A systematic review on motion, margins and delineation variability in thoraco-abdominal pediatric RT

For radiotherapy of thoracic and abdominal tumors, safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, inter- and intrafractional organ motion, and delineation variability. For pediatric patients, no standardized margins are defined since studies on these geometrical uncertainties are relatively scarce. Therefore, we aim to present a literature overview of organ motion, variations in applied margin sizes, and delineation variability in patients <18 years.
A systematic search in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and the International Clinical Trials Registry Platform from 2000 to 2020 resulted in 5102 studies. Using predefined in- and exclusion criteria, study selection based on title/abstract and full text followed by data extraction was performed independently by three authors. Overall, 107 studies were included reporting on organ motion (N=16), margin sizes (N=89), and delineation variability (N=2). Besides reported motion, margin sizes, and delineation results, data on variables such as age, tumor types, use of general anesthesia (GA), and image (guidance) modalities were extracted.
Studies were heterogeneous concerning age, tumor types, GA, and imaging modalities. Use of image guidance techniques (CBCT, orthogonal kV port films) was reported in 16% of the studies. Overall, cranio-caudal inter- and intrafractional motion as reported for different organs ranged from -9.1 to 10.0 mm and -4.4 to 19.5 mm, respectively (Table 1). Motion quantification methodologies differed between studies concerning measures of displacement (e.g. center of mass, border of organs) and definitions of motion direction. GTV-CTV and CTV-PTV margin sizes were reported for thoracic, abdominal, spinal and pelvic sites for different primary tumor types and metastases, treated with different radiation techniques (e.g. CRT, IMRT, VMAT, protons). GTV-CTV margins ranged from 5‒20 mm for thoracic and abdominal targets, and from 1‒10 mm and 5‒15 mm for spinal and pelvic targets, respectively (Figure 1). CTV-PTV margins for thoracic and abdominal targets varied from 3‒20 mm, and for spinal and pelvic from 3‒15 mm and 3‒10 mm, respectively. Most studies specified one margin size, however, in 24% of the studies a range of margin sizes was reported. Delineation studies assessed inter-observer variability of target volumes and showed that variability in delineated target volumes affected dose distributions to both target volumes and organs at risk.
The wide variations in organ motion and applied margin sizes in pediatric patients as summarized in this systematic review, might be caused by diverse variables involved that hamper the use of standardized margins. More research is needed to increase the knowledge on organ and tumor motion in children to account for geometrical uncertainties.