Colophonium-related Allergic Contact Dermatitis Caused by Medical Adhesive Tape Used to Prevent Skin Lesions in Soldiers.

Medical adhesive tapes are commonly recommended for the prevention of friction blisters during hiking and military marches. The aim of this paper is to report on the results of investigations into an outbreak of tape-related foot dermatitis in 26 military conscripts following continuous use of medical adhesive tapes for several days during a field exercise. Patch tests were performed using baseline series and aimed testing was performed with colophonium-related substances and different medical adhesive tapes. Contact allergy to the adhesive tapes used was found in 20 (77%) subjects, and contact allergy to colophonium in 16 (61%). Chemical analysis detected colophonium-related substances in the culprit tapes. Compared with consecutive dermatitis patients investigated at our Department of Occupational and Environmental Dermatology in the previous 10 years, conscripts with colophonium allergy had increased odds ratios for concomitant contact allergy to phenol formaldehyde resins and fragrance substances including hydroperoxides of limonene and linalool. The results show that prolonged use of medical adhesive tapes on intact skin carries a high risk for allergic contact dermatitis. Prior to their introduction on the market, medical devices should be assessed for possible side-effects.

Developing and designing an internet-based support and education program for patients awaiting kidney transplantation with deceased donors through: a Delphi study.

AIMS: The aim of this study was to develop and refine the content and design of an internet-based support and education program for patients awaiting kidney transplantation from deceased donors. DESIGN: A Delphi process was used. METHODS: A prototype internet-based intervention was drafted, based on previous research. The intervention included educational and psychological support to manage the uncertain waiting time and specific education enabling preparation for transplantation and adjustment to life after transplantation. In a two-round Delphi process, patients who had received a kidney transplant from a deceased donor within the last 2 years (n = 27), significant others (n = 6), health-care personnel with renal (n = 20) or transplant (n = 14) expertise, rated importance of content and design aspects of the prototype intervention on a 5-point scale using web questionnaires. A median of ≥ 3 was considered as consensus. Quantitative data was analyzed using descriptive statistics. Free text answers were encouraged and analyzed using deductive content analysis. The STROBE-checklist was used. RESULTS: Consensus was reached for all suggested content and design items in round 1, with median ratings of 4 or 5. Qualitative analysis from round 1 suggested four new content and design items which were rated in round 2, on all which consensus was reached; information about life with young children as relatives, expansion of kidney transplantation specific information, program extension by one week and individualization by making information available based on individual needs. CONCLUSION: There was consensus among heterogenous experts regarding suggested educational and psychological support content and design aspects, and additional content and design aspects were identified for an internet-based support and education program for patients awaiting kidney transplantation from deceased donors.

Waiting for kidney transplantation from deceased donors: Experiences and support needs during the waiting time -A qualitative study.

OBJECTIVES: The study aimed to explore and describe patients' experiences of the transplantation process and the support they had received during the waiting time. METHOD: Semi-structured interviews were conducted with 14 patients currently waiting for kidney transplantation from deceased donors (n = 7) or recently having received kidney transplantation (n = 7). Interviews were transcribed, anonymized and analysed inductively using thematic analysis. RESULTS: Two themes and seven sub-themes were identified. The first theme, "Swaying between hope and despair" describes patients' perceptions of waiting for transplantation as a struggle, their expectations for life after the upcoming transplantation and experienced disappointments. The second theme, "Making your way through the waiting time", describes support, strategies and behaviours used to manage the waiting time. CONCLUSION: Patients described life while waiting for kidney transplantation as challenging, involving unexpected events, not understanding the transplantation process and having unrealistic expectations on life after transplantation. They also described support, strategies and behaviours used, some of which led to unwanted consequences. PRACTICE IMPLICATIONS: Patients waiting for kidney transplantation from deceased donors need continuous and easily available education, practical and emotional support to manage the waiting time. Transplantation specific education is also needed to facilitate preparation for transplantation and adjustment to life after transplantation.

Magnetic resonance imaging detected radiation-induced changes in patients with proton radiation-treated arteriovenous malformations.

BACKGROUND: Treatment of intracranial arteriovenous malformations (AVMs) includes surgery, radiation therapy, endovascular occlusion, or a combination. Proton radiation therapy enables very focused radiation, minimizing dose to the surrounding brain. PURPOSE: To evaluate the presence of radiation-induced changes on post-treatment MRI in patients with AVMs treated with proton radiation and to compare these with development of symptoms and nidus obliteration. MATERIAL AND METHODS: Retrospective review of pre- and post-treatment digital subtraction angiography and MRI and medical records in 30 patients with AVMs treated with proton radiation. Patients were treated with two or five fractions; total radiation dose was 20-35 physical Gy. Vasogenic edema (minimal, perinidal, or severe), contrast enhancement (minimal or annular), cavitation and nidus obliteration (total, partial, or none) were assessed. RESULTS: 26 of 30 patients (87%) developed MRI changes. Vasogenic edema was seen in 25 of 30 (83%), abnormal contrast enhancement in 18 of 26 (69%) and cavitation in 5 of 30 (17%). Time from treatment to appearance of MRI changes varied between 5 and 25 months (median 7, mean 10). Seven patients developed new or deteriorating symptoms that required treatment with corticosteroids; all these patients had extensive MRI changes (severe vasogenic edema and annular contrast enhancement). Not all patients with extensive MRI changes developed symptoms. We found no relation between MRI changes and nidus obliteration. CONCLUSION: Radiation-induced MRI changes are seen in a majority of patients after proton radiation treatment of AVMs. Extensive MRI changes are associated with new or deteriorating symptoms.

Evaluation of four surface surrogates for modeling lung tumor positions over several fractions in radiotherapy.

Patient breathing during lung cancer radiotherapy reduces the ability to keep a sharp dose gradient between tumor and normal tissues. To mitigate detrimental effects, accurate information about the tumor position is required. In this work, we evaluate the errors in modeled tumor positions over several fractions of a simple tumor motion model driven by a surface surrogate measure and its time derivative. The model is tested with respect to four different surface surrogates and a varying number of surrogate and image acquisitions used for model training. Fourteen patients were imaged 100 times with cine CT, at three sessions mimicking a planning session followed by two treatment fractions. Patient body contours were concurrently detected by a body surface laser scanning system BSLS from which four surface surrogates were extracted; thoracic point TP, abdominal point AP, the radial distance mean RDM, and a surface derived volume SDV. The motion model was trained on session 1 and evaluated on sessions 2 and 3 by comparing modeled tumor positions with measured positions from the cine images. The number of concurrent surrogate and image acquisitions used in the training set was varied, and its impact on the final result was evaluated. The use of AP as a surface surrogate yielded the smallest error in modeled tumor positions. The mean deviation between modeled and measured tumor positions was 1.9 mm. The corresponding deviations for using the other surrogates were 2.0 mm (RDM), 2.8 mm (SDV), and 3.0 mm (TP). To produce a motion model that accurately models the tumor position over several fractions requires at least 10 simultaneous surrogate and image acquisitions over 1-2 minutes.

Evaluation of irregular breathing effects on internal target volume definition for lung cancer radiotherapy.

PURPOSE: Irregular breathing may compromise the treated volume for free-breathing lung cancer patients during radiotherapy. We try to find a measure based on a breathing amplitude surrogate that can be used to select the patients who need further investigation of tumor motion to ensure that the internal target volume (ITV) provides reliant coverage of the tumor. MATERIAL AND METHODS: Fourteen patients were scanned with four-dimensional computed tomography (4DCT) during free-breathing. The breathing motion was detected by a pneumatic bellows device used as a breathing amplitude surrogate. In addition to the 4DCT, a breath-hold (BH) scan and three cine CT imaging sessions were acquired. The cine images were taken at randomized intervals at a rate of 12 per minute for 8 minutes to allow tumor motion determination during a typical hypo-fractionated treatment scenario. A clinical target volume (CTV) was segmented in the BH CT and propagated over all cine images and 4DCT bins. The center-of-volume of the translated CTV (CTVCOV ) in the ten 4DCT bins were interconnected to define the 4DCT determined tumor trajectory (4DCT-TT). The volume of CTV inside ITV for all cine CTs was calculated and reported at the 10th percentile (VCTV10% ). The deviations between CTVCOV in the cine CTs and the 4DCT-TT were calculated and reported at its 90th percentile (d90% ). The standard deviation of the bellows amplitude peaks (SDP) and the ratio between large and normal inspirations, κrel , were tested as surrogates for VCTV10% and d90% . RESULTS: The values of d90% ranged from 0.6 to 5.2 mm with a mean of 2.2 mm. The values of VCTV10% ranged from 59-93% with a mean of 78 %. The SDP had a moderate correlation (r = 0.87) to d90% . Less correlation was seen between SDP and VCTV10% (r = 0.77), κrel and d90% (r = 0.75) and finally κrel and VCTV10% (r = 0.75). CONCLUSIONS: The ITV coverage had a large variation for some patients. SDP seems to be a feasible surrogate measure to select patients that needs further tumor motion determination.

Genome-Scale Mapping Reveals Complex Regulatory Activities of RpoN in Yersinia pseudotuberculosis.

RpoN, an alternative sigma factor commonly known as σ54, is implicated in persistent stages of Yersinia pseudotuberculosis infections in which genes associated with this regulator are upregulated. We here combined phenotypic and genomic assays to provide insight into its role and function in this pathogen. RpoN was found essential for Y. pseudotuberculosis virulence in mice, and in vitro functional assays showed that it controls biofilm formation and motility. Mapping genome-wide associations of Y. pseudotuberculosis RpoN using chromatin immunoprecipitation coupled with next-generation sequencing identified an RpoN binding motif located at 103 inter- and intragenic sites on both sense and antisense strands. Deletion of rpoN had a large impact on gene expression, including downregulation of genes encoding proteins involved in flagellar assembly, chemotaxis, and quorum sensing. There were also clear indications of cross talk with other sigma factors, together with indirect effects due to altered expression of other regulators. Matching differential gene expression with locations of the binding sites implicated around 130 genes or operons potentially activated or repressed by RpoN. Mutagenesis of selected intergenic binding sites confirmed both positive and negative regulatory effects of RpoN binding. Corresponding mutations of intragenic sense sites had less impact on associated gene expression. Surprisingly, mutating intragenic sites on the antisense strand commonly reduced expression of genes carried by the corresponding sense strand.IMPORTANCE The alternative sigma factor RpoN (σ54), which is widely distributed in eubacteria, has been implicated in controlling gene expression of importance for numerous functions including virulence. Proper responses to host environments are crucial for bacteria to establish infection, and regulatory mechanisms involved are therefore of high interest for development of future therapeutics. Little is known about the function of RpoN in the intestinal pathogen Y. pseudotuberculosis, and we therefore investigated its regulatory role in this pathogen. This regulator was indeed found to be critical for establishment of infection in mice, likely involving its requirement for motility and biofilm formation. The RpoN regulon involved both activating and suppressive effects on gene expression which could be confirmed with mutagenesis of identified binding sites. This is the first study of its kind of RpoN in Y. pseudotuberculosis, revealing complex regulation of gene expression involving both productive and silent effects of its binding to DNA, providing important information about RpoN regulation in enterobacteria.

Low-Dose Image-Guided Pediatric CNS Radiation Therapy: Final Analysis From a Prospective Low-Dose Cone-Beam CT Protocol From a Multinational Pediatrics Consortium.

BACKGROUND: Lower-dose cone-beam computed tomography protocols for image-guided radiotherapy may permit target localization while minimizing radiation exposure. We prospectively evaluated a lower-dose cone-beam protocol for central nervous system image-guided radiotherapy across a multinational pediatrics consortium. METHODS: Seven institutions prospectively employed a lower-dose cone-beam computed tomography central nervous system protocol (weighted average dose 0.7 mGy) for patients ≤21 years. Treatment table shifts between setup with surface lasers versus cone-beam computed tomography were used to approximate setup accuracy, and vector magnitudes for these shifts were calculated. Setup group mean, interpatient, interinstitution, and random error were estimated, and clinical factors were compared by mixed linear modeling. RESULTS: Among 96 patients, with 2179 pretreatment cone-beam computed tomography acquisitions, median age was 9 years (1-20). Setup parameters were 3.13, 3.02, 1.64, and 1.48 mm for vector magnitude group mean, interpatient, interinstitution, and random error, respectively. On multivariable analysis, there were no significant differences in mean vector magnitude by age, gender, performance status, target location, extent of resection, chemotherapy, or steroid or anesthesia use. Providers rated >99% of images as adequate or better for target localization. CONCLUSIONS: A lower-dose cone-beam computed tomography protocol demonstrated table shift vector magnitude that approximate clinical target volume/planning target volume expansions used in central nervous system radiotherapy. There were no significant clinical predictors of setup accuracy identified, supporting use of this lower-dose cone-beam computed tomography protocol across a diverse pediatric population with brain tumors.

Identification of novel GPR81 agonist lead series for target biology evaluation.

GPR81 is a novel drug target that is implicated in the control of glucose and lipid metabolism. The lack of potent GPR81 modulators suitable for in vivo studies has limited the pharmacological characterization of this lactate sensing receptor. We performed a high throughput screen (HTS) and identified a GPR81 agonist chemical series containing a central acyl urea scaffold linker. During SAR exploration two additional new series were evolved, one containing cyclic acyl urea bioisosteres and another a central amide bond. These three series provide different selectivity and physicochemical properties suitable for in-vivo studies.

Winter City Urbanism: Enabling All Year Connectivity for Soft Mobility.

This study explores connectivity for soft mobility in the winter season. Working with residents from the sub-arctic city of Luleå, Sweden, the research examines how the interaction between the built environment and winter season affects people's use of the outdoor environment. The research questions for this study are (1) How do residents perceive the effects of winter on an areas spatial structure and pattern of streets and pathways? and (2) What enablers and barriers impact resident soft mobility choices and use of the public realm in winter? Methods used were mental mapping and photo elicitation exercises. These were used to gain a better understanding of people's perception of soft mobility in winter. The results were analysed to identify how soft mobility is influenced by the winter season. The discussion highlights that at the neighbourhood scale, residents perceive that the winter alters an areas spatial structure and pattern of streets and pathways. It was also seen to reduce ease of understanding of the public realm and townscape. In conclusion, it is argued that new and re-tooled town planning strategies, such as extending blue/ green infrastructure planning to include white space could help better enable all year outdoor activity in winter cities.

Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic Shock.

Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course after HS.Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgus monkeys) received a pressure-controlled severe HS (60 min at mean arterial pressure 30 mmHg) with subsequent volume resuscitation. Thirty minutes after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n = 4) or with saline alone (n = 4). The observation period lasted 300 min after induction of HS.We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs of mucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40.The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation, and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.

Practice Patterns of Stereotactic Radiotherapy in Pediatrics: Results From an International Pediatric Research Consortium.

PURPOSE/OBJECTIVES: There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium. MATERIALS AND METHODS: Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated. RESULTS: Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and <1% of abdomen/pelvis, lung, and liver cases across sites. Of the hypofractionated SRT cases, 42% were delivered with definitive intent. Median gross tumor volume to planning target volume margins for SRT versus non-SRT plans were 0.2 versus 1.4 cm for brain, 0.3 versus 1.5 cm for spine/other bone, 0.3 versus 2.0 cm for abdomen/pelvis, 0.7 versus 1.5 cm for head and neck, 0.5 versus 1.7 cm for lung, and 0.5 versus 2.0 cm for liver sites. CONCLUSIONS: SRT is commonly utilized in pediatrics across a range of treatment sites. Margins used for SRT were substantially smaller than for non-SRT planning, highlighting the utility of this approach in reducing treatment volumes.

Reproducibility of heart and thoracic wall position in repeated deep inspiration breath holds for radiotherapy of left-sided breast cancer patients.

BACKGROUND: Deep inspiration breath hold (DIBH) for radiotherapy of left-sided breast cancer patients can effectively move the heart away from the target and reduce the heart dose compared to treatments in free breathing. This study aims to investigate the positional reproducibility of heart edge (HE) and thoracic wall (TW) during repeated DIBHs. MATERIAL AND METHODS: At three occasions, 11 left-sided breast cancer patients were CT imaged during 6 minutes of repeated DIBHs with 60 cine CT series. The series were evenly distributed over three bed positions and for each bed position, the heart edge associated maximum heart distance (MHD) and thoracic wall-associated maximum lung distance (MLD) from a reference line were retrospectively analyzed. The high temporal resolution of the CT series enabled intrinsic heart movements to be resolved from breath hold variations. A body surface laser scanning system continuously extracted the thorax height and displayed it in a pair of goggles for patient feedback. To check for 'fake-breathing' movements, e.g. that the patient lifts its back from the couch to reach DIBH, the couch-to-spine distance was also measured in all CT series. RESULTS: The analysis was done for 1432 cine CTs captured during 292 breath holds. The DIBH moved the heart on average 15 mm in medial direction compared with free breathing. For the three bed positions studied, the mean value of the max range, across all patients, was between 11-13 mm for the MHD and 4-8 mm for the MLD. The MHD variation due to breath hold variation was twice as large as the MHD variation due to intrinsic heart movement. The couch-to-spine distance varied less than 3 mm for all fractions, i.e., no fake-breathing was discovered. CONCLUSIONS: The heart edge and thoracic wall reproducibility was high in relation to the medial heart displacement induced by the DIBH.

SIOPE - Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy.

OBJECTIVE: To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy. METHODS AND MATERIALS: During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution. RESULTS: The CTVcranial should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa. If the full length of both optic nerves is not included, the dose received by different volumes of optic nerve should be recorded to correlate with future patterns of relapse (no consensus). The CTVcranial should be modified to include the dural cuffs of cranial nerves as they pass through the skull base foramina. Attempts to spare the cochlea by excluding CSF within the internal auditory canal should be avoided. The CTVspinal should include the entire subarachnoid space, including nerve roots laterally. The lower limit of the spinal CTV is at the lower limit of the thecal sac, best visible on MRI scan. There is no need to include sacral root canals in the spinal CTV. CONCLUSION: This consensus guideline has the potential to improve consistency of craniospinal TV delineation in an era of high-precision radiotherapy. This proposal will be incorporated in the RTQA guidelines of future SIOPE-BTG trials using CSI.

Parents' Experiences and Responses to an Intervention for Psychological Preparation of Children and Families During the Child's Radiotherapy.

The aim of this study was to evaluate parents' experiences and responses to a systematic intervention for psychological preparation of children and families during the child's radiotherapy (RT) treatment. In this case-control study at 3 pediatric RT centers, an intervention with a preparatory kit, including age-adjusted information on tablets, gift of a stuffed toy or a pair of headphones, a parent booklet, and toy models of the computed tomography and RT machines was implemented. For evaluation, a mixed methods data collection was conducted. A total of 113 parents of children undergoing RT were included-n = 59 in the baseline group and n = 54 in the intervention group. Health-related quality of life was rated low, but parents in the intervention group expressed less anxiety after the RT compared with the baseline group. They found information suitable for their young children, siblings, and friends were involved and the toy models were used for play. Parents expressed positive feelings due to close interaction with staff and each other within the family. The solutions developed within a human-centered design approach and shaped as a systematic family-centered strategy contributed to parents understanding and coping with the child's RT.

Reirradiation for Recurrent Pediatric Central Nervous System Malignancies: A Multi-institutional Review.

PURPOSE: Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. METHODS AND MATERIALS: The data from pediatric patients <21 years of age at the initial diagnosis who developed a recurrent CNS malignancy that received repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed. RESULTS: Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. CONCLUSIONS: CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.

Lung toxicity after radiation in childhood: Results of the International Project on Prospective Analysis of Radiotoxicity in Childhood and Adolescence.

BACKGROUND AND PURPOSE: This study presents the evaluation of acute and late toxicities of the lung in children and adolescents after irradiation in terms of dose-volume effects. MATERIALS AND METHODS: Irradiated children and adolescents in Germany have prospectively been documented since 2001 in the "Registry for the Evaluation of Side-Effects after Radiotherapy in Childhood and Adolescence (RiSK)"; in Sweden since 2008 in the RADTOX registry. RESULTS: Up to April 2012, 1,392 children were recruited from RiSK, and up to June 2013, 485 from the RADTOX-registry. Of these patients, 295 were irradiated to the lung. Information about acute toxicity was available for 228 patients. 179 patients have been documented concerning late toxicity (≥grade 1: n = 28). The acute toxicity rate was noticeably higher in children irradiated with 5-20Gy (p < 0.05). In the univariate analysis, a shorter time until late toxicity was noticeably associated with irradiation with 5-15Gy (p < 0.05). CONCLUSION: Acute and late toxicities appear to be correlated with higher irradiation volumes and low doses. Our data indicate that similar to the situation in adult patients, V5, V10, V15 and V20 should be kept as low as possible (e.g., at least V5 < 50%, V10 and V15 < 35% and V20 < 30%) in children and adolescents to lower the risk of toxicity.

Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas.

BACKGROUND: Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. METHOD: A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. RESULTS: The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. CONCLUSIONS: Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for complications.

Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire.

BACKGROUND: We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. MATERIAL AND METHODS: The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. RESULTS: The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. CONCLUSIONS: As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy.