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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 1  |  Page : 131-136

Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy for uterine and cervical cancer using kilovoltage cone-beam computed tomography and its effect on planning target volume margins


1 Department of Radiation Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
2 Department of Radiation Oncology, GBH American Hospital, Udaipur, Rajasthan, India

Date of Web Publication16-May-2017

Correspondence Address:
Nidhi Patni
Department of Radiation Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, JLN Marg, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.199451

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 > Abstract 

Purpose: To achieve the best possible therapeutic ratio using high-precision techniques (image-guided radiation therapy/volumetric modulated arc therapy [IGRT/VMAT]) of external beam radiation therapy in cases of carcinoma cervix using kilovoltage cone-beam computed tomography (kV-CBCT).
Materials and Methods: One hundred and five patients of gynecological malignancies who were treated with IGRT (IGRT/VMAT) were included in the study. CBCT was done once a week for intensity-modulated radiation therapy and daily in IGRT/VMAT. These images were registered with the planning CT scan images and translational errors were applied and recorded. In all, 2078 CBCT images were studied. The margins of planning target volume were calculated from the variations in the setup.
Results: The setup variation was 5.8, 10.3, and 5.6 mm in anteroposterior, superoinferior, and mediolateral direction. This allowed adequate dose delivery to the clinical target volume and the sparing of organ at risks.
Conclusion: Daily kV-CBCT is a satisfactory method of accurate patient positioning in treating gynecological cancers with high-precision techniques. This resulted in avoiding geographic miss.

Keywords: Gynecological malignancy, image guidance, kilovoltage cone-beam computed tomography, margins, setup errors


How to cite this article:
Patni N, Burela N, Pasricha R, Goyal J, Soni TP, Kumar T S, Natarajan T. Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy for uterine and cervical cancer using kilovoltage cone-beam computed tomography and its effect on planning target volume margins. J Can Res Ther 2017;13:131-6

How to cite this URL:
Patni N, Burela N, Pasricha R, Goyal J, Soni TP, Kumar T S, Natarajan T. Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy for uterine and cervical cancer using kilovoltage cone-beam computed tomography and its effect on planning target volume margins. J Can Res Ther [serial online] 2017 [cited 2019 Nov 22];13:131-6. Available from: http://www.cancerjournal.net/text.asp?2017/13/1/131/199451


 > Introduction Top


Radiotherapy for gynecological cancers has benefitted from high-precision techniques when compared to nonconformal techniques.[1] The pelvic structures (urinary bladder, cervix, uterus, and rectum) move relative to each other, so defining clinical target volume (CTV) motion is complex.[2],[3] To ensure an adequate coverage of CTV, internal organ motion needs to be considered.

The planning target volume (PTV) includes margin for uncertainties in shape and motion of organs, beam geometry, and patient setup.[4] Setup errors though undesirable, are inherent part of radiation treatment process and are defined as the difference between actual and intended position with respect to radiation delivery.[5] These setup errors influence the target definition process by contributing to CTV-PTV margin.[6],[7]

For high therapeutic ratio, setup margins should be reduced to prevent irradiation of adjacent normal tissues. The source of these errors is (a) patient related (skin mark movement) (b) fixation related (patient mobility) (c) mechanical (laser misalignment) (d) experience and competence of treating staff (e) time available with radiotherapy staff.[4] These errors alone or in combination may result in compromised therapeutic ratio.

The goal of this study is to objectively describe the setup error during fractionated external beam radiotherapy for cervical and endometrial cancers.

Aim

To assess three dimensional setup errors in image-guided pelvic radiotherapy for uterine and cervical cancer using kilovoltage cone-computed tomography (kV-CBCT) and its effect on PTV margins.

Primary objective

Assessment of systematic errors, random errors, and three-dimensional CTV-PTV margins derived from shifts after 3D-3D matching.


 > Materials and Methods Top


Retrospectively, 105 patients (2078 kV-CBCTs), from May 2011 to December 2014 were enrolled.

Inclusion criteria

  1. Histologically, proven cervical cancer (intact and postoperative) and endometrial cancer (postoperative)
  2. Patients receiving radiotherapy under image guidance with image-guided radiation therapy/intensity-modulated radiation therapy/volumetric modulated arc therapy (IMRT/IGRT/VMAT) on Varian linear accelerator (CLINAC IX).


Immobilization and simulation

All patients underwent radiotherapy treatment planning scan. Initially, patients were immobilized in the supine position using four clamp customized thermoplastic mask on carbon baseplate was later changed to skin marking. A plain and contrast CT scan for radiotherapy planning was done after immobilization in the treatment position as per departmental protocol. Day-to-day reproducibility was achieved by asking the patients to void urine 1 h before each treatment and then drink 500 ml of water. Laxative was prescribed the night before treatment, except to patients experiencing diarrhea. CT Simulation was done by taking 3 mm contiguous sections on Siemens Biograph 16 slice spiral CT scanner. The data were then transferred to the treatment planning system (Eclipse integrated planning system version 10) through local area network. Targets volumes were contoured by single radiation oncologist using RTOG guidelines as basis.

IMRT plans were generated using 7–9 beams or two full arcs for VMAT treatment. The optimum treatment plan was transferred to ARIA for implementation after doing the required quality assurance (QA) tests.

On board imaging and evaluation

Cone-beam computed tomography acquisition

CBCT scan parameters were 125 kVp and 80 mAs, representing a balance between image quality, patient dose (17.7 mGy), and tube overheating. The device operates in half-fan mode with a half-bowtie filter to reduce scatter and adequately cover patient geometry. The gantry rotation range is 360°, exposure 680 mAs, and 2.6 CTDIw (mGy/100 mAs). The images were taken with 655 projections. The typical length of CBCT scan was 15 cm in superoinferior (SI) direction and field of view 45 cm.

All patients underwent CT-based RT planning. Then, kV-CBCT was done once a week in IMRT, daily in IGRT/VMAT. The setup error was calculated by registration of planning CT with the current CBCT using the bony anatomy. A patient-specific alignment box confined the volume for automatic match of the bony anatomy; inside this volume was used as a surrogate for the actual tumor position. After registration, translational errors were recorded. Rotational errors were not recorded. All the translational errors evaluated in this study were determined from the automatic bone match. All translational shifts were applied and recorded in centimeters.

For the purpose of analysis anterior, superior and right-sided shifts were coded as positive shifts and posterior, inferior, and left-sided shifts as negative shifts. Some of the potential sources of errors as laser alignment, display accuracy, and jaw reproducibility were not taken into consideration for the final match results. It was assumed that routine periodic QA employed for the linear accelerator would ensure minimal impact of the aforesaid on daily setup.

The mean and standard deviations (SDs) were calculated for all patients in all three axes - x, y, z for individually recorded errors.

Systematic and random errors

Systematic and random errors were calculated as per conventionally defined norms. [4,8] The systematic component of the displacement represents displacement that was present during the entire course of treatment. The random errors represent day-to-day variation in the setup of the patient.

Mean of individual patient along the respective axes → Σind (Systemic error [SE] of individual patient).

SD of the mean of each patient → Σpop (SE of population).

SD of the individual patient along respective axes → σind (Random error of individual patient).

Root mean square of the random error of each patient (SD) → σpop (Random error of population).[9]

Errors were calculated separately for all three axes: x-axis (left to right), y-axis (SI), and z-axis (anteroposterior; AP).

Using this data, PTV margins were obtained for respective axes (lateral, longitudinal, and vertical) by Van Herk's margin recipe formula (2.5 Σpop + 0.7 σpop).[5],[10]

Statistical analysis

Shifts on three axes of individual patient were noted and entered in Excel sheet to prepare master chart. The SE of individual patient on particular axis was calculated by arithmetic mean of shifts on particular axes for total days of radiation received by particular patient. The random error of individual patient on particular axis was calculated by SD of shifts on particular axes for total days of radiation. SE of population (Σpop) was found out by calculation of arithmetic mean of SE of individual patient (Σind) while random error of population was calculated as SD of random error of individual patient (σind). All statistical calculations were done using Med Calc version 12.2.1.0 software (MedCalc Software, Acacialaan 22, B-8400 Ostend, Belgium).


 > Results Top


Translational displacements were measured in 2078 kV-CBCTs of 105 patients. The mean displacement in AP, SI, and mediolateral (ML) direction are shown in [Table 1]. The population systematic error (Σpop) in AP, SI, and ML was 0.20, 0.35, and 0.19 cm, respectively. The population random error (σpop) in corresponding directions was 0.12, 0.23, and 0.13 cm, respectively. CTV-PTV margins calculated by van Herks formulae in AP, SI, and ML direction were 0.584, 1.036, and 0.566 cm. Total systematic and random deviations (in cm) of all patients in their respective axes are shown in [Figure 1].
Table 1: Mean and standard deviation along respective axes (anteroposterior, superoinferior, and mediolateral)

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Figure 1: Total systematic and random deviations for 105 patients

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 > Discussion Top


Accounting accurately for daily uncertainties in target positioning is an important goal in treating uterine and cervical cancers. Uncertainties can arise due to setup variation caused by both, interfraction and intrafraction motion, former being the greater of two components.[11] All these uncertainties can result in compromised local tumor control rate and an increased risk of side effects. IGRT enhances the precision of patient positioning, allowing for improved sparing of normal tissues through a reduction in treatment margins. Using tighter margins, however, require techniques to ensure precise target localization. In this study, we evaluated patient setup errors (translational errors) using kV-CBCT before delivering treatment fraction. Rotational errors were not recorded. To eliminate interobserver variations, automatic registration strategies using bone anatomy recognition were employed.

The parameters such as population systematic error (Σpop), population random error (σpop), and CTV-PTV margins were also analyzed by Santanam et al.,[12] Laursen et al.,[13] and Yao et al.,[14] A comparative chart of these parameters with present study are compiled in [Table 2].
Table 2: Selected studies showing Σpop, σpop, and clinical target volume planning target volume margin (cm)

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Stromberger et al.[15] analyzed setup errors in the treatment of gynecologic malignancy by matching the daily megavoltage CT (MVCT) with the planning CT. This group found that the total systematic deviations had means of - 2.0, 0.5, 0.5 mm AP, SI, ML, respectively, while the total random deviations were 3.8, 3.4, 6.1 mm, respectively.

Many factors, including different patient immobilization positions (prone or supine), varying measurement methods (electronic portal imaging device, kV-CBCT, MVCT, magnetic resonance imaging) or measurement frequencies (daily or weekly), and different treatment techniques (3DCRT, IMRT, and VMAT) can all influence decisions regarding the optimal PTV. In the treatment of gynecologic malignancies, a wide range of different margins of PTV (MPTV) is observed in the published literature.[12],[13],[15],[16],[17],[18]

For adequate volume coverage, while increasing organ at risk sparing, individualized MPTV was calculated. The corresponding CTV-PTV margins derived in our study was 5.8, 10.3 and 5.6 mm in AP, SI, and ML direction, respectively. In Yao et al.,[14] MPTV obtained from initial interfraction errors were 5.6, 8.3 and 7.6 mm along AP, SI, and ML direction. Laursen et al. calculated margins of 11.6 AP, 8.2 SI, and 9.6 mm ML, respectively.[13] Li et al.[18] studied using daily MVCT images with online correction before treatment and no immobilization device for patients with pelvic malignancies calculated the CTV-to-PTV margins at 8.3 mm. Santanam et al.[12] recommend a 7 mm CTV-PTV margins in all directions when using daily imaging and daily setup corrections. Stroom et al.[17] proposed a 5 mm CTV-PTV margin based on a study on 14 patients with user-defined landmarks (kV, MV orthogonal portal imaging). Although a CTV-PTV margin of 20/10 mm was used in the study, Lim et al.[19] could show that a 5 mm margin might be appropriate for most patients treated with IMRT with the use of a small bowel displacement system, if daily setup control is used.

In our study, the systematic and random errors yielded asymmetric margins for the CTV-PTV for gynecologic patients treated by IGRT using kV-CBCT. The margins derived in AP and ML are consistent with published literature. Our results suggested larger setup errors in longitudinal (SI) direction (10.36 mm). Large longitudinal differences were also seen by Drabik et al.,[20] for other sites using MVCT scans for daily patient positioning. The margins estimated in this study are based only on setup errors and do not account for organ motion.

In due course of time from 2011 to 2014 in our institution, patient treatment with orfit had changed to skin marking. This reduced the mean shifts in all three directions [Table 3].
Table 3: Mean shifts of all three axes for patients treated in years 2011-2012 and 2014

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Daily kV-CBCT is a satisfactory method of accurate patient positioning in treating gynecological cancers with high-precision techniques. This resulted in avoiding geographic miss.

One could use the available daily imaging techniques for patient setups and retrospectively use the setup errors to estimate site-specific margins. Establishing online correction protocols could help in improving treatment positioning accuracy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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van de Bunt L, van der Heide UA, Ketelaars M, de Kort GA, Jürgenliemk-Schulz IM. Conventional, conformal, and intensity-modulated radiation therapy treatment planning of external beam radiotherapy for cervical cancer: The impact of tumor regression. Int J Radiat Oncol Biol Phys 2006;64:189-96.  Back to cited text no. 1
    
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Kutcher GJ, Mageras GS, Liebel SA. Control, correction, and modeling of setup errors and organ motion. Semin Radiat Oncol 1995;5:134-45.  Back to cited text no. 7
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Stroom JC, Heijmen BJ. Geometrical uncertainties, radiotherapy planning margins, and the ICRU-62 report. Radiother Oncol 2002;64:75-83.  Back to cited text no. 8
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van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol 2004;14:52-64.  Back to cited text no. 9
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van Herk M, Remeijer P, Rasch C, Lebesque JV. The probability of correct target dosage: Dose-population histograms for deriving treatment margins in radiotherapy. Int J Radiat Oncol Biol Phys 2000;47:1121-35.  Back to cited text no. 10
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Chan P, Dinniwell R, Haider MA, Cho YB, Jaffray D, Lockwood G, et al. Inter- and intrafractional tumor and organ movement in patients with cervical cancer undergoing radiotherapy: A cinematic-MRI point-of-interest study. Int J Radiat Oncol Biol Phys 2008;70:1507-15.  Back to cited text no. 11
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Santanam L, Esthappan J, Mutic S, Klein EE, Goddu SM, Chaudhari S, et al. Estimation of setup uncertainty using planar and MVCT imaging for gynecologic malignancies. Int J Radiat Oncol Biol Phys 2008;71:1511-7.  Back to cited text no. 12
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Laursen LV, Elstrøm UV, Vestergaard A, Muren LP, Petersen JB, Lindegaard JC, et al. Residual rotational set-up errors after daily cone-beam CT image guided radiotherapy of locally advanced cervical cancer. Radiother Oncol 2012;105:220-5.  Back to cited text no. 13
    
14.
Yao L, Zhu L, Wang J, Liu L, Zhou S, Jiang S, et al. Positioning accuracy during VMAT of gynecologic malignancies and the resulting dosimetric impact by a 6-degree-of-freedom couch in combination with daily kilo voltage cone beam computed tomography. Radiother Oncol 2015;10:104.  Back to cited text no. 14
    
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Stromberger C, Gruen A, Wlodarczyk W, Budach V, Koehler C, Marnitz S. Optimizing image guidance frequency and implications on margins for gynecologic malignancies. Radiat Oncol 2013;8:110.  Back to cited text no. 15
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Weiss E, Vorwerk H, Richter S, Hess CF. Interfractional and intrafractional accuracy during radiotherapy of gynecologic carcinomas: A comprehensive evaluation using the ExacTrac system. Int J Radiat Oncol Biol Phys 2003;56:69-79.  Back to cited text no. 16
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Stroom JC, Olofsen-van Acht MJ, Quint S, Seven M, de Hoog M, Creutzberg CL, et al. On-line set-up corrections during radiotherapy of patients with gynecologic tumors. Int J Radiat Oncol Biol Phys 2000;46:499-506.  Back to cited text no. 17
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Li XA, Qi XS, Pitterle M, Kalakota K, Mueller K, Erickson BA, et al. Interfractional variations in patient setup and anatomic change assessed by daily computed tomography. Int J Radiat Oncol Biol Phys 2007;68:581-91.  Back to cited text no. 18
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Lim K, Kelly V, Stewart J, Xie J, Cho YB, Moseley J, et al. Pelvic radiotherapy for cancer of the cervix: Is what you plan actually what you deliver? Int J Radiat Oncol Biol Phys 2009;74:304-12.  Back to cited text no. 19
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Drabik DM, MacKenzie MA, Fallone GB. Quantifying appropriate PTV setup margins: Analysis of patient setup fidelity and intrafraction motion using post-treatment megavoltage computed tomography scans. Int J Radiat Oncol Biol Phys 2007;68:1222-8.  Back to cited text no. 20
[PUBMED]    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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