Overall survival after reirradiation of spinal metastases – independent validation of predictive models

Background: It is unknown if survival prediction tools (SPTs) sufficiently predict survival in patients who undergo palliative reirradiation of spinal metastases. We therefore set out to clarify if SPTs can predict survival in this patient population. Methods: We retrospectively analyzed spinal reirradiations performed (n = 58, 52 patients, 44 included in analysis). SPTs for patients with spinal metastases were identified and compared to a general palliative score and to a dedicated SPT to estimate prognosis in palliative reirradiation independent of site (SPT-Nieder). Results: Consistently in all tests, SPT-Nieder showed best predictive performance as compared to other tools. Items associated with survival were general condition (KPS), liver metastases, and steroid use. Other factors like primary tumor site, pleural effusion, and bone metastases were not correlated with survival. We adapted an own score to the data which performed comparable to SPT-Nieder but avoids the pleural effusion item. Both scores showed good performance in identifying long-term survivors with late recurrences. Conclusions: Survival prediction in case of spinal reirradiation is possible with sufficient predictive separation. Applying SPTs in case of reirradiation helps to identify patients with good life expectancy who might benefit from dose escalation or longer treatment courses

Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases

Background: Stereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose–response relationship is analyzed based on Biologically Equivalent Dose (BED). Patients and methods: 50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5x12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed. Results: The median BED2 was 83 Gy. 12 lesions were treated with a BED2 of &lt;80 Gy, and 38 lesions with a BED2 of <80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%. Conclusion: Intensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control

Automated VMAT planning for postoperative adjuvant treatment of advanced gastric cancer

Background: Postoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners. Methods: For 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis. Results: Both manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by &gt; 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p &lt;  0.001)). Median dose to the liver was lower as well (18.8 ± 2.3 Gy vs. 17.1 ± 3.6 Gy, p = 0.048). In addition, Dmax of the spinal cord was significantly reduced (38.3 ± 3.7 Gy vs. 31.6 ± 2.6 Gy, p &lt;  0.001). Substantial improvements in dose conformity and integral dose were achieved with autoVMAT plans (4.2% and 9.1%, respectively; p &lt;  0.001). Due to the better OAR sparing in the autoVMAT plans compared to manVMAT plans, the predicted NTCPs for the left and right kidney and the liver-PTV were significantly reduced by 11.3%, 12.8%, 7%, respectively (p ≤ 0.001). Delivery time and total number of monitor units were increased in autoVMAT plans (from 168 ± 19 s to 207 ± 26 s, p = 0.006) and (from 781 ± 168 MU to 1001 ± 134 MU, p = 0.003), respectively. Conclusions: For postoperative/adjuvant radiotherapy of advanced gastric cancer, involving a complex target shape, automated VMAT planning is feasible and can substantially reduce the dose to the kidneys and the liver, without compromising the target dose delivery

Neue synthetische Eisenchelatoren auf der Basis von Monosacchariden in Analogie zu bakteriellen Siderophoren

Im Rahmen der vorliegenden Arbeit wurde erstmalig die Synthese von artifiziellen Siderophoren auf Kohlenhydratbasis verwirklicht. Die nach dem Vorbild der natürlichen Siderophore Enterobaktin und Desferrichrom hergestellten Catecholat- und Hydroxamat- Verbindungen sollten anschließend einer breiten physikochemischen und biologischen Testung unterzogen werden, um ihre Eigenschaften als Eisenchelatoren zu untersuchen. Des Weiteren sollte ein Beitrag zur Klärung des Transportmechanismus von Eisen-Siderophor- Komplexen geleistet werden. Es wurden verschiedene mehrstufige Synthesewege ausgearbeitet, die für die Herstellung von vorwiegend Methyl-a-D-Pyranosiden mit Catecholateinheiten einerseits und Hydroxamatbzw. Revershydroxamateinheiten andererseits geeignet sind. Monosaccharide wurden als Grundgerüstsubstanzen ausgewählt, da diese eine vorgegebene stereochemische Struktur, die im Laufe der Synthese beibehalten werden sollte, und eine im Allgemeinen gute physiologische Verträglichkeit beim Menschen haben

Desodorierung : mathematisch-mechanistische Modellierung, Experimente

Marc HeggemannPaderborn, Univ., Diss., 200

The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases

Background: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO)stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n= 213 pts.; 300 lesions) and breast cancer (n= 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control

Zell- und molekularbiologische Charakterisierung neuartiger Zell-Zell-Verbindungsarten in Glioma-Zellen und mesenchymalen Stammzellen

Zell-Zell-Verbindungen ("Junctions") der Adhaerens-Kategorie sind durch zelltypische Kombinationen von Transmembran-Glykoproteinen der Cadherin-Großfamilie und damit assoziierten cytoplasmatischen Plaque-Proteinen bestimmt, die meist Actin-Mikrofilamente verankern. Sie stellen Hauptstrukturelemente des spezifischen Gewebe-Aufbaus und Zusammenhalts dar und sind darüberhinaus auch an vielen dynamischen Zellfunktionen beteiligt. In den letzten Jahren hatte sich zunehmend deutlicher herausgestellt, dass viele "Adhering Junction" (AJ) besonderer Zelltypen nicht unter die bisher bekannten Klassen bzw. Typen von AJ subsumieren lassen, sondern aufgrund ihrer Struktur, vor allem aber ihrer besonderen molekularen Zusammensetzung eigene Strukturtypen sui generis darstellen. Im Rahmen dieser Arbeit sind zwei AJ-Typen menschlicher Zellen und Gewebe in ihrer molekularen Zusammensetzung bestimmt worden, wobei Untersuchungen an Zellkulturen sowie zellbiologische, biochemische, immunologische und molekularbiologische Methoden benutzt wurden. Astrocytom-Zellen, auch Astrocyten, und Glioblastom-Zellen bilden viele AJ unterschiedlicher Größe aus, die durch einen recht kompakten Plaque ausgezeichnet sind und die Cadherine N-Cadherin, Cadherin-11 sowie in einigen Zellkolonien immer wieder auch VE-Cadherin enthalten, die auf der Binnenseite mit den Plaque-Proteinen alpha- und beta-Catenin, den weiteren armadillo-Proteinen p120ctn, ARVCF und Plakoglobin sowie - überraschenderweise - dem von Desmosomen her bekannten Protein Plakophilin 2 und den - von "Tight Junctions" bekannten - Plaque-Proteinen ZO-1, ZO-2 und Cingulin komplexiert sind und zusammen mit Afadin und dem Actin-bindenden Protein Vinculin Mikrofilament-Bündel des Actin-Typs verankern. Molekulare Interaktionen innerhalb dieser Struktur werden aufgrund erster Immunpräzipitations-Ergebnisse ebenso diskutiert wie die mögliche Bedeutung dieses AJ-Typs, dem der Name Colligatio permixta gegeben wurde, in Embryologie, Histologie und Pathologie. Dabei ist das spontane klonale Auftreten einer Unterform, die das - erstmals außerhalb von Gefäß-Endothelien nachgewiesene - VE-Cadherin enthält, auch deshalb von besonderem Interesse, weil der Astrocyt - gewissermaßen seiner natürlichen Position nach - oft eine räumliche wie funktionale Beziehung zu Blutgefäßen, besonders Kapillaren erkennen lässt. Neue tumordiagnostischen Möglichkeiten wie entwicklungsbiologischen Implikationen der Entdeckung dieses neuen Junction-Typs werden besprochen. Gleichzeitig ist in Kulturen bestimmter menschlicher Knochenmarkzellen, sogenannter "mesenchymaler Stammzellen", ein anderer - in seiner molekularen Zusammensetzung äußerst schlichter - AJ-Typ entdeckt worden, der ebenfalls N-Cadherin und Cadherin-11 in Verbindung mit signifikanten Mengen der Plaque-Proteine alpha- und beta-Catenin, Protein p120ctn und Afadin enthält und vielfach auch Actinfilament-Bündel verankert. Dieser AJ-Typ erscheint in der Regel in Form kleiner Puncta adhaerentia (Durchmesser meist im Bereich 30-200 nm), wobei diese sowohl am eigentlichen zentralen Zellkörper als auch auf tentakel-artigen Zellausläufern verschiedener, teils sehr großer Länge (bis über 400 µm lang) vorkommen, die einerseits durch Actinfilament-Bündel in Verbindung mit Ezrin, alpha-Actinin und Myosin stabilisiert sind, andererseits aber auch Mikrotubuli enthalten. Solche Zellausläufer (Processus adhaerentes) können dabei sowohl über durch Puncta hergestellte Brückenstrukturen mit Ausläufern anderer Zellen verbunden sein, andererseits aber auch tief und eng in entsprechenden, z.T. sehr häufigen und langen (bis über 40 µm) Invaginationen von Nachbarzellen verankert sein, wobei die AJ-Regionen der Puncta beider Zellen gewissermaßen zu einer riesigen Doppelhülle (Manubrium adhaerens) fusioniert sein können. Hinweise auf ein Vorkommen solcher Processus adhaerentes in der Embryogenese und mögliche biologische Funktionen solcher Strukturen werden ebenso besprochen wie Einsatzmöglichkeiten und mögliche Bedeutung in der Diagnostik

"Jag måste andas, verkligen." Om förtrollning, genuskonstruktioner och homosocialitet i Twilightfandomen

This essay examines the Twilight fandom and the experience of being a fan. Our main purpose is to show the fandom culture from the fan’s point of view. This ambition stems from the notion that the Twilight fans themselves seldom are addressed and allowed to speak in their own words in regards to what it means to be a Twilight fan and how they pratice their fandom. The mediated discourses tends to devalue the Twilight fandom and in the end even the Twilight fans themselves. We have interviewed five female Twilight fans and in our thematic analysis we have not only answered the questions about how they relate to their own consumption process, but also how they construct and maintain gender, homosociality and heteronormativity within the fandom. Through our analysis we demonstrate how the fans read and watch Twilight and how this act constitutes an identification with their own gender and excludes other forms of gender. This is also demonstrated by how the fans relate to each other, members of other fandoms and boys

Primary sarcoma of the pancreas, a rare histopathological entity. A case report with review of literature

<p>Abstract</p> <p>Aims</p> <p>primary pancreatic sarcomas represent an extremely rare histopathological entity accounting for less than 0.1% of all pancreatic malignancies. Pancreatic sarcomas tend to be more aggressive and have a poor prognosis.</p> <p>Methods</p> <p>the case of a 52 year old patient presenting with jaundice is presented and the available literature was reviewed.</p> <p>Results</p> <p>primary pancreatic sarcomas are extremely rare. Pancreatic sarcomas are more aggressive than other pancreatic neoplasms.</p> <p>Conclusion</p> <p>primary sarcomas of the pancreas are extremely rare, are aggressive and are associated with very poor prognosis.</p

Data-driven Planning for the Conservation of Grassland Birds in the Central Hardwoods Bird Conservation Region

The Central Hardwoods Joint Venture held two workshops in 2006 to delineate bobwhite focus areas across the Central Hardwoods Bird Conservation Region (BCR) for targeting on-the-ground conservation efforts. From 2008 – 2012, we conducted randomized sets of point counts within counties containing bobwhite focal areas to assess the efficacy of that method for monitoring grassland birds within focal areas, and to assess relationships of conservation practices with bird species occupancy and abundance. We collected data on nine species of Partners in Flight priority species, including northern bobwhite (Colinus virginianus). Land cover types within a 200-m buffer of each point were derived from year National Agricultural Statistics Service data, and information related to the location of conservation practices deemed beneficial to grassland birds was attained from the National Resources Conservation Service. We fit occupancy and abundance models for each species using Akaike’s Information Criterion adjusted for small sample sizes. We then used the model covariates to map predicted abundances of three species, northern bobwhite, eastern meadowlark (Sturnella magna), and Henslow’s sparrow (Ammodramus henslowii) across the BCR. The spatial patterns of predicted abundance varied among species, suggesting that focus areas should be somewhat species-specific. We will use data collected around the nests of each species at Ft. Campbell, a military base straddling the Kentucky-Tennessee border where grassland management has occurred at relatively large scales over more than two decades, to assess the with-in patch structure preferred by each species to develop grazing practices that will result in the desired structure for the species suite