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Zürich, Switzerland

Halg R.A.,City Hospital Triemli | Besserer J.,Radiotherapy Hirslanden AG | Schneider U.,University of Zurich | Schneider U.,Radiotherapy Hirslanden AG
Medical Physics | Year: 2011

Purpose: In the clinical environment phantom materials are usually used to simulate the patient for neutron dosimetric measurements. It is not clear that the results of such phantom measurements represent the actual neutron dose in the patient. The aim of this study was to compare the difference in secondary neutron equivalent dose for different phantom materials to that in human tissue, for both proton and carbon ion radiation therapy.Methods: In order to compare the neutron equivalent dose induced by primary particles in different materials, Monte Carlo simulations were performed using the FLUKA Monte Carlo package. The scored dosimetric quantities were absorbed dose and neutron ambient dose equivalent for monoenergetic proton and carbon ion beams of clinically relevant energies. It was shown that neutron equivalent dose, for which no scoring routine exists in the current FLUKA release, can be approximated by neutron ambient dose equivalent within 4 for the investigated energies of proton and carbon ion beams.Results: The Monte Carlo simulations performed in this work showed differences in neutron ambient dose equivalent in radiation therapy phantom materials compared to ICRP soft tissue for primary proton and carbon ion beams. For Alderson soft tissue the maximum deviation was 11 for protons and 8 for carbon ions. For water the maximum deviation was 10 for protons and 9 for carbon ions. In the case of RW3 solid water, the maximum deviation compared to ICRP soft tissue was as large as 28 and 21 for protons and carbon ions, respectively.Conclusions: Alderson soft tissue and water are suitable phantom materials for neutron dosimetry for the accuracy which is achievable. When using solid water phantoms, the chemical and therefore nuclear composition of the phantom material has to be accounted for. © 2011 American Association of Physicists in Medicine. Source

Blank A.,TU Munich | Blank A.,University of Bern | Schmitt A.M.,University of Bern | Korpershoek E.,Rotterdam University | And 8 more authors.
Endocrine-Related Cancer | Year: 2010

Prediction of malignant behaviour of pheochromocytomas/sympathetic paragangliomas (PCCs/PGLs) is very difficult if not impossible on a histopathological basis. In a familial setting, it is well known that succinate dehydrogenase subunit B (SDHB)-associated PCC/PGL very often metastasise. Recently, absence of SDHB expression as measured through immunohistochemistry was shown to be an excellent indicator of the presence of an SDH germline mutation in PCC/PGL. SDHB loss is believed to lead to tumour formation by activation of hypoxia signals. To clarify the potential use of SDHB immunohistochemistry as a marker of malignancy in PCC/PGL and its association with classic hypoxia signalling we examined SDHB, hypoxia inducible factor-1α (Hif-1α) and its targets CA-9 and GLUT-1 expression on protein level using immunohistochemistry on a tissue micro array on a series of familial and sporadic tumours of 115 patients. Survival data was available for 66 patients. SDHB protein expression was lost in the tumour tissue of 12 of 99 patients. Of those 12 patients, 5 had an SDHB germline mutation, in 4 patients no germline mutation was detected and mutational status remained unknown in parts in 3 patients. Loss of SDHB expression was not associated with increased classic hypoxia signalling as detected by Hif-1α, CA-9 or GLUT-1 staining. Loss of SDHB expression was associated with an adverse outcome. The lack of correlation of SDHB loss with classic hypoxia signals argues against the current hypoxia hypothesis in malignant PCC/PGL. We suggest SDHB protein loss as a marker of adverse outcome both in sporadic and in familial PCC/PGL. © 2010 Society for Endocrinology. Source

Mazaraki K.,City Hospital Triemli | Fassnacht-Riederle H.,City Hospital Triemli | Blum R.,City Hospital Triemli | Becker M.,City Hospital Triemli | And 3 more authors.
British Journal of Ophthalmology | Year: 2015

Aim: Evaluation of effects of intravitreal aflibercept therapy on choroidal thickness (CT) in neovascular age-related macular degeneration. Methods: Retrospective cohort study evaluating the change in CT following a loading dose of three intravitreal aflibercept injections at 4 weeks interval. Pretreated and treatment-naive eyes as well as untreated fellow eyes were evaluated at five retinal locations (subfoveal, 300 and 2500 mm nasal and temporal to the fovea) using spectral domain optical coherence tomography prior to and 4 weeks after a loading dose of three intravitreal aflibercept injections. Results: A total of 84 treated eyes (61 pretreated, 23 treatment naive) and 48 fellow eyes were enrolled into the study. Treatment-naive and pretreated eyes showed a significant reduction in CT at all retinal locations. The effect was more pronounced in treatmentnaive eyes. In the pretreated group, the mean reduction in CT was greatest at 2500 mm temporal to the fovea at 10.7 mm compared with 22.4 at 300 mm nasal to the fovea in the treatment-naive group. Only the fellow eyes in the treatment-naive group showed a significant CT reduction 12 weeks after initiation of therapy to the partner eye. Conclusions: Aflibercept induces a reduction in CT in treatment-naive and pretreated eyes with neovascular age-related macular degeneration. There is some evidence of a systemic effect of aflibercept reflected by CT reduction in untreated fellow eyes. Source

Stahel M.,City Hospital Triemli | Becker M.,City Hospital Triemli | Becker M.,University of Heidelberg | Graf N.,Graf Biostatistics | And 2 more authors.
Retina | Year: 2016

Purpose: To evaluate the effect of systemic interleukin 1β inhibition using canakinumab (Ilaris) on retinal neovascularizations in proliferative diabetic retinopathy. Methods: Patients with proliferative diabetic retinopathy were enrolled in a prospective uncontrolled pilot study. Canakinumab (150 mg) was given 3 times subcutaneously. The primary end point was the change in the area of neovascularization from baseline to Week 24. Secondary end points were the change in retinal edema measured and best-corrected visual acuity (BCVA), as well as systemic safety evaluation, HbA1c, and systemic inflammatory parameters. Results: Systemic canakinumab treatment was well tolerated. None of the 8 eyes showed progression of neovascularizations within 24 weeks. Their mean size remained unchanged comparing 0.60 mm 2 at baseline with 0.62 mm 2 at Week 24 (P 0.944). Median BCVA remained stable with 80 ETDRS letters at baseline and 82 ETDRS letters at Week 24. A not statistically significant reduction in retinal edema was detectable for the foveal central subfield thickness (mean, 313-295 m). Mean HbA1c improved significantly from 7.92% to 7.30% within the 24 weeks (P 0.046). Systemic inflammatory parameters remained overall unchanged. Conclusion: Systemic canakinumab showed no change in neovascularizations in diabetic retinopathy. Promising effects were seen on diabetic macular edema. Source

Fassnacht-Riederle H.,City Hospital Triemli | Becker M.,City Hospital Triemli | Becker M.,University of Heidelberg | Graf N.,Graf Biostatistics | And 2 more authors.
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2014

Purpose: Evaluation of three aflibercept injections at 4-week intervals in patients with neovascular AMD showing an "insufficient anatomic response" to prior anti-VEGF therapy with ranibizumab or bevacizumab. Methods: The retrospective analysis included 96 eyes that had received at least three intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab injections over a period of no more than 4 months prior to switching to aflibercept. In addition, the selected eyes had to have evidence of persisting or increasing sub- or intraretinal fluid, observed in optical coherence tomography (OCT). All patients received a loading dose of three intravitreal 2 mg aflibercept injections at 4-week intervals. Evaluation included central retinal thickness (CRT) and maximum pigment epithelium (PED) height measured by spectral domain OCT and best-corrected visual acuity (BCVA) prior to the switch of therapy and 4 weeks after the third aflibercept injection. Results: A significant reduction of mean CRT (-39 μm; p < 0.001) and maximum PED height (-46 μm; p < 0.001) as found 4 weeks after the third aflibercept injection. Eighty-two out of 96 eyes (85 %) had a PED just prior to switching to aflibercept. There was an improvement in BCVA of 1.9 letters 4 weeks after the last aflibercept injection; the vision gain, however, did not reach statistical significance (p = 0.061). The further analysis did not show any correlation of the change in CRT, maximum PED, and BCVA with the number of prior anti-VEGF treatments. Conclusion: Retinal edema and PEDs regressed significantly after switching to aflibercept in patients insufficiently responding to prior therapy with ranibizumab or bevacizumab. No correlation could be found with regard to the number of prior treatments. © 2014 The Author(s). Source

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