Page 160 - Organ motion in children for high-precision radiotherapy - Sophie Huijskens

Continuous developments of effective multimodality treatment strategies for pediatric cancer have led to a steep increase in the number of childhood cancer survivors during the last decades. Inextricably, with the enhanced cancer survival, the incidence of treatment-related adverse events has become evident. Particularly, treatment with radiotherapy significantly contributes to the risk of developing adverse events. Radiotherapy uses ionizing radiation to kill the tumor cells. Unavoidably, radiation will pass through the patient’s body and healthy tissues will receive dose as well, resulting in acute and/or late toxicities and complications. Therefore, solely focusing on cure of cancer is not enough and reduction of adverse events deserves more attention. Although delivering adequate tumor dose to kill the tumor cells is the primary goal in radiotherapy, sparing the vital and long-term functions of adjacent organs at risk (OARs) is also paramount. Especially in children, who have a relative long life expectancy when surviving cancer, organs are still growing and have low tolerance to radiation. Therefore, extremely high precision in irradiation and avoiding collateral damage is pertinent. However, geometrical uncertainties are present and limit the accuracy. To account for these uncertainties, the clinical tumor volume (CTV) is extended with an isotopic safety margin, thereby defining the planning target volume (PTV). Similar margin definitions are also taken into consideration for OARs to define adequate planning risk volumes (PRVs). In adults, many studies focus on quantification of the geometrical uncertainties in order to define accurate population-based driven margins for specific tumor sites. Since childhood cancer is a rare disease, the small population makes it difficult to derive population-based margins for children. More importantly, childhood cancer patients are a highly diverse group, varying from infants to adolescents with varying heights and weights. Therefore, margins for children should be defined with more distinction. Moreover, achievements in radiotherapy are mainly focused on adult patients and pragmatically translated and implemented into a pediatric setting. Data on the geometrical uncertainties in pediatric radiotherapy is lacking, and clinically used margins are mainly based on experience of the radiotherapist or knowledge based on available adult data. Since the introduction of image guidance in pediatric radiotherapy, imaging data has become available to quantify the geometrical uncertainties in children, which can be described by interfractional position variation (i.e., day-to-day variations of the anatomy) or intrafractional motion (mainly caused by respiration). These geometrical uncertainties are a superposition of a systematic and a random error that form the basis for the population-based CTV- to-PTV or PRV margins. Systematic errors originate in the treatment preparation phase and therefore affect all treatment fractions. Random errors occur arbitrarily and could have a different effect each single fraction. Quantification and an extensive understanding of these uncertainties in children must lead to appropriate child-specific based margins, which is essential for high-accuracy image-guided radiotherapy in children.
Children are treated with abdominal and thoracic radiotherapy for a wide range of primary cancer diagnosis. Especially in the abdominal and thoracic area, tumors and organs are prone to motion, and the tumor can be in very close proximity to radiosensitive OARs. In the first part of this thesis we focused on interfractional abdominal organ position variation. In chapter 2 we described our retrospective multicenter study in which we quantified interfractional position variation of the kidneys and the diaphragm in a cohort of 39 childhood cancer patients in order to estimate the standard deviation (SD) of systematic errors (Σ) and the root mean square of random errors (σ). We also analyzed the possible correlations between the interfractional position variation and patient-specific factors, such as age, height, and weight. Σ in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions was on average 1.2, 4.0, 1.8 mm and σ in these three directions was on average 1.2,
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