Page 142 - Organ motion in children for high-precision radiotherapy - Sophie Huijskens

Delineation uncertainty
Target delineation is performed by a radiation oncologist at the start of the radiotherapy process and the delineation uncertainty is another component of the margin recipe, albeit not investigated in this thesis. Inter-observer variability in delineation has been presented in numerous adult studies [12], but pediatric delineation studies are scarce, due to the large variety of tumor locations and site- specific protocols. A few studies, with a varying focus on medulloblastoma [13, 14], nephroblastoma [15], Hodgkin’s lymphoma [16–18], and rhabdomyosarcoma [17, 18] patients, demonstrated considerable inter-observer variability in delineation of the target volumes (conformity index ranging from 0.3 to 0.7). Differences were caused by ambiguities in the guidelines, interpretation differences of both guidelines and images, and varying levels of experience and individual performance. Inter- observer variability in delineation not only affected target volume delineation, but also the dose distribution in the surrounding healthy OARs [15, 17, 18]. These studies emphasize the need for highly specific protocol definitions and training to improve uniformity in target delineation and sparing of OARs. Improvements in diagnostic imaging (further discussed in paragraph 8.4) might also lead to higher uniformity in target definition. Nevertheless, although we did not study the delineation uncertainty in this thesis, it is clear that this component adds another significant contribution to the planning target volume (PTV) and planning risk volume (PRV) margins. It might be even a bigger contribution than the inter- and intrafractional uncertainties, as we know from adult studies [19–22]. However, current available pediatric literature only reported the conformity index, and from this metric no definitive statement regarding the delineation error (Σdelineation) can be made.
Resulting safety margins and clinical application
The margin used greatly varies depending on availability of imaging and the planning strategy used in the clinic [23–25]. Current protocols for pediatric abdominal and thoracic tumors recommend an isotropic margin around the clinical tumor volume (CTV), defining the PTV, ranging from 10-20 mm [26–29], but no details are given on the origin of these margins. In general, they mention that institutional and individual experience should be a determining factor for choosing the appropriate margin size. According to van Herk’s CTV-to-PTV (2.5Σ+0.7σ) and McKenzies PRV (1.3Σ+0.5σ) recipes, these margins should be derived from population-based systematic (Σ) and random errors (σ) [30, 31]. However, small pediatric patient cohorts and large variation in childhood cancer types, subtypes, and treatment sites complicate this process. Next, the variety in age, height, and weight and the lack of correlation of organ position variation and respiratory motion with these patient-specific factors, make margins based on age or height not (yet) feasible. Nevertheless, we have summarized our results with the available literature on interfractional position variation and intrafractional motion (Table 8.1 and 8.2), which form the basis of a first estimation of population-based child-specific margins. The delineation and setup uncertainty had not been measured for our cohort. We used a set-up error from [2], and considered a delineation error of 3 or 5 mm, which was estimated based on values available from adult literature [19–21]. Systematic and random errors should be added quadratically, accounting for the geometric uncertainties by:
139