a b s t r a c t: Objective: To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI guidance. Material and methods: For 15 patients (18 lesions) receiving fSRS only (fSRSonly) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRSpostop), a treatment planning MRI (MR0) and repeated MRI during treatment (MR1) were acquired. The impact of target volume changes on the target coverage was analyzed by evaluating the planned dose distribution (based on MR0) on the planning target volume (PTV) during treatment as defined on MR1. The predictive value of target volume changes before treatment (using the diagnostic MRI (MRD)) was studied to identify patients that experienced the largest changes during treatment. Results: Target volume changes during fSRS did result in large declines of the PTV dose coverage up to 34.8% (median = 3.2%) for fSRSonly patients. For fSRSpostop the variation and declines were smaller (median PTV dose coverage change = 0.5% (4.5% to 1.9%)). Target volumes changes did also impact the minimum dose in the PTV (fSRSonly; 2.7 Gy (16.5 to 2.3 Gy), fSRSpostop; 0.4 Gy (4.2 to 2.5 Gy)). Changes in target volume before treatment (i.e. seen between the MRD and MR0) predicted which patients experienced the largest dose coverage declines during treatment. Conclusion: Target volume changes in brain metastases during fSRS can result in worsening of the target dose coverage. Patients benefiting the most from a repeated MRI during treatment could be identified before treatment.
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Purpose/Objective: Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy. Material and Methods: For 24 glioblastoma patients a photon- and proton-based dose escalation treatment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribution on this specific high dose region. Results: The median time between the planning MRI and additional MRI was 26 days (range 16–37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3–11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treatment plans, respectively. Conclusion: Our study showed that only for a limited number of patients anatomical changes during photon or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvolume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.
BackgroundPhysical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory.MethodsChemotherapy-exposed breast cancer patients (stage I-III, 2–4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale ‘fatigue’ of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients.ResultsMultiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 – 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = −52.3 mm3, 95 % CI = −100.3 – −4.4)), which was related to improved memory functioning (HVLT-R total recall: B = −0.022, 95 % CI = −0.039 – −0.005; ACS Wordlist Learning: B = −0.039, 95 % CI = −0.062 – −0.015).ConclusionsNo exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.
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In the coming four years, the Hedwige-Prosperpolder in the Schelde estuary will be reopened for nature restoration. This creates opportunities, within a binational Dutch-Belgian consortium, to experiment with the existing dike and to perform targeted dike breach experiments and breach monitoring. We will exploit this opportunity to investigate a newly described, potentially valuable contribution of vegetated foreshores to flood safety: the restriction of dike breach extent, and thus of flooding volume, in the case of failure of the dike. Fostering marsh development in front of realigned dikes could improve safety more than hitherto thought. Not only does it reduce dike failure probabilities, it may also restrict the consequences of failures. Even though this is not the primary goal of the HPP realignment, in this Living Lab we will study how management realignment can be used as a nature-based solution for flood safety. We will model the contribution of vegetated foreshores to breach development, calculate its contribution to reduction of risks, and validate the model using the breach experiment. We will also study the conditions for, and rates of, vegetation and soil strength development in front of realigned dikes. We will explore novel designs and maintenance schemes for realigned dikes connected to a vegetated foreshore. Finally, we will study how people experience physical changes in the landscape in terms of place attachment: will they be reconnected to the changed landscape when properly informed on the new role of this landscape in ecosystem development and safety enhancement? The project consortium is composed of engineers, ecologists and social scientists with a strong track record in multidisciplinary co-operation. It is externally supported by national and regional water authorities, contractors and engineering companies. It is ideally situated to translate new knowledge into operational procedures, and incorporate this into the education of future coastal professionals.
