Prognostic factors for survival and radiation necrosis after stereotactic radiosurgery alone or in combination with whole brain radiation therapy for 1-3 cerebral metastases

Background: In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. Patients and methods: 340 patients with 1-3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Results: Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS 2.5 ml: 234 days), prescribed dose ( 18 Gy: 351 days), gender (male: 235 days; female: 327 days) and whole brain radiotherapy (+ WBRT: 341 days/-WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA class and gender. MRI and clinical symptoms suggested radiation necrosis in 21 patients after SRS +/-whole brain radiotherapy (WBRT). In five patients clinically relevant radiation necrosis was confirmed by PET imaging. Conclusions: SRS alone or in combination with WBRT represents a feasible option as initial treatment for patients with brain metastases; however a significant subset of patients may develop neurological complications. Performance status, RPA class and gender were identified to predict improved survival in cerebral metastasized patients

Strengthening resilience in reconstruction after extreme events – Insights from flood affected communities in Germany

Disaster resilience and building back better (BBB) are key concepts in the disaster risk and resilience discourse; however, these concepts often remain vague for many stakeholders involved in recovery. Based on the reconstruction process in Germany after the extreme floods of 2021 that caused more than 180 deaths, we explore challenges and opportunities to strengthen resilient recovery in one of the world's wealthiest and most technologically advanced countries. We examine factors that contributed to severe losses and damages and assess different phases of the reconstruction process. In addition, we identify and discuss measures to support resilience building, focusing particularly on issues of land management, planning and infrastructure. Our findings provide new insights into how funding schemes and planning approaches contribute to or block resilience building and BBB. The results are also highly relevant for other world regions hit by extreme events and for the international discourse on disaster resilience, loss and damage and BBB, for example, how funding arrangements and quality criteria need to be designed to support disaster resilient reconstruction

Adeno-Associated Viral Vector-Mediated Transgene Expression Is Independent of DNA Methylation in Primate Liver and Skeletal Muscle

Recombinant adeno-associated viral (rAAV) vectors can support long-term transgene expression in quiescent tissues. Intramuscular (IM) administration of a single-stranded AAV vector (ssAAV) in the nonhuman primate (NHP) results in a peak protein level at 2–3 months, followed by a decrease over several months before reaching a steady-state. To investigate transgene expression and vector genome persistence, we previously demonstrated that rAAV vector genomes associate with histones and form a chromatin structure in NHP skeletal muscle more than one year after injection. In the mammalian nucleus, chromatin remodeling via epigenetic modifications plays key role in transcriptional regulation. Among those, CpG hyper-methylation of promoters is a known hallmark of gene silencing. To assess the involvement of DNA methylation on the transgene expression, we injected NHP via the IM or the intravenous (IV) route with a recombinant ssAAV2/1 vector. The expression cassette contains the transgene under the transcriptional control of the constitutive Rous Sarcoma Virus promoter (RSVp). Total DNA isolated from NHP muscle and liver biopsies from 1 to 37 months post-injection was treated with sodium bisulfite and subsequently analyzed by pyrosequencing. No significant CpG methylation of the RSVp was found in rAAV virions or in vector DNA isolated from NHP transduced tissues. Direct de novo DNA methylation appears not to be involved in repressing transgene expression in NHP after gene transfer mediated by ssAAV vectors. The study presented here examines host/vector interactions and the impact on transgene expression in a clinically relevant model

Reactivation of Floodplains in River Restorations: Long-Term Implications on the Mobility of Floodplain Sediment Deposits

Nowadays, national and international requirements and laws emphasize the “natural” development of river-floodplain systems. One goal is to increase the connectivity between the river and its floodplains and thus reactivate floodplains as flooding areas, which potentially increases the mobility of fine sediments. The objective of this study is to analyze the long-term effects of reactivated floodplains on the mobility of floodplain deposits of small rivers based on two river restoration scenarios: elevating the riverbed or lowering the floodplains. Past channel fixation and degradation as well as the subsequent increase in the floodplain elevation led to the decoupling of the channel and floodplain morphodynamics associated with the reduction of the habitat connectivity. Here, the floodplain sedimentation rates were determined using a numerical model based on the Delft3D software. The novelty of these numerical investigations is the morphological long-term analysis over timescales of decades, which is not comparable to other short-term hydrodynamic and morphodynamic studies for small meandering lowland rivers. The results of 11 river restoration scenarios show that lowering the floodplain and raising the riverbed elevation both lead to an increase in the fine sediment deposition on the floodplain. However, lowering the floodplain elevation is generally more effective. Based on the numerical model results and the assumption of a fixed river channel, only anthropogenic activity might have increased the amount of fine sediments deposited on floodplains and has accelerated the decoupling of the floodplains from the riverbed in the past centuries

Helical tomotherapy: Comparison of Hi-ART and Radixact clinical patient treatments at the Technical University of Munich.

The helical tomotherapy (HT) Hi-ART system was installed at our department in April 2007. In July 2018 the first Radixact system in Germany has been launched for clinical use. We present differences, advantages and disadvantages and show future perspectives in patient treatment using two HT devices. We investigate patient characteristics, image quality, radiotherapy treatment specifications and analyze the time effort for treatments with the Hi-ART system from April 2010 until May 2017 and compare it to the data acquired in the first nine months of usage of the Radixact system. Comparing the Hi-ART and Radixact system, the unique option of integrated MVCT image acquisition has experienced distinct improvement in image quality. Time effort for irradiation treatment could be improved resulting in a mean beam on time for craniospinal axis treatment of 636.2 s for the Radixact system compared to 915.9 s for the Hi-ART system. The beneficial use of tomotherapy for complex target volumes is demonstrated by a head and neck tumor case and craniospinal axis treatment. With the Radixact system MVCT image quality has been improved allowing for fast and precise interfraction dose adaptation. The improved time effort for patient treatment could increase the accessibility for clinical usage

First experiences with PET-MRI/CT in radiotherapy planning for cervical cancer.

Purpose: PET-CT has recently been included in the NCCN staging recommendations for cervical cancer stages II–IV and is already routinely applied to radiotherapy planning for other malignancies, as it is expected to provide higher accuracy for the detection of areas with tumor cell spread. In this study, we report on our first experiences of PET-based radiotherapy planning for cervical cancer. Methods: 19 patients with cervical cancer that underwent pre-therapeutic PET imaging treated at our institution between January 2016 and April 2019 were included in the study. Information on the primary tumor, lymph node involvement, metastatic spread and changes in the radiotherapy procedure based on the PET findings are described. Results: A previously unknown primary tumor extension that was detected by PET imaging in one patient. In patients who underwent a PET before the systematic pelvic and paraaortic lymphonodectomy (n = 2), PET was false negative for pelvic lymph node metastases in 50%. In patients who underwent a PET after the systematic LNE (n = 13), additional lymph node metastases were detected in seven patients (53.80%). Distant metastases were suspected in three patients (15.7%) based on PET imaging. The suspicion was confirmed in one patient (peritoneal spread) and excluded in two patients (supra-diaphragmatic lymph nodes). In 13 patients (68.4%), RT procedures were altered due to findings in PET imaging. Conclusion: PET-based radiochemotherapy planning may improve control rates by identifying areas of tumor cell spread eligible for dose escalation. False positivity, however, should be excluded in patients with findings that lead to major modifications of the therapeutic strategy