Introduction
The clinical target volume (CTV) to the planning target volume (PTV) expansion, as outlined by International Commission on Radiation Units (ICRU), is added to account for delineation uncertainties, internal organ motion, patient motion and set-up uncertainties.Reference Purdy 1 It is applied to both adult and paediatric patients.
Van Herk et al.Reference van Herk, Remeijer, Rasch and Lebesque 2 defined the PTV margin as the margin needed to ensure, in the presence of set-up and other uncertainties, that the dose to the CTV was 95% in 90% of the treated patients. Many centres use an empirical PTV expansion of 5–10 mm based on historical practice and clinical experience.Reference Alcorn, Chen and Claude 3 There are several published formulations for calculating the necessary PTV.Reference McKenzie 4 , Reference Stroom, de Boer, Huizenga and Visser 5
The factors affecting the PTV margin are different in different tumour sites and also differ based on delineation uncertainties, immobilisation devices used, imaging frequency, imaging modality and the whole image-guided radiotherapy (IGRT) strategy implemented. This is why most radiotherapy protocols define fixed CTV margin based on the treatment site but give some flexibility for PTV margin for each individual institution considering the factors mentioned above which are different from one centre to another.
Some of these factors are likely to be similar in adults and paediatrics patients such as delineation uncertainties while other factors like organ motion and setup errors may be different in adults compared with paediatric patients.Reference Nazmy, Khafaga, Mousa and Khalil 6 In spite of this, many centres apply the same PTV margin based on the treatment site in both adult or paediatric patients.Reference Nazmy, O’Shea, McCrickard and O’Sullivan 7
While the PTV margin calculation has been evaluated in adult patients in numerous publications,Reference Hurkmans, Remeijer, Lebesque and Mijnheer 8 – Reference Nabavizadeh, Elliott and Chen 10 the evidences of evaluation of PTV margin for paediatric patients are sparse,Reference Alcorn, Chen and Claude 3 , Reference Eldebawy, Attalla, Eldesoky and Zaghloul 11 , Reference Beltran, Krasin and Merchant 12 with very few data available regarding the need for different PTV margin in paediatric patients compared with adult patients. Recently conducted analyses of the PTV margin in adult patients (>18 year old) and paediatric patients (<7 year old) treated in one centre showed a clinically significant difference (>2 mm) of the PTV margin needed in the longitudinal direction in the abdominal region.Reference Nazmy, O’Shea, McCrickard and O’Sullivan 7
The aim of this study was to evaluate the international patterns of practice regarding the PTV margin in paediatric versus adult patients and to identify the PTV margins employed per treatment site in both paediatric and adult patients treated in the same institution.
Materials and Methods
Paediatric Radiation Oncology Society (PROS) members were selected to participate in this study to evaluate the patterns of PTV margin practice in the treatment of paediatric patients (this was done as a part of a comprehensive survey including other aspects like IGRT). A total of 119 members in 116 institution were eligible to participate. Eligibility was granted to departments that treat both paediatric and adult patients, and employ IGRT. Data regarding PTV margin will be discussed in this paper.
Each participant was provided with a four-item survey comprised of closed and open-ended questions (Appendix) related to five treatment sites: central nervous system (CNS), head and neck (H&N), torso, pelvis and others. The presence of PTV margin guidelines was investigated, and whether these guidelines were specific to adult and paediatric patients.
Data was collected by means of an anonymous questionnaire distributed via SurveyMonkey. This survey was distributed to all participants along with a participant information leaflet and cover letter by email. Participation was voluntary and without remuneration. Participants returned completed surveys on the SurveyMonkey site. The survey was open from 1st of September 2015 until 31 October 2015.
Ethical approval for this study was sought and obtained from the School of Medicine Research Ethics Committee, Trinity College Dublin in August 2015.
Results
In total, 43 out of 119 (n=43) (36%) participants responded to the survey over a 2-month period.
PTV margin guidelines
The majority of the responders 74% (32/43) have written guidelines for CTV to PTV expansion in different treatment sites. Details are shown in Table 1.
Answer to question 1 (Do you have written guidelines regarding the planning target volume margin in different sites?)
Abbreviation: CNS, central nervous system.
Different PTV margins for adults and paediatrics
Only one-third, 33% (14/43), of the responders use separate guidelines for adult and paediatric patients. Details are shown in Table 2.
Answer to question 2 (Do you have separate guidelines regarding the planning target volume margin for adults and paediatrics?)
Note: The % not having separate guidelines are of all respondents, including those that do not have guidelines at all.
Abbreviation: CNS, central nervous system.
Centres that do not have separate guidelines were asked to comment on whether they feel the need for paediatric specific guidelines for PTV margins in the major sites. In total, 23 commented on this part. Four said yes, they feel there is a need for consensus guidelines, for both paediatric and adult patients. Two said no, they do not feel there is a need for it. Seven said margins are applied on an individual basis, while six elaborated on the different other factors affecting the PTV margin. Four commented that they treat patients in a paediatric protocol and they follow the protocol guidelines for the PTV.
PTV expansions
There are slight differences recorded in PTV margins between adult and paediatric patients. Figures 1a–1d show the PTV margin for adult and paediatric patients reported for different treatment sites. For CNS and head and neck regions the majority of the responders apply margins of 3–5 mm with 3 mm used more frequently in paediatric patients (27 versus 23 in CNS and 19 versus 12 in H&N). For torso and pelvic area, the majority of the responders apply PTV margin of 5–10 mm with 5 mm used more frequently in paediatric patients (21 versus 14 in the torso region and 22 versus 13 in the pelvic region). These differences were not statistically significant as shown in Table 3.
(a) Planning target volume (PTV) margins for central nervous system area. (b) PTV margins for head and neck area. (c) PTV margins for torso area. (d) PTV margins for pelvic area.
Difference in the planning target volume margin implemented in adults and paediatrics
Abbreviation: CNS, central nervous system.
Additional comments
In all, 17 participants highlighted other points like, the difference in tumour type between both patient groups, the reduction in PTV margin depends on immobilisation technique and individual protocol, anisotropic PTV margins are often applied and individual patient considerations are often taken into account.
Discussion
A recent publication showed that the average response rate of physicians to mailed surveys has traditionally been demonstrated to be only 54–58%, and among oncologists varied from 31 to 61%.Reference Martins, Lederman and Lowenstein 13 Although low, the response rate to this survey was within this range at 36% and to the best of our knowledge the absolute number of the responders (43 institutions) is the highest for paediatric radiation oncology surveys published ever.Reference Alcorn, Chen and Claude 3
The PTV margin policy used in different radiation oncology departments was explored in this study and it was found that 74% of responders have written guidelines for CTV–PTV expansion in different treatment sites, with 33% having separate guidelines for both adult and paediatric patients.
Factors affecting the PTV margins may be different between adult and paediatric patients, so it was important to look at the PTV margin needed for adult as compared with paediatric patients especially if the patients are treated in the same institution with the same IGRT strategy and level of expertise.
In paediatrics, a recently published survey of seven institutions showed that half reported the use of different PTV expansions when treating with or without IGRT. The PTV margin was based on data from the literature, clinical data or margins suggested by Children’s Oncology Group protocols. The PTV expansions used for CNS ranged from 3 to 5 mm regardless of IGRT use and there was notable institutional variability in the ranges of PTV expansions in other sites with or without IGRT ranging from 3 mm to 20 mm.Reference Alcorn, Chen and Claude 3 Eldebawy et al. reported that the required PTV margins of 4, 4·5 and 5·5 mm in the lateral, longitudinal and vertical directions, respectively, for the H&N area in the paediatric age group, and PTV margins of 5·5, 7·5 and 4·5 mm in the lateral, longitudinal and vertical directions, respectively, for the abdomen and pelvis area. In this work they defined the paediatric population as age 2–16 years old.Reference Eldebawy, Attalla, Eldesoky and Zaghloul 11
In adults, PTV margins of as low as 3·0 mm in the lateral direction, 1·3 mm in longitudinal direction and 2·6 mm in vertical direction were recommended for nasopharyngeal cancer patients undergoing Intensity Modulated Radiotherapy (IMRT) with weekly Cone Beam CT scans.Reference Chen, Su and Wei 9 A recent survey of the American Society for Radiation Oncology members showed that the PTV margin used for H&N/CNS is 3–5 mm and the PTV margin used for torso/pelvis is 5–10 mm.Reference Nabavizadeh, Elliott and Chen 10
The data of the trials mentioned aboveReference Alcorn, Chen and Claude 3 , Reference Chen, Su and Wei 9 – Reference Eldebawy, Attalla, Eldesoky and Zaghloul 11 showed a difference in the PTV margin required in paediatrics versus adults especially in the torso regions. The results of this survey present the lack of consensus regarding the magnitude of the difference and the need to have a consensus.
Both patient age and height are numerical continuous variables. Panandiker et al. assessed renal motion in paediatric patients aged between 2 and 18 year old. The amount of renal motion increased for every yearly increase in the patients’ age. Renal motion in the mediolateral direction correlated with height as well. For every 10 mm increase in height, the left kidney’s movement increased by 0·006±0·002 mm (p=0·017) and the right kidney moved 0·006±0·003 mm (p=0·042).Reference Pai Panandiker, Sharma and Naik 14 It is clear from the data above that the required PTV margin for a 1-year-old baby is not the same as for a mature adult. Most of the paediatric protocols include patients up to 16–18 years old. Applying different PTV margin for adults and paediatric patients or per pubertal and post-pubertal patients may not be the simple answer. On the other hand it is not practical to consider different PTV margin for each patient based on age or height. Nazmy et al. showed a clinically significant difference in the PTV margin in the abdominal region between adult and paediatric patients treated in the same institution but they defined adult patients as age >18 and paediatric patients as age <7.Reference Nazmy, O’Shea, McCrickard and O’Sullivan 7 A group exists in-between 7 and 18 years old wherein the margin should be considered individually.
Reduction of the PTV margin is crucial in paediatrics; it will decrease both the acute and long-term side effects. The relatively bigger radiation dose in children presents a greater risk to the Organs At Risks (OARs). This correlates directly with the size of the patient; OARs are closer in proximity in a child than in an adult.Reference Hall 15 So while our paper highlights the need to develop consensus guidelines on PTV margins for paediatrics, it is important to take into consideration the size/height of the patient, not just the age. The relative increase in the irradiated volume by adding few mm margin in an adult patient is less than the relative increase of adding similar margin in young child.Reference Nazmy, Khafaga, Mousa and Khalil 6
As with most research, we have identified limitations to the study specifically treatment technique (e.g., IMRT, 3D conformal radiotherapy) and modality (e.g., photons, protons) are not identified. Immobilisation devices are also not recorded and may have been useful given their impact on PTV margins. The survey did not elicit whether centres apply different planning goals (target coverage, OAR dose limits) to paediatric cases or other methods to treat paediatric patients in consideration of the different dose implications to this population. Finally, the relation between the PTV margin and IGRT protocol implemented or the use of anaesthesia has not been addressed, so a direct comparison is difficult to make between centres. During preparation for this survey it was important to spend time to phrase the questions in a way that will give usable answer. For example when we sought of asking about the immobilisation device used and we tried to make a list, we found a large number of commercially available fixation devices, the same applies to the IGRT protocol like frequency of imaging and action level. Even for anaesthesia, in the paediatric radiation oncology practice, it is known that many patients may start treatment under anaesthesia and after being familiar with the place they can get few fractions without anaesthesia so we felt addressing these issues will make the survey more complicated (lengthy and it is unlikely to get a usable information considering the wide variation of practice expected).
We did not also examine either the effect of treatment technique on the PTV margin or anisotropic margins, both of which are of salience in clinical practice. Treatment technique has been shown to impact on PTV expansion,Reference Huijskens, van Dijk and de Jong 16 while anisotropic margins are important in the delineation of treatment volumes where internal motion is greater in one direction than in another. In two studies published on extra-cranial paediatric organ motion, Huijskens et al. (2015)Reference Huijskens, van Dijk and de Jong 16 and Nazmy et al. (2012)Reference Nazmy, Khafaga, Mousa and Khalil 6 found motion to be greatest in the cranial caudal direction for abdominal paediatric patients. Huijskens et al. suggested an individualised margin, with further research into inter- and intra-fraction motion warranted.
Because of the limitations above, it was not possible to draw conclusions regarding the PTV margin to be implemented in spite of the fact that the majority of the responders used PTV margins 3–5 mm for paediatric patients for brain and H&N and 5–10 mm for torso and pelvic region. But these limitations do not affect the main aim of the survey which was addressed mainly in questions 1 and 2. The results of this survey provide insight into current paediatric PTV margin protocols within radiotherapy departments, the variation that exists in practice and the absence of consensus on the margin of the PTV. Based on the current information from 43 responders treating paediatric patients this study supports the need for the development of PTV margin guidelines in the treatment of this vulnerable patient cohort in each treatment centre based on the immobilisation technique and IGRT strategy.
Conclusion
In conclusion, the results of this study illustrate that the majority of responders employ a series of site-specific PTV margin protocols that are applied to both adults and paediatrics, and do not take into consideration patient age or size. These results highlight the need of a separate policy for PTV margin in adults and paediatrics in every institution.
Acknowledgements
None.
Financial support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Conflicts of interest
None.
Ethical standards
This article does not contain any studies with human or animal subjects performed by any of the authors.
Appendix: Survey Questions
1. Do you have written guidelines regarding PTV margin in different sites:
(a) CNS
(b) Head and neck
(c) Torso
(d) Pelvis
(e) Other
2. Do you have separate guidelines regarding the PTV margin for adults and paediatrics?
(a) CNS
(b) Head and neck
(c) Torso
(d) Pelvis
(e) Other
If no. Please comment on whether you feel the need for paediatric specific guidelines regarding PTV margins for the major sites.
3. Please indicate PTV margins employed for these sites
(a) CNS adults ____________ mm Paediatrics ____________ mm
(b) Head and neck Adults ____________ mm Paediatrics ____________ mm
(c) Torso Adults ____________ mm Paediatrics ____________ mm
(d) Pelvis Adults____________ mm Paediatrics ____________ mm
(e) Other Adults ____________ mm Paediatrics ____________ mm
4. Any additional comments
______________________________________________________
