In this first –baseline– survey we assessed the current clinical IGRT practice among 33 European institutes treating children. With this survey, currently the most extensive one on pediatric IGRT, we followed the entire workflow including treatment preparation, planning and radiation delivery. Modern EBRT techniques and IGRT modalities were widely available and accepted, marking a trend that has been described in previous surveys (2007–2017; Table 3) (9–14). Sophisticated high-precision techniques using smaller margins require high-standard (daily online) image guidance (13, 24). For example, IMRT/VMAT techniques lead to a steep dose gradient, where IGRT becomes extremely important to prevent the risk of partially missing the target. Site-specific questions revealed some variations in treatment preparation, planning and delivery techniques, including IGRT devices (Table 1). The widest variation was found in isotropic CTV-to-PTV margin sizes, especially for brain as a consequence of two respondents reporting a 1 mm and a 10 mm margin, respectively, and for abdominal tumors due to a single respondent reporting a 1 mm margin. The large variations in margin sizes for brain and spine as part of CSA could be explained by the relatively low percentage of 3D-CBCT use in CSA treatment (57%). Margins sizes were not found to be correlated with the number of annually treated children.
Table 3. Overview of surveys on IGRT/IGPT.
Study
|
Jefferies 20099
|
Mayles 201010
|
Alcorn 201414*
|
Nabavizadeh 201511
|
Padayachee 201713
|
Batumalai 201712
|
Wall 201815*
|
Bolsi 201834
|
Windmeijer
|
Survey sent:
|
2007
|
2009
|
Not specified
|
2014
|
2015
|
2015
|
2015
|
2016
|
2018
|
Geographical
|
UK
|
UK
|
Worldwide
|
USA
|
New Zealand
|
Australia
|
International†
|
Europe
|
Europe
|
Responded/invited
Response rate (%)
|
48/58
83
|
50/58
86
|
7/9
88
|
601/5979
10
|
7/9
88
|
33/46
72
|
43/119
36
|
19/19
100
|
42/70‡
60§
|
Treatment preparation
Patient positioning
Immobilization
devices
Pre-treatment
imaging
Treatment planning
Imaging for field
simulation
Treatment
technique
PTV margins
Treatment delivery
Use of IGRT devices
Imaging frequency
(on/offline)
|
-
-
+
+
-
-
+
-
|
-
-
-
-
+
-
+
-
|
-
+
-
-
-
+
+
+
|
-
-
-
-
-
+
+
+
|
-
-
-
-
+
-
+
+
|
-
-
+
+
+
-
+
+
|
-
-
-
-
-
-
-
+
|
+
+
-
+
+
+
+
|
+
+
+
+
+
+
+
+
|
Aim
|
· Evaluate current image acquisition in RT.
· Evaluate assessment of target volume definition.
· Review types of radiation technology being used.
· Evaluate IGRT implementation next 2 years.
|
· Evaluate increase of IMRT and shortfall of patient treatments compared to Jefferies et al.9
· Availability of IGRT.
|
· Evaluate range of pediatric IGRT practices.
|
· Define US IGRT utilization and impact on workflow.
· Evaluate relation IGRT use and applied PTV margin.
|
· Assess current in-room IGRT practice.
· Assess IGRT quality using White Paper recommendations.
· Understand barriers to implementation/ improvement in New Zealand.
|
· Evaluate current use of imaging for planning/ delivery of EBRT.
|
· Evaluate IGRT in adults vs. pediatric patients.
|
· Assess differences between centres in terms of IGPT usage for treatment preparation, planning and delivery.
· Identification of development needed to improve IGPT.
· Identification of research activities.
|
· Evaluate pediatric IGRT, following the clinical workflow from pre-treatment imaging to treatment delivery.
|
Main outcomes
|
· Lack of IMRT and IGRT implementation due to multi-fold barriers.
· Lack of formal training in tumour and normal tissue outlining in several staff groups.
|
· Inverse-planned IMRT falls short of what clinicians feel should be offered.
· IMRT implementation developed as was found by Jefferies et al.9
· High IGRT uptake in centers that have the necessary equipment.
|
· High IGRT prevalence, but treatment site-specific variability in IGRT use and technique between institutes. Practices varied less in proton centers.
· No consensus on optimal PTV margin per treatment site.
|
· High prevalence of IGRT and daily CBCT.
· Wide variability in site-specific imaging frequency and verification methodologies.
· No statistically significant association between IGRT frequency and PTV margin selection.
· Poor resident involvement in IGRT practices.
|
· IGRT widely used, with wide variation in application between institutes.
· IGRT complies highly to ASTRO White Paper recommendations.
· Multi-fold barriers restricting IGRT implementation.
|
· IGRT widely used, and the installation of new imaging modalities is expected to increase.
|
· Most institutes apply site-specific protocols, not considering patient size and age.
|
· Confirmed variety in clinical IGPT practices and procedures
|
· General agreement in IGRT application, but wide variability in isotropic PTV margin use.
|
Abbreviations: CBCT = cone-beam computed tomography; EBRT = external beam radiotherapy; IGRT = image-guided radiotherapy; IMRT = intensity modulated radiotherapy; PTV = planning target volume; + = applicable topic; - = not applicable;
* Survey focusses on children.
† International; region not specified.
‡ 33/42 institutes denoted to treat children and were included in the analysis.
§ Weighted average response rate pediatric surveys Alcorn and Wall: 39%.
|
Prone positioning for photon irradiation was rare, possibly because prone positioning could be subjected to larger setup and residual uncertainties than supine positioning (25). Also, prone positioning may be considered to potentially induce patient discomfort, and might not be appreciated for anesthesia. On the other hand, treating under anesthesia in prone position is safe and feasible (26). Besides, in proton therapy, prone positioning could be favorable because of healthy tissue sparing, or due to beam configuration limitations, e.g. in CSA treatment, to avoid radiation through the treatment couch. Contrarily, when the couch and immobilization devices are properly modeled by the treatment planning system, treating with beams traversing some devices was proved feasible, which counters this limitation (27).
As immobilization is of great importance, especially for complex targets in in pediatric patients, we would have expected knee/foot supports to be used even more frequently than reported. However, knee/foot supports are not always used as on the one hand pediatric specific supports are lacking and in-house made or adjusted devices are used, whilst on the other hand small children do not need them when immobilized in a vacuum cushion. Similar to Alcorn et al (14), we found an extensive use of vacuum cushions (> 62%) for thoracic, abdominal and pelvic treatments. Our survey did not disclose anesthesia practices, whereas anesthesia or sedation is often required in the very young to ensure complete immobility during radiotherapy (28).
Additional pre-treatment imaging for GTV-to-CTV definition was used more extensively among our participants than reported earlier by Jefferies et al (9). Batumalai et al reported the use of PET-CT to prepare for CSA treatment in adults, whereas our survey showed that PET-CT was hardly used in children. For H&N, thoracic and abdominal/pelvic sub-sites the use of PET-CT was comparable or higher than in our sample (12); differences might be due to the typically different cancer types in children and adults. Imaging for planning purposes included 3D-CT in all institutes. Besides 3D-CT, two institutes also used conventional 2D-simulations. This could be explained by them being in a transition period, having acquired newer techniques only recently. This is consistent with Jefferies et al, who predicted that conventional 2D-simulation would decline in favor of 3D-CT (9). All participants in our survey had access to CT simulators, and frequently used additional MRI and PET-CT, in alignment with Batumalai et al (12). We also notice the use of breath-hold techniques during 3D-CT acquisitions for thoracic and abdominal treatment simulations. Implementation of breath-hold protocols depends on the patients’ ability to comply with instructions (29, 30), but is promising, and dosimetric benefit has already been shown even in a vulnerable adult patient group (31). Most centers using 4D-CT scans for treatment simulation define an ITV. This approach needs less quality assurance compared to other techniques (e.g. gating/tracking). Only two institutes used gating/tracking techniques, suggesting that more development is needed to confidently apply these methods in children, but we did not enquire about specific details.
Regarding photon therapy, we found that IMRT/VMAT were widely applied. This corresponds to the results of surveys focusing on adults (12, 13), and indicates development of the field since 2010, when Mayles et al reported a low IMRT use (10). Interestingly, we found that a number of institutes still used 3D-CRT, even with IMRT/VMAT available. An explanation could be the concerns about the large low dose volume in IMRT/VMAT with a potentially increased risk of secondary cancer induction (32). Alternatively, even when the hardware is available, the planning software is not always fit to deal with extensive volumes or the implementation is time consuming. Few institutes indicated to use simulator-based 2D techniques, but we did not specifically enquire in which situations. Similarly, information on specific proton treatment techniques such as passive scattering or pencil beam scanning was not collected. Technical developments have led to a transition from passive scattering proton therapy to active pencil-beam scanning (33). Scanning techniques potentially realize an even better conformal target volume coverage, and facilitate intensity-modulated proton therapy (IMPT) minimizing dose to healthy tissues (33, 34). As IGRT in photon therapy, image-guided particle therapy (IGPT) is a crucial step in the treatment workflow (35). The EPTN (European Particle Therapy Network) survey confirmed a variety in IGPT practice in European particle therapy centers, and identified the priority of research to improve daily image guidance (35).
In accordance with previous surveys on IGRT use in both pediatric and adult patients (9, 11–14), 3D-CBCT was the most frequently used device for in-room IGRT. Padayachee et al found that kV-planar and CBCT imaging were, averaged over all sites, used in similar frequency (13). The low prevalence of abdominal and thoracic MV and kV-planar imaging is encouraging as position verification based on bony anatomy might not always be sufficient. CBCT scanning is superior in visualizing soft tissue compared to 2D-imaging, but the extra imaging dose of (daily) CBCT has to be considered. To account for this, IGRT protocols to minimize imaging dose and volume are being introduced for pediatric IGRT. This comes at the expense of image quality but not of registration accuracy (24). On the other hand, high quality IGRT to improve geometrical accuracy may yield a significant shrinkage of the target margins. This should outweigh the concern of imaging dose in children and needs to be further investigated. Besides, MV imaging dose is often integrated in the treatment plan. Nevertheless, the wide use of IGRT for children across different European institutes as shown in the present survey reflects the significance of geometrical accuracy.
The use of daily online position verification by our participants is higher compared to Alcorn’s results in 2014 (~ 35 to ~ 60%) (14), and compared to adult surveys, where daily online imaging is frequently, but not continuously used (11–13). Also eNAL protocols are used widely in adults (11–13), similar to our sample. We did not specifically inquire on the decision when to use daily online, or offline protocols, or both. Theoretically, this decision strongly depends on treatment planning technique and the margin applied. For example, an offline protocol will be sufficient for whole brain irradiation, whereas partial brain irradiation will require an online protocol.
Margins applied by our participants are similar to those reported by Alcorn et al in all treatment sites except thorax (mean 6.6 mm in our study vs. 10.8 mm in Alcorn (14)). Nabavizadeh et al found similar lung tumor margins in adults, distinguishing between treatment planned on 4D-CT (median 5 mm; IQR 5–7 mm) and 3DCT (median 10 mm; IQR 7–13 mm) (11). Comparing the brain and H&N sites of our study and Nabavizadeh et al, margins were also similar (both median 5 mm, IQR 3–5 mm). Margin sizes should be in line with IGRT facilities and all steps in the chain of the (department-specific) radiotherapy workflow (5, 16). Complementary to the standardization and optimization of the organization of patient care, education and clinical research (36), knowledge of geometrical uncertainties including organ motion (37–44) is necessary to develop ‘best practice’ guidelines, distinguishing between hospital and patient specific factors.
The sample size might form a limitation. Eligible participants included European PROS members and our IGRT project-based consortium, totaling 70 institutes. The 60% response rate is comparable to that of other IGRT surveys, and it appeared that almost 33 of the 42 (80%) responding institutes actually treat children. Additional analyses to investigate the possible risk of bias due to the relatively high number of participating Dutch institutes (n = 7) did not change the results. Therefore, we consider our results a reasonable representation of pediatric radiotherapy in Europe, although non-IGRT-users or IGRT-users working with less sophisticated equipment might have been less likely to respond, resulting in a potential overestimation of the availability of modern techniques. Our survey specifically focused on pediatric IGRT and since pediatric tumors and their treatment substantially differ from that from adults, we have not compared pediatric and adult IGRT practices within participating institutes. The survey did not include specific questions how long each institute has practiced their reported use of IGRT methods. While our standardized electronic form assured complete responses since empty fields were not allowed, some uncertainties were still involved in the study design and response analysis. Firstly, numerical fields are vulnerable for typing errors, potentially leading to under/overestimations. Secondly, the possibility to select more than one answer on multiple-choice questions could have led to erroneous answers, which hampered investigation of associations between e.g. treatment techniques, IGRT modalities, online-offline protocols and margin size definitions. Thirdly, open fields for additional free-text responses were non-obligatory and only part of the participants elaborated on their answers, which may have led to misinterpretations (e.g. referral to proton centers). Finally, completing the survey was estimated to take 45 minutes. Although participants could save their answers to continue later, lengthy surveys might lead to inaccuracies in questions that were enquired later on, or were forgotten altogether. We will consider these issues when conducting the follow-up survey, aiming to involve the participants into a new consensus driven practice. Subsequent steps, preferably in collaboration with experts (e.g. PROS, SIOPE) include the development of guidelines, and the definition of optimal margin sizes considering available IGRT facilities and workflows among institutes.