Prostate bed radiation therapy: the utility of ultrasound volumetric imaging of the bladder.

AIMS: To evaluate the effect of incorporating daily ultrasound scanning to reduce variation in bladder filling before prostate bed radiotherapy. The primary aim was to confirm that coverage of the planning target volume (PTV) with the 95% isodose was within tolerance when the ultrasound-determined bladder volume was within individualised patient limits. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images were acquired on 10 occasions during the course of treatment to assess systematic changes in rectal or bladder volume as part of a standard offline image-guided radiotherapy (IGRT) protocol. In addition, through a two-part study an ultrasound scan of the bladder was added to the IGRT protocol. In the Part 1 study, the ultrasound-determined bladder volume at the time of treatment simulation in 26 patients was compared with the simulation computed tomography cranio-caudal bladder length. The relationship between the two was used to establish bladder volume tolerance limits for the interventional component of the Part 2 study. In the Part 2 study, 24 patients underwent ultrasound scanning before treatment. When bladder volumes were outside the specified limits, they were asked to drink more water or void as appropriate until the volume was within tolerance. RESULTS: Based on the results of the Part 1 study, a 100 ml tolerance was applied in the Part 2 study. Seventy-six per cent of patients found to have bladder volumes outside tolerance were able to satisfactorily adjust their bladder volumes on demand. Comparing the bladder volumes with the CBCT data revealed that the bladder scanner correctly predicted that the target volume would be accurately targeted (using surrogate end points) in 83% of treatment fractions. CONCLUSION: A simple hand-held ultrasound bladder scanner provides a practical, inexpensive, online solution to confirming that the bladder volume is within acceptable, patient-specific limits before treatment delivery, with the potential to improve overall treatment accuracy.

Cost minimisation analysis: kilovoltage imaging with automated repositioning versus electronic portal imaging in image-guided radiotherapy for prostate cancer.

AIMS: To compare the treatment time and cost of prostate cancer fiducial marker image-guided radiotherapy (IGRT) using orthogonal kilovoltage imaging (KVI) and automated couch shifts and orthogonal electronic portal imaging (EPI) and manual couch shifts. MATERIALS AND METHODS: IGRT treatment delivery times were recorded automatically on either unit. Costing was calculated from real costs derived from the implementation of a new radiotherapy centre. To derive cost per minute for EPI and KVI units the total annual setting up and running costs were divided by the total annual working time. The cost per IGRT fraction was calculated by multiplying the cost per minute by the duration of treatment. A sensitivity analysis was conducted to test the robustness of our analysis. Treatment times without couch shift were compared. RESULTS: Time data were analysed for 8648 fractions, 6057 from KVI treatment and 2591 from EPI treatment from a total of 294 patients. The median time for KVI treatment was 6.0 min (interquartile range 5.1-7.4 min) and for EPI treatment it was 10.0 min (interquartile range 8.3-11.8 min) (P value < 0.0001). The cost per fraction for KVI was A$258.79 and for EPI was A$345.50. The cost saving per fraction for KVI varied between A$66.09 and A$101.64 by sensitivity analysis. In patients where no couch shift was made, the median treatment delivery time for EPI was 8.8 min and for KVI was 5.1 min. CONCLUSIONS: Treatment time is less on KVI units compared with EPI units. This is probably due to automation of couch shift and faster evaluation of imaging on KVI units. Annual running costs greatly outweigh initial setting up costs and therefore the cost per fraction was less with KVI, despite higher initial costs. The selection of appropriate IGRT equipment can make IGRT practical within radiotherapy departments.

Patient-reported complications from fiducial marker implantation for prostate image-guided radiotherapy.

OBJECTIVES: To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy. METHODS: 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale. RESULTS: Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5). CONCLUSION: Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

Electronic portal imaging vs kilovoltage imaging in fiducial marker image-guided radiotherapy for prostate cancer: an analysis of set-up uncertainties.

OBJECTIVES: The purpose of this study was to compare interfraction prostate displacement data between electronic portal imaging (EPI) and kilovoltage imaging (KVI) treatment units and discuss the impact of any difference on margin calculations for prostate cancer image-guided radiotherapy (IGRT). METHODS: Prostate interfraction displacement data was collected prospectively for the first 4 fractions in 333 patients treated with IGRT with daily pre-treatment EPI or KVI orthogonal imaging. Displacement was recorded in the anteroposterior (AP), left-right (LR) and superoinferior (SI) directions. The proportion of displacement <3 mm and the difference in median absolute displacements were calculated in all directions. RESULTS: 1088 image pairs were analysed in total, 448 by EPI and 640 by KVI. There were 23% (95% confidence interval [CI] 18-28%) more displacements under 3 mm for EPI than for KVI in the AP direction, 14% (95% CI 10-19%) more in the LR direction and 10% (95% CI 5-15%) more in the SI direction. The differences in absolute median displacement (KVI>EPI) were AP 1 mm, LR 1 mm and SI 0.5 mm. Wilcoxon rank-sum test showed that distributions were significantly different for all three dimensions (p<0.0001 for AP and LR and p=0.02 for SI). CONCLUSION: EPI has a statistically significant smaller set-up error distribution than KVI. We would expect that, because fiducial marker imaging is less clear for EPI, the clinical target volume to planning target volume margin would be greater when using IGRT; however, relying wholly on displacement data gives the opposite result. We postulate that this is owing to observer bias, which is not accounted for in margin calculation formulas.

Interfraction patient motion and implant displacement in prostate high dose rate brachytherapy.

PURPOSE: To quantify movement of prostate cancer patients undergoing treatment, using an in-house developed motion sensor in order to determine a relationship between patient movement and high dose rate (HDR) brachytherapy implant displacement. METHODS: An electronic motion sensor was developed based on a three axis accelerometer. HDR brachytherapy treatment for prostate is delivered at this institution in two fractions 24 h apart and 22 patients were monitored for movement over the interval between fractions. The motion sensors functioned as inclinometers, monitoring inclination of both thighs, and the inclination and roll of the abdomen. The implanted HDR brachytherapy catheter set was assessed for displacement relative to fiducial markers in the prostate. Angle measurements and angle differences over a 2 s time base were binned, and the standard deviations of the resulting frequency distributions used as a metric for patient motion in each monitored axis. These parameters were correlated to measured catheter displacement using regression modeling. RESULTS: The mean implant displacement was 12.6 mm in the caudal direction. A mean of 19.95 h data was recorded for the patient cohort. Patients generally moved through a limited range of angles with a mean of the exception of two patients who spent in excess of 2 h lying on their side. When tested for a relationship between movement in any of the four monitored axes and the implant displacement, none was significant. CONCLUSIONS: It is not likely that patient movement influences HDR prostate implant displacement. There may be benefits to patient comfort if nursing protocols were relaxed to allow patients greater freedom to move while the implant is in situ.

In pursuit of individualised margins for prostate cancer patients undergoing image-guided radiotherapy: the effect of body mass index on intrafraction prostate motion.

AIMS: To analyse the relationship between body mass index (BMI) and intrafraction displacement in patients undergoing prostate cancer image-guided radiotherapy. MATERIALS AND METHODS: An analysis was carried out on 151 prostate cancer patients treated with radical dose radiotherapy between January 2007 and March 2009. Patients had their height, weight and daily intrafraction prostate displacement data collected prospectively during fiducial marker image-guided radiotherapy with orthogonal imaging. For each of anterior-posterior, left-right and superior-inferior axes, a univariable linear regression analysis was carried out with the individual patient standard deviation of shift as the response variable and BMI as a continuous explanatory variable. RESULTS: Displacement measurements were recorded from 4764 pre- and post-treatment image sets. Patients were grouped according to BMI as normal weight (24%), overweight (52%), obese (18%), severely obese (3%) or morbidly obese (3%). For intrafraction displacement, a one unit increase in BMI affected the standard deviation of shift by: anterior-posterior -0.02 (95% confidence interval -0.040 to 0.000), left-right -0.006 (95% confidence interval -0.020 to 0.008) and superior-inferior -0.020 (95% confidence interval -0.037 to -0.003). CONCLUSIONS: Our data indicate that patients with a higher BMI have less intrafraction displacement of the prostate in the superior-inferior dimension compared with patients with a lower BMI. This has implications for individualised treatment margins for future prostate cancer patients undergoing image-guided radiotherapy. Further study is recommended.

Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2010 consensus guidelines for definitive external beam radiotherapy for prostate carcinoma.

External beam radiotherapy for prostate cancer has undergone substantial technological and clinical advances in the recent years. The Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group undertook a process to develop consensus clinical practice guidelines for external beam radiotherapy for prostate carcinoma delivered with curative intent, aiming to provide guidance for clinicians on the appropriate integration of clinical evidence and newer technologies. Draft guidelines were presented and discussed at a consensus workshop in May 2009 attended by radiation oncologists, radiation therapists and medical physicists. Amended guidelines were distributed to radiation oncologists in Australia, New Zealand and Singapore for comment, and modifications were incorporated where appropriate. Evidence based recommendations for risk stratification, the role of image-guided and intensity-modulated radiation therapy, prescribed dose, simulation and treatment planning, the role and duration of neo-adjuvant/adjuvant androgen deprivation therapy and outcome reporting are presented. Central to the guidelines is the recommendation that image-guided radiation therapy should be used when definitive external beam radiotherapy for prostate cancer is prescribed. The consensus guidelines provide a co-operatively developed, evidence-based framework for contemporary treatment of prostate cancer with external beam radiotherapy.

Prospective development of an individualised predictive model for treatment coverage using offline cone beam computed tomography surrogate measures in post-prostatectomy radiotherapy.

The aim of this study is to prospectively evaluate and model surrogate explanatory variables (SEVs) of target coverage and rectal dose pertaining to soft tissue anatomy visualised on cone beam computed tomography (CBCT) for incorporation into post-prostatectomy treatment coverage verification protocols. Twenty post-prostatectomy patients treated with conformal prostate bed radiotherapy (64-74 Gy) underwent CBCT daily at fractions 1 to 5, and then weekly. Treatment coverage was defined on each CBCT using 'PTV95', percentage of the CBCT PTV covered by original treatment fields, and 'RECTD50', dose delivered to 50% of CBCT rectal volume by original treatment fields. Three candidate SEVs for treatment coverage were defined for each scan: anterior rectal wall movement, change in bladder length and bladder base movement. Both anterior rectal wall movement and increase in bladder length predicted for the decreased PTV95 (P < 0.001 for each). Anterior movement of the anterior rectal wall predicted for increased RECTD50 (P < 0.001). Predictive models for the PTV95 and RECTD50 that accept the significant SEVs as inputs were developed. We developed simple CBCT-acquired soft tissue anatomic surrogate measures that signal changes in target coverage and rectal dose during post-prostatectomy radiotherapy. Conventional bony anatomy patient position verification protocols were inadequate in accounting for soft tissue target and organ variation seen with CBCT.

Rectal filling at planning does not predict stability of the prostate gland during a course of radical radiotherapy if patients with large rectal filling are re-imaged.

AIMS: It has been suggested that large rectal filling is associated with an increased risk of prostate motion in radiotherapy. The aim of the present study was to determine if there is a correlation between rectal distension on planning computed tomography and the intrafraction and interfraction stability of the prostate gland during a course of radical radiotherapy for prostate cancer if a protocol was used to rescan patients with excessive rectal diameter during planning. MATERIALS AND METHODS: The computed tomography planning scans of 89 patients with adenocarcinoma of the prostate treated with conformal radiotherapy were reviewed. All patients had three gold seed fiducial markers implanted into the prostate before planning computed tomography. About one in five patients had repeat computed tomography because their rectum was judged to be too large at the time of the first planning computed tomography. Rectal distension was assessed on planning computed tomography using outlines following European Organization for Research and Treatment of Cancer guidelines by measuring the rectal volume, the average cross-sectional area and the mean anterior-posterior diameter of the rectum. Daily kV images were obtained before and after treatment delivery to determine positional matching of the fiducial markers in the superior-inferior, anterior-posterior and right-left dimensions. RESULTS: In total, 2860 pre- and post-treatment daily kV image pairs were obtained of 89 patients (average 32.1 image pairs per patient). The median rectal cross-sectional area was 7.3cm(2) (range 2.8-17.1), the median rectal volume was 54.8cm(3) (range 20.9-128.2), and the median anterior-posterior rectal diameter was 3.03cm (range 1.58-8.30). Unifactor linear regression models showed no statistically significant relationship between intra- and interfraction prostate stability and rectal volume on planning computed tomography. CONCLUSIONS: No statistically significant relationship between rectal distension on planning computed tomography and the intra- and interfraction stability of the prostate gland was identified if patients with a large rectal volume were rescanned for planning.

Verification of target position in the post-prostatectomy cancer patient using cone beam CT.

We present the results of a pilot study designed to investigate methods that may be applied to develop a patient position correction protocol for the post-prostatectomy patient receiving radiotherapy. Imaging was carried out with cone beam CT (CBCT) to investigate its suitability for detecting changes in rectal and bladder volumes and movements of these organs relative to the treatment planning CT. Eligible patients were imaged daily during the first week of treatment and weekly thereafter. Surrogate explanatory variables, including distance from the isocentre to the anterior rectum and bladder length, were tested for their potential to substitute for contouring entire organs and predict for changes in coverage of the planning treatment volume (PTV) by the 95% isodose (PTV95) and the maximum dose delivered to 50% of the rectal volume (RECTD50). The PTV defined on the CBCT images was larger than that defined on the planning CT and resulted in a decrease in the PTV95. Bladder length correlated with bladder volume and changes in bladder volume were associated with a decrease in PTV95. Rectal volumes changed randomly during treatment. There was a trend for the rectum to move anteriorly as treatment progressed. CBCT may be used to define the PTV, rectum and bladder though the reason for an apparent increase in PTV on CBCT requires further investigation. The bladder length and distance to the anterior rectal wall are potential surrogate explanatory variables. Further studies will be designed to test values of these surrogates that predict the need for a change in isocentre position.

Offline adaptive radiotherapy for bladder cancer using cone beam computed tomography.

We investigated if an adaptive radiotherapy approach based on cone beam CT (CBCT) acquired during radical treatment was feasible and resulted in improved dosimetric outcomes for bladder cancer patients compared to conventional planning and treatment protocol. A secondary aim was to compare a conventional plan with a theoretical online process where positioning is based on soft tissue position on a daily basis and treatment plan choice is based on bladder size. A conventional treatment plan was derived from a planning CT scan in the radical radiotherapy of five patients with muscle invasive bladder cancer. In this offline adaptive protocol using CBCT, the patients had 10 CBCT: daily CBCT for the first five fractions and then CBCT scan on a weekly basis. The first five daily CBCT in each patient were used to create a single adaptive plan for treatment from fraction eight onwards. A different process using the planning CT and the first five daily CBCT was used to create small, average and large bladder volumes, giving rise to small, average and large adaptive bladder treatment plans, respectively. In a retrospective analysis using the CBCT scans, we compared the clinical target volume (CTV) coverage using three protocols: (i) conventional; (ii) offline adaptive; and (iii) online adaptive with choice of 'plan of the day'. Daily CBCT prolonged treatment time by an average of 7 min. Two of the five patients demonstrated such variation in CTV that an offline adaptive plan was used for treatment after the first five CBCT. Comparing the offline adaptive plan with the conventional plan, the CTV coverage improved from a minimum of 60.1 to 94.7% in subsequent weekly CBCT. Using the CBCT data, modelling an online adaptive protocol showed that coverage of the CTV by the 95% prescribed dose line by small, medium and large adaptive plans were 34.9, 67.4 and 90.7% of occasions, respectively. More normal tissue was irradiated using a conventional CTV to planning target volume margin (1.5 cm) compared to an online adaptive process (0.5 cm). An offline adaptive strategy improves dose coverage in certain patients to the CTV and results in a higher conformity index compared to conventional planning. Further research in online adaptive radiation therapy for bladder cancer is indicated.

Inter-observer variability of clinical target volume delineation for bladder cancer using CT and cone beam CT.

To compare the image quality of cone beam CT (CBCT) with that of planning CT (pCT) scan, and quantify inter-observer differences in therapeutic indices based on these scans prior to the introduction of an adaptive radiation therapy protocol for bladder cancer. Four consecutive patients were selected with muscle invasive bladder cancer receiving radical dose radiation therapy. Four radiation oncologists specializing in genitourinary malignancies contoured the clinical target volume (CTV) and rectum on both a pCT and a randomly chosen CBCT of the same patient. A conformity index (CI) for CTV and the rectum was determined for both pCT and CBCT. The maximal lateral, anterior, posterior, cranial and caudal extensions of the CTV for both CT and CBCT were determined for each observer. Variation in volumes of both the CTV and rectum for both pCT and were also compared using Varian Eclipse planning software (Varian Medical Systems, Palo Alto, CA, USA). Using pCT the mean CI for the CTV was 0.79; using CBCT the mean CI for the CTV was 0.75. For the rectum, the mean CI for using CT was 0.80 and for CBCT was 0.74. Greatest variation on CBCT CTV contours was seen in the supero-inferior direction with variation up to 2.1 cm between different radiation oncologists. With the variation in CI for pCT and CBCT of the CTV and rectum (0.04 and 0.06 respectively), CBCT is not significantly inferior to the pCT in terms of inter-observer contouring variability.

Planning and implementing an implanted fiducial programme for prostate cancer radiation therapy.

Using implanted gold seeds as fiducial markers to verify the position of the prostate in radiation therapy is well accepted and is becoming the standard of practice and requirement for international multicentre trials. In 2006 the decision was made at the Peter MacCallum Caner Centre (Peter Mac) to plan for and implement this process as standard clinical practice for radical dose prostate treatments (74-78 Gy). Before this, programme verification of field placement for prostate cancer radiation treatment was routinely carried out using regular off-line electronic portal imaging with matching of bony anatomy. A small multidisciplinary team investigated and assisted in the implementation of this new practice across the Peter Mac sites at East Melbourne and our three satellite centres. Issues considered included seed size, number and position in the prostate, implant equipment, imaging equipment and procedure and consent and information forms. The use of a custom made fiducial pack, comprehensive patient information and a daily on-line imaging process was implemented. The experience of the first 28 patients at Peter Mac from January 2007 to May 2007 inclusive is reported on.

Australian and New Zealand three-dimensional conformal radiation therapy consensus guidelines for prostate cancer.

Three-dimensional conformal radiation therapy (3DCRT) has been shown to reduce normal tissue toxicity and allow dose escalation in the curative treatment of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group initiated a consensus process to generate evidence-based guidelines for the safe and effective implementation of 3DCRT. All radiation oncology departments in Australia and New Zealand were invited to complete a survey of their prostate practice and to send representatives to a consensus workshop. After a review of the evidence, key issues were identified and debated. If agreement was not reached, working parties were formed to make recommendations. Draft guidelines were circulated to workshop participants for approval prior to publication. Where possible, evidence-based recommendations have been made with regard to patient selection, risk stratification, simulation, planning, treatment delivery and toxicity reporting. This is the first time a group of radiation therapists, physicists and oncologists representing professional radiotherapy practice across Australia and New Zealand have worked together to develop best-practice guidelines. These guidelines should serve as a baseline for prospective clinical trials, outcome research and quality assurance.

Three-dimensional conformal radiotherapy in the treatment of prostate cancer in Australia and New Zealand: Report on a survey of radiotherapy centres and the proceedings of a consensus workshop.

There is an increasing use of 3-D conformal radiotherapy (3DCRT) in the radiotherapeutic management of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group carried out a survey of Australian and New Zealand radiotherapy centres in the preparation of a consensus workshop. Of the 19 centres that were represented, there were 24 radiation oncologists, 16 radiation therapists and 12 medical physicists. The survey collected demographic information and data on the practices undertaken at those centres when delivering curative radiotherapy in the treatment of prostate cancer. There was much variation in the delivery of treatment in the areas of patient set-up, contouring of target volumes and organs of interest during computer planning, the techniques and the dose constraints used in these techniques, the use of adjuvant androgen deprivation therapy and the quality assurance processes used in monitoring effects of treatment. This variability reflects the range of data in the published literature. Emerging trends of practices were also identified. This is a first report on a multi-disciplinary approach to the development of guidelines in 3DCRT of prostate cancer.