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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 374-378

Rectal complication probability from composite volumes derived from daily cone beam computed tomography in prostate cancer radiotherapy


1 Department of Physical Sciences, Peter MacCallum Cancer Centre, St. Andrew Place, East Melboure, Vic 3002; Bendigo Radiotherapy Centre, Peter MacCallum Cancer Centre, Stewart Street, Vic 3550; School of Med Sciences, RMIT University, Bundoora Campus, Bundoora, Vic 3083, Australia
2 Bendigo Radiotherapy Centre, Peter MacCallum Cancer Centre, Stewart Street, Vic 3550, Australia
3 School of Med Sciences, RMIT University, Bundoora Campus, Bundoora, Vic 3083, Australia
4 Department of Physical Sciences, Peter MacCallum Cancer Centre, St. Andrew Place, East Melboure, Vic 3002, Australia

Date of Web Publication13-Apr-2016

Correspondence Address:
Ramachandran Prabhakar
Physical Sciences, Peter MacCallum Cancer Centre, Melbourne
Australia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.174529

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 > Abstract 

Aim: The aim of this study is to investigate the rectal complication probabilities for various rectum volumes with intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in patients undergoing prostate cancer radiotherapy.
Materials and Methods: Thirteen patients undergoing prostate cancer radiotherapy were consecutively selected for this study. All patients were treated with IMRT to a dose of 78 Gy in 39 fractions. Three different rectum volumes: (i) planned rectum (plan-rectum) (ii) Boolean sum of rectum volume based on the cone-beam computed tomography (CBCT) for first five fractions (planning organ at risk volumes [PRV]-CBCT-5), (iii) Boolean sum of rectum volume from all the CBCTs (PRV-CBCT-All) in addition to an average rectal complication (PRV-CBCT-AV) were used for computing the probabilities of rectal complications. To assess the rectal complications with 3D-CRT, a five-field plan was generated for comparison with IMRT. The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was used to assess the rectal complications for all of the defined rectal volumes.
Results: The NTCPs for rectum as assessed from plan-rectum, PRV-CBCT-5, PRV-CBCT-All, and PRV-CBCT-AV with IMRT were 9.71% ±4.69%, 16.34% ±9.51%, 19.39% ±9.71%, and 12.81% ±7.22%, respectively. Similarly, with 3D-CRT, the NTCPs were 17.41% ±10.44%, 19.61% ±11.08%, 21.03% ±11.06%, and 17.72% ±10.29%, respectively.
Conclusion: Our results showed that the rectal complications are reduced significantly with IMRT as compared to 3D-CRT. As such, the analyses of NTCP with various defined composite rectum volumes indicate that IMRT requires image-guided adaptive radiotherapy as opposed to 3D-CRT.

Keywords: Cone beam computed tomography, intensity modulated radiation therapy, planning organs at risk volume, radiotherapy, three-dimensional conformal radiation therapy


How to cite this article:
Prabhakar R, Oates R, Daryl J, Chang J, Geso M, Cramb J. Rectal complication probability from composite volumes derived from daily cone beam computed tomography in prostate cancer radiotherapy. J Can Res Ther 2016;12:374-8

How to cite this URL:
Prabhakar R, Oates R, Daryl J, Chang J, Geso M, Cramb J. Rectal complication probability from composite volumes derived from daily cone beam computed tomography in prostate cancer radiotherapy. J Can Res Ther [serial online] 2016 [cited 2019 Jan 22];12:374-8. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/374/174529




 > Introduction Top


Prostate cancer is the second most common cancer in men worldwide [1] and accounts for more than 30% of cancers diagnosed each year in Australian men.[2] Radiotherapy (RT), in particular, has been proven to improve the local control and overall survival of these patients. One of the major concerns with radiotherapy is the rectal and bladder complications. Several studies have demonstrated that intensity-modulated radiation therapy (IMRT) has the potential to control early and late toxicity associated with radiotherapy.[3],[4] Dose escalation improves local control in prostate cancer radiotherapy but is limited by bladder and rectal toxicities.[5] Current literature suggests that rectal complications vary widely as a result of factors including treatment technique, prescribed dose, definition of rectum, department protocol, planners, and radiation oncologists.[6],[7],[8],[9],[10] Definition of the rectum length or volume during treatment planning differs broadly among clinics. Hence, applying literature dose constraints to the rectum will highly depend on the definition of the rectum as an organ at risk (OAR). International Commission on Radiation Units 62 (ICRU 62) recommends the use of planning organ at risk volumes (PRV) to account for changes resulting from organ motion and setup inaccuracies during the whole course of treatment.[11] The PRV encapsulates dose in the region in space where the relevant OAR is likely to be located. The definition of PRV margin varies widely between centers and is not often used during treatment planning due to a lack of supporting clinical data. Despite this, ICRU 83 now recommends the use of PRV in most clinical sites.[12] In our recently published study, we have shown that the rectal PRV margin is not uniform and tapers down as the margin proceeds in the caudal direction.[13] Most of the complications quoted in the literature were correlated to the rectal volumes as defined during treatment planning. The rectal volume is likely to change throughout the course of treatment due to a number of factors that include diet, water intake, respiration, and rectal contents (gas or feces). There is a need to compare the difference in the rectal complications as predicted from treatment planning rectal volumes and those computed during the course of treatment from cone-beam computed tomography (CBCT) defined volumes. Thus, in this study, we have sought to assess the rectal complication probabilities with IMRT and three-dimensional conformal radiotherapy (3D-CRT) for various composite rectal volumes observed during the treatment course.


 > Materials and Methods Top


Thirteen patients with histologically proven adenocarcinoma of the prostate, previously treated at our center with radical radiotherapy were selected for this study. To keep the bladder volume uniform during the course of treatment, the patients were asked to consume 750 cc of water 30 min before treatment. Contouring was performed on a Focal workstation (Computerized Medical Systems™, Missouri), and the CT datasets and RT structure sets were transferred to an Eclipse treatment planning system (Varian Medical Systems™). Seven-field sliding window IMRT plans were generated on the Eclipse treatment planning system for all of the selected patients with predetermined gantry angles of 0, 50, 100, 150, 210, 260, and 310. All patients were planned with 6 MV photon field arrangements. A dose of 78 Gy in 39 fractions was delivered to all patients with 95% of the prescribed dose covering 99% of the target volume. All treatment fractions were aligned to the isocenter with pretreatment image-guided radiotherapy (IGRT) of kV/kV orthogonal imaging matched to gold seed fiducials implanted in the prostate with a 0 mm action threshold. A Varian Clinac 21iX (Varian Medical Systems, Palo Alto) with On-Board Imager was used to acquire CBCT. CBCTs were acquired at the end of treatment for the first five fractions and subsequently every alternate fraction. To compare the difference in normal tissue complication probability (NTCP) between IMRT and 3D-CRT, a five-field 3D-CRT treatment plan employing 6 MV and 18 MV photon beams was also generated. [Figure 1] shows the typical beam arrangement of the 3D-CRT and IMRT treatment plans.
Figure 1: Three-dimensional conformal radiotherapy and intensity modulated radiation therapy beam arrangements for a typical patient

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To determine the PRV margin, CBCTs obtained at the end of treatment for the first five fractions and every alternate fraction were considered. Post-treatment CBCTs closely mimic the treatment conditions with the patient aligned to the treatment isocenter. The CBCTs were transferred to a Focal workstation for contouring of the critical structures. The CBCTs were fused to the planning CT at the position of the pretreatment IGRT alignment. The rectum and other structures were contoured on all acquired CBCTs. The rectum contour was defined as the outer rectal wall extending from approximately 1 cm inferior to the superior border of the treatment fields to approximately 1 cm superior to the inferior border of the treatment fields. Three separate rectal volumes were created: (i) the rectal contour based on the planning CT scan (Plan-Rectum), (ii) the Boolean sum of rectum volumes based on the CBCT for the first five fractions (PRV-CBCT-5), and (iii) the Boolean sum of rectum volumes from all the CBCTs (PRV-CBCT-All).

Rectal complications were assessed by the Lyman-Kutcher- Burman (LKB) NTCP model to assess ≥ grade-2 rectal toxicity.[14],[15] Differential dose volume histograms (dDVHs) were generated for Plan-Rectum, PRV-CBCT-5, and PRV-CBCT-All. An average rectal DVH (PRV-CBCT-AV) was created by averaging the dose volume bins of the rectal DVHs for each patient from all of the acquired CBCTs. An Excel worksheet (Microsoft™ Corporation) was developed to compute the LKB-based NTCP wherein the dDVHs were imported and analyzed. The SPSS (IBM SPSS 10.0, IBM Corporation, USA) computer package was used for statistical analyses. The Wilcoxon signed rank test with an alpha of 0.05 was used for comparing NTCPs for the different rectal volumes and planning methods.


 > Results Top


[Figure 2] shows the comparison of volumes of rectum contoured in different situations. The mean rectal volume of all the patients contoured for plan-rectum, PRV-CBCT-5, and PRV-CBCT-All were 40.28 ± 11.74 (22.50–64.30), 77.39 ± 30.07 (35.70–130.30), and 103.83 ± 25.05 (62.40–144.30), respectively. [Figure 3] illustrates the variation in the cumulative dose volume histogram of rectum based on the treatment plan generated on CBCTs acquired during the course of radiotherapy for a typical patient. [Figure 4] and [Figure 5] show the normal tissue complication probabilities for different rectal volumes with 3D-CRT and IMRT, respectively. [Table 1] clearly demonstrates the advantage of IMRT over 3D-CRT in prostate cancer radiotherapy. An average of approximately 8% and 5% reduction in rectal complications for plan-rectum and PRV-CBCT-AV, respectively, is achieved with IMRT. Statistically significant difference in rectal NTCP with IMRT has been observed between plan-rectum and PRV-CBCT-5 (P < 0.004) and also between plan-rectum and rectum-all (P < 0.002). We also observed statistically significant difference (P < 0.009) with 3D-CRT between plan-rectum and rectum-all [Table 2]. PRV-CBCT-AV depicts the average dose received from all variations in rectal volume during the course of radiotherapy. Hence, PRV-CBCT-All indicates the dose that the rectum could have received, and this parameter can be used for assessing the rectal complications. [Table 2] also shows that there is a statistical difference between plan-rectum and PRV-CBCT-AV with IMRT. Statistically significant difference was observed between Plan-rectum and PRV-CBCT-AV for IMRT, and no difference was seen with 3D-CRT. [Table 1] and [Table 2] also illustrate that the difference in NTCP values between plan-rectum and PRV-CBCT-AV is <1% (not significant) for 3D-CRT, whereas an average of 3% change in rectal complications was seen with IMRT.
Figure 2: Comparison of volumes of rectum contoured in different situations

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Figure 3: Cumulative dose volume histogram of rectum for different treatment fractions during the course of radiotherapy for a typical patient

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Figure 4: Normal tissue complication probabilities for different rectal volumes with three-dimensional conformal radiotherapy

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Figure 5: Normal tissue complication probabilities for different rectal volumes with intensity modulated radiation therapy

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Table 1: Normal tissue complication probability for rectum with three-dimensional conformal radiotherapy and intensity modulated radiation therapy

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Table 2: Statistical significance (P values) of different rectal volumes for three-dimensional conformal radiotherapy and intensity modulated radiation therapy treatment plans

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 > Discussion Top


In radiotherapy, there are several approaches to ensure the tumor volume receives the prescribed dose in the midst of uncertainties influenced by the operator, equipment-related errors, and the relative movement of adjacent structures to the target volume. The most common tool utilized is an addition of a margin to the clinical target volume that accounts for setup error and organ motion. Adaptive radiotherapy is an approach where individualized treatment plans are correlated with daily imaging to precisely target the tumor volume. The former is widely employed in standard practice, whereas the latter is gradually finding its place in radiotherapy. Currently, IGRT is commonly used in prostate cancer radiotherapy due to the dose escalation. Routinely, kV/kV orthogonal images are used to verify the patient position to the isocenter. The position of the target volume in prostate cancer radiotherapy is dependent on the movement and/or volumetric changes of the bladder, rectum, and bowel volumes. The consistency in the volume of the bladder could be improved by adopting a strict water intake protocol prior to treatment. Unfortunately, due to our CBCT scan length, we could not include an assessment of bladder NTCP or bladder volume consistency as the bladder dome regularly extended beyond the superior border of the CBCT.

The rectum is one of the critical structures that can seriously affect the dose to the target volume and is prone to serious complications in prostate cancer radiotherapy. In practice, the location of the rectum forces the treating physician to reduce the posterior margin of the planning target volume (PTV) to avoid any rectal complications. Our study illustrates that there are significant changes in the rectal volume during the course of treatment, as observed from CBCTs. This change alters the dose received by the rectal volume, thus affecting the total dose to the rectum. During treatment planning, the plan is generated based on the planning CT. Most of the published data on rectal complications are based on this planning CT study sets, but changes in the rectal volume during the course of treatment suggest that a PRV margin should be used during treatment planning. Currently, PRV margins for the rectum are rarely used in prostate planning. Our present study compares the rectal complications computed for 3D-CRT and IMRT techniques by applying the LKB model to quantify any difference between varying PRV volumes and the correlation with rectal complications. The advantage of IMRT over 3D-CRT in reducing the rectal complications is obvious from our results [Table 1]. Though IMRT is proven to be efficient in reducing the dose to surrounding critical structures, in the midst of gross organ motion and large setup error it may lose significance. Statistical analysis of different rectal volumes defined in this study reveals a significant difference between plan-rectum and PRV-CBCT-AV (P < 0.02) for IMRT and no difference with 3D-CRT (0.86). Though PRV-CBCT-All encompasses all possible uncertainties of rectum volume during the complete course of treatment, in reality, the volume is quite large and PRV-CBCT-AV would be more meaningful to compare with plan-rectum. We observed that the dose received by the rectum during IMRT treatment delivery is more sensitive to changes in the rectal volume than 3D-CRT. Therefore, IMRT is more suitable for adaptive radiotherapy that leads to modification of the treatment plan according to the position of both the PTV and rectal volume at any given fraction. This may be due to the fact that there is a significant dose gradient with IMRT as opposed to 3D-CRT, and it is more likely that regions of high dose may be delivered to the rectum due to a change in the rectal volume. Hence for IMRT, PRV margin derived from the first five fractions may not accurately account for toxicity with all fractions, thus adaptive radiotherapy would be an ideal approach to control rectal toxicity and potentially aid further dose escalation. As previously stated, the volume of rectum could change during the course of treatment due to several factors, and the use of adaptive techniques should be delivered within a short time frame to avoid an unwanted variation in intrafractional rectal volume.

Our results [Table 2] also revealed a significant difference between PRV-CBCT-5 and PRV-CBCT-All in the case of IMRT. This shows that for IMRT patients, the PRV volume derived from the first five fractions cannot be used as a representative margin for the remaining fractions. In contrast, 3D-CRT observed no difference between PRV-CBCT-5 and PRV-CBCT-All. However, both of the PRVs obtained through the CBCT acquisition are significantly different from plan-rectum. This indicates that the PRV volume generated during the first five fractions could be used as a margin in 3D-CRT treatment planning to account for rectum volume changes for the remaining treatment fractions.

To confirm the results of this study, a larger sample size is required. To implement a rectum PRV margin into clinical practice requires several considerations. This study has not aimed to describe a PRV margin expansion, other than PRV-CBCT-5 may be a useful PRV in a replanning approach for 3D-CRT. In our previous study, we demonstrated that PRV margin is not uniform around the rectum in the craniocaudal direction,[13] so implementing a rectum PRV will require a reliable contouring method to account for this difference. Though introducing PRV margin for rectum during treatment planning would reduce the rectal complication, it may pose a challenge for the planners in achieving an optimal PTV coverage. We observed from our clinical experience that the region overlapping the PTV and rectum affects the plan quality significantly. It is our routine practice to isolate the volume separately and apply dose volume constraints during IMRT optimization. With the addition of a PRV margin to the rectum, it may increase the overlap volume between the PTV and PRV which needs to be considered in a clinical context with respect to toxicity. One limitation of our study is the alternate nature of CBCT acquisition, rather than on a daily basis.


 > Conclusion Top


Our results clearly demonstrated that the rectal complications are reduced significantly with the IMRT technique when compared to the 3D-CRT. The analysis of NTCP with various defined composite rectum volumes indicates that IMRT treatment delivery lends itself more to image-guided adaptive radiotherapy, as opposed to 3D-CRT. In the case of 3D-CRT, PRV margins derived from the first five fractions could be used to control rectal toxicity and may be a better indicator for correlating the rectal toxicity.

Financial support and sponsorship

Nil

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013.  Back to cited text no. 1
    
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Australian Institute of Health and Welfare. Cancer Incidence Projections: Australia, 2011-2020. Cancer Series No. 66. Cat. No. CAN 62. Canberra, Australia: AIHW; 2012.  Back to cited text no. 2
    
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Zelefsky MJ, Fuks Z, Hunt M, Yamada Y, Marion C, Ling CC, et al. High-dose intensity modulated radiation therapy for prostate cancer: Early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 2002;53:1111-6.  Back to cited text no. 3
    
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Cahlon O, Zelefsky MJ, Shippy A, Chan H, Fuks Z, Yamada Y, et al. Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: Toxicity and biochemical outcomes. Int J Radiat Oncol Biol Phys 2008;71:330-7.  Back to cited text no. 4
    
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Kuban DA, Levy LB, Cheung MR, Lee AK, Choi S, Frank S, et al. Long-term failure patterns and survival in a randomized dose-escalation trial for prostate cancer. Who dies of disease? Int J Radiat Oncol Biol Phys 2011;79:1310-7.  Back to cited text no. 5
    
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Leborgne F, Fowler J. Acute toxicity after hypofractionated conformal radiotherapy for localized prostate cancer: Nonrandomized contemporary comparison with standard fractionation. Int J Radiat Oncol Biol Phys 2008;72:770-6.  Back to cited text no. 6
    
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Huang SH, Catton C, Jezioranski J, Bayley A, Rose S, Rosewall T. The effect of changing technique, dose, and PTV margin on therapeutic ratio during prostate radiotherapy. Int J Radiat Oncol Biol Phys 2008;71:1057-64.  Back to cited text no. 7
    
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Fiorino C, Vavassori V, Sanguineti G, Bianchi C, Cattaneo GM, Piazzolla A, et al. Rectum contouring variability in patients treated for prostate cancer: Impact on rectum dose-volume histograms and normal tissue complication probability. Radiother Oncol 2002;63:249-55.  Back to cited text no. 8
    
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Livsey JE, Wylie JP, Swindell R, Khoo VS, Cowan RA, Logue JP. Do differences in target volume definition in prostate cancer lead to clinically relevant differences in normal tissue toxicity? Int J Radiat Oncol Biol Phys 2004;60:1076-81.  Back to cited text no. 9
    
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Koper PC, Heemsbergen WD, Hoogeman MS, Jansen PP, Hart GA, Wijnmaalen AJ, et al. Impact of volume and location of irradiated rectum wall on rectal blood loss after radiotherapy of prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:1072-82.  Back to cited text no. 10
    
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ICRU 62. Prescribing, Recording and Reporting Photon Beam Therapy. Bethedsa, MD: International Commission on Radiation Units and Measurements; 1999.  Back to cited text no. 11
    
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ICRU 83. Prescribing, Recording, and Reporting Photon-Beam Intensity-Modulated Radiation Therapy (IMRT). J ICRU 2010;10:41-53.  Back to cited text no. 12
    
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Prabhakar R, Oates R, Jones D, Kron T, Cramb J, Foroudi F, et al. A study on planning organ at risk volume for the rectum using cone beam computed tomography in the treatment of prostate cancer. Med Dosim 2014;39:38-43.  Back to cited text no. 13
    
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Kutcher GJ, Burman C. Calculation of complication probability factors for non-uniform normal tissue irradiation: The effective volume method. Int J Radiat Oncol Biol Phys 1989;16:1623-30.  Back to cited text no. 14
    
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Kutcher GJ, Burman C, Brewster L, Goitein M, Mohan R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int J Radiat Oncol Biol Phys 1991;21:137-46.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

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