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Adaptive radiotherapy for bladder cancer using deformable image registration of empty and full bladder. P. Juneja1, 2, H. Caine1, P. Hunt1, J. Booth1, 2, ...
Adaptive radiotherapy for bladder cancer using deformable image registration of empty and full bladder P. Juneja1, 2, H. Caine1, P. Hunt1, J. Booth1, 2, D. Thwaites2, J. O’Toole1, A. Vestergaard3, J. Kallehauge3, A. Kneebone1 and T. Eade1 1 2

Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065, Australia Institute of Medical Physics, School of Physics, University of Sydney, NSW 2006, Australia 3 Department of Medical Physics, Aarhus University Hospital, Denmark

Abstract— A common objective of various adaptive radiotherapy (ART) strategies for bladder cancer is to reduce irradiation of normal tissue, thereby reduce the risk of radiation induced toxicity, and maintain or improve the target coverage. Bladder radiotherapy, typically involves generous margins (up to 20 mm) for bladder planning target volume (PTV). The goal of this retrospective study is to define, evaluate and optimize new patient-specific anisotropic PTVs (a-PTVs) using deformable image registration (DIR) between empty and full bladder computed tomography (CT) scans. This will provide an ART that incorporates the extreme deformations of the bladder, and is applicable from the first day of treatment. Deformation vector fields (DVFs), measured from the deformable image registration between empty and full bladder CTs, were scaled and constrained to construct the a-PTVs. For each patient, four a-PTVs were constructed such that a-PTV1 was the largest and a-PTV4 was the smallest. All the a-PTVs were defined such that they covered at least the bladder volume plus 5 mm margin. These a-PTVs were retrospectively evaluated and compared to the current clinical standard (conv-PTV), with 10 mm uniform margins, using 5 bladder cancer patients and a total of 100 fractions. It was found that the smaller a-PTV, a-PTV4 and a-PTV3, were appropriate in 87% of the fractions, while a-PTV2 and aPTV1 were required in 12% of the fractions respectively. The use of the a-PTVs reduced the PTV volume by 32% (28-36%) as compared to conv-PTV. In conclusion, the results of this pilot study indicate that the use of a-PTVs could result in substantial decrease in the course averaged planning target volume. This reduction in the PTV is likely to decrease the radiation related toxicity and benefit bladder cancer patients. Currently, more patients are being investigated to strengthen these findings, and also dosimetric analysis is underway. Keywords— Bladder cancer, adaptive radiotherapy, deformation vector field, deformable image registration.

I. INTRODUCTION

Radiation therapy (RT) is an effective treatment for bladder cancer, particularly in patients unfit for surgery [1]. Generally the whole bladder is the clinical target volume (CTV). In order to ensure the prescribed coverage of the CTV generous margins of up to 20 mm are used to construct planning target volume (PTV), and account for variations in bladder shape and size. These large margins lead to unnecessary irradiation of surrounding organs at risk (OAR), such as small bowel, and increased risk of radiotoxicity. Various adaptive radiotherapy (ART) approaches to spare OAR and ensure the desired target coverage have been developed [2-8]. A commonly used ART approach, daily plan selection, requires planning computed tomography (CT) and daily cone-beam CTs (CBCTs) from the first week of treatment to create a plan library [2, 4, 6-8]. This only provides adaptation from treatment week 2 or later and in case of four week treatment this would result in at best 75% fractions receiving ART. Another approach, daily plan reoptimization [6] is not widely feasible as it requires the plan to be re-optimized based on the CBCT at each fraction. An ART strategy that could be applied from the first fraction is based on the generation of multiple PTVs using multiple planning CTs [3, 5]. Previously, for five patients, Tuomikoski et al. [3] quantified the benefit of ART based on four or five planning CTs of different filling states of the bladder. However, in routine clinical practice it is not practical to have four or five planning CTs for each bladder cancer patient. Meijer et al. [5], developed and used a plan library based on the interpolation of empty and full bladder CT scans. They did not quantify the geometric and dosimetric benefit of this ART. In this retrospective study, ART for bladder cancer based on the empty and full bladder CTs and using deformable image registration (DIR) was developed and compared to the conventional uniform margin approach. Furthermore, the number of plans required for ART was optimized.

© Springer International Publishing Switzerland 2015 D.A. Jaffray (ed.), World Congress on Medical Physics and Biomedical Engineering, June 7-12, 2015, Toronto, Canada, IFMBE Proceedings 51, DOI: 10.1007/978-3-319-19387-8_94

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Adaptive radiotherapy for bladder cancer using deformable image registration of empty and full bladder

Fig. 1 Sample full (left) and empty (right) bladder CT slices: (a) Axial view, and (b) Sagittal view.

II.

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CTs with empty and full bladder were performed. Next, intensity-based DIRs using SmartAdapt® (Varian Medical Systems, Palo Alto, CA) were performed between the empty bladder CT (floating image) and full bladder CT (fixed image). DVFs from the DIRs were used to estimate the deformations (DVFbladder) from the empty to full bladder for each patient. These deformations were applied to the empty bladder volume, in order to generate four a-PTVs for each patient. In case of a-PTV2, a-PTV3 and a-PTV4, the magnitude of DVFbladder in all the directions was constrained to maximum of 10 mm. The a-PTV1 was generated using the unscaled DVFbladder, while a-PTV2 was generated using the unscaled but constrained DVFbladder. For the a-PTV3 and aPTV4, DVFbladder were scaled to 50% and 33% respectively, and constrained. For all the four a-PTVs, it was ensured that they covered at least the bladder volume plus 5 mm margin (see figure 2 for example a-PTVs). The a-PTV1 has the largest a-PTV volume followed by a-PTV2, a-PTV3, and aPTV4.

METHOD

A. Study dataset Five bladder cancer patients treated with intensity modulated radiotherapy (IMRT) at Northern Sydney Cancer Centre (Royal North Shore Hospital, Sydney) were retrospectively investigated for the development and evaluation of the ART. The patients underwent CT imaging with both empty and full bladder at the time of planning, see figure 1. These patients were treated with empty bladder because full bladder had limited positioning benefit, and empty bladder treatment is preferable for comfort and reproducibility. For treatment, bladder PTV was defined as the empty bladder plus isotropic margin of 10 mm. Table 1 gives the summary of patient data.

Table 1 Summary of study dataset Patient age (yrs)

Empty bladder Full bladder volume (cm3) volume (cm3)

Median

84

101

297

(Range)

(78-88)

(88-180)

(172-349)

Bladder prescription 50 Gy / 20 Fx

B. Definition of anisotropic PTVs (a-PTVs) based on DIR Target volumes based on the deformation vector fields (DVFs) were generated using the method developed by Vestergaard et al. [8]. Firstly, rigid registrations between the

Fig. 2 Sample bladder volumes and PTVs: empty bladder (pink) with (a) Full bladder, (b) conv-PTV, (c) a-PTV1, (d) a-PTV2, (e) a-PTV3, (f) aPTV4.

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C. Daily a-PTVs selection For the investigation of the ART based on the four aPTVs developed in this study, daily plan selection was simulated using the patient data. For each fraction, daily pretreatment CBCT was registered to the planning CT using the soft-tissue match as per the institutional protocol. After the registration, gross tumor volume (GTV) was matched, and subsequently bladder coverage by the a-PTV was verified. In all the cases, firstly, the smallest a-PTV was evaluated and if the coverage was inadequate the larger a-PTVs were evaluated; the investigation order was a-PTV4, aPTV3, a-PTV2, and a-PTV1.

all four a-PTVs were used, the mean (range) PTV was reduced by 34% (31-37%) w.r.t. conv-PTV.

Fig. 3 Distribution of a-PTVsmall and a-PTVlarge across the five patients.

D. Analysis The effectiveness of this ART strategy was studied through comparison with the current clinical standard (conv-PTV). For each patient’s treatment course, the reduction in PTV due to the ART was measured relative to convPTV. The bladder volumes at each fraction were compared to the bladder volume on the planning CT and were ranked (smaller, same or bigger) accordingly by a radiation therapist (HC). The effect of relative bladder volume at each fraction and the ratio of the full and empty volumes from the CTs on the distribution of daily a-PTV selections were analyzed. III.

RESULTS

A. Evaluation of the ART The mean (range) volumes of the four a-PTVs were, aPTV1: 256 cm3 (213-341 cm3); a-PTV2: 244 cm3 (204-324 cm3); a-PTV3: 211 cm3 (169-294 cm3); and a-PTV4: 204 cm3 (163-289 cm3). These four a-PTVs were investigated for ART for all the 100 fractions, and it was found that aPTV1, a-PTV2, a-PTV3, and a-PTV4 were required for 2%, 10%, 15%, and 72% of the fractions respectively. For one of the fractions, none of the a-PTVs was appropriate, as discussed below. The relative volume differences between a-PTV1 and aPTV2 and between a-PTV3 and a-PTV4, for all the cases were small (1-10%). Therefore, only two of these volumes which were substantially different from each other, a-PTV1 and a-PTV-3, were chosen for the ART. For the rest of the analysis, a-PTV2 and a-PTV4 fractions were combined with a-PTV1 (a-PTVlarge) and a-PTV3 (a-PTVsmall) respectively. Figure 3 present the distribution of the two a-PTVs (aPTVsmall and a-PTVlarge) across the five patients. The ART with these two a-PTVs, reduced the mean (range) PTV by 32% (28-36%) as compared to conv-PTV. Whereas when

B. Distribution of daily a-PTVs The distribution of daily a-PTV selections with respect to the relative bladder volume at each fraction is presented in figure 4. In the fractions where the bladder volume was smaller or the same compared to the volume at the time of planning, a-PTVsmall provided the necessary coverage in most of the fractions (smaller: 97% & same: 95%). For the fractions which had bigger bladder volume relative to the volume at the time of planning, a-PTVsmall was useful for only 60% of the fractions. The mean ratio (range) of full to empty bladder volume on the planning CTs was 2.5 (1.7-3.9). There was strong positive correlation (R2=0.80) between the ratio of full to empty bladder volume and the reduction in the PTV with the ART.

Fig. 4 Distribution of a-PTVsmall and a-PTVlarge with the size of bladder volume at each treatment fraction relative to the volume at the time of planning.

IV.

DISCUSSION AND CONCLUSIONS

This study developed and evaluated a new ART strategy for bladder cancer. This ART approach was found to result in considerable reduction of PTV (28-36%), similar to other published ART strategies [2-4, 6-8]. The advantage of this

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ART strategy is its applicability from the first day of treatment and coverage of extreme bladder deformation. The ART approach developed here is based on the DIR of empty and full bladder. In the presence of large deformations between full and empty bladder, the DIR is a challenging problem and therefore is not expected to accurately match the empty and full bladder. The ART does not require perfect registration; however it does need the DIR to at least produce DVFs which are indicative of the deformation directions. In one patient, who had the largest deformation between full and empty bladder on CTs (ratio=3.9), the DVFs were not correctly estimated. Consequently, this patient had a fraction where none of the a-PTVs could fit the bladder volume. For cases like this, it is necessary to adjust the DIR in order to produce realistic DVFs and thereafter a-PTVs. In this study, DIRs were reviewed but not adjusted, because user intervention in the definition of a-PTVs is undesirable. For the cases with poor DIR, another approach, presented by Meijer et al. [5], involving interpolation between full and empty bladder contours might be more suitable. The a-PTVs defined in this studied were found to be useful in most of the cases (99 out of 100 fractions) and resulted in a substantial reduction of PTV. This was achieved with just two PTVs. In contrast, most plan selection studies have more than two PTVs. We plan to investigate more patients and perform a dosimetric investigation to quantify the advantages of this ART approach. Furthermore, the bladder a-PTVs developed in this study would be extended to the cases which have additional PTVs, e.g. if the GTV is planned to receive a higher dose than rest of the bladder. In conclusion, the results indicate that adaptive radiotherapy for bladder cancer using deformable image registration between empty and full bladder can substantially decrease the planning target volume and potentially benefit bladder cancer patients.

ACKNOWLEDGMENT We would like to acknowledge Ludvig Muren and Jørgen B. Petersen for their contribution to the development

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of the code used for applying the DVFs to a structure. Prabhjot Juneja is supported by funding from the University of Sydney, the BARO (Better Access to Radiation Oncology) initiative of the Australian Department of Health and Northern Sydney Cancer Centre.

CONFLICT OF INTEREST The authors declare that they have no conflict of interest.

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Milosevic, M., et al., (2007) Radiotherapy for Bladder Cancer. Urology, 69:80-92. Burridge, N., et al., (2006) Online adaptive radiotherapy of the bladder: small bowel irradiated-volume reduction. Int. J Rad Onco Bio Phys, 66:892-897. Tuomikoski, L., et al., (2011) Adaptive radiotherapy in muscle invasive urinary bladder cancer–an effective method to reduce the irradiated bowel volume. Rad Onco, 99:61-66. Foroudi, F., et al., (2011) Online adaptive radiotherapy for muscle-invasive bladder cancer: results of a pilot study. Int. J Rad Onco Bio Phys, 81:765-771. Meijer, G.J., et al., (2012) High precision bladder cancer irradiation by integrating a library planning procedure of 6 prospectively generated SIB IMRT plans with image guidance using lipiodol markers. Rad Oncol, 105:174-179. Vestergaard, A., et al., (2013) Adaptive plan selection vs. reoptimisation in radiotherapy for bladder cancer: A dose accumulation comparison. Rad Oncol, 109:457-462. Webster, G.J., et al., (2013) Comparison of adaptive radiotherapy techniques for the treatment of bladder cancer. BJR, 86, 20120433. Vestergaard, A., et al., (2014) An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields. Rad Oncol, 112: 371-375

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Prabhjot Juneja Institute of Medical Physics, School of Physics (A28) University of Sydney Australia [email protected]