Dosimetric feasibility of hypofractionation for metastatic bone/bone marrow lesions from paediatric solid tumours

Background and purpose: The aim of this study was to determine the feasibility of hypofractionated schedules for metastatic bone/bone marrow lesions in children and to investigate dosimetric differences to the healthy surrounding tissues compared to conventional schedules. Methods: 27 paediatric patients (mean age, 7 years) with 50 metastatic bone/bone marrow lesions (n = 26 cranial, n = 24 extra-cranial) from solid primary tumours (neuroblastoma and sarcoma) were included. The PTV was a 2 mm expansion of the GTV. A prescription dose of 36 and 54 Gy EQD2 α / β =10 was used for neuroblastoma and sarcoma lesions, respectively. VMAT plans were optimized for each single lesion using different fractionation schedules: conventional (30/20 fractions, V 95% ≥ 99%, D 0.1cm 3 ≤ 107%) and hypofractionated (15/10/5/3 fractions, V 100% ≥ 95%, D 0.1cm 3 ≤ 120%) . Relative EQD2 differences in OARs D mean between the different schedules were compared. Results: PTV coverage was met for all plans independently of the fractionation schedule and for all lesions (V 95% range 95.5–100%, V 100% range 95.1–100%), with exception of the vertebrae (V 100% range 63.5–91.0%). For most OARs, relative mean reduction in the D mean was seen for the hypofractionated plans compared to the conventional plans, with largest sparing in the 5 fractions (< 43%) followed by the 3 fractions schedule (< 40%). In case of PTV overlap with an OAR, a significant increase in dose for the OAR was observed with hypofractionation. Conclusions: For the majority of the cases, iso-effective plans with hypofractionation were feasible with similar or less dose in the OARs. The most suitable fractionation schedule should be personalised depending on the spatial relationship between the PTV and OARs and the prescription dose

Radical radiotherapy for paediatric solid tumour metastases:An overview of current European protocols and outcomes of a SIOPE multicenter survey

Purpose/objective: About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries. Materials/methods: Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating >= 50 children annually were invited to participate in an online survey. Results: Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing. Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied. Conclusion: Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST. (C) 2020 The Author(s). Published by Elsevier Ltd

Radical radiotherapy for paediatric solid tumour metastases: An overview of current European protocols and outcomes of a SIOPE multicenter survey

Metàstasis; Pediatria; RadioteràpiaMetástasis; Pediatría; RadioterapiaMetastases; Paediatrics; RadiotherapyPurpose/objective About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries. Materials/methods Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating ≥50 children annually were invited to participate in an online survey. Results Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing. Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied. Conclusion Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST.Stichting Kinderen Kankervrij [project no. 343]. KiKa (Children Cancer Free) foundation, grant number 343 and title: Towards optimization of radiotherapy techniques for metastatic lesions in children stage IV disease. The funding source had no role in the study design, collection, analysis and interpretation of data, writing of this manuscript or the decision to submit the article for publication

The effectiveness of 4DCT in children and adults: A pooled analysis

Background: While four-dimensional computed tomography (4DCT) is extensively used in adults, reluctance remains to use 4DCT in children. Day-to-day (interfractional) variability and irregular respiration (intrafractional variability) have shown to be limiting factors of 4DCT effectiveness in adults. In order to evaluate 4DCT applicability in children, the purpose of this study is to quantify inter- and intrafractional variability of respiratory motion in children and adults. The pooled analysis enables a solid comparison to reveal if 4DCT application for planning purposes in children could be valid. Methods/materials: We retrospectively included 90 patients (45 children and 45 adults), for whom the diaphragm was visible on abdominal/thoracic free-breathing cone beam CTs (480 pediatric, 524 adult CBCTs). For each CBCT, the cranial–caudal position of end-exhale and end-inhale positions of the right diaphragm dome were manually selected in the projection images. The difference in position between both phases defines the amplitude. Cycle time equaled inspiratory plus expiratory time. We analyzed the variability of the inter- and intrafractional respiratory-induced diaphragm motion. Results: Ranges of respiratory motion characteristics were large in both children and adults (amplitude: 4–17 vs 5–24 mm, cycle time 2.1–3.9 vs 2.7–6.5 s). The mean amplitude was slightly smaller in children than in adults (10.7 vs 12.3 mm; P = 0.06). Interfractional amplitude variability was statistically significantly smaller in children than in adults (1.4 vs 2.2 mm; P = 0.00). Mean cycle time was statistically significantly shorter in children (2.9 vs 3.6 s; P = 0.00). Additionally, intrafractional cycle time variability was statistically significantly smaller in children (0.5 vs 0.7 s; P = 0.00). Conclusions: Overall variability is smaller in children than in adults, indicating that respiratory motion is more regular in children than in adults. This implies that a single pretreatment 4DCT could be a good representation of daily respiratory motion in children and will be at least equally beneficial for planning purposes as it is in adults

Pediatric radiotherapy for thoracic and abdominal targets: Organ motion, reported margin sizes, and delineation variations – A systematic review

For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and delineation variability. For pediatric patients no standardized margins are defined. Moreover, studies on these geometrical uncertainties are relatively scarce. Therefore, this systematic review presents an overview of organ motion, applied margin sizes and delineation variability in patients <18 years. A search from January 2000 to March 2021 in Medline, Embase, Web of Science, ClinicalTrials.gov and the International Trials Registry Platform resulted in the inclusion of 117 studies reporting on organ motion, margin sizes and/or delineation variability. Studies were heterogeneous concerning age, tumor types, the use of general anesthesia, imaging modalities; image guidance techniques were reported in 39% of the studies. Inter- and intrafractional motion as reported for different organs was largest in cranio-caudal direction and ranged from −9.1 to 10.0 mm and −4.4 to 19.5 mm, respectively. Motion quantification methodologies differed between studies regarding measures of displacement and definitions of motion direction. Reported CTV–PTV margins varied from 3 to 20 mm for both thoracic and abdominal targets, and for spinal and pelvic from 3to 15 mm and 3 to 10 mm, respectively. Studies reported wide variation in interobserver variability of target volume delineation, which may affect dose distributions to both target volumes and organs at risk. Results of this review indicate possible reduction of margin sizes for children, however, wide variation in organ motion and delineation variability caused by differences in methodologies and outcomes hamper the use of standardized margins

Abdominal organ position variation in children during image-guided radiotherapy

Abstract Background Interfractional organ position variation might differ for abdominal organs and this could have consequences for defining safety margins. Therefore, the purpose of this study is to quantify interfractional position variations of abdominal organs in children in order to investigate possible correlations between abdominal organs and determine whether position variation is location-dependent. Methods For 20 children (2.2–17.8 years), we retrospectively analyzed 113 CBCTs acquired during the treatment course, which were registered to the reference CT to assess interfractional position variation of the liver, spleen, kidneys, and both diaphragm domes. Organ position variation was assessed in three orthogonal directions and relative to the bony anatomy. Diaphragm dome position variation was assessed in the cranial-caudal (CC) direction only. We investigated possible correlations between position variations of the organs (Spearman’s correlation test, ρ), and tested if organ position variations in the CC direction are related to the diaphragm dome position variations (linear regression analysis, R2) (both tests: significance level p < 0.05). Differences of variations of systematic (∑) and random errors (σ) between organs were tested (Bonferroni significance level p < 0.004). Results In all directions, correlations between liver and spleen position variations, and between right and left kidney position variations were weak (ρ ≤ 0.43). In the CC direction, the position variations of the right and left diaphragm domes were significantly, and stronger, correlated with position variations of the liver (R2 = 0.55) and spleen (R2 = 0.63), respectively, compared to the right (R2 = 0.00) and left kidney (R2 = 0.25). Differences in ∑ and σ between all organs were small and insignificant. Conclusions No (strong) correlations between interfractional position variations of abdominal organs in children were observed. From present results, we concluded that diaphragm dome position variations could be more representative for superiorly located abdominal (liver, spleen) organ position variations than for inferiorly located (kidneys) organ position variations. Differences of systematic and random errors between abdominal organs were small, suggesting that for margin definitions, there was insufficient evidence of a dependence of organ position variation on anatomical location

Interfractional renal and diaphragmatic position variation during radiotherapy in children and adults: is there a difference?

<p><b>Background:</b> Pediatric safety margins are generally based on data from adult studies; however, adult-based margins might be too large for children. The aim of this study was to quantify and compare interfractional organ position variation in children and adults.</p> <p><b>Material and methods:</b> For 35 children and 35 adults treated with thoracic/abdominal irradiation, 850 (range 5–30 per patient) retrospectively collected cone beam CT images were registered to the reference CT that was used for radiation treatment planning purposes. Renal position variation was assessed in three orthogonal directions and summarized as 3D vector lengths. Diaphragmatic position variation was assessed in the cranio-caudal (CC) direction only. We calculated means and SDs to estimate group systematic (Σ) and random errors (σ) of organ position variation. Finally, we investigated possible correlations between organ position variation and patients’ height.</p> <p><b>Results:</b> Interfractional organ position variation was different in children and adults. Median 3D right and left kidney vector lengths were significantly smaller in children than in adults (2.8, 2.9 mm vs. 5.6, 5.2 mm, respectively; <i>p</i> < .05). Generally, the pediatric Σ and σ were significantly smaller than in adults (<i>p</i> < .007). Overall and within both subgroups, organ position variation and patients’ height were only negligibly correlated.</p> <p><b>Conclusions:</b> Interfractional renal and diaphragmatic position variation in children is smaller than in adults indicating that pediatric margins should be defined differently from adult margins. Underlying mechanisms and other components of geometrical uncertainties need further investigation to explain differences and to appropriately define pediatric safety margins.</p

Quantification of renal and diaphragmatic interfractional motion in pediatric image-guided radiation therapy:A multicenter study

Background and purpose: To quantify renal and diaphragmatic interfractional motion in order to estimate systematic and random errors, and to investigate the correlation between interfractional motion and patient-specific factors. Material and methods: We used 527 retrospective abdominal-thoracic cone beam CT scans of 39 childhood cancer patients ( Results: Inter-patient organ motion varied widely, with the largest movements in the CC direction. Values of Sigma in LR, CC, and AP directions were 1.1, 3.8, 2.1 mm for the right, and 1.3, 3.0, 1.5 mm for the left kidney, respectively. The sigma in these three directions was 1.1, 3.1, 1.7 mm for the right, and 1.2, 2.9, 2.1 mm for the left kidney, respectively. For the diaphragm we estimated Sigma = 5.2 mm and sigma = 4.0 mm. No correlations were found between organ motion and height. Conclusions: The large inter-patient organ motion variations and the lack of correlation between motion and patient-related factors, suggest that individualized margin approaches might be required. (C) 2015 Elsevier Ireland Ltd. All rights reserved