Page 143 - Organ motion in children for high-precision radiotherapy - Sophie Huijskens

When a conventional free-breathing 3D planning CT is used without daily pre-fraction imaging, the required abdominal CTV-to-PTV margins in the left-right (LR) and anterior-posterior (AP) direction should be approximately 10-12 mm (PRV 6 mm) and 14-16 mm in the cranial-caudal (CC) direction (PRV 8-9 mm). If 3DCT imaging is followed by daily imaging and online set-up verification using bony anatomy, the interfractional setup uncertainty (Σsetup) is negligible [1, 2], resulting in slightly smaller margins; 9-10 mm in the LR and AP directions, and 12-15 mm in CC direction. In case 4DCT imaging is available, the systematic intrafractional component (Σintra) will be accounted for by an individualized internal target volume (ITV) margin, leading to slightly smaller ITV-to-PTV margins, but will result in overall larger PTV margins. If the delineation error would be considered 5 mm, it will greatly impact the margin size, adding approximately 4-5 mm up to the PTV and 2-3 mm to PRV margins. These estimated margins, as also recommended in chapter 2, 3 and 4, suggest that safety margins should be applied anistropically rather than isotropically. Additionally, current pediatric protocols do not report on specific PRV margins. Presented PRV margins could support the radiation oncologist in optimizing treatment plans with better sparing of dose to the OARs. In conclusion, the expected delineation error and the interfractional position variation seem to show the largest contribution to the size of the margin. Therefore, pediatric delineation studies are needed to accurately quantify the Σdelineation and the feasibility of target-based setup verification should be investigated.
It should be noted that the currently available literature describes varying methodologies for the quantification of geometrical uncertainties, and consistency in reporting outcomes is lacking, varying in means, medians, ranges or confidence intervals. This makes it difficult to make a definitive statement on systematic and random errors. A pooled analysis of all (raw) available pediatric data would allow for suggestions based on a larger scale, or quantitative studies including more patients of different age, height, and weight are needed. The establishment of such an international database has large potential as a source of information and knowledge exchange, and would provide a solution to reach consensus, which is also suggested by several others [23, 32–35].
In children, treatments involving radiotherapy directed at abdominal and thoracic areas show good local control rates [7, 36–39]. This could imply that the used margins were sufficient for target coverage. However, radiation-induced adverse events later in life remain of great concern in children. Investigation of the dose-response relationship and the treatment-related risk factors for the occurrence and severity of these adverse events is ongoing research [40–46], providing fundamental information on which organs are more sensitive and likely to develop adverse events. Knowledge on organ position variation provides a lower bound on the achievable precision of patient selection, when (automating) selecting similar patients from a database of patients’ CT scans is applied for historical dose reconstruction [42, 43]. With this valuable information on organ dose- effect relationships in children, sparing of OARs in abdominal and thoracic radiotherapy will play an important role in future decision making.
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