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ORIGINAL ARTICLE
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Observational study of cone beam computed tomography based interfractional urinary bladder filling variation during image guided radiation therapy in pelvic malignancies


1 Department of Radiation Oncology, Jaypee Hospital, Noida; Department of Radiation Oncology, Max Super Specialty Hospital, Vaishali, Uttar Pradesh, India
2 Department of Radiation Oncology, Max Super Specialty Hospital, Patparganj, Delhi, India
3 Department of Radiation Oncology, Max Super Specialty Hospital, Vaishali, Uttar Pradesh, India
4 Department of Radiation Oncology, All India Institute of Medical Science, Rishikesh, Uttarakhand, India
5 Department of Radiation Oncology, Jaypee Hospital, Noida, Uttar Pradesh, India

Correspondence Address:
Manjari Shah,
Department of Radiation Oncology, Jaypee Hospital, Noida, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_626_18

 > Abstract 


Background: Organ motion is an important factor that limits the precision of radiation treatment. Bladder filling variation has significant impact on the position of target volumes in pelvic malignancies.
Aims and Objective: This study was an effort to maintain a consistent urinary bladder volume after following a bladder protocol, which was then analyzed by in-room cone-beam computed tomography (CBCT) imaging.
Material and Methods: A total number of 26 patients/300 scans, i.e. 26 planning scan and 274 CBCT were analyzed. The bladder volumes and bladder wall dimension were analyzed comprehensively, thus adding considerable understanding to the bladder wall motions.
Result: The mean bladder volume for all 26 patients was 183.07 cc with standard deviation of 90.43 cc. The mean +/- standard deviation of transverse, anteroposterior and longitudinal diameter was 8.35+/- 1.03, 6.69+/-1.05 and 5.59+/-1.79 cm.
Conclusion: This study showed considerable reduction of margin could be done on the lateral side, as there is less displacement on transverse diameter and more liberal margins should be considered in anteroposterior dimension and longitudinal dimensions. This study has reached the conclusion that bladder-filling protocol is necessary to maintain the consistent bladder volume, but it is too preliminary to state that it will translate into reduction of margin.

Keywords: Bladder variation, cone-beam computed tomography, image-guided radiation therapy, organ motion



How to cite this URL:
Shah M, Agarwal S, Agarwal R, Subramanian B, Gupta S, De S, Mishra S. Observational study of cone beam computed tomography based interfractional urinary bladder filling variation during image guided radiation therapy in pelvic malignancies. J Can Res Ther [Epub ahead of print] [cited 2019 Nov 21]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=269913




 > Introduction Top


With advancement, comes limitations. Similarly, in radiotherapy, advanced machines and treatment techniques had several associated factors that limits its precision. Organ motion is one of the important factors limiting the precision of advanced radiation techniques, especially for pelvic malignancies. Bladder-filling variation has significant impact on the position of target volumes in pelvic malignancies. The inter- and intra-fractional movement of the bladder wall can be as much as 3 cm due to the changes in volume of the bladder and rectum.[1] If the bladder wall motion is not taken into consideration while planning the treatment, target miss is likely to occur, resulting in reduced local tumor control. Thus, to compensate this, the treatment margins were increased for the uncertainty of the bladder wall motion. Increasing the irradiated margins also increases the possibility, a critical structure to be irradiated beyond tolerance leading to unacceptable complications. Another approach to reduce the bladder motion influence on the target location is by controlling the bladder volume, a protocol instructing the patient to drink a certain amount of water before starting the treatment, but the studies showed that even with detailed instruction, patients were unable to maintain consistent bladder volumes. This study was an effort to maintain a consistent urinary bladder volume after following a strict bladder protocol, which was then analyzed by in-room cone-beam computed tomography (CBCT) imaging. The bladder volumes and bladder wall dimension in all the three directions were analyzed comprehensively, thus adding considerable understanding to the bladder wall motions.

Aims and objectives

The aim of this study is to observe interfractional urinary bladder-filling volume variation during image-guided radiotherapy in pelvic malignancies, with the help of cone-beam CT after following strict bladder-filling protocol.


 > Materials and Methods Top


This study was conducted on patients of pelvic malignancies excluding urinary bladder carcinoma. It was a single institution, nonrandomized, prospective study and the duration of study was 6 months.

Inclusion criteria

  1. Patients with the histopathological diagnosis of cancer who were taken up for the treatment with curative intent
  2. Patients having urine holding capacity for 30 min.


Exclusion criteria

  1. Carcinoma urinary bladder patients
  2. Patients who earlier have received pelvic radiotherapy
  3. Patients having metastatic disease
  4. Patients having urinary tract infection (Urine examination was done to rule out)
  5. Patients having Eastern Cooperative Oncology Group Performance Score of 3 or more.


The patients fulfilling the study criteria were individually staged according to their disease. All patients were counseled in detail regarding bladder-filling protocol, and a pretest was carried out to confirm that patients were able to hold urine for 30 min. All the patients who were included in the study were explained in detail regarding the study procedure in their native languag, and informed consent was obtained before starting treatment from all the patients.

The following bladder-filling protocol was used in this study

  1. The patients were instructed to void the bladder 40 min prior to radiation treatment and to drink 600 ml of water within 10 min
  2. The patients were scanned after 30 min of taking last glass of water. Time of last glass of water and CBCT was noted
  3. Twice weekly CBCT was done to quantify the volumetric changes of the bladder throughout the treatment period, but the bladder-filling protocol was followed during the planning CT as well as whole course of radiation treatment
  4. Patients were advised not to take tea/coffee/alcoholic beverages 1 h prior to coming for radiation treatment
  5. No other dietary restriction were advised
  6. No routine laxatives were advised unless patients had complaint of constipation.


Statistical analysis

Statistical analysis was performed using the SPSS program for Windows, version 17.0 (SPSS Inc., 233 South Wacker Drive, Chicago, USA). Data were checked for normality before statistical analysis. One-way analysis of variance was used to determine whether there are any significant differences between means of different patients. For all statistical tests, P < 0.05 was taken to indicate a significant difference.


 > Results Top


A total number of 26 patients of pelvic malignancies were enrolled, including cervical cancer, endometrial, prostate, and colorectal cancer patients. All patients in the study group underwent planning CT scan then twice weekly CBCT scan, minimum of 10 CBCTs were performed for each patient. Planned sample size was 100 CBCTs/10 patients, but we were able to study 26 patients. A total of 300 scans (26 Planning CT + 274 CBCTs) were analyzed in these 26 patients. Urinary bladder was contoured in all 300 scans by same radiation oncologist and bladder was then measured in all three maximum dimensions; transverse, longitudinal, and anteroposterior diameter. Bladder volume measured and time of CBCT were noted. All these parameters were compared with the planning CT scan, considering it as baseline.

The study group was heterogeneous, as we had patients of all common pelvic malignancies. The females form the 70% bulk of our study group, and we had more number of cervical and endometrial cancer in our group. Cervical cancer form the major portion, i.e., 9 of the 26 patients followed by the endometrium (7/26), prostate (5/26), and colorectal cancer (5/26) patients.

All patients underwent minimum of 10 CBCTs, twice weekly CBCTs during the radiation treatment. All 300 (100%) scans were done after 30 min. While 57.3% patients (n = 172) had their scans as per the study protocol, 41.7% (n = 125) patients CBCT done after 40 min but before 50 min. Only 1% (n = 3) got their CBCT done after 50 min of taking the first glass of water.

Mean and standard deviation of bladder wall transverse diameter is shown in [Graph 1]. Patients had maximum mean transverse diameter of 10.2 cm and minimum diameter of 5.58 cm. 69% of patients (n = 18) fall in between mean of 8–10 cm, while 31% (n = 8) patients extend beyond this mean.[INLINE: 1]

As shown in [Graph 2], the mean anteroposterior wall diameter in all 26 patients with maximum mean anteroposterior diameter of 10.2 cm and minimum diameter of 4.56 cm. About 53.8% (n = 14) patients fall in mean of 6–8 cm and 46.2% (n = 12) extend beyond this mean.[INLINE: 2]

Maximum mean as observed in longitudinal dimension was 10.04 cm and minimum mean was 2.82 cm with a wide range. 54% (n = 14/26) patients fall in mean range of 4–6 cm, while 46% (n = 12/26) patients extend beyond this mean as shown in [Graph 3].[INLINE: 3]

The mean bladder volume was noted in all 26 patients and then compared with all other patients of pelvic malignancies. Maximum bladder volume was 475 cc and minimum bladder volume was 62 cc. The mean bladder volume for all 26 patients was 183.07 cc with standard deviation (SD) of 90.43 cc and P = 0.761 which was nonsignificant. Similarly, the mean time was 40.12 min with SD of 2.15 min and P = 0.059 which was nonsignificant.

On analysis of all these patients as a group consisting of a total of 300 bladder images (26 planning CT scan + 274 CBCTs), the findings are shown in [Table 1] with mean ± SD of bladder wall in all three dimensions and its P value.
Table 1: Mean±standard deviation of bladder wall movements in all 26 patients

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 > Discussion Top


Bladder motion is the most debatable topic in pelvic radiation treatment. Most of the studies exploring bladder motion during radiation treatment have been in bladder malignancies.[2],[3] Several studies on pelvic malignancies have observed bladder motion as target but only few studies have observed bladder motion as organ at risk (OAR).[4],[5],[6] Thus, it is difficult to extrapolate the results of these studies to find out the bladder motion. Moreover, the studies looking at OAR motion have focused on bladder volume changes rather than bladder wall motion per se. To the best of our knowledge and extensive review of literature, very few of the studies of pelvic malignancies (excluding bladder carcinoma) has observed the bladder wall motion.[6]

All patients underwent minimum of ten CBCTs. Eighteen of the 26 (70%) of patients underwent 10 CBCT. Daily CBCT can increase the concern of increase radiation dose, so most of the center uses once or twice weekly CBCTs. In our institute, we do twice weekly CBCTs. In contrast to our study, Yee et al. conducted the study on ten bladder cancer patients and did daily CBCT. They obtained 262 CBCTs in ten bladder cancer patients.[2] As the dose of CBCT is a concern, it is reasonable to compare the dose of CBCTs to radical dose of radiation. However, we were not able to compare the dose of CBCTs as dosimetric data were not analyzed. Wang et al. showed that the dose received by a patient, while doing CBCT pelvis is 17.7 mGy which is almost negligible in comparison of radical treatment dose which ranges from (50–76 Gy).[7]

Urinary bladder wall movements in all three dimensions; transverse, longitudinal, and anteroposterior diameter were analyzed. 14 of the 26 (53%) patient showed significant changes in anteroposterior diameter followed by longitudinal diameter which showed significant changes in 10 of the 26 (38%) patients. In transverse diameter, only 6 of the 26 (23%) patients showed significant changes. Although the number of patients with significant changes was more in anteroposterior diameter, variation was seen more in longitudinal diameter with a range of 7.18 cm as compared to anteroposterior diameter which has range of 5.64 cm as shown in [Table 2].
Table 2: Mean/range of 26 patients in all three dimensions

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Yee et al. 2010 quantify daily bladder size and position variations during bladder cancer radiotherapy in ten bladder cancer patients undergoing daily CBCTs.[2] Anterior bladder wall shifted the most (mean = −0.58 cm). In our study, patients underwent twice/thrice weekly CBCTs, while Yee et al. patients underwent daily CBCTs, but the results were similar in both the study with anteroposterior bladder wall movement being more. Another study by Fokdal et al. 2004, on 15 patients of bladder carcinoma showed bladder movement was more pronounced in the anterior and cranial directions.[8]

Jhingran et al. 2012, observed the movements of fiducial markers implanted on 24 patients of carcinoma cervix patients and showed more movements in anteroposterior direction followed by superior–inferior direction and least in the right–left direction.[4] Mean diameter for 26 patients in our study was 8.35, 6.69, and 5.59 cm in transverse, anteroposterior, and longitudinal dimension, respectively. Standard deviation was 1.039, 1.05, and 1.798 cm in transverse, anteroposterior, and longitudinal direction, respectively, and these results were consistent with above-mentioned studies.

The number of patients in our study was 26, while it is 24, 15, and 10 in Jhingran et al., Fokdal et al., and Yee et al., respectively, still the results are consistent with these studies. Yee et al. and Fokdal et al. have done its study in carcinoma bladder patients and Jhingran et al. did his study on carcinoma cervix, but our study group was heterogeneous, and we were able to replicate the results of above-mentioned studies.

Majewski et al. estimated bladder movements in the patients of bladder cancer receiving conformal radiotherapy.[9] Bladder movements were mainly observed cranially; similarly in our study, cranial movements were more.

Pinkawa et al. observed the variability in bladder filling during pelvic radiotherapy.[6] Fifty patients with localized prostate cancer were prospectively evaluated with multiple CT scans.

This study has focused on bladder volume variation and bladder wall displacements during a fractionated pelvis external beam radiotherapy. He showed wall displacement in all six directions and observed maximum wall displacements in anterior and superior direction. The standard deviation was 19.3 and 10.3 cm in cranial and anterior direction. The result of this study is consistent with our study as shown in [Table 3]. The standard deviation in longitudinal direction is 1.79 cm and in anteroposterior direction is 1.05 cm. Despite variable assessment method for organ motion used in different studies, maximum movements occur in anteroposterior and longitudinal direction. Hence, it is proved that despite using different assessment technique, the results remain the same.
Table 3: Comparison of bladder wall displacement in different studies

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Similar conclusions were made by the studies mentioned in [Table 3]. They have also shown similar results with bladder wall movements, and these results can be explained well on the basis of anatomical limitation of the urinary bladder. An empty bladder can well expand in posterior and lateral directions. With increasing volume the lateral movement is limited strongly by the pelvic bones, the posterior bladder wall movements are limited by rectum (including filling and sacral bones). Further expansion is a lot easier in the anterior and superior directions, where soft tissue and bowel loop can be shifted.

The results of our study were in concordance with those of above-mentioned studies. The most important challenging factor in this study was limitation of literature. As already mentioned, most of the studies exploring the bladder wall motion have been in bladder cancer patients.[2],[3] Contrary to this bladder carcinoma patients were excluded from our study because here it was an organ of interest. We focused on OAR rather than organ of interest. There are studies of other pelvic malignancies such as cervical, prostate, and rectum, but they did not per se observed the bladder wall motion and the volume of bladder.[4],[5] Another problem with this study was the availability of different methodologies to observe the organ motion.[10],[11],[12] There were different techniques available for determining organ motion, and different studies have used their different techniques, so the results were interpreted with the limited studies available with the same technique, i.e., perimeter displacement technique which we have used in our study.

The findings of this study indicate that the development of technological and clinical aspects in radiation treatment should go hand in hand. The study shows that to use the full potential of image-guided radiation therapy (IGRT) in pelvic malignancies in terms of margin reduction; it is also necessary to implement measures to control the bladder volume by bladder-filling protocol. Daily CBCT imaging may not be considered feasible in a routine setting, so we can switch to twice/thrice weekly CBCTs and planar imaging on other days in a week.

This study showed considerable reduction of margin could be done on the lateral side, as there is less displacement on transverse diameter and more liberal margins should be considered in anteroposterior dimension and longitudinal dimensions. Even if bladder volume is controlled with the bladder-filling protocol variation is always expected, so the benefit can even be greater while using IGRT. With the bladder-filling protocol, an attempt is made to control the bladder volume, but this led to small reduction in variation of bladder volume but did not translate into margin reduction.

The challenges posed by internal organ motion in patient treated with pelvic malignancies can be overcome by image-guidance technologies, of which CBCT is the best modality as it is noninvasive and the most common IGRT method, providing the volumetric-anatomic information and the opportunity to localize target volumes in a few minutes before each treatment fraction. Pretreatment CBCT has received much attention for its ability to reduce setup error and the required margins, thereby reducing the dose to the OAR in external beam radiotherapy.


 > Conclusion Top


This prospective study has been done to quantify the variation in bladder wall motion and volume after following strict bladder-filling protocol. The aim of our study is to observe interfractional bladder-filling variation after following strict bladder-filling protocol. All the patients followed the bladder-filling protocol religiously and no discomfort was reported. Patients showed variation in bladder volume with mean 184 cc and standard deviation of 90 cc which was nonsignificant. Bladder volumes increase with increasing waiting time. As the volume increases, bladder showed asymmetrical change in size and shape, with most significant changes observed in anteroposterior dimension, followed by longitudinal dimension and least changes were observed in transverse diameter.

The purpose of this study was to find a possible answer to a very pertinent question on bladder wall motion and bladder volume variations during different days of radiation therapy. This study has reached the conclusion that bladder-filling protocol is necessary to maintain the consistent bladder volume, but it is too preliminary to state that it will translate into reduction of margin. Further studies are required specifically for margin reduction if we want to reduce the margins utilizing, the information we have analyzed doing this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Pos FJ, Koedooder K, Hulshof MC, van Tienhoven G, González González D. Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy. Int J Radiat Oncol Biol Phys 2003;55:835-41.  Back to cited text no. 1
    
2.
Yee D, Parliament M, Rathee S, Ghosh S, Ko L, Murray B. Cone beam CT imaging analysis of interfractional variations in bladder volume and position during radiotherapy for bladder cancer. Int J Radiat Oncol Biol Phys 2010;76:1045-53.  Back to cited text no. 2
    
3.
Nishioka K, Shimizu S, Kinoshita R, Inoue T, Onodera S, Yasuda K, et al. Evaluation of inter-observer variability of bladder boundary delineation on cone-beam CT. Radiat Oncol 2013;8:185.  Back to cited text no. 3
    
4.
Jhingran A, Salehpour M, Sam M, Levy L, Eifel PJ. Vaginal motion and bladder and rectal volumes during pelvic intensity-modulated radiation therapy after hysterectomy. Int J Radiat Oncol Biol Phys 2012;82:256-62.  Back to cited text no. 4
    
5.
Ahmad R, Hoogeman MS, Quint S, Mens JW, de Pree I, Heijmen BJ. Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a por[table 3]-dimensional ultrasound bladder scanner. Radiother Oncol 2008;89:172-9.  Back to cited text no. 5
    
6.
Pinkawa M, Asadpour B, Siluschek J, Gagel B, Piroth MD, Demirel C, et al. Bladder extension variability during pelvic external beam radiotherapy with a full or empty bladder. Radiother Oncol 2007;83:163-7.  Back to cited text no. 6
    
7.
Wang J, Li T, Xing L. Low-dose CBCT imaging for external beam radiotherapy. Int J Radiat Oncol Biol Phys 2008;72:S109-10.  Back to cited text no. 7
    
8.
Fokdal L, Honoré H, Høyer M, Meldgaard P, Fode K, von der Maase H. Impact of changes in bladder and rectal filling volume on organ motion and dose distribution of the bladder in radiotherapy for urinary bladder cancer. Int J Radiat Oncol Biol Phys 2004;59:436-44.  Back to cited text no. 8
    
9.
Majewski W, Wesolowska I, Urbanczyk H, Hawrylewicz L, Schwierczok B, Miszczyk L. Dose distribution in bladder and surrounding normal tissues in relation to bladder volume in conformal radiotherapy for bladder cancer. Int J Radiat Oncol Biol Phys 2009;75:1371-8.  Back to cited text no. 9
    
10.
Barney BM, Lee RJ, Handrahan D, Welsh KT, Cook JT, Sause WT. Image-guided radiotherapy (IGRT) for prostate cancer comparing kV imaging of fiducial markers with cone beam computed tomography (CBCT). Int J Radiat Oncol Biol Phys 2011;80:301-5.  Back to cited text no. 10
    
11.
Moseley DJ, White EA, Wiltshire KL, Rosewall T, Sharpe MB, Siewerdsen JH, et al. Comparison of localization performance with implanted fiducial markers and cone-beam computed tomography for on-line image-guided radiotherapy of the prostate. Int J Radiat Oncol Biol Phys 2007;67:942-53.  Back to cited text no. 11
    
12.
Létourneau D, Martinez AA, Lockman D, Yan D, Vargas C, Ivaldi G, et al. Assessment of residual error for online cone-beam CT-guided treatment of prostate cancer patients. Int J Radiat Oncol Biol Phys 2005;62:1239-46.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

 
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