|Ahead of print publication
A prospective study to assess and quantify the setup errors with cone-beam computed tomography in head-and-neck cancer image-guided radiotherapy treatment
Vidhi Jain1, Tej Prakash Soni1, Dinesh Kumar Singh1, Nidhi Patni1, Naresh Jakhotia1, Anil Kumar Gupta2, Tara Chand Gupta3, Harish Singhal4
1 Department of Radiation Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
2 Department of Surgical Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
3 Department of Medical Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
4 Department of Clinical Trial, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India
|Date of Submission||06-Nov-2021|
|Date of Acceptance||05-Jan-2022|
|Date of Web Publication||13-Oct-2022|
Tej Prakash Soni,
Department of Radiation Oncology, Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
Introduction: This study was done to quantify the translational setup errors with cone-beam computed tomography (CBCT) in the image-guided radiation therapy (IGRT) treatment of head-and-neck cancer (HNC) patients.
The objective was to quantify the setup errors by CBCT.
Methodology: One hundred patients of HNC were enrolled from March 2020 to March 2021 for IGRT treatment. Pretreatment kV-CBCT images were obtained at the first 3 days of irradiations, and setup error corrections were done in the mediolateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions. Subsequently, a weekly kV-CBCT was repeated for whole duration of radiotherapy for the next 6–7 weeks. Adequacy of planning target volume (PTV) margins was assessed by van Herk's formula.
Results: Total 630 CBCT scans of 100 patients were analyzed. Setup errors greater than 3 mm and 5 mm were seen in 11.4% and 0.31% of the patients, respectively. Systematic errors and random errors before correction in ML, SI, and AP directions were 0.10 cm, 0.11 cm, and 0.12 cm and 0.24 cm, 0.20 cm, and 0.21 cm, respectively. Systematic errors and random errors after correction in ML, SI, and AP directions were 0.06 cm, 0.07 cm, and 0.07 cm and 0.13 cm, 0.10 cm, and 0.12 cm, respectively.
Conclusion: CBCT at the first 3 fractions and then weekly during radiotherapy is effective to detect the setup errors. An isotropic PTV margin of 5 mm over clinical target volume is safe to account for setup errors, however, in the case of close organ at risk, or with IGRT, a PTV margin of 3 mm can be considered.
Keywords: Cone-beam computed tomography, head-and-neck cancer, image-guided radiation therapy, planning target volume margins, setup error
|How to cite this URL:|
Jain V, Soni TP, Singh DK, Patni N, Jakhotia N, Gupta AK, Gupta TC, Singhal H. A prospective study to assess and quantify the setup errors with cone-beam computed tomography in head-and-neck cancer image-guided radiotherapy treatment. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=358601
| > Introduction|| |
Head-and-neck cancer (HNC) is one of the most common and predominant cancer subsites in India., HNC is more frequently present and diagnosed in locally advanced stages. Radiotherapy with concurrent chemotherapy is the standard treatment of the locally advanced HNC. The techniques of radiotherapy have significantly improved over the last decades. Two-dimensional (2D) conventional large fields have been replaced by more sophisticated techniques, such as three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT), and image-guided radiation therapy (IGRT). IMRT is a highly conformal radiation technique that delivers very precise and curative radiation doses to the planning target volume (PTV) and high-risk target areas while sparing the adjacent normal organs. IMRT can potentially improve locoregional tumor control, reduce side effects, especially xerostomia, and improve quality of life., As IMRT generates high gradient doses on the target volumes, with rapid drop in the doses around the organ at risk (OAR) structures, it requires an extremely high degree of precision as a minor positioning error can decrease the target coverage and increase the dose to OARs., The patient setup at each radiotherapy fraction is affected by setup uncertainties such as variations in patient positioning, mechanical uncertainties of the equipment (sagging of gantry, collimators and couch, etc.), dosimetric uncertainties, and transfer setup errors from computed tomography (CT) simulator to the treatment unit. Setup errors are defined as any deviation of the patient position during any fraction of radiotherapy treatment compared to the reference patient position at the planning CT simulation. These setup uncertainties constitute systematic error (mean) and random errors (standard deviation [SD]). A systematic error is a treatment preparation or planning error which happens during the process of patient positioning, simulation, or target delineation. Systematic error, if uncorrected, would affect all treatment fractions uniformly. A random error is a treatment execution error which is unpredictable, and varies with each fraction. The margin from clinical target volume (CTV) to PTV accounts for these uncertainties including changes in target shape, organ motion, and patient setup errors.
IGRT is an advanced technique and a step further to IMRT using modern imaging modalities for setup verification and to detect target motion and positional uncertainties., Setup verification is done by acquisition of 2D kilovoltage (kV) or megavoltage (MV) portal images, which are matched with the digitally reconstructed radiographs generated from the planning CT scan. Cone-beam computed tomography (CBCT) is a volumetric imaging technique which has revolutionized the overall quality of IGRT by moving from 2D verification and matching of bony landmarks to 3D assessment of the position of target volumes and of OAR., Several studies with CBCT for head-and-neck radiotherapy have already been published; however, more studies are needed to further establish the best schedule of image verification, its reliability, and utility in clinical radiotherapy practice, especially at busy centers with high patient load and limited resources.,,
The current study was done to assess and quantify the translational setup errors by CBCT in the IGRT treatment of HNC patients.
Aims and objectives
The primary objective of our study was to quantify the setup errors by CBCT in patients of HNC treated with IGRT technique.
| > Methodology|| |
The protocol and informed consent form were reviewed and approved by the Institutional Review Board. Written informed consent was taken from all the patients before enrolling them in the study. One hundred patients of head-and-neck squamous cell carcinoma were enrolled prospectively from March 2020 to March 2021 for IGRT treatment with 3D imaging verification by CBCT. Inclusion criteria were histologically proven cases of carcinoma oropharynx, hypopharynx, larynx, nasopharynx, and oral cavity.
Sample size calculation
Sample size was calculated at 95% confidence level and 20% relative allowable error assuming the maximum SD of setup error by CBCT in any direction to be 1.6 mm as suggested by previously published study.
CT simulation by Philips Brilliance Big Bore-16 was performed with patients in the supine position with a customized thermoplastic immobilization mask. Radiotherapy with IGRT was planned on “Eclipse version 15” treatment planning system (TPS) with RapidArc technique (Varian) by using a double arc with 6 MV photon beam for Clinac iX linear accelerator (Varian). Target volumes were delineated and defined in accordance with ICRU report 62. Gross visible tumor and enlarged lymph nodes identified either by clinical examination, endoscopic findings or radiologic imaging were delineated as gross tumor volume (GTV). CTV-high risk (CTV-HR) was contoured as a target volume that contains GTV and subclinical microscopic malignant disease. CTV-low risk (CTV-LR) was delineated as low-risk area of potential subclinical disease (ipsilateral and contralateral uninvolved neck). CTV delineation was done as per the consensus guidelines., PTV was delineated to provide a margin around each CTV to compensate for the uncertainties of treatment setup and tissue deformation. An isotropic expansion of 5 mm was added around the CTV to define each respective PTV-high risk (PTV-HR) and PTV-low risk (PTV-LR). The PTV-HR and PTV-LR were cropped 2 mm inside the body contour automatically by the TPS. Radiotherapy was planned to total dose of 66–70 Gy in 30–35 fractions, 5 fractions per week, 2 Gy per fraction daily for total 6–7 weeks. If clinically indicated, concurrent weekly cisplatin chemotherapy to dose of 40 mg/m2 for a maximum of 6 cycles was given to the patients during radiotherapy. Standard oral, medical, and supportive treatment was provided to all patients of both the groups. All participants were assessed weekly for weight loss, oral mucositis, dysphagia, and compliance to radiotherapy treatment during chemoradiotherapy treatment.
Setup verification protocol
Patients were repositioned in the treatment room, aligning the signs marked on the mask with room lasers. Couch shifts were applied according to planning indications to reach the treatment isocenter. kV CBCT images were acquired for 3D matching and setup verification by Varian onboard imager integrated into Clinac iX medical linear accelerator. Image acquisition parameters were the following: 100 kV, 25 cm × 15 cm field of view (aS1200), 20 mA, and 370 frames. Image registration was performed by an automatic soft-tissue algorithm applied to an extensive region of interest (clip box) encompassing the whole PTV. A spatial resolution of 1 mm × 1 mm × 1 mm was adopted. In selected cases, registration was optimized manually by the physician. For 3D-3D match, CBCT was volumetrically fused to reference CT images in axial, sagittal, and coronal planes using 3D registration algorithm. All 3D-3D matching were done with manual registration using a defined procedure using Aria online review software. Manual matching was also done utilizing bony landmarks such as skull base, nasal septum, cervical vertebral bodies, and spinous processes. The displacement of portal image from the reference image was recorded in x (lateral), y (longitudinal), and z (vertical) directions. At the end of the treatment of a patient, systematic setup error (mean error) and random error (SD) were calculated. Pretreatment kV-CBCT images were obtained at the first 3 days of irradiations and translational setup error corrections in the three axes: mediolateral (ML), superior-inferior (SI), anterior-posterior (AP) were made before treatment if the translational setup error was greater than 2 mm in any direction. Subsequently, a weekly kV-CBCT was repeated for whole duration of treatment for the next 6–7 weeks of radiotherapy, and if translational shifts in any directions were >2 mm, setup errors were corrected. The mean value of the recorded errors in each of the three axes was then calculated; in the case of a mean error > 2 mm, a systematic setup correction (modifying laser alignment signs on the mask) was performed, impacting all subsequent fractions.
Error analysis and margin calculation
All errors were entered and analyzed separately for each direction (ML, SI, and AP). For each patient, the mean and SD of all recorded errors were calculated. Systematic error (Σ) stands for the overall mean (M) calculated as the average value of all individual means, measuring the overall accuracy of the setup procedure. The SD of the group systematic error (Σ) was calculated as the SD of the individual means. The overall indicator of the group random error (σ) was calculated as the root mean square of the individual SD of all patients. Finally, for the calculation of the margin to be added to CTV to obtain PTV, we used the van Herk's formula (2.5 Σ + 0.7 σ) which ensures that 90% of the doses is given a CTV of at least 95% of the prescribed dose. Statistical analysis was performed using paired t-test for comparison between normally distributed continuous variables. The data were coded and entered into Microsoft Excel spreadsheet. Analysis was done using SPSS version 20 (IBM SPSS Statistics Inc., Chicago, Illinois, USA) Windows software program. Values of P < 0.05 were considered statistically significant. Descriptive statistics included computation of percentages, means, and SDs.
| > Results|| |
Total 630 CBCT scans of 100 patients were analyzed. Out of total 100 patients, 53 patients received radiotherapy to dose of 60 Gy/30 fractions, 29 patients received 70 Gy/35 fractions, and 18 patients received 66 Gy/30 fractions. Eighty-two percent of the patients received concurrent chemotherapy along with radiotherapy, while 18% of the patients received radiotherapy alone. Ninety-seven percent of the patients completed the full course of radiotherapy, while three patients (3%) defaulted after 5–6 weeks of the treatment due to acute toxicities such as oral mucositis. Six patients (6%) needed replanning (re-CT simulation) because of either significant weight loss or tumor shrinkage.
Analysis of setup errors
In our study, setup errors >3 mm (before correction) were seen in 8.9%, 2.2%, and 11.4% of the patients in ML, SI, and AP directions, respectively. Setup errors greater than 5 mm (before correction) were seen in 0.31%, 0.31%, and 0.16% of the patients in ML, SI, and AP directions, respectively. [Table 1] shows the displacement of setup errors after correction. Systematic errors and random errors before setup error correction in ML, SI, and AP directions were 0.10 cm, 0.11 cm, and 0.12 cm and 0.24 cm, 0.20 cm, and 0.21 cm, respectively. Systematic errors and random errors after correction in ML, SI, and AP directions were 0.06 cm, 0.07 cm, and 0.07 cm and 0.13 cm, 0.10 cm, and 0.12 cm, respectively. Mean ± SD setup errors before correction were 0.17 ± 0.07 cm, 0.12 ± 0.12 cm, and 0.17 ± 0.08 cm in ML, SI, and AP directions, respectively. Mean ± SD setup errors after the correction were 0.11 ± 0.03 cm, 0.09 ± 0.0.3 cm, and 0.11 ± 0.03 cm, respectively. The range of setup errors before correction was 0–0.53 cm in the ML direction, 0–1.17 cm in the SI direction, and 0–0.48 cm in the AP direction. The ranges of residual setup errors after correction were 0–0.2 cm in the ML, SI, and AP direction. CTV-to-PTV margins before setup error corrections were 0.42 cm, 0.42 cm, and 0.45 cm in ML, SI, and AP directions, respectively. In our study, a margin of 5 mm in all directions from CTVs to obtain the respective PTVs was adequate to overcome the setup error problem. After the correction of setup errors with CBCT, CTV-to-PTV margin was <3 mm (2.4 mm, 2.4 mm, and 2.5 mm in ML, SI, and AP directions, respectively).
| > Discussion|| |
In this paper, we report our clinical experience with IGRT in the treatment of HNC, with the aim to assess and quantify the setup errors by CBCT. Results of our study show that CBCT for HNC is effective to detect and reduce the setup errors.
In our study, total 630 CBCT scans of 100 patients of HNC were analyzed. Analysis of the setup errors revealed that the systematic errors and random errors were 0.10 cm, 0.11 cm, and 0.12 cm and 0.24 cm, 0.20 cm, and 0.21 cm, respectively, before setup error correction in ML, SI, and AP directions. Systematic errors and random errors after correction in ML, SI, and AP directions were 0.06 cm, 0.07 cm, and 0.07 cm and 0.13 cm, 0.10 cm, and 0.12 cm, respectively. The results of our study suggest that a margin of 5 mm in all directions from CTVs to obtain the PTVs was adequate to overcome the setup error problem. Setup error correction protocol with CBCT led to reduction of systematic errors, random errors, and CTV-to-PTV margins from 5 mm to 3 mm.
Assessment of setup errors is important for every individual institute as it depends on many factors such as availability of immobilization devices, imaging techniques, and the clinical experience of staff members.,,
In 2015, Xu et al. in a prospective study analyzed 201 CBCT scans of 30 patients of carcinoma nasopharynx. The authors reported that translational setup errors in x, y, and z directions were 1.2 ± 0.9 mm, 1.2 ± 1.1 mm, and 1.0 ± 0.8 mm, respectively, and concluded that adding a margin of 3 mm in all directions from the CTV to obtain the respective PTVs was adequate to manage the setup errors. Similar results were reported by Dionisi et al. in a study of 420 CBCT scans of patients with HNC. In this study, the PTV margins calculated after online correction were <2.5 mm in all directions. The authors concluded that CTV-to-PTV margin of 5 mm was adequate to account the setup errors, while with IGRT treatment in cases of re-irradiation or close proximity of OAR, these margins can be reduced to 3 mm. Velec et al. in a prospective study compared the setup errors in patients of HNC treated with IMRT. The authors evaluated 762 CBCT scans and found setup errors before corrections were less than 3 mm in any direction. Results of these studies are similar and comparable to our study.
Several studies have investigated the setup errors in HNC radiotherapy with image verification in the first 3–4 fractions followed by weekly imaging.,, Results of our study also suggest that protocol of CBCT in the first 3 fractions and then every week during radiotherapy is effective to detect and reduce the setup errors.
Kaur et al. analyzed the impact of setup uncertainties on target volume coverage and doses to OAR in HNC patients treated by IGRT. Total 503 kV CBCT images were acquired for evaluation of setup errors in 25 HNC patients. The study showed that there was a significant difference in PTV coverage between 2 plans comparing before and after setup error correction.
Many dosimetric studies also suggest that without IGRT, larger CTV-to-PTV margins are required to compensate for setup errors., Reducing PTV margins with IGRT in head-and-neck region can lead to reduced toxicities without compromising tumor control. Chen et al. showed that with IGRT, smaller PTV margins are safe without clinical detriment. Setup verification with IGRT can potentially lead to improved dose devilry to target volumes and sparing of normal tissue structures.
Our study has certain limitations such as it is a nonrandomized study and daily image guidance with CBCT was not performed. The rotational errors such as roll and pitch were also not assessed in our study. Analysis of rotational errors and its impact on the PTV margin should be investigated for accurate radiation treatment delivery to the target volumes.
| > Conclusion|| |
Detection and correction of setup errors is important for the precise and accurate delivery of radiotherapy. Image guidance allows for pretreatment position verification and setup error correction which improves the precision of patient repositioning with the possibility of reducing PTV margins, sparing organs at risk, and escalating radiation doses. Setup variations should be obtained in each radiotherapy department to calculate institute-specific margins. An isotropic PTV margin of 5 mm over CTV is considered safe to account for setup errors, however, in the case of close proximity of OAR, or re-irradiation or with IGRT, a PTV margin of 3 mm can be considered. Our study suggested that CBCT at the first 3 fractions and then weekly during radiotherapy is effective to detect and reduce the setup errors.
We are thankful to our medical physicists Mr. Natrajan, Mr. Rajkamal, Mr. Vineeth C, and Ms. Ashna Jenny for their important and critical role in radiotherapy treatment planning, radiation treatment implementation, and quality assurance process.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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