken in The Royal Marsden NHS Foundation Trust who received a proportion of its funding from the NHS Executive; the views expressed in this publication are those of the authors and not necessarily those of the NHS Executive. This work was supported by the Institute of Cancer Research, the Bob Champion Cancer Trust and Cancer Research UK Section of Radiotherapy [CUK] grant number C46/A2131. In addition the author wishes to express thanks to A Medhurst, P Hadzhimladenov, M Kanev, J Mangar, I Mangar, F Power, L Barnet and C Parker.
Received for publication July 14, 2006.
Revision received September 18, 2006.
Accepted for publication September 22, 2006.
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Abstract
Introduction
