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.

The goal of this work is to understand adsorption-induced deformation of hierarchically structured porous silica exhibiting well-defined cylindrical mesopores. For this purpose, we performed an in situ dilatometry measurement on a calcined and sintered monolithic silica sample during the adsorption of N2 at 77 K. To analyze the experimental data, we extended the adsorption stress model to account for the anisotropy of cylindrical mesopores, i.e., we explicitly derived the adsorption stress tensor components in the axial and radial direction of the pore. For quantitative predictions of stresses and strains, we applied the theoretical framework of Derjaguin, Broekhoff, and de Boer for adsorption in mesopores and two mechanical models of silica rods with axially aligned pore channels: an idealized cylindrical tube model, which can be described analytically, and an ordered hexagonal array of cylindrical mesopores, whose mechanical response to adsorption stress was evaluated by 3D finite element calculations. The adsorption-induced strains predicted by both mechanical models are in good quantitative agreement making the cylindrical tube the preferable model for adsorption-induced strains due to its simple analytical nature. The theoretical results are compared with the in situ dilatometry data on a hierarchically structured silica monolith composed by a network of mesoporous struts of MCM-41 type morphology. Analyzing the experimental adsorption and strain data with the proposed theoretical framework, we find the adsorption-induced deformation of the monolithic sample being reasonably described by a superposition of axial and radial strains calculated on the mesopore level. The structural and mechanical parameters obtained from the model are in good agreement with expectations from independent measurements and literature, respectively.

To report outcome (freedom from local progression [FFLP], overall survival [OS] and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO).Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose [BED10] ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). Three hundred twenty-six patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall-RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%).Unadjusted FFLP was higher after SBRT vs Pall-RT (P = .026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression.Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. One-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway.

Background: 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. Methods: Longitudinal volumetric analysis was performed in a consecutive cohort of 120 patients and 190 brain metastases (>0.065 cm 3 in volume / > ∼5 mm in diameter) treated exclusively with FSRT (n = 98) and SRS (n = 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. Results: Metastases treated with FSRT were significantly larger at baseline (mean, 4.66 vs. 0.40 cm 3 , p < 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 (p = 0.022). Overall radionecrosis rate at 12 months was 3.4% for FSRT and 14.8% for SRS (p = 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%, p = 0.041). In multivariate analysis, FSRT was associated with reduced risk of progression (HR 0.47, p = 0.015) and reduced risk of radionecrosis (HR 0.18, p = 0.045). Conclusions: 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.

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 N2 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.

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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Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types. Methods. The phenomenon of one cell being internalized into another, which we refer to as “cell-in-cell event,” was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death. Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm2. Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients' survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p = 0.008). Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies.