Publications by authors named "Florian Putz"

41 Publications

A Facile One-Pot Synthesis of Hierarchically Organized Carbon/TiO Monoliths with Ordered Mesopores.

Authors:
Jürgen Schoiber Christian Koczwara Simon Rumswinkel Lawrence Whitmore Christian Prehal Florian Putz Michael S Elsaesser Oskar Paris Nicola Hüsing

Chempluschem 2021 Feb;86(2):275-283

Dept. of Chemistry and Physics of Materials, Paris-Lodron-University of Salzburg, Jakob-Haringer-Straße 2a, 5020, Salzburg, Austria.

Sol-gel processing combined with soft templating and gelation-induced phase separation is very sensitive to the precursor sol composition. In this work we present a straightforward synthesis towards hierarchically structured, macroporous carbon/titania monoliths with ordered mesopores derived from resorcinol/formaldehyde monoliths and a glycolated titanium precursor. We demonstrate the influence of various reaction solvents, where diol-based media and the proportion of the catalyst seem to be essential in controlling spinodal decomposition, obtaining similar monolithic structures under different synthesis conditions. Based on these observations, we further homogeneously incorporated TiO into the carbon structure by an in situ synthesis approach, obtaining structural features similar to pure carbon materials with surface areas of about 400 m  g , periodically arranged mesopores with a mean distance of 10-11 nm and cellular macroporosity.
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http://dx.doi.org/10.1002/cplu.202000740DOI Listing
February 2021

Increase in non-professional phagocytosis during the progression of cell cycle.

Authors:
Alexander Hofmann Florian Putz Maike Büttner-Herold Markus Hecht Rainer Fietkau Luitpold V Distel

PLoS One 2021 5;16(2):e0246402. Epub 2021 Feb 5.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Homotypic or heterotypic internalization of another, either living or necrotic cell is currently in the center of research interest. The active invasion of a living cell called entosis and cannibalism of cells by rapidly proliferating cancers are prominent examples. Additionally, normal healthy tissue cells are capable of non-professional phagocytosis. This project studied the relationship between non-professional phagocytosis, individual proliferation and cell cycle progression. Three mesenchymal and two epithelial normal tissue cell lines were studied for homotypic non-professional phagocytosis. Homotypic dead cells were co-incubated with adherent growing living cell layers. Living cells were synchronized by mitotic shake-off as well as Aphidicolin-treatment and phagocytotic activity was analyzed by immunostaining. Cell cycle phases were evaluated by flow cytometry. Mesenchymal and epithelial normal tissue cells were capable of internalizing dead cells. Epithelial cells had much higher non-professional phagocytotic rates than mesenchymal cells. Cells throughout the entire cell cycle were able to phagocytose. The phagocytotic rate significantly increased with progressing cell cycle phases. Mitotic cells regularly phagocytosed dead cells, this was verified by Nocodazole and Colcemid treatment. Taken together, our findings indicate the ability of human tissue cells to phagocytose necrotic neighboring cells in confluent cell layers. The origin of the cell line influences the rate of cell-in-cell structure formation. The higher cell-in-cell structure rates during cell cycle progression might be influenced by cytoskeletal reorganization during this period or indicate an evolutionary anchorage of the process. Recycling of nutrients during cell growth might also be an explanation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246402PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864402PMC
February 2021

[Vulnerabilities of radiomics: Why the most popular radiomics signature accidentally measured tumor volume].

Authors:
Florian Putz Rainer Fietkau

Strahlenther Onkol 2021 Feb 3. Epub 2021 Feb 3.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, 91054, Erlangen, Deutschland.

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http://dx.doi.org/10.1007/s00066-021-01747-8DOI Listing
February 2021

Volumetric Regression in Brain Metastases After Stereotactic Radiotherapy: Time Course, Predictors, and Significance.

Authors:
Dominik Oft Manuel Alexander Schmidt Thomas Weissmann Johannes Roesch Veit Mengling Siti Masitho Christoph Bert Sebastian Lettmaier Benjamin Frey Luitpold Valentin Distel Rainer Fietkau Florian Putz

Front Oncol 2020 8;10:590980. Epub 2021 Jan 8.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Background: There is insufficient understanding of the natural course of volumetric regression in brain metastases after stereotactic radiotherapy (SRT) and optimal volumetric criteria for the assessment of response and progression in radiotherapy clinical trials for brain metastases are currently unknown.

Methods: Volumetric analysis whole-tumor segmentation in contrast-enhanced 1 mm³-isotropic T1-Mprage sequences before SRT and during follow-up. A total of 3,145 MRI studies of 419 brain metastases from 189 patients were segmented. Progression was defined using a volumetric extension of the RANO-BM criteria. A subset of 205 metastases without progression/radionecrosis during their entire follow-up of at least 3 months was used to study the natural course of volumetric regression after SRT. Predictors for volumetric regression were investigated. A second subset of 179 metastases was used to investigate the prognostic significance of volumetric response at 3 months (defined as ≥20% and ≥65% volume reduction, respectively) for subsequent local control.

Results: Median relative metastasis volume post-SRT was 66.9% at 6 weeks, 38.6% at 3 months, 17.7% at 6 months, 2.7% at 12 months and 0.0% at 24 months. Radioresistant histology and FSRT vs. SRS were associated with reduced tumor regression for all time points. In multivariate linear regression, radiosensitive histology (p=0.006) was the only significant predictor for metastasis regression at 3 months. Volumetric regression ≥20% at 3 months post-SRT was the only significant prognostic factor for subsequent control in multivariate analysis (HR 0.63, p=0.023), whereas regression ≥65% was no significant predictor.

Conclusions: Volumetric regression post-SRT does not occur at a constant rate but is most pronounced in the first 6 weeks to 3 months. Despite decreasing over time, volumetric regression continues beyond 6 months post-radiotherapy and may lead to complete resolution of controlled lesions by 24 months. Radioresistant histology is associated with slower regression. We found that a cutoff of ≥20% regression for the volumetric definition of response at 3 months post-SRT was predictive for subsequent control whereas the currently proposed definition of ≥65% was not. These results have implications for standardized volumetric criteria in future radiotherapy trials for brain metastases.
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http://dx.doi.org/10.3389/fonc.2020.590980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820888PMC
January 2021

The Distribution of Pelvic Nodal Metastases in Prostate Cancer Reveals Potential to Advance and Personalize Pelvic Radiotherapy.

Authors:
Irina Filimonova Daniela Schmidt Sina Mansoorian Thomas Weissmann Hadi Siavooshhaghighi Alexander Cavallaro Torsten Kuwert Christoph Bert Benjamin Frey Luitpold Valentin Distel Sebastian Lettmaier Rainer Fietkau Florian Putz

Front Oncol 2020 8;10:590722. Epub 2021 Jan 8.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Background: Traditional clinical target volume (CTV) definition for pelvic radiotherapy in prostate cancer consists of large volumes being treated with homogeneous doses without fully utilizing information on the probability of microscopic involvement to guide target volume design and prescription dose distribution.

Methods: We analyzed patterns of nodal involvement in 75 patients that received RT for pelvic and paraaortic lymph node metastases (LNs) from prostate cancer in regard to the new NRG-CTV recommendation. Non-rigid registration-based LN mapping and weighted three-dimensional kernel density estimation were used to visualize the average probability distribution for nodal metastases. As independent approach, the mean relative proportion of LNs observed for each level was determined manually and NRG and non-NRG levels were evaluated for frequency of involvement. Computer-automated distance measurements were used to compare LN distances in individual patients to the spatial proximity of nodal metastases at a cohort level.

Results: 34.7% of patients had pelvic LNs outside NRG-consensus, of which perirectal was most common (25.3% of all patients) followed by left common iliac nodes near the left psoas major (6.7%). A substantial portion of patients (13.3%) had nodes at the posterior edge of the NRG obturator level. Observer-independent mapping consistently visualized high-probability hotspots outside NRG-consensus in the perirectal and left common iliac regions. Affected nodes in individual patients occurred in highly significantly closer proximity than at cohort-level (mean distance, 6.6 cm vs. 8.7 cm, p < 0.001).

Conclusions: Based on this analysis, the common iliac level should extend to the left psoas major and obturator levels should extend posteriorly 5 mm beyond the obturator internus. Incomplete coverage by the NRG-consensus was mostly because of perirectal involvement. We introduce three-dimensional kernel density estimation after non-rigid registration-based mapping for the analysis of recurrence data in radiotherapy. This technique provides an estimate of the underlying probability distribution of nodal involvement and may help in addressing institution- or subgroup-specific differences. Nodal metastases in individual patients occurred in highly significantly closer proximity than at a cohort-level, which supports that personalized target volumes could be reduced in size compared to a "one-size-fits-all" approach and is an important basis for further investigation into individualized field designs.
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http://dx.doi.org/10.3389/fonc.2020.590722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820617PMC
January 2021

Evaluation of the influence of susceptibility-induced magnetic field distortions on the precision of contouring intracranial organs at risk for stereotactic radiosurgery.

Authors:
Veit Mengling Florian Putz Frederik Bernd Laun Rosalind Perrin Felix Eisenhut Arnd Dörfler Rainer Fietkau Christoph Bert

Phys Imaging Radiat Oncol 2020 Jul 13;15:91-97. Epub 2020 Aug 13.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitaetsstraße 27, 91054 Erlangen, Germany.

Background And Purpose: Magnetic resonance imaging (MRI) is a crucial factor in optimal treatment planning for stereotactic radiosurgery. To further the awareness of possible errors in MRI, this work aimed to investigate the magnitude of susceptibility induced MRI distortions for intracranial organs at risk (OARs) and test the effectiveness of actively shimming these distortions.

Materials And Methods: Distortion maps for 45 exams of 42 patients (18 on a 1.5 T MRI scanner, 27 on a 3 T MRI scanner) were calculated based on a high-bandwidth double-echo gradient echo sequence. The investigated OARs were brainstem, chiasm, eyes, and optic nerves. The influence of active shimming was investigated by comparing unshimmed 1.5 T data with shimmed 3 T data and comparing the results to a model based prediction.

Results: The median distortion for the different OARs was found to be between 0.13 and 0.18 mm for 1.5 T and between 0.11 and 0.13 mm for 3 T. The maximum distortion was found to be between 1.3 and 1.7 mm for 1.5 T and between 1.1 and 1.4 mm for 3 T. The variation of values was much higher for 1.5 T than for 3 T across all investigated OARs. Active shimming was found to reduce distortions by a factor of 2.3 to 2.9 compared to the expected values.

Conclusions: Using a safety margin for OARs of 1 mm would have encompassed 99.8% of the distortions. Since distortions are inversely proportional to the readout bandwidth, they can be further reduced by increasing the bandwidth. Additional error sources like gradient nonlinearities need to be addressed separately.
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http://dx.doi.org/10.1016/j.phro.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807629PMC
July 2020

Classification of Primary Cerebral Lymphoma and Glioblastoma Featuring Dynamic Susceptibility Contrast and Apparent Diffusion Coefficient.

Authors:
Felix Eisenhut Manuel A Schmidt Florian Putz Sebastian Lettmaier Kilian Fröhlich Soheil Arinrad Roland Coras Hannes Luecking Stefan Lang Rainer Fietkau Arnd Doerfler

Brain Sci 2020 Nov 20;10(11). Epub 2020 Nov 20.

Department of Neuroradiology, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.

This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratio as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratio. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine.
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http://dx.doi.org/10.3390/brainsci10110886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699775PMC
November 2020

Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells.

Authors:
Roger Sun Nora Sundahl Markus Hecht Florian Putz Andrea Lancia Angela Rouyar Marina Milic Alexandre Carré Enzo Battistella Emilie Alvarez Andres Stéphane Niyoteka Edouard Romano Guillaume Louvel Jérôme Durand-Labrunie Sophie Bockel Rastilav Bahleda Charlotte Robert Celine Boutros Maria Vakalopoulou Nikos Paragios Benjamin Frey Jean-Charles Soria Christophe Massard Charles Ferté Rainer Fietkau Piet Ost Udo Gaipl Eric Deutsch

J Immunother Cancer 2020 11;8(2)

Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France

Background: Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions.

Methods: Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient's response.

Results: A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables.

Conclusions: These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.
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http://dx.doi.org/10.1136/jitc-2020-001429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668366PMC
November 2020

Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation.

Authors:
Dorian Gottwald Florian Putz Nora Hohmann Maike Büttner-Herold Markus Hecht Rainer Fietkau Luitpold Distel

BMC Mol Cell Biol 2020 Nov 7;21(1):79. Epub 2020 Nov 7.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054, Erlangen, Germany.

Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.

Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.

Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.
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http://dx.doi.org/10.1186/s12860-020-00326-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648987PMC
November 2020

Implementation of a dedicated 1.5 T MR scanner for radiotherapy treatment planning featuring a novel high-channel coil setup for brain imaging in treatment position.

Authors:
Veit Mengling Christoph Bert Rosalind Perrin Siti Masitho Thomas Weissmann Sina Mansoorian Hadi Siavooshhaghighi Rolf Janka Sylvain Doussin Melanie Habatsch Rainer Fietkau Florian Putz

Strahlenther Onkol 2021 Mar 25;197(3):246-256. Epub 2020 Oct 25.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, 91054, Erlangen, Germany.

Purpose: To share our experiences in implementing a dedicated magnetic resonance (MR) scanner for radiotherapy (RT) treatment planning using a novel coil setup for brain imaging in treatment position as well as to present developed core protocols with sequences specifically tuned for brain and prostate RT treatment planning.

Materials And Methods: Our novel setup consists of two large 18-channel flexible coils and a specifically designed wooden mask holder mounted on a flat tabletop overlay, which allows patients to be measured in treatment position with mask immobilization. The signal-to-noise ratio (SNR) of this setup was compared to the vendor-provided flexible coil RT setup and the standard setup for diagnostic radiology. The occurrence of motion artifacts was quantified. To develop magnetic resonance imaging (MRI) protocols, we formulated site- and disease-specific clinical objectives.

Results: Our novel setup showed mean SNR of 163 ± 28 anteriorly, 104 ± 23 centrally, and 78 ± 14 posteriorly compared to 84 ± 8 and 102 ± 22 anteriorly, 68 ± 6 and 95 ± 20 centrally, and 56 ± 7 and 119 ± 23 posteriorly for the vendor-provided and diagnostic setup, respectively. All differences were significant (p > 0.05). Image quality of our novel setup was judged suitable for contouring by expert-based assessment. Motion artifacts were found in 8/60 patients in the diagnostic setup, whereas none were found for patients in the RT setup. Site-specific core protocols were designed to minimize distortions while optimizing tissue contrast and 3D resolution according to indication-specific objectives.

Conclusion: We present a novel setup for high-quality imaging in treatment position that allows use of several immobilization systems enabling MR-only workflows, which could reduce unnecessary dose and registration inaccuracies.
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http://dx.doi.org/10.1007/s00066-020-01703-yDOI Listing
March 2021

FSRT vs. SRS in Brain Metastases-Differences in Local Control and Radiation Necrosis-A Volumetric Study.

Authors:
Florian Putz Thomas Weissmann Dominik Oft Manuel Alexander Schmidt Johannes Roesch Hadi Siavooshhaghighi Irina Filimonova Charlotte Schmitter Veit Mengling Christoph Bert Benjamin Frey Sebastian Lettmaier Luitpold Valentin Distel Sabine Semrau Rainer Fietkau

Front Oncol 2020 30;10:559193. Epub 2020 Sep 30.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

While the role of stereotactic radiotherapy for brain metastases is increasing, evidence on the comparative efficacy and safety of fractionated stereotactic radiotherapy (FSRT) and single-session radiosurgery (SRS) is scarce. Longitudinal volumetric analysis was performed in a consecutive cohort of 120 patients and 190 brain metastases (>0.065 cm in volume / > ~5 mm in diameter) treated exclusively with FSRT ( = 98) and SRS ( = 92), respectively. A total of 972 tumor segmentations was used, averaging 5.1 time points per metastasis. Progression was defined using a volumetric extension of the RANO-BM criteria. Local control and radionecrosis were compared for lesions treated with FSRT and SRS, respectively. Metastases treated with FSRT were significantly larger at baseline (mean, 4.66 vs. 0.40 cm, < 0.001). Biologically effective dose (BED) for metastases (α/β = 12, linear-quadratic-cubic model) was significantly associated with local control, whereas BED for normal brain (α/β = 2, linear-quadratic model) was significantly associated with radionecrosis. Median time to local progression was 22.9 months in the FSRT group compared to 14.5 months in the SRS group ( = 0.022). Overall radionecrosis rate at 12 months was 3.4% for FSRT and 14.8% for SRS ( = 0.010). Radionecrosis °IV requiring resection with histologic proof of radiation necrosis also was significantly reduced in the FSRT group (FSRT 0.0% vs. SRS 3.9%, = 0.041). In multivariate analysis, FSRT was associated with reduced risk of progression (HR 0.47, = 0.015) and reduced risk of radionecrosis (HR 0.18, = 0.045). This volumetric study provides initial evidence that the improvements in therapeutic ratio expected for FSRT in larger brain metastases, might equally extend into the domain of smaller metastases, traditionally less considered for fractionated treatment. FSRT might constitute an important tool to further increase local control and reduce radionecrosis risk in stereotactic radiotherapy for brain metastases, that should be assessed in randomized intervention trials.
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http://dx.doi.org/10.3389/fonc.2020.559193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554610PMC
September 2020

Low Dose Radiation Therapy, Particularly with 0.5 Gy, Improves Pain in Degenerative Joint Disease of the Fingers: Results of a Retrospective Analysis.

Authors:
Anna-Jasmina Donaubauer Jian-Guo Zhou Oliver J Ott Florian Putz Rainer Fietkau Ludwig Keilholz Udo S Gaipl Benjamin Frey Thomas Weissmann

Int J Mol Sci 2020 Aug 14;21(16). Epub 2020 Aug 14.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

Low-dose radiation therapy (LDRT) has been successfully established for decades as an alternative analgesic treatment option for patients suffering from chronic degenerative and inflammatory diseases. In this study, 483 patients were undergoing LDRT for degenerative joint disease of the fingers and thumb at the University Hospital Erlangen between 2004 and 2019. Radiotherapy was applied according to the German guidelines for LDRT. Several impact factors on therapeutic success, such as the age and gender, the number of affected fingers, the single and cumulative dose, as well as the number of series, were investigated. In summary, 70% of the patients showed an improvement of their pain following LDRT. No significant impact was found for the factors age, gender, the number of series or the cumulative dosage. Patients with an involvement of the thumb showed a significantly worse outcome compared to patients with an isolated affection of the fingers. In this cohort, patients receiving a single dose of 0.5 Gy reported a significantly better outcome than patients receiving 1.0 Gy, strongly suggesting a reduction in the total dose. In summary, LDRT is a good alternative treatment option for patients suffering from degenerative and inflammatory joint disease of the fingers.
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http://dx.doi.org/10.3390/ijms21165854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461565PMC
August 2020

Hierarchically organized materials with ordered mesopores: adsorption isotherm and adsorption-induced deformation from small-angle scattering.

Authors:
Lukas Ludescher Roland Morak Stephan Braxmeier Florian Putz Nicola Hüsing Gudrun Reichenauer Oskar Paris

Phys Chem Chem Phys 2020 Jun;22(22):12713-12723

Institute of Physics, Montanuniversität Leoben, Franz-Josef Strasse 18, 8700, Leoben, Austria.

In situ small angle scattering is used to study the pore filling mechanism and the adsorption induced deformation of a silica sample with hierarchical porosity upon water adsorption. The high structural order of the cylindrical mesopores on a 2D hexagonal lattice allows obtaining adsorption induced strains from the shift of the corresponding Bragg peaks measured by in situ small-angle X-ray scattering (SAXS). However, apparent strains due to scattering contrast induced changes of the Bragg peak shapes emerge in SAXS. In contrast, small-angle neutron scattering (SANS) allows determining the real adsorption induced strains by employing a H2O/D2O adsorbate with net coherent scattering length density of zero. This allows separating the apparent strains from the real strains experimentally and comparing them with strains obtained from model calculations of the SAXS intensity. It is shown that the apparent strains cannot be described at all by a simple mesopore model of film growth and capillary condensation. A hierarchical model taking the scattering of the micropores and the outer surface of the mesoporous struts in the hierarchically porous sample properly into account, together with a modified mesopore filling mechanism based on a corona model, leads to satisfactory description of both, the adsorption isotherm and the measured apparent strains as derived by SAXS.
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http://dx.doi.org/10.1039/d0cp01026jDOI Listing
June 2020

Hierarchically Organized and Anisotropic Porous Carbon Monoliths.

Authors:
Florian Putz Lukas Ludescher Michael S Elsaesser Oskar Paris Nicola Hüsing

Chem Mater 2020 May 20;32(9):3944-3951. Epub 2020 Apr 20.

Materials Chemistry, Paris Lodron University Salzburg, Jakob-Haringer Str. 2a, Salzburg 5020, Austria.

Anisotropy is a key factor regarding mechanical or transport properties and thus the functionality of porous materials. However, the ability to deliberately design the pore structure of hierarchically organized porous networks toward anisotropic features is limited. Here, we report two straightforward routes toward hierarchically structured porous carbon monoliths with an anisotropic alignment of the microstructure on the level of macro- and mesopores. One approach is based on nanocasting (NC) of carbon precursors into hierarchical and anisotropic silica hard templates. The second route, a direct synthesis approach based on soft templating (ST), makes use of the flexibility of hierarchically structured resorcinol-formaldehyde gels, which are compressed and simultaneously carbonized in the deformed state. We present structural data of both types of carbon monoliths obtained by electron microscopy, nitrogen adsorption analysis, and SAXS measurements. In addition, we demonstrate how the degree of anisotropy can easily be controlled via the ST route.
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http://dx.doi.org/10.1021/acs.chemmater.0c00302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222333PMC
May 2020

Evidence for improved survival with bevacizumab treatment in recurrent high-grade gliomas: a retrospective study with ("pseudo-randomized") treatment allocation by the health insurance provider.

Authors:
Susanne Hofmann Manuel Alexander Schmidt Thomas Weissmann Ilker Eyüpoglu Annedore Strnad Sabine Semrau Rainer Fietkau Florian Putz Sebastian Lettmaier

J Neurooncol 2020 Jun 14;148(2):373-379. Epub 2020 May 14.

Department of Radiotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitaetsstraße 27, 91054, Erlangen, Germany.

Introduction: Despite a large number of trials, the role of bevacizumab (BEV) in the treatment of recurrent high-grade gliomas is still controversial. Evidence regarding an effect on overall survival in this context is ultimately inconclusive. At the Department of Radiation Oncology at Erlangen, Germany we treated a large cohort of patients with recurrent gliomas where bevacizumab use was determined exclusively by the health care provider's approval of reimbursement.

Methods: 61 patients (between 06/2008 and 01/2014) with recurrent high-grade gliomas had reimbursement requests for BEV sent to their health insurance. 37 patients out of 61 (60.7%) had their requests approved and therefore received bevacizumab (BEV-arm) as part of their treatment. The remaining 24 (39.3%) patients received standard therapy without bevacizumab (non-BEV-arm). Survival endpoints were defined with reference to the first BEV request to the health insurance provider.

Results: Median overall survival (OS) for the whole cohort was 7.0 months. OS was significantly better for BEV vs. Non-BEV patients (median, 10.3 vs. 4.2 months, logrank p = 0.023). There was an increased BEV benefit in cases of higher-order recurrences (first order recurrence BEV vs. Non-BEV, 12.5 vs. 10.2 months, p = 0.578) (second or higher order of recurrence, 9.9 vs. 2.6 months, p = 0.010). On multivariate analysis for overall survival the prognostic impact of bevacizumab (HR = 0.43, p = 0.034) remained significant.

Conclusion: Our results suggest an influence of BEV on overall survival in a heavily pretreated patient population suffering from high-grade gliomas with BEV benefit being greatest in case of second or later recurrence.
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http://dx.doi.org/10.1007/s11060-020-03533-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316675PMC
June 2020

Magnetic resonance imaging for brain stereotactic radiotherapy : A review of requirements and pitfalls.

Authors:
Florian Putz Veit Mengling Rosalind Perrin Siti Masitho Thomas Weissmann Johannes Rösch Tobias Bäuerle Rolf Janka Alexander Cavallaro Michael Uder Patrick Amarteifio Sylvain Doussin Manuel Alexander Schmidt Arndt Dörfler Sabine Semrau Sebastian Lettmaier Rainer Fietkau Christoph Bert

Strahlenther Onkol 2020 May 23;196(5):444-456. Epub 2020 Mar 23.

Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nürnberg, Universitätsstraße 27, 91054, Erlangen, Germany.

Due to its superior soft tissue contrast, magnetic resonance imaging (MRI) is essential for many radiotherapy treatment indications. This is especially true for treatment planning in intracranial tumors, where MRI has a long-standing history for target delineation in clinical practice. Despite its routine use, care has to be taken when selecting and acquiring MRI studies for the purpose of radiotherapy treatment planning. Requirements on MRI are particularly demanding for intracranial stereotactic radiotherapy, where accurate imaging has a critical role in treatment success. However, MR images acquired for routine radiological assessment are frequently unsuitable for high-precision stereotactic radiotherapy as the requirements for imaging are significantly different for radiotherapy planning and diagnostic radiology. To assure that optimal imaging is used for treatment planning, the radiation oncologist needs proper knowledge of the most important requirements concerning the use of MRI in brain stereotactic radiotherapy. In the present review, we summarize and discuss the most relevant issues when using MR images for target volume delineation in intracranial stereotactic radiotherapy.
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http://dx.doi.org/10.1007/s00066-020-01604-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182639PMC
May 2020

Adaptive radiotherapy and the dosimetric impact of inter- and intrafractional motion on the planning target volume for prostate cancer patients.

Authors:
Felix Böckelmann Florian Putz Karoline Kallis Sebastian Lettmaier Rainer Fietkau Christoph Bert

Strahlenther Onkol 2020 Jul 10;196(7):647-656. Epub 2020 Mar 10.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, 91054, Erlangen, Germany.

Purpose: To investigate the dosimetric influence of daily interfractional (inter) setup errors and intrafractional (intra) target motion on the planning target volume (PTV) and the possibility of an offline adaptive radiotherapy (ART) method to correct larger patient positioning uncertainties in image-guided radiotherapy for prostate cancer (PCa).

Materials And Methods: A CTV (clinical target volume)-to-PTV margin ranging from 15 mm in LR (left-right) and SI (superior-inferior) and 5-10 mm in AP (anterior-posterior) direction was applied to all patients. The dosimetric influence of this margin was retrospectively calculated by analysing systematic and random components of inter and intra errors of 31 consecutive intermediate- and high-risk localized PCa patients using daily cone beam computed tomography and kV/kV (kilo-Voltage) imaging. For each patient inter variation was assessed by observing the first 4 treatment days, which led to an offline ART-based treatment plan in case of larger variations.

Results: Systematic inter uncertainties were larger (1.12 in LR, 2.28 in SI and 1.48 mm in AP) than intra systematic errors (0.44 in LR, 0.69 in SI and 0.80 mm in AP). Same findings for the random error in SI direction with 3.19 (inter) and 2.30 mm (intra), whereas in LR and AP results were alike with 1.89 (inter) and 1.91 mm (intra) and 2.10 (inter) and 2.27 mm (intra), respectively. The calculated margin revealed dimensions of 4-5 mm in LR, 8-9 mm in SI and 6-7 mm in AP direction. Treatment plans which had to be adapted showed smaller variations with 1.12 (LR) and 1.72 mm (SI) for Σ and 4.17 (LR) and 3.75 mm (SI) for σ compared to initial plans with 1.77 and 2.62 mm for Σ and 4.46 and 5.39 mm for σ in LR and SI, respectively.

Conclusion: The currently clinically used margin of 15 mm in LR and SI and 5-10 mm in AP direction includes inter and intra uncertainties. The results show that offline ART is feasible which becomes a necessity with further reductions in PTV margins.
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http://dx.doi.org/10.1007/s00066-020-01596-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305089PMC
July 2020

Early Mortality of Brain Cancer Patients and its Connection to Cytomegalovirus Reactivation During Radiochemotherapy.

Authors:
Nicole L Goerig Benjamin Frey Klaus Korn Bernhard Fleckenstein Klaus Überla Manuel A Schmidt Arnd Dörfler Tobias Engelhorn Ilker Eyüpoglu Paul F Rühle Florian Putz Sabine Semrau Udo S Gaipl Rainer Fietkau

Clin Cancer Res 2020 07 14;26(13):3259-3270. Epub 2020 Feb 14.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Purpose: If routine diagnostics are inconclusive, neurologic deterioration and death of patients with brain cancer are attributed to tumor or therapy. Therefore, diagnosing symptoms of encephalopathy caused by human cytomegalovirus (HCMV) reactivation remains uncommon. We investigated the role of HCMV reactivation in neurologic decline and clinical outcome after the start of radiochemotherapy.

Experimental Design: HCMV analyses and extended MRI studies including additional independent retrospective neuroradiologic evaluation were performed at predetermined intervals and in case of sudden neurologic decline for 118 adult patients: 63 histologically proven high-grade gliomas, 55 with brain metastases. Immunophenotyping from simultaneously taken whole-blood samples was carried out to detect immune cells serving as prognostic marker for HCMV-associated complications. Symptomatic viremia and overall survival (OS) were the endpoints.

Results: Twenty-four percent (28/118) of all patients (12/44 glioblastoma, 3/13 anaplastic astrocytoma; 8/31 non-small cell lung cancer (NSCLC), 13/24 other brain metastases) developed HCMV-viremia during or within 4 weeks after radiotherapy; 21 of 28 patients experienced concurrent major neurologic decline, reversible by antiviral treatment. Identified by immunophenotyping, pretherapeutically low basophil counts predicted a high-risk for HCMV-associated encephalopathy (glioblastoma: = 0.002, NSCLC: = 0.02). Median OS was substantially reduced after HCMV-associated encephalopathy without MRI signs of tumor progression [glioblastoma: 99 vs. 570 days (calculated 1-year OS: 22% vs. 69%; = 0.01) and NSCLC: 47 vs. 219 days (calculated 1-year OS: 0% vs. 32%; = 0.02)].

Conclusions: For patients with brain cancer, HCMV reactivation after the start of radiochemotherapy is a frequent risk for cognitively detrimental but treatable encephalopathy and premature death. Routinely performed HCMV diagnostics, assessing basophil counts and study-based anti-viral regimens, are necessary to combat this hidden threat..
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3195DOI Listing
July 2020

On PTV definition for glioblastoma based on fiber tracking of diffusion tensor imaging data.

Authors:
Barbara Witulla Nicole Goerig Florian Putz Benjamin Frey Tobias Engelhorn Arnd Dörfler Michael Uder Rainer Fietkau Christoph Bert Frederik Bernd Laun

PLoS One 2020 6;15(1):e0227146. Epub 2020 Jan 6.

Institute of Radiology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Radiotherapy (RT) is commonly applied for the treatment of glioblastoma multiforme (GBM). Following the planning target volume (PTV) definition procedure standardized in guidelines, a 20% risk of missing non-local recurrences is present. Purpose of this study was to evaluate whether diffusion tensor imaging (DTI)-based fiber tracking may be beneficial for PTV definition taking into account the prediction of distant recurrences. 56 GBM patients were examined with magnetic resonance imaging (MRI) including DTI performed before RT after resection of the primary tumor. Follow-up MRIs were acquired in three month intervals. For the seven patients with a distant recurrence, fiber tracking was performed with three algorithms and it was evaluated whether connections existed from the primary tumor region to the distant recurrence. It depended strongly on the used tracking algorithm and the used tracking parameters whether a connection was observed. Most of the connections were weak and thus not usable for PTV definition. Only in one of the seven patients with a recurring tumor, a clear connection was present. It seems unlikely that DTI-based fiber tracking can be beneficial for predicting distant recurrences in the planning of PTVs for glioblastoma multiforme.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227146PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944332PMC
May 2020

Paragangliomas of the Head and Neck: Local Control and Functional Outcome Following Fractionated Stereotactic Radiotherapy.

Authors:
Thomas Weissmann Sebastian Lettmaier Johannes Roesch Veit Mengling Christoph Bert Heinrich Iro Joachim Hornung Rolf Janka Sabine Semrau Rainer Fietkau Florian Putz

Am J Clin Oncol 2019 11;42(11):818-823

Departments of Radiation Oncology.

Objectives: To investigate local control and functional outcome following state-of-the-art fractionated stereotactic radiotherapy (FSRT) for paragangliomas of the head and neck.

Methods: In total, 40 consecutive patients with paragangliomas of the head and neck received conventionally FSRT from 2003 to 2016 at the Department of Radiation Oncology of the University Hospital Erlangen. Local control, toxicities, and functional outcome were examined during follow-up. In total, 148 magnetic resonance imaging studies were subjected to longitudinal volumetric analysis using whole tumor segmentation in a subset of 22 patients.

Results: A total of 80.0% (32/40) of patients received radiotherapy as part of their primary treatment. In 20.0% (8/40) of patients, radiation was used as salvage treatment after tumor recurrence in patients initially treated with surgery alone. The median dose applied was 54.0 Gy (interdecile range, 50.4 to 56.0 Gy) in single doses of 1.8 or 2 Gy. Local control was 100% after a median imaging follow-up of 52.2 months (range, 0.8 to 152.9 mo). The volumetric analysis confirmed sustained tumor control in a subset of 22 patients and showed transient enlargement (range, 129.6% to 151.2%) in 13.6% of cases (3/22). After a median volumetric follow-up of 24.6 months mean tumor volume had diminished to 86.1% compared with initial volume. In total, 52.5% (21/40) of patients reported improved symptoms after radiotherapy, 40% (16/40) observed no subjective change with only 7.5% (3/40) reporting significant worsening.

Conclusions: State-of-the-art FSRT provides excellent control and favorable functional outcome in patients with paragangliomas of the head and neck. The volumetric analysis provides improved evidence for sustained tumor control.
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http://dx.doi.org/10.1097/COC.0000000000000614DOI Listing
November 2019

In Situ Small-Angle Neutron Scattering Investigation of Adsorption-Induced Deformation in Silica with Hierarchical Porosity.

Authors:
Lukas Ludescher Roland Morak Christian Balzer Anna M Waag Stephan Braxmeier Florian Putz Sebastian Busch Gennady Y Gor Alexander V Neimark Nicola Hüsing Gudrun Reichenauer Oskar Paris

Langmuir 2019 Sep 22;35(35):11590-11600. Epub 2019 Aug 22.

Institute of Physics , Montanuniversitaet Leoben , Franz-Josef-Str. 18 , 8700 Leoben , Austria.

Adsorption-induced deformation of a series of silica samples with hierarchical porosity has been studied by in situ small-angle neutron scattering (SANS) and in situ dilatometry. Monolithic samples consisted of a disordered macroporous network of struts formed by a 2D lattice of hexagonally ordered cylindrical mesopores and disordered micropores within the mesopore walls. Strain isotherms were obtained at the mesopore level by analyzing the shift of the Bragg reflections from the ordered mesopore lattice in SANS data. Thus, SANS essentially measured the radial strain of the cylindrical mesopores including the volume changes of the mesopore walls due to micropore deformation. A HO/DO adsorbate with net zero coherent neutron scattering length density was employed in order to avoid apparent strain effects due to intensity changes during pore filling. In contrast to SANS, the strain isotherms obtained from in situ dilatometry result from a combination of axial and radial mesopore deformation together with micropore deformation. Strain data were quantitatively analyzed with a theoretical model for micro-/mesopore deformation by combining information from nitrogen and water adsorption isotherms to estimate the water-silica interaction. It was shown that in situ SANS provides complementary information to dilatometry and allows for a quantitative estimate of the elastic properties of the mesopore walls from water adsorption.
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http://dx.doi.org/10.1021/acs.langmuir.9b01375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733155PMC
September 2019

Salivary gland carcinoma (SGC) with perineural spread and/or positive resection margin - high locoregional control rates after photon (chemo) radiotherapy - experience from a monocentric analysis.

Authors:
Marlen Haderlein Claudia Scherl Sabine Semrau Sebastian Lettmaier Markus Hecht Florian Putz Heinrich Iro Abbas Agaimy Rainer Fietkau

Radiat Oncol 2019 Apr 23;14(1):68. Epub 2019 Apr 23.

Department of Radiation Oncology, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054, Erlangen, Germany.

Background: The aim was to evaluate the outcome, especially locoregional control of patients with locally advanced salivary gland carcinoma (SGC) with perineural spread (Pn1) and/or positive resection margins (R1/2) after postoperative photon (chemo) radiotherapy in a single centre.

Methods: We retrospectively reviewed data of 65 patients with newly diagnosed locally advanced SGC without distant metastases who underwent radio (chemo) therapy in the department of radiation oncology of the university hospital of Erlangen from January 2000 until April 2017. Kaplan Meier method was used to calculate survival and recurrence rates. In univariate analysis the log-rank test was used to correlate patient-/tumor- and treatment-related parameters to survival and recurrence rates.

Results: Median follow-up was 45 months (range: 6; 215). After 1, 3, 5 years cumulative incidence of local and locoregional failure was 3.1, 7.0, 7.0% and 3.1, 9.7, 12.9%, whereas cumulative incidence of distant metastases (DM) was 15.6, 36.0, 44.0%. After 1,3, 5 years cumulative Overall (OS) and Disease-free survival (DFS) was 90.5, 74.9, 63.9% and 83.0, 54.8, 49.4%. The only significant predictor for decreased local and locoregional control was a macroscopic resection margin(R2) (p = 0.002 and p = 0.04). High-grade histology (p = 0.006), lymph node metastases with extracapsular spread (p = 0.044) and an advanced T-stage (p = 0.031) were associated with an increased rate of DM. High-grade histology was the only factor predicting for a decreased DFS (p = 0.014).

Conclusion: Photon radiotherapy leads to high local and locoregional control rates in a high-risk patient population with SGC with microscopically positive resection margins and/or perineural spread. The most common site of disease recurrence was distant metastases. Therefore the real challenge for the future should be to prevent distant metastases.
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http://dx.doi.org/10.1186/s13014-019-1260-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480845PMC
April 2019

Time course of pain response and toxicity after whole-nerve-encompassing LINAC-based stereotactic radiosurgery for trigeminal neuralgia-a prospective observational study.

Authors:
Selim Koca Luitpold Distel Dorota Lubgan Thomas Weissmann Ulrike Lambrecht Marga Lang-Welzenbach Ilker Eyüpoglu Barbara Bischoff Michael Buchfelder Sabine Semrau Rainer Fietkau Sebastian Lettmaier Florian Putz

Strahlenther Onkol 2019 Aug 15;195(8):745-755. Epub 2019 Mar 15.

Department of Radiation Oncology, Friedrich-Alexander-University Erlangen-Nuremberg, Universitaetsstraße 27, 91054, Erlangen, Germany.

Purpose: To prospectively evaluate the time course of pain response and toxicity after linear accelerator-based whole-nerve-encompassing radiosurgery (LINAC-SRS) using a uniform treatment schedule for dosing and target volume definition in patients with refractory trigeminal neuralgia.

Methods: From December 2012 to December 2016, 21 patients were treated using a standardized protocol. Patients received LINAC-SRS with 70 Gy to the cisternal portion while aiming for the 90% isodose to fully envelope the nerve in one cross-sectional plane. Data on pain, analgesics, and toxicity were gathered prospectively. Four time intervals (1-6, 6-12, 12-18, and 18-24 months) were defined and compared to baseline and each other.

Results: The median follow-up from radiotherapy was 16 months. Freedom from pain was achieved at least once in 90.5, 81.0, and 85.7% of patients for everyday pain, rest pain, and pain peaks, respectively. At 1-6 months, pain was significantly reduced in everyday routine (mean VAS, 2.0/10 vs. 5.8/10; P = 0.004), at rest (1.5/10 vs. 4.0/10; P = 0.002), and for pain peaks (2.9/10 vs. 10/10; P < 0.001), as was the number of analgesics (mean 1.5 vs. 2.9; P < 0.001). No significant increase in pain or analgesics was observed for subsequent time intervals. At last follow-up, reduction in pain compared to baseline for everyday routine (2.1/10 vs. 5.8/10; P = 0.010) and for pain peaks (3.3/10 vs. 10/10; P < 0.001) was significant, whereas it was not for rest pain (1.8/10 vs. 3.9/10; P = 0.073). Most toxicities were related to trigeminal nerve impairment, with 42.9% reporting new-onset hypoesthesia at last follow-up.

Conclusion: This study provides prospective data after whole nerve encompassing LINAC-SRS for trigeminal neuralgia. No significant pain relapse was observed.
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http://dx.doi.org/10.1007/s00066-019-01450-9DOI Listing
August 2019

Mechanical Characterization of Hierarchical Structured Porous Silica by in Situ Dilatometry Measurements during Gas Adsorption.

Authors:
Christian Balzer Anna M Waag Florian Putz Nicola Huesing Oskar Paris Gennady Y Gor Alexander V Neimark Gudrun Reichenauer

Langmuir 2019 Feb 12;35(8):2948-2956. Epub 2019 Feb 12.

Bavarian Center for Applied Energy Research , Magdalene-Schoch-Str. 3 , 97074 Würzburg , Germany.

Mechanical properties of hierarchically structured nanoporous materials are determined by the solid phase stiffness and the pore network morphology. We analyze the mechanical stiffness of hierarchically structured silica monoliths synthesized via a sol-gel process, which possess a macroporous scaffold built of interconnected struts with hexagonally ordered cylindrical mesopores. We consider samples with and without microporosity within the mesopore walls and analyze them on the macroscopic level as well as on the microscopic level of the mesopores. Untreated as-prepared samples still containing some organic components and the respective calcined and sintered counterparts of varying microporosity are investigated. To determine Young's moduli on the level of the macroscopic monoliths, we apply ultrasonic run time measurements, while Young's moduli of the mesopore walls are obtained by analysis of the in situ strain isotherms during N adsorption at 77 K. For the latter, we extended our previously reported theoretical approach for this type of materials by incorporating the micropore effects, which are clearly not negligible in the calcined and most of the sintered samples. The comparison of the macro- and microscopic Young's moduli reveals that both properties follow essentially the same trends, that is, calcination and sintering increase the mechanical stiffness on both levels. Consequently, stiffening of the monolithic samples can be primarily attributed to stiffening of the backbone material which is consistent with the fact that the morphology on the mesopore level is mainly preserved with the post-treatments applied.
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http://dx.doi.org/10.1021/acs.langmuir.8b03242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393851PMC
February 2019

Fractionated stereotactic radiation therapy for adrenal metastases: contributing to local tumor control with low toxicity.

Authors:
Kim Burjakow Rainer Fietkau Florian Putz Nils Achterberg Sebastian Lettmaier Stefan Knippen

Strahlenther Onkol 2019 Mar 29;195(3):236-245. Epub 2018 Oct 29.

Department of Radiation Oncology, Friedrich-Schiller-University Jena, Bachstraße 18, 07743, Jena, Germany.

Purpose: To report on the Erlangen (UK-Er) experience with linear accelerator stereotactic body radiation therapy (LINAC SBRT) for adrenal metastasis from various primary tumors.

Materials And Methods: 33 patients were treated. Primary sites included lung (n = 19), melanoma (n = 8), colorectal (n = 2), hepatocellular (n = 1), esophageal (n = 2), and breast cancer (n = 1). 14 patients were treated palliatively, 19 patients were treated with local curative intent.

Radiation Treatment: Treatment planning was done based on an exhale, mid-ventilation, and inspiration CT series. Further planning CTs were done to check for the correctness of the breathing pattern. Irradiation was performed using a NOVALIS (Varian, Palo Alto, CA, USA; Brainlab AG, München, Germany) linear accelerator. The isocenter was verified before each treatment session using the BrainLab ExacTrac® (Brainlab AG, München, Germany) system to minimize setup errors. Dose was prescribed to the planning target volume (PTV) surrounding 90% isodose.

Follow-up: Depending on their overall performance status and prognosis, patients received clinical check-ups and radiological imaging. Median follow-up was 11 months.

Statistical Analysis: IBM SPSS v. 24 was used for univariate analysis using Kaplan-Meier curves, nonparametric Kruskal-Wallis test, and the chi-square test for frequency distributions. Toxicity was graded according to NCI CTCAE v4.0. Depending on radiologic imaging, patients were classified as stable, regression, and progression.

Results: Median survival was 11 months, median PFS was 5 months. Median local failure-free survival was 21 months. Patients who were treated with curative intent showed a better survival curve (p < 0.0001) and PFS (p = 0.004). BED ranged from 42 to 108.8 Gy, median BED was 67.2 Gy. Three BED groups were formed. Overall survival curves differed significantly (p = 0.046), favoring the high-dose group. 21 patients were free from any adverse events or discomfort. In 7 cases, a grade I toxicity was noted.
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http://dx.doi.org/10.1007/s00066-018-1390-3DOI Listing
March 2019

Compressible, Thermally Insulating, and Fire Retardant Aerogels through Self-Assembling Silk Fibroin Biopolymers Inside a Silica Structure-An Approach towards 3D Printing of Aerogels.

Authors:
Hajar Maleki Susan Montes Nastaran Hayati-Roodbari Florian Putz Nicola Huesing

ACS Appl Mater Interfaces 2018 Jul 21;10(26):22718-22730. Epub 2018 Jun 21.

Chemistry and Physics of Materials , Paris-Lodron University Salzburg , Jakob-Haringer-Strasse 2a , 5020 Salzburg , Austria.

Thanks to the exceptional materials properties of silica aerogels, this fascinating highly porous material has found high-performance and real-life applications in various modern industries. However, a requirement for a broadening of these applications is based on the further improvement of the aerogel properties, especially with regard to mechanical strength and postsynthesis processability with minimum compromise to the other physical properties. Here, we report an entirely novel, simple, and aqueous-based synthesis approach to prepare mechanically robust aerogel hybrids by cogelation of silk fibroin (SF) biopolymer extracted from silkworm cocoons. The synthesis is based on sequential processes of acid catalyzed (physical) cross-linking of the SF biopolymer and simultaneous polycondensation of tetramethylorthosilicate (TMOS) in the presence of 5-(trimethoxysilyl)pentanoic acid (TMSPA) as a coupling agent and subsequent solvent exchange and supercritical drying. Extensive characterization by solid-state H NMR, Si NMR, and 2D H-Si heteronuclear correlation (HETCOR) MAS NMR spectroscopy as well as various microscopic techniques (SEM, TEM) and mechanical assessment confirmed the molecular-level homogeneity of the hybrid nanostructure. The developed silica-SF aerogel hybrids contained an improved set of material properties, such as low density (ρ = 0.11-0.2 g cm), high porosity (∼90%), high specific surface area (∼400-800 m g), and excellent flexibility in compression (up to 80% of strain) with three orders of magnitude improvement in the Young's modulus over that of pristine silica aerogels. In addition, the silica-SF hybrid aerogels are fire retardant and demonstrated excellent thermal insulation performance with thermal conductivities (λ) of 0.033-0.039 W m K. As a further advantage, the formulated hybrid silica-SF aerogel showed an excellent printability in the wet state using a microextrusion-based 3D printing approach. The printed structures had comparable properties to their monolith counterparts, improving postsynthesis processing or shaping of the silica aerogels significantly. Finally, the hybrid silica-SF aerogels reported here represent significant progress for a mechanically customized and robust aerogel for multipurpose applications, namely, as a customized thermal insulation material or as a dual porous open-cell biomaterial used in regenerative medicine.
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http://dx.doi.org/10.1021/acsami.8b05856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513757PMC
July 2018

Quantifying adsorption-induced deformation of nanoporous materials on different length scales.

Authors:
Roland Morak Stephan Braxmeier Lukas Ludescher Florian Putz Sebastian Busch Nicola Hüsing Gudrung Reichenauer Oskar Paris

J Appl Crystallogr 2017 Oct 14;50(Pt 5):1404-1410. Epub 2017 Sep 14.

Institute of Physics, Montanuniversität Leoben, Franz-Josef Strasse 18, Leoben, 8700, Austria.

A new setup combining small-angle neutron scattering (SANS) and dilatometry was used to measure water-adsorption-induced deformation of a monolithic silica sample with hierarchical porosity. The sample exhibits a disordered framework consisting of macropores and struts containing two-dimensional hexagonally ordered cylindrical mesopores. The use of an HO/DO water mixture with zero scattering length density as an adsorptive allows a quantitative determination of the pore lattice strain from the shift of the corresponding diffraction peak. This radial strut deformation is compared with the simultaneously measured macroscopic length change of the sample with dilatometry, and differences between the two quantities are discussed on the basis of the deformation mechanisms effective at the different length scales. It is demonstrated that the SANS data also provide a facile way to quantitatively determine the adsorption isotherm of the material by evaluating the incoherent scattering contribution of HO at large scattering vectors.
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http://dx.doi.org/10.1107/S1600576717012274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627682PMC
October 2017

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

Authors:
Christian Hoffmann Luitpold Distel Stefan Knippen Thomas Gryc Manuel Alexander Schmidt Rainer Fietkau Florian Putz

Neuro Oncol 2018 01;20(2):268-278

Department of Radiation Oncology, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.

Background: Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance.

Methods: Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes.

Results: On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147).

Conclusion: In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival.
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http://dx.doi.org/10.1093/neuonc/nox150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777481PMC
January 2018

Setting Directions: Anisotropy in Hierarchically Organized Porous Silica.

Authors:
Florian Putz Roland Morak Michael S Elsaesser Christian Balzer Stephan Braxmeier Johannes Bernardi Oskar Paris Gudrun Reichenauer Nicola Hüsing

Chem Mater 2017 Sep 31;29(18):7969-7975. Epub 2017 Aug 31.

Chemistry and Physics of Materials, Paris Lodron University Salzburg, 5020 Salzburg, Austria.

Structural hierarchy, porosity, and isotropy/anisotropy are highly relevant factors for mechanical properties and thereby the functionality of porous materials. However, even though anisotropic and hierarchically organized, porous materials are well known in nature, such as bone or wood, producing the synthetic counterparts in the laboratory is difficult. We report for the first time a straightforward combination of sol-gel processing and shear-induced alignment to create hierarchical silica monoliths exhibiting anisotropy on the levels of both, meso- and macropores. The resulting material consists of an anisotropic macroporous network of struts comprising 2D hexagonally organized cylindrical mesopores. While the anisotropy of the mesopores is an inherent feature of the pores formed by liquid crystal templating, the anisotropy of the macropores is induced by shearing of the network. Scanning electron microscopy and small-angle X-ray scattering show that the majority of network forming struts is oriented towards the shearing direction; a quantitative analysis of scattering data confirms that roughly 40% of the strut volume exhibits a preferred orientation. The anisotropy of the material's macroporosity is also reflected in its mechanical properties; i.e., the Young's modulus differs by nearly a factor of 2 between the directions of shear application and perpendicular to it. Unexpectedly, the adsorption-induced strain of the material exhibits little to no anisotropy.
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http://dx.doi.org/10.1021/acs.chemmater.7b03032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627989PMC
September 2017

Idelalisib may have the potential to increase radiotherapy side effects.

Authors:
Thomas Gryc Florian Putz Nicole Goerig Sonia Ziegler Rainer Fietkau Luitpold V Distel Barbara Schuster

Radiat Oncol 2017 Jun 28;12(1):109. Epub 2017 Jun 28.

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany.

Introduction: Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin's lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells.

Methods: We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL. Radiosensitivity tests were performed for the index patient under Idelalisib and after the addition of Idelalisib to healthy individuals' blood. Radiosensitivity in human lymphocytes was analyzed with a three color in situ hybridization assay. Primary skin fibroblasts were studied after a treatment with Idelalisib for apoptosis, necrosis and cell cycle using flow cytometry. DNA double-strand break repair was analyzed by γH2AX immunostaining.

Results: The index patient presented a strong grade 2 radiodermatitis and grade 3 mucositis after irradiation with 20 Gy and a simultaneous intake of Idelalisib. Irradiations without Idelalisib medication were well tolerated and resulted in not more than grade 1 radiodermatitis. The index patient under Idelalisib had a radiosensitivity of 0.62 B/M which is in the range of clearly radiosensitive patients. A combined treatment of lymphocytes with 2 Gy and 10 nmol/l Idelalisib showed a tendency to an increased radiosensitivity. We found a clear increase of apoptosis as a result of the combined treatment in the Idelalisib dose range of 1 to 100 nmol/l compared to solely irradiated cells or solely Idelalisib treated cells (p = 0.05).

Conclusion: A combined Idelalisib radiotherapy treatment has an increased risk of side effects. However, combined therapy seems to be feasible when patients are monitored closely.
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http://dx.doi.org/10.1186/s13014-017-0827-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490234PMC
June 2017