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Cardiology and Radiation Oncology working together—a new ‘STAR’ on the horizon? Until recently, most cardiologists associated radiation exposure to the heart with potential adverse effects, such as pericarditis, late coronary artery disease or potential damage to cardiac implantable devices. The landmark publication of 2017 reporting a case series of just five patients with recurrent ventricular tachycardia (VT) treated with stereotactic arrhythmia radioablation (STAR) changed this perception and introduced a new area for both cardiac electrophysiology and radiation oncology.

Purpose: To quantify neuroanatomical changes using magnetic resonance imaging (MRI) in patients with cerebral metastasized breast cancer after brain radiotherapy (RT). Methods: Fifteen patients with breast cancer with brain metastases who underwent whole brain RT (WBR), radiosurgery (RS), and/or hypofractionated stereotactic treatment (STX) were examined at four time points (TPs). A total of 48 MRIs were available: prior to RT (TP1), 5–8 months after RT (TP2), 9–11 months after RT (TP3), and >20 months after RT (TP4). Using automatic segmentation, 25 subcortical structures were analyzed. Patients were split into three groups: STX (receiving STX and RS), RS (receiving RS only), and WBR (receiving WBR at least once). After testing for a normal distribution for all values using the Kolmogorov-Smirnov test, a two-sided paired t test was used to analyze volumetric changes. For those values that were not normally distributed, the nonparametric Mann-Whitney test was employed. Results: The left cerebellum white matter ( p = 0.028), the right pallidum ( p = 0.038), and the left thalamus ( p = 0.039) significantly increased at TP2 compared to TP1. The third ventricle increased at all TPs ( p = 0.034–0.046). The left choroid plexus increased at TP3 ( p = 0.037) compared to TP1. The left lateral ventricle increased at TP3 ( p = 0.012) and TP4 ( p = 0.027). Total gray matter showed a trend of volume decline in STX and WBR groups. Conclusions: These findings indicate that alterations in the volume of subcortical structures may act as a sensitive parameter when evaluating neuroanatomical changes and brain atrophy due to radiotherapy. Differences observed for patients who received STX and WBR, but not those treated with RS, need to be validated further.

Purpose Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial. Methods and Materials For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined. Results VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference. Conclusions Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.

Purpose To evaluate the impact of the distance between treatment isocenter and brain metastases on local failure in patients treated with a frameless linear-accelerator-based single-isocenter volumetric modulated arc (VMAT) SRS/SRT for multiple brain metastases. Methods and materials Patients treated with SRT for brain metastases (BM) between April 2014 and May 2019 were included in this retrospective study. BM treated with a single-isocenter multiple-target (SIMT) SRT were evaluated for local recurrence-free intervals in dependency to their distance to the treatment isocenter. A Cox-regression model was used to investigate different predictor variables for local failure. Results were compared to patients treated with a single-isocenter-single-target (SIST) approach. Results In total 315 patients with a cumulative number of 1087 BM were analyzed in this study of which 140 patients and 708 BM were treated with SIMT SRS/SRT. Median follow-up after treatment was 13.9 months for SIMT approach and 11.9 months for SIST approach. One-year freedom from local recurrence was 87% and 94% in the SIST and SIMT group, respectively. Median distance to isocenter (DTI) was 4.7 cm (range 0.2–10.5) in the SIMT group. Local recurrence-free interval was not associated with the distance to the isocenter in univariable or multivariable Cox-regression analysis. Multivariable analysis revealed only volume as an independent significant predictor for local failure (p-value Conclusion SRS/SRT using single-isocenter VMAT for multiple targets achieved high local metastases control rates irrespective of distance to the isocenter, supporting efficacy of single-isocenter stereotactic radiation therapy for multiple brain metastases.

Purpose The treatment of brain metastases (BM) has changed considerably in recent years and in particular, the management of multiple BM is currently undergoing a paradigm shift and treatment may differ from current guidelines. This survey was designed to analyze the patterns of care in the management of multiple BM. Methods An online survey consisting of 36 questions was distributed to the members of the German Society for Radiation Oncology (DEGRO). Results In total, 193 physicians out of 111 institutions within the German Society for Radiation oncology responded to the survey. Prognostic scores for decision making were not used regularly. Whole brain radiotherapy approaches (WBRT) are the preferred treatment option for patients with multiple BM, although stereotactic radiotherapy treatments are chosen by one third depending on prognostic scores and overall number of BM. Routine hippocampal avoidance (HA) in WBRT is only used by a minority. In multiple BM of driver-mutated non-small cell lung cancer origin up to 30% favor sole TKI therapy as upfront treatment and would defer upfront radiotherapy. Conclusion In multiple BM WBRT without hippocampal avoidance is still the preferred treatment modality of choice regardless of GPA and mutational status, while SRT is only used in patients with good prognosis. Evidence for both, SRS and hippocampal avoidance radiotherapy, is growing albeit the debate over the appropriate treatment in multiple BM is yet not fully clarified. Further prospective assessment of BM management—ideally as randomized trials—is required to align evolving concepts with the proper evidence and to update current guidelines.

To explore the prognostic value of the oligometastatic disease (OMD) states as proposed by the European Society for Radiotherapy and Oncology (ESTRO) European Organisation for Research and Treatment of Cancer (EORTC) classification system.This retrospective single-institution study included patients with 1-5 extracranial metastases from any solid malignancy treated with SBRT to all metastases. OMD states were defined according to the ESTRO EORTC classification. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Discriminatory strength of the classification was assessed by GönenHeller's concordance probability estimate (CPE). Univariable and multivariable Cox regression models were used to assess predictors of OS and PFS.In total, 385 patients were included. The median follow-up was 24.1 months. The most frequent OMD states were metachronous oligorecurrence (23.6%) and induced oligoprogression (18.7%). Induced OMD patients had significantly shorter median OS (28.1 months) compared with de-novo (46.3 months, p = 0.002) and repeat OMD (50.3 months, p = 0.002). Median PFS in de-novo OMD patients (8.8 months) was significantly longer than in repeat (5.4 months, p = 0.002) and induced OMD patients (4.3 months, p 0.001). The classification system had moderate discriminatory strength for OS and PFS. Multivariable analyses confirmed that compared with induced OMD, de-novo OMD was associated with longer PFS and repeat with longer OS.All patients were successfully categorized according to the ESTRO EORTC classification system. The discriminatory strength of the classification was confirmed for OMD patients treated with metastases-directed SBRT. Larger multicenter trials are needed to validate the prognostic power for OMD patients irrespective of primary tumor and treatment approach.

Background and purpose Several studies have suggested stereotactic arrhythmia radioablation (STAR) as a treatment option for patients suffering from therapy-refractory ventricular tachycardia or fibrillation (VT/VF). Material and methods We performed a systematic review of human reports of STAR for structural VT/VF to assess its effectivity and safety. All identified publications were assessed for inclusion. This study adheres to the PRISMA guidelines and was registered on PROSPERO (CRD42020183044). Results Thirteen studies were included resulting in a population of 57 patients. Median age was 64 (range 34–83), 31 patients (54%) had ischemic cardiomyopathy and 50 patients (88%) had prior catheter ablation (CA) for VT/VF. A mean planned target volume of 64.4 cc (range 3.5–238) with a mean safety margin of 3.3 mm (0–5) was treated with 25 Gy. Immediately following STAR, four patients (7%) experienced an electrical storm. During a mean follow-up duration of 410 days, all patients suffering from sustained VT/VF prior to STAR (n = 55) had a reduction of their sustained VT/VF-burden after STAR, but recurrence occurred in 41 patients (75%) during follow-up. Forty-six patients (81%) had an adverse effect from therapy, but no treatment-related death occurred. Evidence of scar-formation after STAR either by imaging, invasive mapping or histopathology was found in six of nine examined patients (67%). Conclusion From the still very limited experience, STAR appears effective and safe in patients with structural heart disease and therapy-refractory sustained VT/VF. It is associated with a significant short-term reduction of sustained VT/VF-burden, but recurrences are common.

Background and purpose: A single-isocenter stereotactic body radiotherapy (SBRT) approach for multiple lung metastases has the potential to lower cumulative patient dose and reduce overall treatment time. However, the magnitude of inter-lesion position variation is currently unknown and not incorporated in margin calculations. The aim of this study was to quantify inter-lesion position variation and calculate safety margins for single-isocenter lung SBRT. Materials and methods: A total of 83 pairs of pulmonary metastases from 42 NSCLC patients were used to calculate relative inter-lesion position variation by lesion-based registration of planning CT and verification CBCT. Furthermore, β-value assessment of van Herk's margin formula was performed by evaluating the distance between planned and blurred dose profiles of simulated spherical lesions, to evaluate its validity for heterogeneously planned dose distributions. Population-based ITV to PTV margins were calculated using the entire dataset and using subgroups with significant differences in relative inter-lesion position variation. Results: The mean ± SD inter-lesion position variation was 1.2 ± 1.1 mm as 3D-vector. Inter-lesion position variation was significantly increased if ≥1 lesion was not attached to the pleura or lesions were distant. The simulation showed that the combined SD of the random errors contributed to the margin only in the SI direction with 0.25∙σtot for a 65% dose prescription. When incorporating inter-lesion position variation, the safety margins increased from 5.6, 5.8, 5.2 mm (AP, SI, LR) to 6.0, 6.6, 5.5 mm for the entire cohort. Conclusion: Relative inter-lesion position variation is influenced by inter-target distance and location and can be compensated with additional safety margins of

Purpose Neurocognitive changes are well described after prophylactic or therapeutic whole-brain radiotherapy (WBRT) and have been reported as early as 3 months after radiotherapy (RT). Therefore, WBRT with protection of the hippocampal region (hippocampal avoidance, HA) has been proposed to preserve neurocognition. Our aim was to compare the risk of leukoencephalopathy after prophylactic cranial irradiation (PCI) with or without HA. Methods Patients with small-cell lung cancer who received either lateral-opposed field PCI (non–HA-PCI; n = 9) or hippocampus avoidance PCI (HA-PCI; n = 9) with available magnetic resonance imaging (MRI) follow-up were identified and age matched. Pre-therapeutic and follow-up MRI after RT was analysed for leukoencephalopathy based on the Fazekas score. Bilateral cortical and subcortical brain structures were segmented and analysed for alterations in dosimetric parameters and volumes. Results There was no significant difference of Fazekas scores between groups at baseline. Fazekas score differed in post-treatment with a median of 1 in the HA-PCI group and 2 in the non–HA-PCI group (p = 0.007). Significant increase of Fazekas score over time after RT was observed for HA-PCI patients (p = 0.001) but not for non–HA-PCI patients. Dmax (highest radiation dose) and brain volume receiving doses >25Gy were higher in HA-PCI patients. There were no significant volumetric differences for segmented brain structures between groups. Conclusion Radiological changes are more prominent after HA-PCI than after non–HA-PCI. Although no standardised neurocognitive testing was performed, the significantly increased Fazekas scores after HA-PCI are expected to interfere with neurocognitive function. Prospective long-term neurocognitive studies are warranted before HA-PCI is implemented in routine clinical practice.

Background Main purpose was to describe procedures and identify challenges in the implementation process of adaptive and non-adaptive MR-guided radiotherapy (MRgRT), especially new risks in workflow due to the new technique. We herein report the single center experience for the implementation of (MRgRT) and present an overview on our treatment practice. Methods Descriptive statistics were used to summarize clinical and technical characteristics of treatment and patient characteristics including sites treated between April 2019 and end of March 2020 after ethical approval. A risk analysis was performed to identify risks of the online adaptive workflow. Results A summary of the processes on the MR-Linac including workflows, quality assurance and possible pitfalls is presented. 111 patients with 124 courses were treated during the first year of MR-guided radiotherapy. The most commonly treated site was the abdomen (42% of all treatment courses). 73% of the courses were daily online adapted and a high number of treatment courses (75%) were treated with stereotactic body irradiation. Only 4/382 fractions could not be treated due to a failing online adaptive quality assurance. In the risk analysis for errors, the two risks with the highest risk priority number were both in the contouring category, making it the most critical step in the workflow. Conclusion Although challenging, establishment of MRgRT as a routinely used technique at our department was successful for all sites and daily o-ART was feasible from the first day on. However, ongoing research and reports will have to inform us on the optimal indications for MRgRT because careful patient selection is necessary as it continues to be a time-consuming treatment technique with restricted availability. After risk analysis, the most critical workflow category was the contouring process, which resembles the need of experienced staff and safety check paths.

Purpose To assess the effects of daily adaptive MR-guided replanning in stereotactic body radiation therapy (SBRT) of liver metastases based on a patient individual longitudinal dosimetric analysis. Methods Fifteen patients assigned to SBRT for oligometastatic liver metastases underwent daily MR-guided target localization and on-table treatment plan re-optimization. Gross tumor volume (GTV) and organs at risk (OARs) were adapted to the anatomy-of-the-day. A reoptimized plan (RP) and a rigidly shifted baseline plan (sBP) without re-optimization were generated for each fraction. After extraction of DVH parameters for GTV, planning target volume (PTV), and OARs (stomach, duodenum, bowel, liver, heart) plans were compared on a per-patient basis. Results Median pre-treatment GTV and PTV were 14.9 cc (interquartile range (IQR): 7.7–32.9) and 62.7 cc (IQR: 42.4–105.5) respectively. SBRT with RP improved PTV coverage (V100%) for 47/75 of the fractions and reduced doses to the most proximal OARs (D1cc, Dmean) in 33/75 fractions compared to sBP. RP significantly improved PTV coverage (V100%) for metastases within close proximity to an OAR by 4.0% (≤ 0.2 cm distance from the edge of the PTV to the edge of the OAR; n = 7; p = 0.01), but only by 0.2% for metastases farther away from OAR (> 2 cm distance; n = 7; p = 0.37). No acute grade 3 treatment-related toxicities were observed. Conclusions MR-guided online replanning SBRT improved target coverage and OAR sparing for liver metastases with a distance from the edge of the PTV to the nearest luminal OAR

Background MR-guided online adaptive stereotactic body radiation therapy (SBRT) for prostate cancer aims to reduce toxicity by full compensation of interfractional uncertainties. However, the process of online adaptation currently takes approximately 45 min during which intrafractional movements remain unaccounted for. This study aims to analyze the dosimetric benefit of online adaptation and to evaluate its robustness over the duration of one treatment fraction. Methods Baseline MR-scans at a MR-linear accelerator were acquired for ten healthy male volunteers for generation of mock-prostate SBRT plans with a dose prescription of 5 × 7.25 Gy. On a separate day, online MR-guided adaptation (ViewRay® MRIdian) was performed, and thereafter MR images were acquired every 15 min for 1 h to assess the stability of the adapted plan. Results A dosimetric benefit of online MR-guided adaptive re-planning was observed in 90% of volunteers. The median D95CTV- and D95PTV-coverage was improved from 34.8 to 35.5 Gy and from 30.7 to 34.6 Gy, respectively. Improved target coverage was not associated with higher dose to the organs at risk, most importantly the rectum (median D1ccrectum baseline plan vs. adapted plan 33.3 Gy vs. 32.3 Gy). The benefit of online adaptation remained stable over 45 min for all volunteers. However, at 60 min, CTV-coverage was below a threshold of 32.5 Gy in 30% of volunteers (30.6 Gy, 32.0 Gy, 32.3 Gy). Conclusion The dosimetric benefit of MR-guided online adaptation for prostate SBRT was robust over 45 min in all volunteers. However, intrafractional uncertainties became dosimetrically relevant at 60 min and we therefore recommend verification imaging before delivery of MR-guided online adapted SBRT.

Worldwide, more than 22 million children and adolescents are exposed to repetitive head impacts (RHI) in soccer. Evidence indicates cumulative effects on brain structure, but it is not known whether exposure to RHI affects cognitive improvement in adolescents. The aim of the study was to determine whether exposure to RHI while heading the ball in soccer affects improvement in cognitive performance in adolescents over time. The study group consisted of a convenience sample of 16 male soccer players (mean age 15.7 ± 0.7 years). A comparison cohort of 14 male non-contact sports athletes (mean age 14.9 ± 1.1 years) was recruited from competitive athletic clubs and group-matched in age. Using the ProPoint and AntiPoint tasks, sensorimotor and cognitive functions were measured over both immediate (pre- vs. post-training) as well as across multiple time points within a play season. The number and type of head impacts that occurred during the training were counted. The main outcome measure was the change in response time (RT) in the ProPoint and AntiPoint tasks. The immediate (pre- vs. post-training) and longer-term (across a play season) change in RT was analyzed, and the effect of the number and type of head impacts was tested. Thirty athletes with and without exposure to RHI demonstrated a decrease in RT in both tasks immediately after training. Over the play season, both groups showed improvement in sensorimotor function. While the control group also improved in cognitive performance, the soccer players did not, however. Further, the more long headers performed, the slower the improvement in RT over the season. Youth athletes experience an immediate cognitive improvement after training most likely because of physical exercise. Results of this study also suggest an association between exposure to specific RHI (long headers) and lack of improvement in cognitive performance in youth athletes over time.

BACKGROUND: While some medical associations provide guidelines for the implant-prosthetic rehabilitation of head and neck cancer patients, the circulation and implementation in the everyday routine of practicing dentists remain unknown. PURPOSE: To analyze patterns of care for the prosthetic rehabilitation of head and neck cancer patients after radiotherapy in German speaking countries. MATERIALS AND METHODS: An online survey consisting of 34 questions separated into three sections, (a) general inquiries, (b) treatment concepts, and (c) patient cases, was forwarded to university hospital departments for Prosthetic Dentistry and Oral and Maxillofacial Surgery, and members of different medical associations. Statistical differences between groups were analyzed using chi-squared test (P

Background Radiotherapy treatment of head and neck cancer affects local arteries and increases the risk of stroke. This study aimed at a closer characterization of this damage and its development in time with a longitudinal study set up. Methods Male patients treated between 2011 and 2016 for hypopharyngeal carcinoma were identified from the in-house clinical data base. They were included into the study if besides the planning CT at least one additional CT image was available from follow-up (13 patients) or at least two MRI scans (16 patients of which 2 were already included). All patients received radiotherapy, and chemotherapy was administered to 16 patients. The time from the beginning of radiotherapy to the last available image ranged from 2 months to 4.5 years. For six segments of the carotid arteries, the number and volume of atherosclerotic plaques were determined from the CT scans, and the intima media thickness from the MRI scans. Information on comorbid cardiovascular disease, hypertension and diabetes mellitus was retrieved from medical records. Results Total plaque volume rose from 0.25 cm3 before to 0.33 cm3 after therapy but this was not significant (p = 0.26). The mean number of plaques increased from 5.7 to 8.1 (p = 0.002), and the intima media thickened from 1.17 mm to 1.35 mm (p = 0.002). However, the mean intima media thickness practically did not change in patients with comorbid diabetes mellitus (p-value for homogeneity: 0.03). For patients without diabetes mellitus, dynamics of both plaque number and intima media thickness, was consistent with an increase until about one year after therapy and no further progression thereafter. Conclusion Our study confirmed the thickening of artery walls and the increase in the number of plaques. Results imply that definitive radiation damage to the artery walls can be determined not earlier than about one year after radiotherapy and there is no substantial deterioration thereafter. Reasons for the absence of an observable intima media thickening in patients with diabetes are unclear.

Background The cranial border of the target volume (TV) in rectal cancer patients treated with neoadjuvant chemoradiation (nCRT) is mostly defined at the level of L5/S1. However, current studies have shown that relapse cranially of the target volume after neoadjuvant nCRT and surgery is very rare. A reduction of cranial TV margins could be reasonable to reduce toxicity to the organs at risk (OAR). In this study we compared the dose distribution to the OAR for different cranial longitudinal margins using a dose-volume histogram (DVH) analysis. Methods Ten patients with loco regional advanced rectal cancer were analysed retrospectively. All patients were planned for Volumetric Arc Therapy Radiation Therapy (VMAT). Next to the original PTV (PTV0), three new planning target volumes (PTV) were defined for each patient: The PTV0 reduced by 1 cm, 2 cm and 3 cm on cranial extension. For each PTV a treatment plan with a total dose of 50.4 Gy with daily doses of 1.8 Gy was calculated. Dose to the OAR were evaluated and compared. Results For the bone marrow, the small bowel and the peritoneal space all clinically relevant relative dose parameters (V10-V50) as well as the Dmedian could be significantly reduced with every cranial target volume reduction of 1 cm. For V10 of the peritoneal space the dose could be nearly halved with a 3 cm shortened TV. After TV reduction of 3 cm also for the urinary bladder a significant dose reduction of the Dmedian could be achieved. Conclusions Considering the very low recurrence rates in the TME and IMRT era, the distribution patterns of these relapses as well as the relevant side effects of nCRT, we would agree with existing recommendations of reduction of the cranial target volume in nCRT treated rectal cancer patients.

Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

INTRODUCTION The ano-inguinal lymphatic drainage (AILD) is located in the subcutaneous adipose tissue of the proximal medial thigh. Findings from fluorescence methods give us new information about anatomical conditions of the AILD. Current contouring guidelines do not advise the inclusion of the 'true' AILD into the clinical target volume (CTV). Aim of this work was the retrospective analysis of the incidental dose to the AILD in an anal cancer (AC) patient cohort who underwent definitive chemoradiation (CRT) therapy with Volumetric Arc Therapy - Intensity Modulated Radiation Therapy (VMAT-IMRT). METHODS VMAT-IMRT plans of 15 AC patients were analyzed. Based on findings from new fluorescence methods we created a new volume, the expected AILD. The examined dosimetric parameters were the minimal, maximal and mean dose and V10-V50 that were delivered to the AILD, respectively. RESULTS The median volume of AILD was 1047 cm³. Mean Dmin, Dmax and Dmean were 7.5 Gy, 58.9 Gy and 40.8 Gy for AILD. The clinical relevant dose of 30.0 Gray covered in mean 76% of the volume of the AILD, respectively. CONCLUSIONS Only 76% of the AILD-volume received at least an expected required treatment dose of 30 Gy incidentally. Concerning the low number of loco-regional relapses in AC patients after definitive CRT one has to balance increased side effects against a rigid oncological-anatomical interpretation of the local lymphatic drainage by including the AILD into the standard CTV.

The aim of this study was to evaluate longitudinal changes in the diffusion characteristics of brain white matter (WM) in collegiate athletes at three time points: prior to the start of the football season (T1), after one season of football (T2), followed by six months of no-contact rest (T3). Fifteen male collegiate football players and 5 male non-athlete student controls underwent diffusion MR imaging and computerized cognitive testing at all three timepoints. Whole-brain tract-based spatial statistics (TBSS) were used to compare fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and trace between all timepoints. Average diffusion values were obtained from statistically significant clusters for each individual. No athlete suffered a concussion during the study period. After one season of play (T1 to T2), we observed a significant increase in trace in a cluster located in the brainstem and left temporal lobe, and a significant increase in FA in the left parietal lobe. After six months of no-contact rest (T2 to T3), there was a significant decrease in trace and FA in clusters that were partially overlapping or in close proximity with the initial clusters (T1 to T2), with no significant changes from T1 to T3. Repetitive head impacts (RHI) sustained during a single football season may result in alterations of the brain’s WM in collegiate football players. These changes appear to return to baseline after 6 months of no-contact rest, suggesting remission of WM alterations. Our preliminary results suggest that collegiate football players might benefit from periods without exposure to RHI.

Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2To investigate the role of CCR2Pulmonary CCR2Frequencies of CCR2Pulmonary CCR2

Soccer is played by more than 250 million people worldwide. Repeatedly heading the ball may place soccer players at high risk for repetitive subconcussive head impacts (RSHI). This study evaluates the long-term effects of RSHI on neurochemistry in athletes without a history of clinically diagnosed concussion, but with a high exposure to RSHI. Eleven former professional soccer players (mean age 52.0±6.8 years) and a comparison cohort of 14 age- and gender-matched, former non-contact sport athletes (mean age 46.9±7.9 years) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation. In the soccer players a significant increase was observed in both choline (Cho), a membrane marker, and myo-inositol (ml), a marker of glial activation, compared with control athletes. Additionally, ml and glutathione (GSH) were significantly correlated with lifetime estimate of RSHI within the soccer group. There was no significant difference in neurocognitive tests between groups. Results of this study suggest an association between RSHI in soccer players and MRS markers of neuroinflammation, suggesting that even subconcussive head impacts affect the neurochemistry of the brain and may precede neurocognitive changes. Future studies will need to determine the role of neuroinflammation in RSHI and the effect on neurocognitive function.

Current research on concussion is primarily focused on injury identification and treatment. Prevention initiatives are, however, important for reducing the incidence of brain injury. This report examines the development and implementation of an interactive electronic teaching program (an e-module) that is designed specifically for concussion education within an adolescent population. This learning tool and the accompanying consolidation rubric demonstrate that significant engagement occurs in addition to the knowledge gained among participants when it is used in a school curriculum setting.

Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere.We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis.Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD).DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume.The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers.

Object Concussion is a common injury in ice hockey and a health problem for the general population. Traumatic axonal injury has been associated with concussions (also referred to as mild traumatic brain injuries), yet the pathological course that leads from injury to recovery or to long-term sequelae is still not known. This study investigated the longitudinal course of concussion by comparing diffusion MRI (dMRI) scans of the brains of ice hockey players before and after a concussion. Methods The 2011–2012 Hockey Concussion Education Project followed 45 university-level ice hockey players (both male and female) during a single Canadian Interuniversity Sports season. Of these, 38 players had usable dMRI scans obtained in the preseason. During the season, 11 players suffered a concussion, and 7 of these 11 players had usable dMRI scans that were taken within 72 hours of injury. To analyze the data, the authors performed free-water imaging, which reflects an increase in specificity over other dMRI analysis methods by identifying alterations that occur in the extracellular space compared with those that occur in proximity to cellular tissue in the white matter. They used an individualized approach to identify alterations that are spatially heterogeneous, as is expected in concussions. Results Paired comparison of the concussed players before and after injury revealed a statistically significant (p < 0.05) common pattern of reduced free-water volume and reduced axial diffusivity and fractional anisotropy following elimination of freewater. These free-water–corrected measures are less affected by partial volumes containing extracellular water and are therefore more specific to processes that occur within the brain tissue. Fractional anisotropy was significantly increased, but this change was no longer significant following the free-water elimination. Conclusions Concussion during ice hockey games results in microstructural alterations that are detectable using dMRI. The alterations that the authors found suggest decreased extracellular space and decreased diffusivities in white matter tissue. This finding might be explained by axonal injury and/or by increased cellularity of glia cells. Even though these findings in and of themselves cannot determine whether the observed microstructural alterations are related to long-term pathology or persistent symptoms, they are important nonetheless because they establish a clearer picture of how the brain responds to concussion.

Object The aim of this study was to examine the brain's white matter microstructure by using MR diffusion tensor imaging (DTI) in ice hockey players with a history of clinically symptomatic concussion compared with players without a history of concussion. Methods Sixteen players with a history of concussion (concussed group; mean age 21.7 ± 1.5 years; 6 female) and 18 players without a history of concussion (nonconcussed group; mean age 21.3 ± 1.8 years, 10 female) underwent 3-T DTI at the end of the 2011–2012 Canadian Interuniversity Sports ice hockey season. Tract-based spatial statistics (TBSS) was used to test for group differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and the measure “trace,” or mean diffusivity. Cognitive evaluation was performed using the Immediate Postconcussion Assessment and Cognitive Test (ImPACT) and the Sport Concussion Assessment Tool–2 (SCAT2). Results TBSS revealed a significant increase in FA and AD, and a significant decrease in RD and trace in several brain regions in the concussed group, compared with the nonconcussed group (p < 0.05). The regions with increased FA and decreased RD and trace included the right posterior limb of the internal capsule, the right corona radiata, and the right temporal lobe. Increased AD was observed in a small area in the left corona radiata. The DTI measures correlated with neither the ImPACT nor the SCAT2 scores. Conclusions The results of the current study indicate that a history of concussion may result in alterations of the brain's white matter microstructure in ice hockey players. Increased FA based on decreased RD may reflect neuroinflammatory or neuroplastic processes of the brain responding to brain trauma. Future studies are needed that include a longitudinal analysis of the brain's structure and function following a concussion to elucidate further the complex time course of DTI changes and their clinical meaning.