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The impact of rectal and bladder variability on target coverage during post-prostatectomy intensity modulated radiotherapy
Radiotherapy and Oncology 110 (2014) 245–250
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Prostate radiotherapy
The impact of rectal and bladder variability on target coverage during post-prostatectomy intensity modulated radiotherapy Linda J. Bell a,b,⇑, Jennifer Cox a,b, Thomas Eade a,c, Marianne Rinks a,1, Andrew Kneebone a,c a Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards; b Faculty of Health Sc iences, University of Sydney, Lidcombe; and c Northern Clinical School, University of Sydney, St. Leonards, Australia
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Article history: Received 25 May 2013 Received in revised form 23 October 2013 Accepted 28 October 2013 Available online 20 February 2014 Keywords: Post-prostatectomy radiotherapy Rectal size Bladder size Geographic miss IGRT Cone beam CT
a b s t r a c t Background and purpose: Accuracy when delivering post-prostatectomy intensity modulated radiotherapy (IMRT) is crucial. The aims of this study were to quantify prostate bed movement and determine what amount of bladder or rectum size variation creates the potential for geographic miss. Methods and materials: The Cone Beam CT (CBCT) images (n = 377) of forty patients who received postprostatectomy IMRT with daily on-line alignment to bony anatomy were reviewed. Prostate bed movement was estimated using the location of surgical clips in the upper and lower sections of the PTV and correlated with rectal and bladder filling (defined as changes in the cross sectional diameter at defined levels). The number of potential geographic misses caused by bladder and rectum variation was calculated assuming a uniform CTV to PTV expansion of 1 cm except 0.5 cm posteriorly. Results: Variations in bladder filling of >2 cm larger, ±1 cm, or >2 cm smaller occurred in 3.4%, 56.2%, and 15.1% of images respectively with potential geographic misses in the upper prostate bed of 61.5%, 9.9% and 26.3% respectively. Variations in rectal filling in the upper prostate bed of >1.5 cm larger, 1.5 cm larger to 1 cm smaller, and >1 cm smaller occurred in 17.2%, 75.6%, and 7.2% of images respectively. These variations resulted in geographic misses in the upper prostate bed in 29.2%, 12.3%, and 63.0% of images respectively. Variations in bladder and rectal filling in the lower prostate bed region had minimal impact on geographic misses. Conclusions: Bladder and rectal size changes at treatment affect prostate bed coverage, especially in the upper aspect of the prostate bed. The greatest potential for geographic miss occurred when either the bladder increased in size or when the rectum became smaller. Ensuring a full bladder and empty rectum at simulation will minimise this risk. Our data also support anisotropic PTV margins with larger margins superiorly than inferiorly. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 245–250
Prostate cancer is the most prevalent cancer in men in Australia [1] with radical prostatectomy the most common treatment [2]. It is now standard of care to consider adjuvant [3–6] or salvage [7–9] radiotherapy to the prostate bed in patients with high risk features or PSA failure following surgery. Although consensus guidelines are available to assist clinicians in defining the clinical target volume (CTV), there is a lack of evidence to inform margin sizes between the CTV and the planning target volume (PTV). The prostate bed is located between the bladder and rectum, which is a highly variable setting, making accuracy of postprostatectomy radiotherapy challenging. The effects of bladder ⇑ Corresponding author. Address: Northern Sydney Cancer Centre, Radiation Oncology Department, Level 1 ASB Building, Royal North Shore Hospital, Pacific Highway, St. Leonards, NSW 2065, Australia. E-mail address: [email protected] (L.J. Bell). 1 Present address: Radiation Oncology, Shoalhaven Cancer Care Centre, Illawarra Shoalhaven Local Health District, Nowra, NSW 2541, Australia. http://dx.doi.org/10.1016/j.radonc.2013.10.042 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
and rectum variability on prostate position are well known in the definitive prostate setting [10,11], but less work has been done in the post-prostatectomy setting [12,13]. During surgery many patients have surgical clips placed in the prostate bed area which can be identified using cone beam CT (CBCT) imaging during a patient’s radiotherapy treatment. The clips can act as a surrogate for prostate bed motion in both the upper and lower portions of the treatment volume [14]. The CBCT can also be used to quantify variations in rectal and bladder filling that might explain variability in clip position. The European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group [15] and the Australian and New Zealand Radiation Oncology Genito-Urinary Group (FROGG) [16] both have consensus guidelines that recommend planning target volume (PTV) expansions for use in post-prostatectomy radiotherapy. The EORTC recommend that a minimum of a 0.5 cm uniform PTV expansion be used. The FROGG guidelines recommend a uniform
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1 cm margin but state a 0.5 cm posterior expansion is acceptable, especially if rectal dose volume histograms exceed guidelines. It should be noted that neither of these guidelines provide evidence for the margins used. For the purposes of this study, anterior–posterior movement of surgical clips greater than 1 cm anteriorly or 0.5 cm posteriorly was deemed a potential geographic miss. The specific aims of this study were (1) to quantify the variation in bladder and rectal filling during post-prostatectomy radiotherapy when adopting a uniform full bladder and empty rectum protocol, (2) to assess the impact of this variability on prostate bed coverage in both the upper and lower part of the target, and (3) to determine what amount of bladder or rectal variation causes geographic miss in post-prostatectomy radiotherapy. Methods and materials Ethics approval was granted from the Northern Sydney Central Coast Health Human Research Ethics Committee (1103-082M) and the University of Sydney Human Research Ethics Committee (13721) before the commencement of this study. A retrospective study was conducted where forty patients who received post-prostatectomy radiotherapy at the Northern Sydney Cancer Centre (NSCC) with the image guided-intensity modulated radiotherapy (IG-IMRT) technique were sequentially selected over the period 2009–2011. To be eligible patients needed to have surgical clips in the upper and lower portions of the treatment volume. Selected patients needed to have had at least one CBCT taken during treatment. See Appendix I for demographic details. A surgical clip was selected in the upper and lower portions of the CTV as the matching clip and for determining the levels at which the bladder and rectum were measured. A clip in midline was selected if possible. The average position of these clips was also calculated in relation to the superior aspect of the pubic symphysis. The mean position of the superior clip was 0.84 cm (SD ±0.84 cm) superiorly to the superior aspect of the pubic symphysis and the inferior clip was 2.78 cm (SD ±0.72 cm) inferior. At simulation the patients were instructed to have a comfortably full bladder and an empty rectum by emptying their bladder and bowels and then drinking 600 ml of water 1 h prior to simulation. A BladderScanÒ (Verathon Incorporated, Bothell, WA, USA) ultrasound device was used to check that the patient had adequate bladder filling prior to the planning CT being acquired. Prior to simulation, patients were placed on a low residue diet with magnesium to try to maintain an empty rectum. If the rectal diameter in the anterior–posterior direction was greater than 3.5 cm on the planning CT the patient was given an enema and a new planning scan acquired. Radiation Oncologists contoured the CTV on each of the planning CT scans according to the FROGG consensus guidelines [16]. During treatment all patients followed the same bladder and rectal protocol with feedback from CBCT scans acquired during treatment. In an attempt to reproduce bladder and rectal volumes seen at simulation, bladder filling was assessed at CBCT review and the BladderScanÒ could be used to tailor water intake if required. Patients were asked to have an empty bowel before treatment and to continue with the low residue diet and magnesium to try to control this. CBCT scans were taken using the on-board imagerÒ (Varian Medical Systems, Palo Alto, CA, USA) on the first 3 fractions and then weekly for the remainder of the treatment course, as per standard department protocol. For this study CBCT scans taken in the first week of treatment and one CBCT scan from each subsequent week were used for analysis. If patients had more than one CBCT taken per fraction because an intervention was required prior to treatment, only the CBCT acquired first was used for analysis. Some of the patients were replanned during the course of their treatment
to correct patient changes or systematic issues that were detected. In these cases the CBCT scans after the replan commenced treatment were matched to the replan planning CT scan. For this study the CBCT scans and planning CT scan were first matched to bony anatomy. The shift co-ordinates in the superior– inferior, anterior–posterior, and left–right directions were recorded. The scans were then rematched to the chosen superior clip and the match co-ordinates were recorded. The scans were then matched a third time to the inferior clip and the match co-ordinates were recorded. The bladder diameter in the anterior–posterior direction was measured at the superior clip level (i.e. at a mean of 0.84 cm above the top of the pubic symphysis) and the difference in bladder diameter between the planning CT and each of the CBCT scans was calculated. The rectum diameter in the anterior–posterior direction was measured at three levels, superior clip level, inferior clip level (i.e. at a mean of 2.78 cm below the top of the pubic symphysis) and midway between these two points. The difference in rectal diameter between the planning CT and each CBCT scan was then calculated. Patients were deemed to have a geographic miss if clip movement was greater than 0.5 cm posteriorly or 1 cm in any other direction. This expansion was deemed the minimum acceptable expansion in the FROGG guidelines [16]. To determine the amount of bladder variation that causes geographic miss in post-prostatectomy patients, the superior and inferior clip movement was plotted against the bladder variation. To determine the amount of rectum variation that causes geographic miss in post-prostatectomy patients, the superior clip movement was plotted against superior rectum variation and the inferior clip movement was plotted against the inferior rectum variation. The combined effect of bladder and rectal variation on geographic miss was also assessed. Microsoft ExcelÒ (Microsoft Corporation, Redmond, WA, USA) and Statistical Package for the Social SciencesÒ (SPSS) (IBM Corporation, Armonk, NY, USA) were used to conduct statistical analyses on the data collected. Chi-square analysis was conducted to determine the effect of bladder and rectal change on movement in the upper and lower prostate bed with a value of p < 0.01 considered to indicate significance. Correlation of clip movement and bladder and rectal size change was used to determine which organ changes caused potential geographic miss. Rectal and bladder size changes were divided into 5 easily measurable sizes for on-line assessment to determine which change was most likely to cause potential geographic miss. Results A total of 377 CBCT scans were reviewed for 40 postprostatectomy patients (median number of CBCT 9, range of 8–11 per patient). Forty-five planning CT scans were reviewed with 5 of these being rescan planning CT scans taken during the course of the patients’ radiotherapy. Bladder and rectum volumes and diameters at simulation The initial mean bladder volumes at simulation were 398.34 cc (SD 199.6 cc, range 82.99–882.19 cc) and the initial mean bladder diameter was 8.87 cm (SD 1.74 cm, range 4.69–12.42 cm). The initial mean rectum volume at simulation was 73.31 cc (SD 24.8 cc, range 40.40–148.03 cc). The initial mean rectal diameter at simulation in the superior section of the rectum was 2.93 cm (SD 0.91 cm, range 0.42–4.96 cm) compared to the mid rectum mean of 3.65 cm (SD 1.0 cm, range 1.96–5.92 cm) and inferior rectum mean of 3.34 cm (SD 0.81 cm, range 2.05–6.22 cm). No volumes were measured on the CBCT scans. This was for two reasons. Firstly, the CBCT length is shorter than the planning CT scan so the full organs were rarely scanned, and secondly because
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this study was designed to inform on-line intervention and voluming tools are currently unavailable at the treatment machine. Bladder variation Large variations in bladder filling were seen. The mean bladder diameter change was 0.62 cm (SD 1.64 cm, range 7.2 to +5 cm), with the negative value indicating smaller bladder diameters during treatment than at simulation. Table 1 shows the proportion of CBCTs acquired by change in bladder diameter. 56.2% of images showed less than 1 cm variation from the simulated size. 10.6% of images showed a bladder diameter increase of greater than 1 cm and 33.1% showed a bladder diameter decrease of greater than 1 cm. Changes in bladder diameter had a greater effect on potential geographic miss in the upper prostate bed (Chi-Square p < 0.01), compared to the lower prostate bed, in the anterior–posterior direction (Fig. 1a). A negative value for the clip motion in the anterior–posterior direction indicates the clip moving posteriorly. Table 1 relates the variation in bladder diameter to the potential for geographic miss in the upper and lower prostate bed. In the upper prostate bed, variations in bladder diameter of more than 2 cm larger, ±1 cm, and more than 2 cm smaller resulted in geographic misses in 61.5%, 9.9% and 26.3% of images respectively. Variations in bladder diameter in the lower prostate bed had minimal impact on geographic misses with less than 2% of all images demonstrating a geographic miss.
mon, when the rectal diameter reduced by >1 cm at treatment compared to planning (seen in 7.2% of images), the potential for geographic miss was high (63%). Variations in rectal filling in the lower prostate bed region had minimal impact on geographic miss with less than 2% of all images demonstrating a geographic miss.
Combined effect of bladder and rectum variation on potential geographic miss Appendix II illustrates the combined effect of bladder and rectal variation on potential geographic miss in the upper sections of the prostate bed. The numbers of geographic misses are highest when the opposite ends of the ranges are experienced together. For example, when the bladder was larger by >2 cm and the rectum was smaller by >1.1 cm, 55.6% of images showed a geographic miss, and when the bladder was smaller by >2 cm and the rectum was larger by >1.1 cm, 34.5% of images showed a geographic miss. One of the most common factors in potential geographic miss was a smaller rectum, no matter what variation was seen in the bladder: for example, when the rectum was >1.1 cm smaller, 100% of images showed a geographic miss if the bladder was 1.1–2 cm either larger or smaller. In 40.3% of the images the bladder and rectum stayed within ±1 cm of the planned size. The numbers of geographic misses were minimal (7.1%) in this group. Discussion
Rectum variation A large variation in the rectal diameter during treatment was seen. With negative values indicating smaller rectal diameters we found that variations were greatest in the superior section of the rectum (mean 0.59 cm; SD 1.24 cm, range 2.1 to +5.4 cm; median 0.41 cm) compared to the mid rectum (mean 0.37 cm; SD 0.92 cm, range 2.2 to +4.7 cm; median 0.31 cm) and inferior section of the rectum (mean 0.30 cm; SD 0.73 cm, range 2.4 to +2.9 cm; median 0.28 cm). Table 2 shows the proportion of CBCTs with rectal diameter change in the superior and inferior sections of the rectum. The superior rectum stayed within 1 cm of the planned size in 65.8% of images, increased in size by greater than 1 cm in 27.0% of images, and decreased in size by greater than 1 cm in 7.2% of images. The inferior rectum stayed within 1 cm of the planned size in 83.6% of images, increased in size by greater than 1 cm in 13.0% of images and decreased in size by greater than 1 cm in 3.5% of images. Changes in rectal diameter had the greatest effect on potential geographic miss in the upper prostate bed (Chi-Square p < 0.01) compared with the lower prostate bed, with this effect occurring in the anterior–posterior direction (Fig. 2a). A negative value for the clip motion in the anterior–posterior direction indicates the clip moving posteriorly. Table 2 relates variation in rectal filling to the potential for geographic miss in the upper and lower part of the prostate bed. In the upper prostate bed region, variations in rectum filling > 1.5 cm larger, 1.5 cm larger to 1 cm smaller, and more than 1 cm smaller resulted in geographic misses in 29.2%, 12.3%, and 63.0% of images respectively. Although uncom-
There is little literature available on the relationship between organ filling and geographic miss during post-prostatectomy radiotherapy. Fiorino et al. [12] used weekly CT scans to assess rectal and bladder change during post-prostatectomy radiotherapy in 9 patients, and found that the bladder tended to progressively reduce in size during treatment. Showalter et al. [17] also used CBCT scans to assess rectal and bladder change during post-prostatectomy radiotherapy in 10 patients. They too found that the mean posterior bladder wall moved anteriorly which matches both Fiorino et al. and our findings. In regard to the rectum both Fiorino and Showalter found the rectum tended to become slightly smaller during treatment, whereas in our series 69.7% of images showed some degree of increase in rectal size. This could be because our simulation protocol recommended the use of a gentle laxative (magnesium) and diet modification prior to simulation as well as to give an enema if the planning CT rectum size was larger than 3.5 cm. They also found that movement was greater in the upper prostate bed and was influenced by the degree of rectal and bladder filling. Our study highlights the importance of bladder and rectum stability to prevent geographic miss. Despite a rigorous full bladder/empty rectum protocol and education programme, the bladder remained within 1 cm of the planned size in only 56.2% of cases and the superior rectum within 1 cm of the planned size in 65.8% of images. When the bladder or rectum remains within 1 cm of the planned size, approximately 90% of images showed no potential geographic miss.
Table 1 Bladder change resulting in potential geographic miss of the prostate bed. The number and percentage of images where certain ranges of bladder variation occurred and when this has resulted in a potential geographic miss of the treatment area. bladder change
>2 cm larger 1.1–2 cm larger 1 to +1 cm 1.1–2 cm smaller >2 cm smaller
Images showing bladder change
Superior clip out of PTV acceptable expansion
Inferior clip out of PTV acceptable expansion
Number/total
Percentage (%)
Number/total
Percentage (%)
Number/total
Percentage (%)
13/377 27/377 212/377 68/377 57/377
3.4 7.2 56.2 18.0 15.1
8/13 10/27 21/212 17/68 15/57
61.5 37.0 9.9 25.0 26.3
0/13 1/27 4/212 1/68 1/57
0.0 3.7 1.9 1.5 1.8
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Fig. 1. Bladder variation causing potential geographic miss in the upper prostate bed. Amount of bladder variation that is clinically significant for post-prostatectomy patients in the upper area of the prostate bed (a–c) and the lower section of the prostate bed (d–f) in the anterior–posterior (a and d), superior–inferior (b and e), and left–right (c and f) directions. The grey shaded area represents the FROGG acceptable PTV expansions. Any points that fall outside this area are a potential geographic miss. The black dashed boxes indicate the variations in bladder filling that are most likely to cause a potential geographic miss of the treatment area. A negative value for the clip motion indicates that the clip is moving posteriorly (in the anterior–posterior direction), superiorly (in the superior–inferior direction), and left (in the left–right direction).
Table 2 Rectum change resulting in potential geographic miss of the prostate bed. The number and percentage of images where certain ranges of rectum variation occurred and when this has resulted in a potential geographic miss of the treatment area. Rectum (sup) change
>1.5 cm larger 1.1–1.5 cm larger 1 to +1 cm 1.1–1.5 cm smaller >1.5 cm smaller Rectum (inf) change
>1.5 cm larger 1.1–1.5 cm larger 1 to +1 cm 1.1–1.5 cm smaller >1.5 cm smaller
Images showing rectum (sup) change
Superior clip out of PTV acceptable expansion
Number/total
Percentage (%)
Number/total
Percentage (%)
65/377 37/377 248/377 15/377 12/377
17.2 9.8 65.8 4.0 3.2
19/65 2/37 33/248 10/15 7/12
29.2 5.4 13.3 66.7 58.3
Images showing rectum (inf) change
Inferior clip out of PTV acceptable expansion
Number/total
Percentage (%)
Number/total
16/377 33/377 315/377 1/377 12/377
4.2 8.8 83.6 0.3 3.2
0/16 1/33 6/315 0/1 0/12
Percentage (%) 0.0 3.0 1.9 0.0 0.0
L.J. Bell et al. / Radiotherapy and Oncology 110 (2014) 245–250
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Fig. 2. Rectum variation causing potential geographic miss in the upper prostate bed. Amount of rectum variation that is clinically significant for post-prostatectomy patients in the upper area of the prostate bed (a–c) and the lower section of the prostate bed (d–f) in the anterior–posterior (a and d), superior–inferior (b and e), and left–right (c and f) directions. The grey shaded area represents the FROGG acceptable PTV expansions. Any points that fall outside this area are a potential geographic miss. The black dashed boxes indicate the variations in rectal filling that are most likely to cause a potential geographic miss of the treatment area. A negative value for the clip motion indicates that the clip is moving posteriorly (in the anterior–posterior direction), superiorly (in the superior–inferior direction), and left (in the left–right direction).
Variations of >1 cm in rectal and bladder filling had a significant impact on coverage, with the greatest movement seen with the rectum reducing and/or the bladder increasing. For example, a >1 cm reduction in rectal size results in surgical clip miss in 63% of these cases. In the images with a potential geographic miss, we found that the median bladder increase was 1.23 cm and median decrease was 1.9 cm. A median superior rectum increase of 0.89 cm and decrease of 1.11 cm was found in the images that had potential geographic misses. Reducing rectal size seems to have a larger effect on potential geographic miss than bladder filling (Appendix II). Hence, it is important to ensure that the rectum is small at the time of simulation. This was also found in a number of other studies [12,18,19]. At NSCC we now administer an enema prior to simulation for all post-prostatectomy patients. Caution should also be taken when instructing a patient to increase their bladder filling for treatment in response to a small bladder at simulation and unfavourable dose volume histogram characteristics. This could have the unintended result of a geographic miss of the treatment area. In our series, having the
bladder 2 cm larger during treatment resulted in a 61.5% rate of geographic miss. At NSCC we now routinely perform a bladder ultrasound prior to simulation to ensure adequate bladder filling. This study has not investigated the impact of strict rectal and bladder filling protocols. In recent work by McNair et al. [20] it was shown that strict rectal filling guidelines still did not prevent rectal size changes due to the inability to control bowel gas. Therefore stricter protocols might not be the answer to this problem. Simply changing the on-line matching technique from matching to bony anatomy to matching to surgical clips would not always help reduce geographic miss because the upper and lower prostate bed move independently creating a prostate bed pitch rotation. This variable is difficult to correct with standard on-line matching techniques, as most treatment couches do not tilt and those that do have a limited range [21]. Prostate bed pitch rotation is a continuing area of research in our department, including the role of anisotropic PTV margins. Larger margins might be required in the upper region to protect against geographic miss due to its greater movement. Less motion was seen in the inferior section
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of the prostate bed, so it might be possible to decrease margins here to reduce normal tissue irradiation. Bladder and rectum size change could be a good surrogate to indicate potential geographic miss when there are no surgical clips in situ. A major advantage of this work is that non-volumetric tools were used to assess the organ size variations. These tools are available in routine imaging software and enable assessment of and correction for organ size change to be completed in the on-line setting. There are a number of limitations to this study. Surgical clips are only a surrogate for prostate bed motion and geographic miss. It could be argued that using soft tissue is a more accurate way to evaluate movement and geographic miss, but defining specific measurement points in an asymmetric structure such as the PTV is problematic. In this study a large number of images was reviewed (n = 377), but these images belong to only 40 patients. Patients who have systematic issues that cause prostate bed movement resulting in geographic miss could have influenced our findings. Some of the patients involved in this study (5 of 40) had new plans generated during treatment to correct for issues such as movement, geographic miss, or contour variation. This intervention might therefore have caused an overall underestimation of the extent of movement and geographic miss. Only measurement tools available in the on-line setting were used, to allow a strategy for on-line intervention to be determined. There might be better off-line tools available to investigate movement of geographic miss that could give more robust answers, but this would not allow on-line interventions to occur. Conclusion Bladder and rectal size changes affect prostate bed coverage with the greatest risk of geometric miss seen with a smaller rectum and a larger bladder during treatment. The majority of movement caused by bladder and rectum variation is seen in the upper aspect of the prostate bed. If the bladder or rectum stayed within 1 cm of the planned size, approximately 90% of images showed no geographic miss. When both the bladder and rectum are within 1 cm of the planned size, this percentage increases to 93% of images. It is therefore important to ensure that a comfortably large bladder and small rectum are achieved at simulation. It is also very important to take note of which patients are showing systematic variations in the bladder and rectum early in the treatment course, so intervention can occur to ensure treatment is delivered accurately. Greater movement in the upper prostate bed than in the lower prostate bed is difficult to correct for in an on-line setting, even when aligning to clips or fiducial markers. Anisotropic PTV margins allowing for greater movement superiorly than inferiorly are therefore recommended. Conflict of interest statement None. Acknowledgements The authors gratefully acknowledge all the staff at the Northern Sydney Cancer Centre.
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.radonc.2013.10. 042.
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Prostate radiotherapy
The impact of rectal and bladder variability on target coverage during post-prostatectomy intensity modulated radiotherapy Linda J. Bell a,b,⇑, Jennifer Cox a,b, Thomas Eade a,c, Marianne Rinks a,1, Andrew Kneebone a,c a Northern Sydney Cancer Centre, Radiation Oncology Department, Royal North Shore Hospital, St. Leonards; b Faculty of Health Sc iences, University of Sydney, Lidcombe; and c Northern Clinical School, University of Sydney, St. Leonards, Australia
a r t i c l e
i n f o
Article history: Received 25 May 2013 Received in revised form 23 October 2013 Accepted 28 October 2013 Available online 20 February 2014 Keywords: Post-prostatectomy radiotherapy Rectal size Bladder size Geographic miss IGRT Cone beam CT
a b s t r a c t Background and purpose: Accuracy when delivering post-prostatectomy intensity modulated radiotherapy (IMRT) is crucial. The aims of this study were to quantify prostate bed movement and determine what amount of bladder or rectum size variation creates the potential for geographic miss. Methods and materials: The Cone Beam CT (CBCT) images (n = 377) of forty patients who received postprostatectomy IMRT with daily on-line alignment to bony anatomy were reviewed. Prostate bed movement was estimated using the location of surgical clips in the upper and lower sections of the PTV and correlated with rectal and bladder filling (defined as changes in the cross sectional diameter at defined levels). The number of potential geographic misses caused by bladder and rectum variation was calculated assuming a uniform CTV to PTV expansion of 1 cm except 0.5 cm posteriorly. Results: Variations in bladder filling of >2 cm larger, ±1 cm, or >2 cm smaller occurred in 3.4%, 56.2%, and 15.1% of images respectively with potential geographic misses in the upper prostate bed of 61.5%, 9.9% and 26.3% respectively. Variations in rectal filling in the upper prostate bed of >1.5 cm larger, 1.5 cm larger to 1 cm smaller, and >1 cm smaller occurred in 17.2%, 75.6%, and 7.2% of images respectively. These variations resulted in geographic misses in the upper prostate bed in 29.2%, 12.3%, and 63.0% of images respectively. Variations in bladder and rectal filling in the lower prostate bed region had minimal impact on geographic misses. Conclusions: Bladder and rectal size changes at treatment affect prostate bed coverage, especially in the upper aspect of the prostate bed. The greatest potential for geographic miss occurred when either the bladder increased in size or when the rectum became smaller. Ensuring a full bladder and empty rectum at simulation will minimise this risk. Our data also support anisotropic PTV margins with larger margins superiorly than inferiorly. Ó 2014 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 110 (2014) 245–250
Prostate cancer is the most prevalent cancer in men in Australia [1] with radical prostatectomy the most common treatment [2]. It is now standard of care to consider adjuvant [3–6] or salvage [7–9] radiotherapy to the prostate bed in patients with high risk features or PSA failure following surgery. Although consensus guidelines are available to assist clinicians in defining the clinical target volume (CTV), there is a lack of evidence to inform margin sizes between the CTV and the planning target volume (PTV). The prostate bed is located between the bladder and rectum, which is a highly variable setting, making accuracy of postprostatectomy radiotherapy challenging. The effects of bladder ⇑ Corresponding author. Address: Northern Sydney Cancer Centre, Radiation Oncology Department, Level 1 ASB Building, Royal North Shore Hospital, Pacific Highway, St. Leonards, NSW 2065, Australia. E-mail address: [email protected] (L.J. Bell). 1 Present address: Radiation Oncology, Shoalhaven Cancer Care Centre, Illawarra Shoalhaven Local Health District, Nowra, NSW 2541, Australia. http://dx.doi.org/10.1016/j.radonc.2013.10.042 0167-8140/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
and rectum variability on prostate position are well known in the definitive prostate setting [10,11], but less work has been done in the post-prostatectomy setting [12,13]. During surgery many patients have surgical clips placed in the prostate bed area which can be identified using cone beam CT (CBCT) imaging during a patient’s radiotherapy treatment. The clips can act as a surrogate for prostate bed motion in both the upper and lower portions of the treatment volume [14]. The CBCT can also be used to quantify variations in rectal and bladder filling that might explain variability in clip position. The European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group [15] and the Australian and New Zealand Radiation Oncology Genito-Urinary Group (FROGG) [16] both have consensus guidelines that recommend planning target volume (PTV) expansions for use in post-prostatectomy radiotherapy. The EORTC recommend that a minimum of a 0.5 cm uniform PTV expansion be used. The FROGG guidelines recommend a uniform
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1 cm margin but state a 0.5 cm posterior expansion is acceptable, especially if rectal dose volume histograms exceed guidelines. It should be noted that neither of these guidelines provide evidence for the margins used. For the purposes of this study, anterior–posterior movement of surgical clips greater than 1 cm anteriorly or 0.5 cm posteriorly was deemed a potential geographic miss. The specific aims of this study were (1) to quantify the variation in bladder and rectal filling during post-prostatectomy radiotherapy when adopting a uniform full bladder and empty rectum protocol, (2) to assess the impact of this variability on prostate bed coverage in both the upper and lower part of the target, and (3) to determine what amount of bladder or rectal variation causes geographic miss in post-prostatectomy radiotherapy. Methods and materials Ethics approval was granted from the Northern Sydney Central Coast Health Human Research Ethics Committee (1103-082M) and the University of Sydney Human Research Ethics Committee (13721) before the commencement of this study. A retrospective study was conducted where forty patients who received post-prostatectomy radiotherapy at the Northern Sydney Cancer Centre (NSCC) with the image guided-intensity modulated radiotherapy (IG-IMRT) technique were sequentially selected over the period 2009–2011. To be eligible patients needed to have surgical clips in the upper and lower portions of the treatment volume. Selected patients needed to have had at least one CBCT taken during treatment. See Appendix I for demographic details. A surgical clip was selected in the upper and lower portions of the CTV as the matching clip and for determining the levels at which the bladder and rectum were measured. A clip in midline was selected if possible. The average position of these clips was also calculated in relation to the superior aspect of the pubic symphysis. The mean position of the superior clip was 0.84 cm (SD ±0.84 cm) superiorly to the superior aspect of the pubic symphysis and the inferior clip was 2.78 cm (SD ±0.72 cm) inferior. At simulation the patients were instructed to have a comfortably full bladder and an empty rectum by emptying their bladder and bowels and then drinking 600 ml of water 1 h prior to simulation. A BladderScanÒ (Verathon Incorporated, Bothell, WA, USA) ultrasound device was used to check that the patient had adequate bladder filling prior to the planning CT being acquired. Prior to simulation, patients were placed on a low residue diet with magnesium to try to maintain an empty rectum. If the rectal diameter in the anterior–posterior direction was greater than 3.5 cm on the planning CT the patient was given an enema and a new planning scan acquired. Radiation Oncologists contoured the CTV on each of the planning CT scans according to the FROGG consensus guidelines [16]. During treatment all patients followed the same bladder and rectal protocol with feedback from CBCT scans acquired during treatment. In an attempt to reproduce bladder and rectal volumes seen at simulation, bladder filling was assessed at CBCT review and the BladderScanÒ could be used to tailor water intake if required. Patients were asked to have an empty bowel before treatment and to continue with the low residue diet and magnesium to try to control this. CBCT scans were taken using the on-board imagerÒ (Varian Medical Systems, Palo Alto, CA, USA) on the first 3 fractions and then weekly for the remainder of the treatment course, as per standard department protocol. For this study CBCT scans taken in the first week of treatment and one CBCT scan from each subsequent week were used for analysis. If patients had more than one CBCT taken per fraction because an intervention was required prior to treatment, only the CBCT acquired first was used for analysis. Some of the patients were replanned during the course of their treatment
to correct patient changes or systematic issues that were detected. In these cases the CBCT scans after the replan commenced treatment were matched to the replan planning CT scan. For this study the CBCT scans and planning CT scan were first matched to bony anatomy. The shift co-ordinates in the superior– inferior, anterior–posterior, and left–right directions were recorded. The scans were then rematched to the chosen superior clip and the match co-ordinates were recorded. The scans were then matched a third time to the inferior clip and the match co-ordinates were recorded. The bladder diameter in the anterior–posterior direction was measured at the superior clip level (i.e. at a mean of 0.84 cm above the top of the pubic symphysis) and the difference in bladder diameter between the planning CT and each of the CBCT scans was calculated. The rectum diameter in the anterior–posterior direction was measured at three levels, superior clip level, inferior clip level (i.e. at a mean of 2.78 cm below the top of the pubic symphysis) and midway between these two points. The difference in rectal diameter between the planning CT and each CBCT scan was then calculated. Patients were deemed to have a geographic miss if clip movement was greater than 0.5 cm posteriorly or 1 cm in any other direction. This expansion was deemed the minimum acceptable expansion in the FROGG guidelines [16]. To determine the amount of bladder variation that causes geographic miss in post-prostatectomy patients, the superior and inferior clip movement was plotted against the bladder variation. To determine the amount of rectum variation that causes geographic miss in post-prostatectomy patients, the superior clip movement was plotted against superior rectum variation and the inferior clip movement was plotted against the inferior rectum variation. The combined effect of bladder and rectal variation on geographic miss was also assessed. Microsoft ExcelÒ (Microsoft Corporation, Redmond, WA, USA) and Statistical Package for the Social SciencesÒ (SPSS) (IBM Corporation, Armonk, NY, USA) were used to conduct statistical analyses on the data collected. Chi-square analysis was conducted to determine the effect of bladder and rectal change on movement in the upper and lower prostate bed with a value of p < 0.01 considered to indicate significance. Correlation of clip movement and bladder and rectal size change was used to determine which organ changes caused potential geographic miss. Rectal and bladder size changes were divided into 5 easily measurable sizes for on-line assessment to determine which change was most likely to cause potential geographic miss. Results A total of 377 CBCT scans were reviewed for 40 postprostatectomy patients (median number of CBCT 9, range of 8–11 per patient). Forty-five planning CT scans were reviewed with 5 of these being rescan planning CT scans taken during the course of the patients’ radiotherapy. Bladder and rectum volumes and diameters at simulation The initial mean bladder volumes at simulation were 398.34 cc (SD 199.6 cc, range 82.99–882.19 cc) and the initial mean bladder diameter was 8.87 cm (SD 1.74 cm, range 4.69–12.42 cm). The initial mean rectum volume at simulation was 73.31 cc (SD 24.8 cc, range 40.40–148.03 cc). The initial mean rectal diameter at simulation in the superior section of the rectum was 2.93 cm (SD 0.91 cm, range 0.42–4.96 cm) compared to the mid rectum mean of 3.65 cm (SD 1.0 cm, range 1.96–5.92 cm) and inferior rectum mean of 3.34 cm (SD 0.81 cm, range 2.05–6.22 cm). No volumes were measured on the CBCT scans. This was for two reasons. Firstly, the CBCT length is shorter than the planning CT scan so the full organs were rarely scanned, and secondly because
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this study was designed to inform on-line intervention and voluming tools are currently unavailable at the treatment machine. Bladder variation Large variations in bladder filling were seen. The mean bladder diameter change was 0.62 cm (SD 1.64 cm, range 7.2 to +5 cm), with the negative value indicating smaller bladder diameters during treatment than at simulation. Table 1 shows the proportion of CBCTs acquired by change in bladder diameter. 56.2% of images showed less than 1 cm variation from the simulated size. 10.6% of images showed a bladder diameter increase of greater than 1 cm and 33.1% showed a bladder diameter decrease of greater than 1 cm. Changes in bladder diameter had a greater effect on potential geographic miss in the upper prostate bed (Chi-Square p < 0.01), compared to the lower prostate bed, in the anterior–posterior direction (Fig. 1a). A negative value for the clip motion in the anterior–posterior direction indicates the clip moving posteriorly. Table 1 relates the variation in bladder diameter to the potential for geographic miss in the upper and lower prostate bed. In the upper prostate bed, variations in bladder diameter of more than 2 cm larger, ±1 cm, and more than 2 cm smaller resulted in geographic misses in 61.5%, 9.9% and 26.3% of images respectively. Variations in bladder diameter in the lower prostate bed had minimal impact on geographic misses with less than 2% of all images demonstrating a geographic miss.
mon, when the rectal diameter reduced by >1 cm at treatment compared to planning (seen in 7.2% of images), the potential for geographic miss was high (63%). Variations in rectal filling in the lower prostate bed region had minimal impact on geographic miss with less than 2% of all images demonstrating a geographic miss.
Combined effect of bladder and rectum variation on potential geographic miss Appendix II illustrates the combined effect of bladder and rectal variation on potential geographic miss in the upper sections of the prostate bed. The numbers of geographic misses are highest when the opposite ends of the ranges are experienced together. For example, when the bladder was larger by >2 cm and the rectum was smaller by >1.1 cm, 55.6% of images showed a geographic miss, and when the bladder was smaller by >2 cm and the rectum was larger by >1.1 cm, 34.5% of images showed a geographic miss. One of the most common factors in potential geographic miss was a smaller rectum, no matter what variation was seen in the bladder: for example, when the rectum was >1.1 cm smaller, 100% of images showed a geographic miss if the bladder was 1.1–2 cm either larger or smaller. In 40.3% of the images the bladder and rectum stayed within ±1 cm of the planned size. The numbers of geographic misses were minimal (7.1%) in this group. Discussion
Rectum variation A large variation in the rectal diameter during treatment was seen. With negative values indicating smaller rectal diameters we found that variations were greatest in the superior section of the rectum (mean 0.59 cm; SD 1.24 cm, range 2.1 to +5.4 cm; median 0.41 cm) compared to the mid rectum (mean 0.37 cm; SD 0.92 cm, range 2.2 to +4.7 cm; median 0.31 cm) and inferior section of the rectum (mean 0.30 cm; SD 0.73 cm, range 2.4 to +2.9 cm; median 0.28 cm). Table 2 shows the proportion of CBCTs with rectal diameter change in the superior and inferior sections of the rectum. The superior rectum stayed within 1 cm of the planned size in 65.8% of images, increased in size by greater than 1 cm in 27.0% of images, and decreased in size by greater than 1 cm in 7.2% of images. The inferior rectum stayed within 1 cm of the planned size in 83.6% of images, increased in size by greater than 1 cm in 13.0% of images and decreased in size by greater than 1 cm in 3.5% of images. Changes in rectal diameter had the greatest effect on potential geographic miss in the upper prostate bed (Chi-Square p < 0.01) compared with the lower prostate bed, with this effect occurring in the anterior–posterior direction (Fig. 2a). A negative value for the clip motion in the anterior–posterior direction indicates the clip moving posteriorly. Table 2 relates variation in rectal filling to the potential for geographic miss in the upper and lower part of the prostate bed. In the upper prostate bed region, variations in rectum filling > 1.5 cm larger, 1.5 cm larger to 1 cm smaller, and more than 1 cm smaller resulted in geographic misses in 29.2%, 12.3%, and 63.0% of images respectively. Although uncom-
There is little literature available on the relationship between organ filling and geographic miss during post-prostatectomy radiotherapy. Fiorino et al. [12] used weekly CT scans to assess rectal and bladder change during post-prostatectomy radiotherapy in 9 patients, and found that the bladder tended to progressively reduce in size during treatment. Showalter et al. [17] also used CBCT scans to assess rectal and bladder change during post-prostatectomy radiotherapy in 10 patients. They too found that the mean posterior bladder wall moved anteriorly which matches both Fiorino et al. and our findings. In regard to the rectum both Fiorino and Showalter found the rectum tended to become slightly smaller during treatment, whereas in our series 69.7% of images showed some degree of increase in rectal size. This could be because our simulation protocol recommended the use of a gentle laxative (magnesium) and diet modification prior to simulation as well as to give an enema if the planning CT rectum size was larger than 3.5 cm. They also found that movement was greater in the upper prostate bed and was influenced by the degree of rectal and bladder filling. Our study highlights the importance of bladder and rectum stability to prevent geographic miss. Despite a rigorous full bladder/empty rectum protocol and education programme, the bladder remained within 1 cm of the planned size in only 56.2% of cases and the superior rectum within 1 cm of the planned size in 65.8% of images. When the bladder or rectum remains within 1 cm of the planned size, approximately 90% of images showed no potential geographic miss.
Table 1 Bladder change resulting in potential geographic miss of the prostate bed. The number and percentage of images where certain ranges of bladder variation occurred and when this has resulted in a potential geographic miss of the treatment area. bladder change
>2 cm larger 1.1–2 cm larger 1 to +1 cm 1.1–2 cm smaller >2 cm smaller
Images showing bladder change
Superior clip out of PTV acceptable expansion
Inferior clip out of PTV acceptable expansion
Number/total
Percentage (%)
Number/total
Percentage (%)
Number/total
Percentage (%)
13/377 27/377 212/377 68/377 57/377
3.4 7.2 56.2 18.0 15.1
8/13 10/27 21/212 17/68 15/57
61.5 37.0 9.9 25.0 26.3
0/13 1/27 4/212 1/68 1/57
0.0 3.7 1.9 1.5 1.8
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Fig. 1. Bladder variation causing potential geographic miss in the upper prostate bed. Amount of bladder variation that is clinically significant for post-prostatectomy patients in the upper area of the prostate bed (a–c) and the lower section of the prostate bed (d–f) in the anterior–posterior (a and d), superior–inferior (b and e), and left–right (c and f) directions. The grey shaded area represents the FROGG acceptable PTV expansions. Any points that fall outside this area are a potential geographic miss. The black dashed boxes indicate the variations in bladder filling that are most likely to cause a potential geographic miss of the treatment area. A negative value for the clip motion indicates that the clip is moving posteriorly (in the anterior–posterior direction), superiorly (in the superior–inferior direction), and left (in the left–right direction).
Table 2 Rectum change resulting in potential geographic miss of the prostate bed. The number and percentage of images where certain ranges of rectum variation occurred and when this has resulted in a potential geographic miss of the treatment area. Rectum (sup) change
>1.5 cm larger 1.1–1.5 cm larger 1 to +1 cm 1.1–1.5 cm smaller >1.5 cm smaller Rectum (inf) change
>1.5 cm larger 1.1–1.5 cm larger 1 to +1 cm 1.1–1.5 cm smaller >1.5 cm smaller
Images showing rectum (sup) change
Superior clip out of PTV acceptable expansion
Number/total
Percentage (%)
Number/total
Percentage (%)
65/377 37/377 248/377 15/377 12/377
17.2 9.8 65.8 4.0 3.2
19/65 2/37 33/248 10/15 7/12
29.2 5.4 13.3 66.7 58.3
Images showing rectum (inf) change
Inferior clip out of PTV acceptable expansion
Number/total
Percentage (%)
Number/total
16/377 33/377 315/377 1/377 12/377
4.2 8.8 83.6 0.3 3.2
0/16 1/33 6/315 0/1 0/12
Percentage (%) 0.0 3.0 1.9 0.0 0.0
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Fig. 2. Rectum variation causing potential geographic miss in the upper prostate bed. Amount of rectum variation that is clinically significant for post-prostatectomy patients in the upper area of the prostate bed (a–c) and the lower section of the prostate bed (d–f) in the anterior–posterior (a and d), superior–inferior (b and e), and left–right (c and f) directions. The grey shaded area represents the FROGG acceptable PTV expansions. Any points that fall outside this area are a potential geographic miss. The black dashed boxes indicate the variations in rectal filling that are most likely to cause a potential geographic miss of the treatment area. A negative value for the clip motion indicates that the clip is moving posteriorly (in the anterior–posterior direction), superiorly (in the superior–inferior direction), and left (in the left–right direction).
Variations of >1 cm in rectal and bladder filling had a significant impact on coverage, with the greatest movement seen with the rectum reducing and/or the bladder increasing. For example, a >1 cm reduction in rectal size results in surgical clip miss in 63% of these cases. In the images with a potential geographic miss, we found that the median bladder increase was 1.23 cm and median decrease was 1.9 cm. A median superior rectum increase of 0.89 cm and decrease of 1.11 cm was found in the images that had potential geographic misses. Reducing rectal size seems to have a larger effect on potential geographic miss than bladder filling (Appendix II). Hence, it is important to ensure that the rectum is small at the time of simulation. This was also found in a number of other studies [12,18,19]. At NSCC we now administer an enema prior to simulation for all post-prostatectomy patients. Caution should also be taken when instructing a patient to increase their bladder filling for treatment in response to a small bladder at simulation and unfavourable dose volume histogram characteristics. This could have the unintended result of a geographic miss of the treatment area. In our series, having the
bladder 2 cm larger during treatment resulted in a 61.5% rate of geographic miss. At NSCC we now routinely perform a bladder ultrasound prior to simulation to ensure adequate bladder filling. This study has not investigated the impact of strict rectal and bladder filling protocols. In recent work by McNair et al. [20] it was shown that strict rectal filling guidelines still did not prevent rectal size changes due to the inability to control bowel gas. Therefore stricter protocols might not be the answer to this problem. Simply changing the on-line matching technique from matching to bony anatomy to matching to surgical clips would not always help reduce geographic miss because the upper and lower prostate bed move independently creating a prostate bed pitch rotation. This variable is difficult to correct with standard on-line matching techniques, as most treatment couches do not tilt and those that do have a limited range [21]. Prostate bed pitch rotation is a continuing area of research in our department, including the role of anisotropic PTV margins. Larger margins might be required in the upper region to protect against geographic miss due to its greater movement. Less motion was seen in the inferior section
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of the prostate bed, so it might be possible to decrease margins here to reduce normal tissue irradiation. Bladder and rectum size change could be a good surrogate to indicate potential geographic miss when there are no surgical clips in situ. A major advantage of this work is that non-volumetric tools were used to assess the organ size variations. These tools are available in routine imaging software and enable assessment of and correction for organ size change to be completed in the on-line setting. There are a number of limitations to this study. Surgical clips are only a surrogate for prostate bed motion and geographic miss. It could be argued that using soft tissue is a more accurate way to evaluate movement and geographic miss, but defining specific measurement points in an asymmetric structure such as the PTV is problematic. In this study a large number of images was reviewed (n = 377), but these images belong to only 40 patients. Patients who have systematic issues that cause prostate bed movement resulting in geographic miss could have influenced our findings. Some of the patients involved in this study (5 of 40) had new plans generated during treatment to correct for issues such as movement, geographic miss, or contour variation. This intervention might therefore have caused an overall underestimation of the extent of movement and geographic miss. Only measurement tools available in the on-line setting were used, to allow a strategy for on-line intervention to be determined. There might be better off-line tools available to investigate movement of geographic miss that could give more robust answers, but this would not allow on-line interventions to occur. Conclusion Bladder and rectal size changes affect prostate bed coverage with the greatest risk of geometric miss seen with a smaller rectum and a larger bladder during treatment. The majority of movement caused by bladder and rectum variation is seen in the upper aspect of the prostate bed. If the bladder or rectum stayed within 1 cm of the planned size, approximately 90% of images showed no geographic miss. When both the bladder and rectum are within 1 cm of the planned size, this percentage increases to 93% of images. It is therefore important to ensure that a comfortably large bladder and small rectum are achieved at simulation. It is also very important to take note of which patients are showing systematic variations in the bladder and rectum early in the treatment course, so intervention can occur to ensure treatment is delivered accurately. Greater movement in the upper prostate bed than in the lower prostate bed is difficult to correct for in an on-line setting, even when aligning to clips or fiducial markers. Anisotropic PTV margins allowing for greater movement superiorly than inferiorly are therefore recommended. Conflict of interest statement None. Acknowledgements The authors gratefully acknowledge all the staff at the Northern Sydney Cancer Centre.
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.radonc.2013.10. 042.
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