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- van Griensven, Martijn, et al.
(författare)
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PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK
- 2019
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Ingår i: Shock. - Alphen aan den Rijn : LIPPINCOTT WILLIAMS & WILKINS. - 1073-2322 .- 1540-0514. ; 51:1, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- 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 afterHS. Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgusmonkeys) received a pressure-controlled severe HS (60min 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 ofmucosal 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.
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- Ajithkumar, Thankamma, et al.
(författare)
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SIOPE - Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy
- 2018
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Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 128:2, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Alcorn, Sara, et al.
(författare)
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Practice Patterns of Stereotactic Radiotherapy in Pediatrics : Results From an International Pediatric Research Consortium
- 2018
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Ingår i: Journal of pediatric hematology/oncology (Print). - : Lippincott Williams & Wilkins. - 1077-4114 .- 1536-3678. ; 40:7, s. 522-526
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Alcorn, Sara R., et al.
(författare)
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Low-Dose Image-Guided Pediatric CNS Radiation Therapy : Final Analysis From a Prospective Low-Dose Cone-Beam CT Protocol From a Multinational Pediatrics Consortium
- 2020
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Ingår i: Technology in Cancer Research & Treatment. - : SAGE PUBLICATIONS INC. - 1533-0346 .- 1533-0338. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Alcorn, Sara R, et al.
(författare)
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Practice patterns of photon and proton pediatric image guided radiation treatment : results from an International Pediatric Research consortium
- 2014
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Ingår i: Practical radiation oncology. - : Elsevier BV. - 1879-8500. ; 4:5, s. 336-341
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Image guided radiation therapy (IGRT) has become common practice for both photon and proton radiation therapy, but there is little consensus regarding its application in the pediatric population. We evaluated clinical patterns of pediatric IGRT practice through an international pediatrics consortium comprised of institutions using either photon or proton radiation therapy.METHODS AND MATERIALS: Seven international institutions with dedicated pediatric expertise completed a 53-item survey evaluating patterns of IGRT use in definitive radiation therapy for patients ≤21 years old. Two institutions use proton therapy for children and all others use IG photon therapy. Descriptive statistics including frequencies of IGRT use and means and standard deviations for planning target volume (PTV) margins by institution and treatment site were calculated.RESULTS: Approximately 750 pediatric patients were treated annually across the 7 institutions. IGRT was used in tumors of the central nervous system (98%), abdomen or pelvis (73%), head and neck (100%), lung (83%), and liver (69%). Photon institutions used kV cone beam computed tomography and kV- and MV-based planar imaging for IGRT, and all proton institutions used kV-based planar imaging; 57% of photon institutions used a specialized pediatric protocol for IGRT that delivers lower dose than standard adult protocols. Immobilization techniques varied by treatment site and institution. IGRT was utilized daily in 45% and weekly in 35% of cases. The PTV margin with use of IGRT ranged from 2 cm to 1 cm across treatment sites and institution.CONCLUSIONS: Use of IGRT in children was prevalent at all consortium institutions. There was treatment site-specific variability in IGRT use and technique across institutions, although practices varied less at proton facilities. Despite use of IGRT, there was no consensus of optimum PTV margin by treatment site. Given the desire to restrict any additional radiation exposure in children to instances where the exposure is associated with measureable benefit, prospective studies are warranted to optimize IGRT protocols by modality and treatment site.
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- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby
- 2015
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Ingår i: Dagens Nyheter. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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- Baumann, Pia, et al.
(författare)
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Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.
- 2009
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 27:20, s. 3290-6
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study. PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume. RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027). CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.
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- Correia de Verdier, Maria, et al.
(författare)
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Magnetic resonance imaging detected radiation-induced changes in patients with proton radiation-treated arteriovenous malformations
- 2021
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Ingår i: Acta Radiologica Open. - : Sage Publications. - 2058-4601. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTreatment 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.PurposeTo 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 MethodsRetrospective 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.Results26 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.ConclusionRadiation-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.
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