Background and purpose: To analyse the variability of respiratory motion during image-guided radiotherapy in paediatric cancer patients and to investigate possible relationships thereof with... Show moreBackground and purpose: To analyse the variability of respiratory motion during image-guided radiotherapy in paediatric cancer patients and to investigate possible relationships thereof with patient-specific factors.Material and methods: Respiratory-induced diaphragm motion was retrospectively analysed on 480 cone beam CTs acquired during the treatment course of 45 children (<18 years). The cranial-caudal positions of the top of the right diaphragm in exhale and inhale phases were manually selected in the projection images. The difference in position between both phases defines the amplitude. The cycle time equalled inspiratory plus expiratory time. We analysed the variability of the intra- and interfractional respiratory motion and studied possible correlations between respiratory-induced diaphragm motion and age, height, and weight.Results: Over all patients, mean amplitude and cycle time were 10.7 mm (range 4.1-17.4 mm) and 2.9 s (range 2.1-3.9 s). Intrafractional variability was larger than interfractional variability (2.4 mm vs. 1.4 mm and 0.5 s vs. 0.4 s for amplitude and cycle time, respectively). Correlations between mean amplitude and patient-specific factors were significant but weak (p < 0.05, p <= 0.45).Conclusions: Large ranges of amplitude and cycle time and weak correlations confirm that respiratory motion is patient-specific and requires an individualized approach to account for. Since interfractional variability was small, we suggest that a pre-treatment 4DCT in children could be sufficiently predictive to quantify the respiratory motion. (C) 2017 Elsevier B.V. All rights reserved. Show less
Houweling, A.C.; Crama, K.; Visser, J.; Fukata, K.; Rasch, C.R.N.; Ohno, T.; ... ; Horst, A. van der 2017
Radiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can... Show moreRadiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can greatly affect the robustness of particle therapy. Therefore, we compared the dosimetric impact of interfractional anatomical changes (i.e. body contour differences and gastrointestinal gas volume changes) in photon, proton and carbon ion therapy for pancreatic cancer patients.In this retrospective planning study, photon, proton and carbon ion treatment plans were created for 9 patients. Fraction dose calculations were performed using daily cone-beam CT (CBCT) images. To this end, the planning CT was deformably registered to each CBCT; gastrointestinal gas volumes were delineated on the CBCTs and copied to the deformed CT. Fraction doses were accumulated rigidly. To compare planned and accumulated dose, dose-volume histogram (DVH) parameters of the planned and accumulated dose of the different radiotherapy modalities were determined for the internal gross tumor volume, internal clinical target volume (iCTV) and organs-at-risk (OARs; duodenum, stomach, kidneys, liver and spinal cord).Photon plans were highly robust against interfractional anatomical changes. The difference between the planned and accumulated DVH parameters for the photon plans was less than 0.5% for the target and OARs. In both proton and carbon ion therapy, however, coverage of the iCTV was considerably reduced for the accumulated dose compared with the planned dose. The near-minimum dose (D98%) of the iCTV reduced with 8% for proton therapy and with 10% for carbon ion therapy. The DVH parameters of the OARs differed less than 3% for both particle modalities.Fractionated radiotherapy using photons is highly robust against interfractional anatomical changes. In proton and carbon ion therapy, such changes can severely reduce the dose coverage of the target. Show less
Dijk, I.W.E.M. van; Huijskens, S.C.; Jong, R. de; Visser, J.; Fajardo, R.D.; Rasch, C.R.N.; ... ; Bel, A. 2017
Background: 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... Show moreBackground: 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.Material and methods: 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 (sigma) and random errors (sigma) of organ position variation. Finally, we investigated possible correlations between organ position variation and patients' height.Results: 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, 2.9mm vs. 5.6, 5.2mm, respectively; p<.05). Generally, the pediatric sigma and sigma were significantly smaller than in adults (p<.007). Overall and within both subgroups, organ position variation and patients' height were only negligibly correlated.Conclusions: 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. Show less
Schoot, A.J.A.J. van de; Boer, P. de; Visser, J.; Stalpers, L.J.A.; Rasch, C.R.N.; Bel, A. 2017
Background: Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study... Show moreBackground: Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer.Material and methods: Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D-98%>95%) and in V-0.5Gy, V-1.5Gy, V-2Gy, D-50% and D-2% for rectum, bladder and bowel were assessed.Results: Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p<0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p<0.01) improvements for daily V-0.5Gy, V-1.5Gy, V-2Gy, D-50% and D-2%. However, daily plan selection significantly increased the bladder V-1.5Gy, V-2Gy, D-50% and D-2%.Conclusions: In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT. Show less
The Pareto front reflects the optimal trade-offs between conflicting objectives and can be used to quantify the effect of different beam configurations on plan robustness and dose-volume histogram... Show moreThe Pareto front reflects the optimal trade-offs between conflicting objectives and can be used to quantify the effect of different beam configurations on plan robustness and dose-volume histogram parameters. Therefore, our aim was to develop and implement a method to automatically approach the Pareto front in robust intensity-modulated proton therapy (IMPT) planning. Additionally, clinically relevant Pareto fronts based on different beam configurations will be derived and compared to enable beam configuration selection in cervical cancer proton therapy.A method to iteratively approach the Pareto front by automatically generating robustly optimized IMPT plans was developed. To verify plan quality, IMPT plans were evaluated on robustness by simulating range and position errors and recalculating the dose. For five retrospectively selected cervical cancer patients, this method was applied for IMPT plans with three different beam configurations using two, three and four beams. 3D Pareto fronts were optimized on target coverage (CTV D99%) and OAR doses (rectum V30Gy; bladder V40Gy). Per patient, proportions of non-approved IMPT plans were determined and differences between patient-specific Pareto fronts were quantified in terms of CTV D99%, rectum V30Gy and bladder V40Gy to perform beam configuration selection.Per patient and beam configuration, Pareto fronts were successfully sampled based on 200 IMPT plans of which on average 29% were non-approved plans. In all patients, IMPT plans based on the 2-beam set-up were completely dominated by plans with the 3-beam and 4-beam configuration. Compared to the 3-beam set-up, the 4-beam set-up increased the median CTV D-99% on average by 0.2 Gy and decreased the median rectum V-30Gy and median bladder V-40Gy on average by 3.6% and 1.3%, respectively.This study demonstrates a method to automatically derive Pareto fronts in robust IMPT planning. For all patients, the defined four-beam configuration was found optimal in terms of plan robustness, target coverage and OAR sparing. Show less
Schoot, A.J.A.J. van de; Boer, P. de; Crama, K.F.; Visser, J.; Stalpers, L.J.A.; Rasch, C.R.N.; Bel, A. 2016
Background Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation... Show moreBackground Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation therapy (RT). In this study, the potential dosimetric advantages of IGAPT compared with photon-based image-guided adaptive RT (IGART) were investigated.Material and methods For 13 cervical cancer patients, full and empty bladder planning computed tomography (CT) images and weekly CTs were acquired. Based on both primary clinical target volumes (pCTVs) [i.e. gross tumor volume (GTV), cervix, corpus-uterus and upper part of the vagina] on planning CTs, the pretreatment observed full range primary internal target volume (pITV) was interpolated to derive pITV subranges. Given corresponding ITVs (i.e. pITVs including lymph nodes), patient-specific photon and proton plan libraries were generated. Using all weekly CTs, IGART and IGAPT treatments were simulated by selecting library plans and recalculating the dose. For each recalculated IGART and IGAPT fraction, CTV (i.e. pCTV including lymph nodes) coverage was assessed and differences in fractionated substitutes of dose-volume histogram (DVH) parameters (V-15Gy, V-30Gy, V-45Gy, D-mean, D-2cc) for bladder, bowel and rectum were tested for significance (Wilcoxon signed-rank test). Also, differences in toxicity-related DVH parameters (rectum V-30Gy, bowel V-45Gy) were approximated based on accumulated dose distributions.Results In 92% (96%) of all recalculated IGAPT (IGART) fractions adequate CTV coverage (V-95%>98%) was obtained. All dose parameters for bladder, bowel and rectum, except the fractionated substitute for rectum V-45Gy, were improved using IGAPT. Also, IGAPT reduced the mean dose to bowel, bladder and rectum significantly (p<0.01). In addition, an average decrease of rectum V-30Gy and bowel V-45Gy indicated reductions in toxicity probabilities when using IGAPT.Conclusion This study demonstrates the feasibility of IGAPT in cervical cancer using a plan-library based plan-of-the-day approach. Compared to photon-based IGART, IGAPT maintains target coverage while significant dose reductions for the bladder, bowel and rectum can be achieved. Show less
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... Show moreBackground 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 (<18 years) to quantify renal motion relative to bony anatomy in the left-right (LR), cranio-caudal (CC) and anterior-posterior (AP) directions, and diaphragmatic motion in the CC direction only. Interfractional motion was quantified by distributions of systematic and random errors in each direction (standard deviations Sigma and sigma, respectively). Also, correlation between organ motion and height was analyzed.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. Show less
Recurrent miscarriage affects 1-2% of women. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent... Show moreRecurrent miscarriage affects 1-2% of women. In more than half of all recurrent miscarriage the cause still remains uncertain. Thrombophilia has been identified in about 50% of women with recurrent miscarriage and thromboprophylaxis has been suggested as an option of treatment. A randomised double-blind (for aspirin) multicentre trial was performed among 207 women with three or more consecutive first trimester (< 13 weeks) miscarriages, two or more second trimester (13-24 weeks) miscarriages or one third trimester fetal loss combined with one first trimester miscarriage. Women were analysed for thrombophilia. After complete work-up, women were randomly allocated before seven weeks' gestation to either enoxaparin 40 mg and placebo (n=68), enoxaparin 40 mg and aspirin 100 mg (n=63) or aspirin 100 mg (n=76). The primary outcome was live-birth rate. Secondary outcomes were pregnancy complications, neonatal outcome and adverse effects. The trial was ended prematurely because of slow recruitment. A live birth rate of 71% [relative risk (RR) 1.17, 95% confidence interval (CI) 0.92-1.48] was found for enoxaparin and placebo and 65% [RR 1.08, 95% CI 0.83-1.39] for enoxaparin and aspirin when compared to aspirin alone (61%, reference group). In the whole study group the live birth rate was 65% (95% CI 58.66-71.74) for women with three or more miscarriages (n=204). No difference in pregnancy complications, neonatal outcome or adverse effects was observed. No significant difference in live birth rate was found with enoxaparin treatment versus aspirin or a combination of both versus aspirin in women with recurrent miscarriage. Show less
