@phdthesis{Glueer2000, author = {Gl{\"u}er, Wibke}, title = {Kosmetische Ergebnisse nach Bestrahlung bei Brusterhaltender Therapie des Mammakarzinoms}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-452}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2000}, abstract = {Ziel: Auswirkungen der strahlentherapeutischen Vorgehensweise, insbesondere der lokalen Dosisaufs{\"a}ttigung auf das kosmetische Langzeitergebnis und die Rezidivrate nach Brusterhaltender Therapie. Material und Methoden: In die Studie aufgenommen wurden 451 Patientinnen mit Mammakarzinom, die zwischen 1984-1994 in der Universit{\"a}tsfrauenklinik und der Klinik und Poliklinik f{\"u}r Strahlentherapie der Universit{\"a}t W{\"u}rzburg brusterhaltend therapiert wurden und bei denen Informationen zum kosmetischen Langzeitergebnis vorlagen. Behandlung: Alle Patientinnen unterzogen sich einer operativen Tumorentfernung und Axilladissektion, sowie einer Strahlenbehandlung. Die Strahlentherapie bestand aus einer homogenen Bestrahlug der betroffenen Brust (50Gy) und einer Tuorbettaufs{\"a}ttigung (20Gy), entweder als interstitieller Boost mit Ir-192 (77 Prozent) oder als Elektronenboost (16 Prozent). Ergebnisse: Die {\"U}berlebensrate betrug nach 5 und 10 Jahren 88 bzw. 73 Prozent. Die lokoregion{\"a}re Kontrollrate betrug nach 5 und 10 Jahren 90 und 75 Prozent. Es konnte kein statistisch signifikanter Zusammenhang mit der Art der angewandten Tumorbettaufs{\"a}ttigung festgestellt werden. Ein gutes bis exzellentes kosmetisches Ergebnis konnte bei 61 Prozent der Patientinnen erreicht werden. Auch hier besteht kein statistisch signifikanter Zusammenhang mit der gew{\"a}hlten Boostart.}, language = {de} } @phdthesis{Schulte2002, author = {Schulte, Stephanie}, title = {Strahlensensibilit{\"a}t von Fibroblasten und Lymphozyten bei Brustkrebspatientinnen: Vergleich des alkalischen Comet Assay mit der klinisch beobachteten Hautreaktion nach Bestrahlung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-6415}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2002}, abstract = {Wichtiges Forschungsthema der letzten Jahre war die Entwicklung eines pr{\"a}diktiven Testsystems zur Bestimmung der individuellen Strahlenempfindlichkeit von Tumorpatienten im Vorfeld einer Strahlentherapie. Ziel ist eine individuelle Dosisanpassung mit m{\"o}glichst effizienter Tumorzerst{\"o}rung bei maximaler Schonung des Normalgewebes. Standardmethode zur Messung der zellul{\"a}ren Strahlenempfindlichkeit ist der Koloniebildungstest, der sich jedoch f{\"u}r eine pr{\"a}diktive Testung nicht eignet, da es mehrere Wochen, wenn nicht Monate dauert, bis die Resultate vorliegen. In dieser Arbeit sollte untersucht werden, ob der Comet Assay als pr{\"a}diktiver Test zur Erfassung der Strahlenempfindlichkeit normaler Gewebe geeignet ist. Dazu wurden bestrahlte Hautfibroblasten und periphere Blutlymphozyten von 30 Brustkrebspatientinnen im Comet Assay analysiert und die Resultate mit den akuten radiogenen Hautreaktionen der Patientinnen verglichen. Vor allem die Versuche mit Lymphozyten ergaben eine gute Korrelation zwischen initialem DNS-Schaden bzw. Schaden nach 40min{\"u}tiger Reparatur und den klinisch beobachteten fr{\"u}hen Normalgewebsnebenwirkungen. Anhand der in vitro-Ergebnisse konnte klar zwischen durchschnittlich und {\"u}berdurchschnittlich strahlenempfindlichen Patientinnen unterschieden werden. Bei den Fibroblasten waren die Patientinnen mit durchschnittlichen Reaktionen und die mit st{\"a}rkeren radiogenen Nebenwirkungen nur im Initialschaden deutlich voneinander verschieden. Der Comet Assay scheint demzufolge ein g{\"u}nstiger Test zu sein, um eine erh{\"o}hte Strahlenempfindlichkeit zu erfassen, vor allem wenn Lymphozyten aus dem peripheren Blut analysiert werden. Er kann schnell und mit wenigen Zellen durchgef{\"u}hrt werden und ist bei standardisierten Versuchsbedingungen gut reproduzierbar. Mit dem Comet Assay ist es m{\"o}glich, in kurzer Zeit mehrere Malignompatienten auf ihre Radiosensitivit{\"a}t hin zu untersuchen, wobei diese nur eine Blutprobe zur Lymphozytenisolation abgeben m{\"u}ssen. Im Hinblick auf die Anwendung als pr{\"a}diktiver Test im klinischen Alltag ist die Kombination mit anderen Methoden wie z. B. dem Mikronukleus-Test und der FISH-Technik empfehlenswert, was die Zuverl{\"a}ssigkeit und Aussagekraft der Resultate noch steigern w{\"u}rde.}, language = {de} } @phdthesis{Assenbrunner2012, author = {Assenbrunner, Bernadette}, title = {Palliative hypofraktionierte Bestrahlung bei nicht kleinzelligem Bronchialkarzinom}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-90159}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {F{\"u}r die palliative Bestrahlung des NSCLC stehen mehrere, sehr unterschiedliche hypofraktionierte Behandlungsschemata zur Verf{\"u}gung. Prospektive Studien in der Vergangenheit konnten keine {\"U}berlegenheit f{\"u}r eines dieser Regime zeigen. Ziel vorliegender retrospektiver Arbeit war es, die Effektivit{\"a}t der Radiatio mit 13 bis 15 Fraktionen zu 3 Gy zu {\"u}berpr{\"u}fen. Hierzu untersuchten wir die Daten von 57 Patienten, die sich in den Jahren 2006 bis 2008 in der Strahlentherapie der Universit{\"a}tsklinik W{\"u}rzburg einer solchen Therapie unterzogen. Das Patientengut unterteilten wir f{\"u}r die Untersuchung in zwei Gruppen M0 und M1, deren Prognose wir unterschiedlich einsch{\"a}tzten. Der Einteilung lag das Vorhandensein von Fernmetastasen zu Behandlungsbeginn zugrunde. Das Gesamt{\"u}berleben war f{\"u}r Patienten der M0-Gruppe signifikant besser und lag f{\"u}r M1-Patienten in einem zu erwartenden Bereich. 17,5\% unserer Patienten lebten 18 Monate oder l{\"a}nger. Welche Ursachen hinter diesem prolongierten {\"U}berleben stehen k{\"o}nnten, blieb jedoch weitgehend unklar. F{\"u}r das Gesamt{\"u}berleben zeigten sich verschiedene u.a. aus der Literatur bekannte Prognosefaktoren wie das UICC-Stadium, der Allgemeinzustand und eine chemotherapeutische Behandlung. Andere Faktoren, deren Einfluss wir vermuteten, f{\"u}hrten zu keinen signifikanten bzw. widerspr{\"u}chlichen Ergebnissen. Hierzu z{\"a}hlten insbesondere der Charlson comorbidity score und das Alter. F{\"u}r die H{\"o}he der Gesamtdosis und die Gr{\"o}ße des PTV wurde interessanterweise kein Einfluss auf das {\"U}berleben nachgewiesen. Die lokale Kontrolle war von diesen beiden Variablen ebenfalls unabh{\"a}ngig. Ein systemischer Progress trat bei unseren Patienten tendenziell fr{\"u}her auf als ein lokaler Progress. Der Allgemeinzustand der Patienten wurde von der Bestrahlung im Wesentlichen nicht negativ beeinflusst, Infektionen traten so gut wie gar nicht auf. Wie bereits aus prospektiven Studien zur hypofraktionierten Bestrahlung bekannt, waren Akuttoxizit{\"a}ten, insbesondere {\"O}sophagitiden, relativ h{\"a}ufig.}, subject = {Nicht-kleinzelliges Bronchialkarzinom}, language = {de} } @article{HomolaJbabdiBeckmannetal.2012, author = {Homola, Gy{\"o}rgy A. and Jbabdi, Saad and Beckmann, Christian F. and Bartsch, Andreas J.}, title = {A Brain Network Processing the Age of Faces}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75513}, year = {2012}, abstract = {Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.}, subject = {Medizin}, language = {en} } @article{KreisslHaenscheidLoehretal.2012, author = {Kreissl, Michael C. and H{\"a}nscheid, Heribert and L{\"o}hr, Mario and Verburg, Frederik A. and Schiller, Markus and Lassmann, Michael and Reiners, Christoph and Samnick, Samuel S. and Buck, Andreas K. and Flentje, Michael and Sweeney, Reinhart A.}, title = {Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75540}, year = {2012}, abstract = {Background: External beam radiotherapy (EBRT) is the treatment of choice for irresectable meningioma. Due to the strong expression of somatostatin receptors, peptide receptor radionuclide therapy (PRRT) has been used in advanced cases. We assessed the feasibility and tolerability of a combination of both treatment modalities in advanced symptomatic meningioma. Methods: 10 patients with irresectable meningioma were treated with PRRT (177Lu-DOTA0,Tyr3 octreotate or - DOTA0,Tyr3 octreotide) followed by external beam radiotherapy (EBRT). EBRT performed after PRRT was continued over 5-6 weeks in IMRT technique (median dose: 53.0 Gy). All patients were assessed morphologically and by positron emission tomography (PET) before therapy and were restaged after 3-6 months. Side effects were evaluated according to CTCAE 4.0. Results: Median tumor dose achieved by PRRT was 7.2 Gy. During PRRT and EBRT, no side effects>CTCAE grade 2 were noted. All patients reported stabilization or improvement of tumor-associated symptoms, no morphologic tumor progression was observed in MR-imaging (median follow-up: 13.4 months). The median pre-therapeutic SUVmax in the meningiomas was 14.2 (range: 4.3-68.7). All patients with a second PET after combined PRRT + EBRT showed an increase in SUVmax (median: 37\%; range: 15\%-46\%) to a median value of 23.7 (range: 8.0-119.0; 7 patients) while PET-estimated volume generally decreased to 81 ± 21\% of the initial volume. Conclusions: The combination of PRRT and EBRT is feasible and well tolerated. This approach represents an attractive strategy for the treatment of recurring or progressive symptomatic meningioma, which should be further evaluated.}, subject = {Medizin}, language = {en} } @article{GuckenbergerHawkinsFlentjeetal.2012, author = {Guckenberger, Matthias and Hawkins, Maria and Flentje, Michael and Sweeney, Reinhart A.}, title = {Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75853}, year = {2012}, abstract = {Background One third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70 \% of these patients. Conventional radiotherapy with of 1-10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3-6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology - intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery - have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept. Methods / Design It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two-centre phase II trial. Conclusions Results of this study will refine the methods of patient selection, target volume definition, treatment planning and delivery as well as quality assurance for radiosurgery. It is the intention of this study to form the basis for a future randomized controlled trial comparing conventional radiotherapy with fractionated radiosurgery for palliation of painful vertebral metastases. Trial registration ClinicalTrials.gov Identifier: NCT01594892}, subject = {Medizin}, language = {en} } @phdthesis{Saur2012, author = {Saur, Gabriella-Sofie}, title = {Klinische Ergebnisse und Lebensqualit{\"a}t nach neoadjuvanter Radiochemotherapie von Rektumkarzinomen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78562}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {Die derzeitige Standardtherapie bei fortgeschrittenen Rektumkarzinomen der UICC Stadien II und III besteht aus der neoadjuvanten Radio(chemo)therapie mit nachfolgender chirurgischer Intervention. Hierbei werden die beiden Therapiemodalit{\"a}ten, der Kurzzeit-Radiotherapie(5x5Gy) und unmittelbare Operation von der Langzeit-Radiochemotherpaie (28x1,8Gy) mit einem Intervall von 4-6 Wochen bis zur Operation, unterschieden. Im Hinblick auf das Auftreten von Lokalrezidiven sowie auf das Gesamt{\"u}berleben sprechen die Ergebnisse f{\"u}r eine bessere Wirksamkeit der LZ-RChT. Dennoch gibt es klinische Situation, bei denen eine KZ-Radiotherapie sinnvoller sein kann. Somit kann als Konsequenz eine differenzierte Indikationsstellung f{\"u}r diese beiden Therapiemodalit{\"a}ten abgeleitet werden.}, subject = {Rektumkarzinom}, language = {de} } @phdthesis{Niewidok2013, author = {Niewidok, Natalia}, title = {Modulation of radiosensitivity of human tumor and normal cells by inhibition of heat shock proteins Hsp90 and Hsp70}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78728}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Cancer is the leading cause of death in economically developed countries (Jemal et al. 2011). Heat shock protein 90 can be a promising target in cancer treatment as it is responsible for sustaining protein homeostasis in every human cell by folding and activating of more than 200 client proteins (Picard et al. 2002). Apart from strong anti-tumor activities in vitro (Smith et al. 2005) and in vivo (Supko et al. 1995), Hsp90 inhibitors can sensitize tumor cells to radiation (Bisht et al. 2003, Stingl et al.2010, Schilling et al. 2011). Recently, our group showed the radiosensitizing potential of novel Hsp90 inhibitors: NVP-AUY922 and NVP-BEP800 (Stingl et al. 2010). The drugs were administered to cancer cell lines of different origin 24 hours before irradiation (drug-first treatment). In the present work, we explored the effects of a schedule other than drug-first treatment on A549 and SNB19 tumor cell lines. Cell samples were treated with either NVP-AUY922 or NVP-BEP800 one hour before IR and kept in the drug-containing medium for up to 48 hours (simultaneous drug-IR treatment). Our findings showed that depending on the tumor cell line, the combination of Hsp90 inhibition and irradiation may result in radiosensitization or apoptosis of cancer cell lines. It is advised to adjust the sequence of treatment, involving Hsp90 inhibition and irradiation, on the basis of the genetic background of tumor cells. Before entering the clinic, novel therapeutics should be tested on non-malignant tissue to exclude their possible toxic activities. Thus, we applied the simultaneous drug-IR treatment on human skin fibroblast strains. This work showed that Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 preferentially sensitize tumor cells to radiation, whereas the effect(s) on normal fibroblasts was much weaker. The exact mechanisms underlying the Hsp90 inhibitors' selectivity towards malignant cells remain to be elucidated. It was shown previously that the administration of Hsp90 inhibitors, including NVP-AUY922 and NVP-BEP800, induces heat shock response (Niewidok et al. 2012). Heat shock response triggers the up-regulation of Hsp70, which, due to its strong anti-apoptotic properties, might be responsible for reducing the effects of Hsp90 inhibition. The transfection with Hsp70 siRNA suppressed the NVP-AUY922-induced over-expression of the target protein. However, on the long-term scale, it did not influence the radiosensitivity of A549 and SNB19 cells. To summarize, the use of siRNA proved that Hsp70 inhibition could be used to support Hsp90 inhibition on the short-term scale. Therefore, for future works, more potent and stable methods of Hsp70 inhibition are needed. This thesis presented the effects induced by two novel Hsp90 inhibitors NVP-AUY922 and NVP-BEP800, in combination with irradiation in tumor cell lines as well as in normal skin fibroblasts. Hsp70 pre-silencing was tested as a method for improving radiosensitizing potential of NVP-AUY922. These results support the use of NVP-AUY922 and NVP-BEP800 in combination with irradiation in future clinical trials.}, subject = {Tumorzelle}, language = {en} } @article{DjuzenovaElsnerKatzeretal.2013, author = {Djuzenova, Cholpon S. and Elsner, Ines and Katzer, Astrid and Worschech, Eike and Distel, Luitpold V. and Flentje, Michael and Polat, B{\"u}lent}, title = {Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci}, series = {Radiation Oncology}, journal = {Radiation Oncology}, doi = {10.1186/1748-717X-8-98}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96110}, year = {2013}, abstract = {Background High expression of constitutive histone γ-H2AX, a sensitive marker of DNA damage, might be indicative of defective DNA repair pathway or genomic instability. 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. This study explores the relationship between the clinical radiosensitivity of tumor patients and the expression/induction of γ-H2AX and 53BP1 in vitro. Methods Using immunostaining, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53 BP1 in peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=57) undergoing radiotherapy (RT). Cells from apparently healthy donors (n=12) served as references. Results Non-irradiated cells from controls and unselected BC patients exhibited similar baseline levels of DNA damage assessed by γ-H2AX and 53BP1 foci. At the same time, the γ-H2AX assay of in vitro irradiated cells revealed significant differences between the control group and the group of unselected BC patients with respect to the initial (0.5 Gy, 30 min) and residual (2 Gy, 24 h post-radiation) DNA damage. The numbers of 53BP1 foci analyzed in 35 BC patients were significantly higher than in controls only in case of residual DNA damage. A weak correlation was found between residual foci of both proteins tested. In addition, cells from cancer patients with an adverse acute skin reaction (grade 3) to RT showed significantly increased radiation-induced γ-H2AX foci and their protracted disappearance compared to the group of BC patients with normal skin reaction (grade 0-1). The mean number of γ-H2AX foci after 5 clinical fractions was significantly higher than that before RT, especially in clinically radiosensitive patients. Conclusions The γ-H2AX assay may have potential for screening individual radiosensitivity of breast cancer patients.}, subject = {DNS-Sch{\"a}digung}, language = {en} } @article{FlentjeRichter2021, author = {Flentje, Michael and Richter, J{\"u}rgen}, title = {Professor Dr. Werner Bohndorf gestorben}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, number = {7}, issn = {1439-099X}, doi = {10.1007/s00066-021-01792-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264838}, pages = {664-665}, year = {2021}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @phdthesis{Kielkopf2022, author = {Kielkopf, Julian Alexander}, title = {Beurteilung der Pr{\"a}diktivit{\"a}t eines automatisierten Palliativscreenings bei uro-onkologischen Patienten}, doi = {10.25972/OPUS-27045}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270459}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Um Patienten mit Palliativbedarf proaktiv zu identifizieren wurde am Universit{\"a}tsklinikum W{\"u}rzburg am 01.03.2019 ein Palliativscreening auf Basis der Pflegeanamnese etabliert. Dessen Pr{\"a}diktivit{\"a}t auf das 6-Monats {\"U}berleben wurde in der vorliegenden Arbeit in einer uro-onkologischen Patientenkohorte untersucht. F{\"u}r die Patientenkohorte wurden aus dem klinischen Informationssystem aufenthalts-, personen- und tumorspezifische Daten sowie das Palliativscreening aus der Pflegeanamnese ausgelesen. Erg{\"a}nzend zur Auswertung des automatisiert generierten Palliativscreenings wurden die Einzelitems rechnerisch in einem berechneten Palliativscreening zusammengef{\"u}hrt um eine Zuverl{\"a}ssigkeitspr{\"u}fung des automatisiert generierten Palliativscreenings zu erm{\"o}glichen. In einer zweiten Auswertung wurde gepr{\"u}ft, ob der Patient im 6-Monats Nachbeobachtungszeitraum nach Aufnahme verstorben ist. Unsere Studie belegt die Pr{\"a}diktivit{\"a}t des Palliativscreenings in einer uro-onkologischen Kohorte f{\"u}r das 6-Monats {\"U}berleben. Ein automatisiert generiertes Screening, ist in unserer Studie vergleichbar pr{\"a}diktiv auf das 6-Monats {\"U}berleben als eine manuelle rechnerische Rekonstruktion. Bei Patienten mit Prostatakarzinom weist das Palliativscreening eine niedrigere Korrelation mit dem 6-Monats {\"U}berleben auf als bei Patienten mit anderen urologischen Entit{\"a}ten.}, subject = {Palliativmedizin}, language = {de} } @article{KlementPoppKauletal.2022, author = {Klement, Rainer J. and Popp, Ilinca and Kaul, David and Ehret, Felix and Grosu, Anca L. and Polat, B{\"u}lent and Sweeney, Reinhart A. and Lewitzki, Victor}, title = {Accelerated hyper-versus normofractionated radiochemotherapy with temozolomide in patients with glioblastoma: a multicenter retrospective analysis}, series = {Journal of Neuro-Oncology}, volume = {156}, journal = {Journal of Neuro-Oncology}, number = {2}, issn = {1573-7373}, doi = {10.1007/s11060-021-03926-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269806}, pages = {407-417}, year = {2022}, abstract = {Background and Purpose The standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis. Materials and Methods A total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset. Results After a median follow-up of 15.7 months (range 0.8-88.6 months), median OS was 16.9 months (15.0-18.7 months) in the NFRT group and 14.9 months (13.2-17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p < 0.01). Treatment differences (HFRT versus NFRT) had no significant effect on OS in either univariable or multivariable analysis. Conclusions Since HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time.}, language = {en} } @phdthesis{Liebendoerfer2022, author = {Liebend{\"o}rfer, Volker}, title = {Untersuchung der Biomarker Osteopontin, CD44 und Isovariante 6 beim Rektumkarzinom}, doi = {10.25972/OPUS-25422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254229}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Diese Arbeit besch{\"a}ftigt sich mit den Biomarkern Osteopontin und CD44 Standard, sowie CD44 Isovariante 6 beim Rektumkarzinom. Wir konzentrierten uns auf die prognostische Bedeutung von Osteopontin und CD44 Standard, sowie CD44 Isovariante 6. In einigen Vorg{\"a}ngerarbeiten zeigten sich Zusammenh{\"a}nge vor allem bei der Tumorinduktion, Metastasierung und {\"U}berleben. In unserer Arbeit konnten wir best{\"a}tigen, dass sich hohe Serumkonzentrationen von OPN bei Patienten mit Rektumkarzinom hochsignifikant negativ auf das Gesamt{\"u}berleben auswirken. Niedrigere Serumkonzentrationen sind daher mit einer g{\"u}nstigeren Prognose assoziiert. Dies zeigte sich auch in der durchgef{\"u}hrten multivariaten Analyse. Wir kommen daher zu dem Schluss, dass sich OPN als prognostischer Marker eignet. In der Literatur zeigte sich CD44v6 mit verst{\"a}rkter Metastasierung assoziiert. Dies konnten wir nicht best{\"a}tigen. Wir sahen CD44std und auch CD44v6 weder mit Gesamt{\"u}berleben, noch mit Tumorstadium und Metastasierung assoziiert. Auch wenn wir CD44 mit OPN gemeinsam auf das Gesamt{\"u}berleben untersuchten, fanden wir keinen signifikanten Einfluss. Als m{\"o}gliche Schlussfolgerung dieser Arbeit k{\"o}nnte man die aktuelle Therapie des Rektumkarzinoms bei hohen OPN Werten reevaluieren. Bei hohen Osteopontin Werten w{\"a}ren dann ggfs. aggressivere Therapieprotokolle vorstellbar.}, subject = {Osteopontin}, language = {de} } @phdthesis{Luttenberger2023, author = {Luttenberger, Ines Maria}, title = {Anteriore Mantelfeldtechniken in der Strahlentherapie des Morbus Hodgkin: 3-D-Rekonstruktion der kardialen Dosisverteilung bei Langzeit{\"u}berlebenden}, doi = {10.25972/OPUS-30358}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303586}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {F{\"u}r diese Arbeit wurden die Daten von 55 (zum Zeitpunkt der Auswertung lebenden) Patienten der Klinik f{\"u}r Strahlentherapie der Universit{\"a}t W{\"u}rzburg, die zwischen 1978 und 1985 wegen M. Hodgkin mediastinal bestrahlt wurden, ausgewertet. Es wurde f{\"u}r jeden Patienten die zweidimensionale Fl{\"a}che des Herzens, die durch Bleibl{\"o}cke ausgeblockt wurde, berechnet. Außerdem erfolgte mit Hilfe von Testpatienten, von denen ein 3-D-CT-Datensatz vorhanden war und die anhand der Herzform zugeteilt wurden, eine dreidimensionale Dosisrekonstruktion an kardialen Strukturen (linker Vorhof, linker Ventrikel, rechter Vorhof, rechter Ventrikel, A. coronaria dextra, Ramus intraventricularis anterior und Ramus circumflexus). 26 der 55 Patienten sind weiblich, 29 m{\"a}nnlich. Zu Bestrahlungsbeginn waren die Patienten im Durchschnitt 24,7(±9,7) Jahre alt. 22 Patienten wurden mit einer kombinierten Radio-Chemotherapie behandelt, 33 Patienten erhielten eine alleinige Bestrahlung. Die Patienten wurden in vier Gruppen eingeteilt: 26 Patienten wurden mit alleinigem anteriorem Mantelfeld bestrahlt, 18 Patienten mit anteriorem Mantelfeld und Rotationsboost auf das Mediastinum, sieben Patienten wurden mit einem anterioren Mantelfeld und einem dorsalen Boost des Mediastinums bestrahlt und vier Patienten wurden mit sonstigen Techniken mediastinal bestrahlt. Im Vergleich der mediastinalen Herddosen der Gruppen untereinander konnte ein signifikanter Unterschied der Gruppen mit Rotations- oder dorsalem Boost zur Gruppe mit alleiniger anteriorer Mantelfeldbetsrahlung festgestellt werden. F{\"u}r die kardialen Strukturen wurden Dosis-Volumen-Histogramme errechnet. Es konnte zum Beispiel gezeigt werden, dass bei alleiniger anteriorer Mantelfeldbetsrahlung eine relative Dosis{\"u}berh{\"o}hung der vorderen Herzabschnitte (rechter Ventrikel, rechte Koronararterie) erfolgte. Zudem wurden die Daten der zweidimensionalen Herzausblockung mit Parametern der Dosis-Volumen-Histogramme korreliert.}, subject = {Strahlentherapie}, language = {de} } @phdthesis{Pollmann2023, author = {Pollmann, Stephan}, title = {Herstellung und dosimetrische Evaluation flexibler, 3D-konformaler Boli f{\"u}r die adjuvante volumenmodulierte Radiotherapie bei Kopf-Hals-Tumoren}, doi = {10.25972/OPUS-30368}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303681}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {In der vorliegenden Arbeit wurde ein standardisiertes Verfahren zur Herstellung individueller Boli mithilfe von FDM und Silikon-Guss vorgestellt. Die Technik schien den Vorteil einer relativ preisg{\"u}nstigen Bolus-Produktion vor Ort bei verh{\"a}ltnism{\"a}ßig geringen Anspr{\"u}chen an infrastrukturelle Voraussetzungen in der Klinik zu bieten, auch wenn eine Untersuchung {\"o}konomischer Aspekte nicht Ziel der Arbeit war. Gleichzeitig konnten flexible und f{\"u}r den Patienten m{\"o}glicherweise komfortablere Boli erzeugt werden, die konformaler bzw. l{\"u}ckenloser auflagen als die konventionellen Modelle (Superflabs), eine geringf{\"u}gige Dosiserh{\"o}hung im oberfl{\"a}chlichen Zielvolumen bewirkten und zudem eine deutliche Hautschonung erm{\"o}glichten. {\"U}ber den gesamten Anwendungszeitraum hielten die Boli den mechanischen Belastungen stand, die mit der Behandlung der Patienten einhergingen. Im Rahmen vorausgegangener Untersuchungen an einem Plattenphantom konnte die {\"A}quivalenz der Materialien in Bezug auf den Dosisaufbau erwiesen werden, sodass die Zusammensetzung des von uns verwendeten Materials als sowohl mechanisch wie physikalisch geeignet angesehen werden konnte. Der Einfluss unterschiedlich großer Bolus-Hohlr{\"a}ume auf eine oberfl{\"a}chliche Dosisreduktion wurde am Plattenphantom ebenfalls abgesch{\"a}tzt. Am RANDO-Phantom konnte ein geeignetes Messverfahren identifiziert werden. Die Ergebnisse unserer Untersuchungen an 3D-konformalen Boli zeigten sich als mit der aktuellen Studienlage weitgehend kongruent. Eine weitere Optimierung der vorgestellten Technik k{\"o}nnte {\"u}ber die Verwendung von 3D-Scans der Kopf-Hals-Konturen erreicht werden, da dies eine Integration von Bolus- und Maskenanbringung erm{\"o}glicht. Hohlr{\"a}ume unter einer Lagerungsmaske h{\"a}tten damit weniger Einfluss auf den Bolus-Haut-Abstand. Ebenso erscheint die klinische Evaluation der Rezidivh{\"a}ufigkeit bzw. der Hautschonung als sinnvoll. Es k{\"o}nnte beispielsweise die Verhinderung akuter und chronischer Strahlen-wirkungen an der sensiblen Kopf-Hals-Region quantifiziert werden. Die vorgestellte 3D-Druck- und Gusstechnik zur Herstellung flexibler und 3D-konformaler Boli erscheint bei der Optimierung strahlentherapeutischer Behandlungsm{\"o}glichkeiten vielversprechend.}, language = {de} } @article{ColvillBoothNilletal.2016, author = {Colvill, Emma and Booth, Jeremy and Nill, Simeon and Fast, Martin and Bedford, James and Oelfke, Uwe and Nakamura, Mitsuhiro and Poulsen, Per and Worm, Esben and Hansen, Rune and Ravkilde, Thomas and Rydh{\"o}g, Jonas Scherman and Pommer, Tobias and af Rosenschold, Per Munck and Lang, Stephanie and Guckenberger, Matthias and Groh, Christian and Herrmann, Christian and Verellen, Dirk and Poels, Kenneth and Wang, Lei and Hadsell, Michael and Sothmann, Thilo and Blanck, Oliver and Keall, Paul}, title = {A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking}, series = {Radiotherapy and Oncology}, volume = {119}, journal = {Radiotherapy and Oncology}, number = {1}, doi = {10.1016/j.radonc.2016.03.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189605}, pages = {159-165}, year = {2016}, abstract = {Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2\%/2 mm gamma-fail rate of 1.6\% with adaptation and 15.2\% without adaptation (p < 0.001). For all prostate the mean 2\%/2 mm gamma-fail rate was 1.4\% with adaptation and 17.3\% without adaptation (p < 0.001). The difference between the four systems was small with an average 2\%/2 mm gamma-fail rate of <3\% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.}, language = {en} } @article{LewitzkiKlementKosmalaetal.2019, author = {Lewitzki, Victor and Klement, Rainer J. and Kosmala, Rebekka and Lisowski, Dominik and Flentje, Michael and Polat, B{\"u}lent}, title = {Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma}, series = {Radiation Oncology}, volume = {14}, journal = {Radiation Oncology}, doi = {10.1186/s13014-019-1427-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202614}, pages = {227}, year = {2019}, abstract = {Background Current standard of treatment for newly diagnosed patients with glioblastoma (GBM) is surgical resection with adjuvant normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) which was known as an option from randomized controlled trials before the temozolomide era has not been compared to the standard therapy in a randomized setting combined with TMZ. Methods Data of 152 patients with newly diagnosed GBM treated from 10/2004 until 7/2018 at a single tertiary care institution were extracted from a clinical database and retrospectively analyzed. Thirty-eight patients treated with NFRT of 60 Gy in 30 fractions (34 with simultaneous and 2 with sequential TMZ) were compared to 114 patients treated with HFRT of 54.0 Gy in 30 fraction of 1.8 Gy twice daily (109 with simultaneous and 3 with sequential TMZ). The association between treatment protocol and other variables with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis; the latter was performed using variables selected by the LASSO method. Results Median overall survival (OS) was 20.3 month for the entire cohort. For patients treated with NFRT median OS was 24.4 months compared to 18.5 months in patients treated with HFRT (p = 0.131). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 2.21 (95\% CI 1.47-3.31, p = 0.0001). In multivariable analysis adjusted for O6-methylguanine-DNA methyl-transferase (MGMT) promotor methylation status, salvage treatment and secondary GBM, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95\% CI 1.21-3.13, p = 0.006). Positive MGMT-methylation status and salvage treatment were highly significant positive prognostic factors. There was no strong association between treatment protocol and OS (p = 0.504). Conclusions Our retrospective analysis supports the hypothesis of equivalence between HFRT and the standard protocol of treatment for GBM. For those patients who are willing to obtain the benefit of shortening the course of radiochemotherapy, HFRT may be an alternative with comparable efficacy although it was not yet tested in a large prospective randomized study against the current standard. The positive influence of salvage therapy and negative impact of concomitant use of corticosteroids should be addressed in future prospective trials. To confirm our results, we plan to perform a pooled analysis with other tertiary clinics in order to achieve better statistical reliability.}, language = {en} } @article{KroeberWengerSchwegleretal.2015, author = {Kroeber, Jana and Wenger, Barbara and Schwegler, Manuela and Daniel, Christoph and Schmidt, Manfred and Djuzenova, Cholpon S and Polat, B{\"u}lent and Flentje, Michael and Fietkau, Rainer and Distel, Luitpold V.}, title = {Distinct increased outliers among 136 rectal cancer patients assessed by \(\gamma\)H2AX}, series = {Radiation Oncology}, volume = {10}, journal = {Radiation Oncology}, number = {36}, doi = {10.1186/s13014-015-0344-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144085}, year = {2015}, abstract = {Background: In recent years attention has focused on \(\gamma\)H2AX as a very sensitive double strand break indicator. It has been suggested that \(\gamma\)H2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by \(\gamma\)H2AX in a large cohort. Methods: In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-\(\gamma\)H2AX antibodies and microscopic images with an extended depth of field were acquired. \(\gamma\)H2AX foci counting was performed using a semi-automatic image analysis software. Results: Distinct increased values of preexisting and remaining \(\gamma\)H2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12\% of the RC patients after ex vivo IR. Conclusions: The \(\gamma\)H2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae.}, language = {en} } @article{LvZhangZhuetal.2015, author = {Lv, Xiaoqun and Zhang, Lingyun and Zhu, Yanyan and Said, Harun M. and Shi, Jimin and Xu, Guoxiong}, title = {Regulative effect of Nampt on tumor progression and cell viability in human colorectal cancer}, series = {Journal of Cancer}, volume = {6}, journal = {Journal of Cancer}, number = {9}, doi = {10.7150/jca.12341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144516}, pages = {849-858}, year = {2015}, abstract = {Colorectal cancer (CRC) is the third most common cancer disease. Here we examined Nampt expression in patients with CRC and the effect of Nampt on cell viability in CRC cells. Nampt protein was overexpressed in colorectal adenoma as well as colorectal carcinoma. The immunoreactive staining of Nampt was negative in the adjacent normal colorectal tissue, weak in colorectal adenoma, and strong in colorectal carcinoma, which may represent tumor progression. Further evaluation of clinical data showed that Nampt expression was not correlated with the clinicopathological characteristics of CRC. Additionally, our in vitro studies demonstrated that Nampt promotes CRC cell viability, whereas the Nampt inhibitor FK866 suppressed CRC cell viability, which was in concordance with the previous studies in other cancer cells. Treatment with Nampt-siRNA reduced the Nampt protein expression resulting in the inhibition of the cell viability of HCT116 and Caco2. Thus, the involvement of Nampt in cell growth indicates that Nampt may play an important role in colorectal tumorigenesis. As a consequence, our results suggest that Nampt may be considered as a progression marker of colorectal tumor and a potentially therapeutic target for the treatment of CRC.}, language = {en} } @article{PollmannToussaintFlentjeetal.2022, author = {Pollmann, Stephan and Toussaint, Andr{\´e} and Flentje, Michael and Wegener, Sonja and Lewitzki, Victor}, title = {Dosimetric evaluation of commercially available flat vs. self-produced 3D-conformal silicone boluses for the head and neck region}, series = {Frontiers in Oncology}, volume = {12}, journal = {Frontiers in Oncology}, issn = {2234-943X}, doi = {10.3389/fonc.2022.881439}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283156}, year = {2022}, abstract = {Background Boluses are routinely used in radiotherapy to modify surface doses. Nevertheless, considerable dose discrepancies may occur in some cases due to fit inaccuracy of commercially available standard flat boluses. Moreover, due to the simple geometric design of conventional boluses, also surrounding healthy skin areas may be unintentionally covered, resulting in the unwanted dose buildup. With the fused deposition modeling (FDM) technique, there is a simple and possibly cost-effective way to solve these problems in routine clinical practice. This paper presents a procedure of self-manufacturing bespoke patient-specific silicone boluses and the evaluation of buildup and fit accuracy in comparison to standard rectangular commercially available silicone boluses. Methods 3D-conformal silicone boluses were custom-built to cover the surgical scar region of 25 patients who received adjuvant radiotherapy of head and neck cancer at the University Hospital W{\"u}rzburg. During a standard CT-based planning procedure, a 5-mm-thick 3D bolus contour was generated to cover the radiopaque marked surgical scar with an additional safety margin. From these digital contours, molds were 3D printed and poured with silicone. Dose measurements for both types of boluses were performed with radiochromic films (EBT3) at three points per patient—at least one aimed to be in the high-dose area (scar) and one in the lower-dose area (spared healthy skin). Surface-bolus distance, which ideally should not be present, was determined from cone-beam CT performed for positioning control. The dosimetric influence of surface-bolus distance was also determined on slab phantom for different field sizes. The trial was performed with hardware that may be routinely available in every radiotherapy department, with the exception of the 3D printer. The required number of patients was determined based on the results of preparatory measurements with the help of the statistical consultancy of the University of W{\"u}rzburg. The number of measuring points represents the total number of patients. Results In the high-dose area of the scar, there was a significantly better intended dose buildup of 2.45\% (95\%CI 0.0014-0.0477, p = 0.038, N = 30) in favor of a 3D-conformal bolus. Median distances between the body surface and bolus differed significantly between 3D-conformal and commercially available boluses (3.5 vs. 7.9 mm, p = 0.001). The surface dose at the slab phantom did not differ between commercially available and 3D-conformal boluses. Increasing the surface-bolus distance from 5 to 10 mm decreased the surface dose by approximately 2\% and 11\% in the 6 × 6- and 3 × 3-cm2 fields, respectively. In comparison to the commercially available bolus, an unintended dose buildup in the healthy skin areas was reduced by 25.9\% (95\%CI 19.5-32.3, p < 0.01, N = 37) using the 3D-conformal bolus limited to the region surrounding the surgical scar. Conclusions Using 3D-conformal boluses allows a comparison to the commercially available boluses' dose buildup in the covered areas. Smaller field size is prone to a larger surface-bolus distance effect. Higher conformity of 3D-conformal boluses reduces this effect. This may be especially relevant for volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques with a huge number of smaller fields. High conformity of 3D-conformal boluses reduces an unintended dose buildup in healthy skin. The limiting factor in the conformity of 3D-conformal boluses in our setting was the immobilization mask, which was produced primarily for the 3D boluses. The mask itself limited tight contact of subsequently produced 3D-conformal boluses to the mask-covered body areas. In this respect, bolus adjustment before mask fabrication will be done in the future setting.}, language = {en} } @phdthesis{Mechtold2022, author = {Mechtold, Ulrike}, title = {Adjuvante Intensit{\"a}tsmodulierte Radio-/ Radiochemotherapie maligner Tumoren im HNO-Bereich : Eine retrospektive monozentrische Analyse zu Akut- und Sp{\"a}t-Toxizit{\"a}ten, der lokalen Kontrolle und des {\"U}berlebens, April 2007 bis Juli 2016}, doi = {10.25972/OPUS-28004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280046}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Hintergrund: Etwa 75\% der Patienten mit malignen Tumoren im Kopf-Hals-Bereich unterziehen sich im Verlauf ihrer Behandlung einer Strahlentherapie. Zwei Drittel befanden sich bei Erstdiagnose bereits im lokal fortgeschrittenem Stadium. Eine Weiterentwicklung der Bestrahlungstechniken zielt einerseits auf eine Verbesserung der Tumorkontrolle andererseits auf eine Pr{\"a}zisierung der Strahlenapplikation zur Minimierung von Akut- und Sp{\"a}trektionen. Methode: In dieser Arbeit wurde ein Patientenklientel (118 Patienten (39 Frauen/79 M{\"a}nner) untersucht, bei welchem aufgrund eines malignen Tumors im Kopf-Hals-Bereich eine kurative adjuvante intensit{\"a}tsmodulierte Radiotherapie (IMRT) durchgef{\"u}hrt wurde (zweistufig 60/66Gy). 46,6 \% der Patienten mit Tumoren im UICC-Stadium III und IV erhielten risikoadaptiert eine simultane Chemotherapie. Das Follow-Up der Dokumentation der Nebenwirkungen lag median bei 16 Monaten. Die minimale Nachbeobachtungszeit des {\"U}berlebens betrug 60 Monate. Ergebnisse: Das 3-Jahres- bzw. 5-Jahres-Gesamt{\"u}berleben des betrachteten Patientenkollektivs betrug 69,4 \% bzw. 53,4 \%. Bei 16 Patienten (13,9 \%) wurden Fernmetastasen diagnostiziert. 17 Patienten (14,7 \%) entwickelten ein lokales Tumorrezidiv. Die lokoregion{\"a}re Tumorkontrolle betrug 84,3 \% nach 3 Jahren und 82,9 \% nach 5 Jahren. Als st{\"a}rkster Prognosefaktor erwies sich das pr{\"a}therapeutische Gesamttumorvolumen von > 22ml. Die am h{\"a}ufigsten beobachtete h{\"o}hergradige Fr{\"u}htoxizit{\"a}t war die orale Mukositis Grad 3, die radiogene Dysphagie Grad 3 sowie Xerostomie Grad 3. Zum Zeitpunkt der Erfassung der Sp{\"a}tnebenwirkungen wurde bei 2,8 \% (alleinige RT) bzw. bei 4,2 \% (RCHT) der Patienten eine Xerostomie Grad-3 beobachtet. 5,4 \% (RT) bzw. 12,5 \% (RCHT) gaben eine Dysphagie Grad 3 an, 8,1 \% (RT) bzw. 12,5 \% (RCHT) beklagten noch St{\"o}rungen der Nahrungsaufnahme Grad 3. 2,8 \% (RT) bzw. 16,7 \% (RCHT) boten eine Heiserkeit Grad 3. Schlussfolgerung: Die vorliegende Arbeit hat ein Patientenkollektiv untersucht, bei dem im Vergleich zu einer historischen Kohorte die Gesamtdosis im unmittelbaren Tumorbett angehoben wurde, bei gleichzeitiger Schonung der Umgebung durch die Technik der Intensit{\"a}tsmodulierten Strahlentherapie (IMRT). Dies wirkte sich positiv in der Vertr{\"a}glichkeit aus. Bei aller Schwierigkeit von Kohortenvergleichen war festzustellen, dass eine moderate Verbesserung der Therapieresultate erreicht wurde und dass insbesondere historisch bekannte Risikofaktoren f{\"u}r Lokalrezidive (R-Status, Perinodale Invasion, H{\"a}mangiose) mit diesem Behandlungskonzept ihre Bedeutung zu verlieren scheinen.}, language = {de} } @phdthesis{Nuernberg2023, author = {N{\"u}rnberg, Niklas}, title = {Erfassung des Palliativbedarfs von haus{\"a}rztlich versorgten Pflegeheimbewohnerinnen und -bewohnern mittels SPICT\(^{TM}\) und IPOS}, doi = {10.25972/OPUS-31307}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313071}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Zur Erfassung des Palliativbedarfs von haus{\"a}rztlich versorgten Pflegeheim-bewohnerinnen und -bewohnern wurden Heimleitungen von Pflegeeinrichtungen kontaktiert, in denen die drei teilnehmenden allgemeinmedizinischen Praxen in W{\"u}rzburg Patientinnen und Patienten betreuten und um die M{\"o}glichkeit einer Befragung der Bewohnerinnen und Bewohner sowie der zust{\"a}ndigen Mitarbeiterinnen und Mitarbeiter gebeten. Die Instrumente SPICT-DETM und IPOS wurden darauf gepr{\"u}ft, ob sie zur Erfassung des Palliativbedarfs von haus{\"a}rztlich versorgten Pflegeheimbewohnerinnen und -bewohnern geeignet sind und ob die Ergebnisse des SPICT-DETM und des IPOS vergleichbar sind. Weiterhin wurde {\"u}berpr{\"u}ft, ob der SPICT-DETM f{\"u}r die Vorhersage einer Ein-Jahres-Mortalit{\"a}t von Pflegeheimbewohnerinnen und -bewohnern geeignet ist und es wurde die Selbst- und die Fremdeinsch{\"a}tzung mittels IPOS verglichen.}, subject = {Palliativpflege}, language = {de} } @phdthesis{Alban2023, author = {Alban, Eva Nicole}, title = {Ergebnisse der intraoperativen Boost-Bestrahlung (IORT) des Tumorbettes gefolgt von perkutaner Ganzbrustbestrahlung (WBRT) bei Mammakarzinompatientinnen}, doi = {10.25972/OPUS-31788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317888}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {In dieser Arbeit wird die intraoperative Boost-Bestrahlung mit 9 oder 20 Gy bei Mammakarzinompatientinnen evaluiert. Es werden das onkologische Ergebnis, die bestrahlungsassoziierte Toxizit{\"a}t, das kosmetische Therapieergebnis und die Lebensqualit{\"a}t ausgewertet. Die Analyse bezieht sich auf 124 F{\"a}lle im fr{\"u}hen Brustkrebsstadium.}, subject = {Intraoperative Strahlentherapie}, language = {de} } @phdthesis{Hartmannsgruber2023, author = {Hartmannsgruber, Johann}, title = {Erfassung und Nutzen von Frailty in der Routine der Radioonkologie}, doi = {10.25972/OPUS-31929}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319298}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Im Rahmen dieser Arbeit wurde ein Frailty-Screening mittels Clinical Frailty Scale (CFS) bei 246 Patienten im Alter ≥70 Jahren in die klinische Routine der Klinik und Poliklinik f{\"u}r Strahlentherapie des Universit{\"a}tsklinikums W{\"u}rzburg eingef{\"u}hrt. Die prospektive Erhebung der CFS erfolgte nach entsprechender Schulung innerhalb eines Zeitraums von 6 Monaten im Rahmen des Erstgespr{\"a}ches vor fraktioniert perkutaner Radiatio. In einem sekund{\"a}ren Projektabschnitt wurden innerhalb eines Nachbeobachtungszeitraumes von insgesamt 365 Tagen nach Bestrahlungsbeginn Komplikationen retrospektiv erfasst. Nach entsprechender Mitarbeiterschulung wurde eine erfolgreiche Implementierung des Frailty-Screenings in die klinische Routine erzielt. In der schließenden statistischen Auswertung zeigte sich ein h{\"o}heres Ausmaß an Frailty pr{\"a}diktiv f{\"u}r einen komplikationsreichen Therapieverlauf. Dabei wurden akute Toxizit{\"a}t, Therapieabbr{\"u}che, station{\"a}re Notaufnahmen, sowie ein Versterben analysiert. Abschließend wurde analysiert, ob sich innerhalb des ECOG Performance Status Subgruppen mittels Frailty identifizieren ließen. Dabei wurde ein besonderes Augenmerk auf das Vorliegen gebrechlicher Patienten innerhalb der Patientengruppen mit verh{\"a}ltnism{\"a}ßig guter Funktion (ECOG 0 bzw. 1) gelegt. In Zusammenschau der Befunde des PS (ECOG) und CFS zeigten sich innerhalb der ECOG Grad 0 und Grad 1 eine heterogene Aufteilung „fitter" bis „gebrechlicher" Patienten. Die Ergebnisse dieser Arbeit zeigen, dass ein Frailty-Screening mittels CFS nach entsprechender Schulung im radioonkologischen Alltag umsetzbar ist und in ein Gesamtkonzept eingebettet werden sollte. Aufgrund des pr{\"a}diktiven Wertes in Bezug auf ein negatives Outcome und dem Vorliegen von Gebrechlichkeit auch bei Patienten mit verh{\"a}ltnism{\"a}ßig gutem PS (ECOG 0, 1), k{\"o}nnten {\"a}ltere Patienten von einem zus{\"a}tzlichen Frailty-Screening profitieren, dies insbesondere im Hinblick auf die zunehmende Inanspruchnahme radioonkologischer Therapien.}, subject = {Frailty}, language = {de} } @article{PolatKaiserWohllebenetal.2017, author = {Polat, B{\"u}lent and Kaiser, Philipp and Wohlleben, Gisela and Gehrke, Thomas and Scherzad, Agmal and Scheich, Matthias and Malzahn, Uwe and Fischer, Thomas and Vordermark, Dirk and Flentje, Michael}, title = {Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer}, series = {BMC Cancer}, volume = {17}, journal = {BMC Cancer}, number = {6}, doi = {10.1186/s12885-016-3024-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157529}, year = {2017}, abstract = {Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.}, language = {en} } @article{BroschKorsaTabanetal.2022, author = {Brosch, Philippa K. and Korsa, Tessa and Taban, Danush and Eiring, Patrick and Hildebrand, Sascha and Neubauer, Julia and Zimmermann, Heiko and Sauer, Markus and Shirakashi, Ryo and Djuzenova, Cholpon S. and Sisario, Dmitri and Sukhorukov, Vladimir L.}, title = {Glucose and inositol transporters, SLC5A1 and SLC5A3, in glioblastoma cell migration}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {23}, issn = {2072-6694}, doi = {10.3390/cancers14235794}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297498}, year = {2022}, abstract = {(1) Background: The recurrence of glioblastoma multiforme (GBM) is mainly due to invasion of the surrounding brain tissue, where organic solutes, including glucose and inositol, are abundant. Invasive cell migration has been linked to the aberrant expression of transmembrane solute-linked carriers (SLC). Here, we explore the role of glucose (SLC5A1) and inositol transporters (SLC5A3) in GBM cell migration. (2) Methods: Using immunofluorescence microscopy, we visualized the subcellular localization of SLC5A1 and SLC5A3 in two highly motile human GBM cell lines. We also employed wound-healing assays to examine the effect of SLC inhibition on GBM cell migration and examined the chemotactic potential of inositol. (3) Results: While GBM cell migration was significantly increased by extracellular inositol and glucose, it was strongly impaired by SLC transporter inhibition. In the GBM cell monolayers, both SLCs were exclusively detected in the migrating cells at the monolayer edge. In single GBM cells, both transporters were primarily localized at the leading edge of the lamellipodium. Interestingly, in GBM cells migrating via blebbing, SLC5A1 and SLC5A3 were predominantly detected in nascent and mature blebs, respectively. (4) Conclusion: We provide several lines of evidence for the involvement of SLC5A1 and SLC5A3 in GBM cell migration, thereby complementing the migration-associated transportome. Our findings suggest that SLC inhibition is a promising approach to GBM treatment.}, language = {en} } @article{KimpelSchindlerSchmidtPenningtonetal.2023, author = {Kimpel, Otilia and Schindler, Paul and Schmidt-Pennington, Laura and Altieri, Barbara and Megerle, Felix and Haak, Harm and Pittaway, James and Dischinger, Ulrich and Quinkler, Marcus and Mai, Knut and Kroiss, Matthias and Polat, B{\"u}lent and Fassnacht, Martin}, title = {Efficacy and safety of radiation therapy in advanced adrenocortical carcinoma}, series = {British Journal of Cancer}, volume = {128}, journal = {British Journal of Cancer}, number = {4}, doi = {10.1038/s41416-022-02082-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324411}, pages = {586-593}, year = {2023}, abstract = {Background International guidelines emphasise the role of radiotherapy (RT) for the management of advanced adrenocortical carcinoma (ACC). However, the evidence for this recommendation is very low. Methods We retrospectively analysed all patients who received RT for advanced ACC in five European centres since 2000. Primary endpoint: time to progression of the treated lesion (tTTP). Secondary endpoints: best objective response, progression-free survival (PFS), overall survival (OS), adverse events, and the establishment of predictive factors by Cox analyses. Results In total, 132 tumoural lesions of 80 patients were treated with conventional RT (cRT) of 50-60 Gy (n = 20) or 20-49 Gy (n = 69), stereotactic body RT of 35-50 Gy (SBRT) (n = 36), or brachytherapy of 12-25 Gy (BT) (n = 7). Best objective lesional response was complete (n = 6), partial (n = 52), stable disease (n = 60), progressive disease (n = 14). Median tTTP was 7.6 months (1.0-148.6). In comparison to cRT\(_{20-49Gy}\), tTTP was significantly longer for cRT\(_{50-60Gy}\) (multivariate adjusted HR 0.10; 95\% CI 0.03-0.33; p < 0.001) and SBRT (HR 0.31; 95\% CI 0.12-0.80; p = 0.016), but not for BT (HR 0.66; 95\% CI 0.22-1.99; p = 0.46). Toxicity was generally mild and moderate with three grade 3 events. No convincing predictive factors could be established. Conclusions This largest published study on RT in advanced ACC provides clear evidence that RT is effective in ACC.}, language = {en} } @phdthesis{Mann2024, author = {Mann, Daniel}, title = {Empowerment bei Krebspatient:innen}, doi = {10.25972/OPUS-34752}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-347524}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Die Fragestellung, ob Question-Prompt-Lists (QPLs) interaktionales Empowerment f{\"o}rdern, wurde nach derzeitigem Kenntnisstand noch nicht untersucht. Bei QPLs handelt es sich um kurze Fragensets oder Kernfragen bez{\"u}glich der eigenen Erkrankung oder der Behandlung, die Patient:innen beispielsweise unmittelbar vor einem Aufkl{\"a}rungsgespr{\"a}ch erhalten, um sich aktiv auf dieses vorzubereiten. Der Nutzen einer solchen QPL konnte bereits in zahlreichen Studien belegt werden. Ebenso kommt der Thematik Empowerment bei der Behandlung von Krebspatient:innen eine wichtige Rolle zu: die Betroffenen sollen dahingehend ermutigt und best{\"a}rkt werden, sich aktiv mit der eigenen Erkrankung, deren Folgen und Behandlung auseinanderzusetzen, um so schließlich ein h{\"o}heres Maß an Kontrolle und Lebensqualit{\"a}t zu erlangen. Ziel der Studie war es, den positiven Effekt einer QPL bez{\"u}glich des Empowerments der Teilnehmer:innen aufzuzeigen. Die Fragestellung dieser prospektiv randomisiert kontrollierten Studie war es, ob eine QPL einen signifikanten Effekt auf das Empowerment von Krebspatient:innen haben kann. Die Datenerhebung erfolgte in der Ambulanz f{\"u}r Strahlentherapie des Universit{\"a}tsklinikums W{\"u}rzburgs. Insgesamt konnten 279 Patient:innen in die Studie eingeschlossen werden, 140 Teilnehmer:innen in der Interventionsgruppe und 139 Teilnehmer:innen in der Kontrollgruppe, die nach Randomisierung jeweils ihrer Gruppe zugeteilt wurden. Die Patient:innen der Interventionsgruppe erhielten unmittelbar vor dem Gespr{\"a}ch mit dem behandelnden Arzt/ der behandelnden {\"A}rztin eine QPL, anhand derer sie sich individuelle Fragen als Vorbereitung auf das Aufkl{\"a}rungsgespr{\"a}ch {\"u}berlegen konnten, wohingegen die Teilnehmer:innen der Kontrollgruppe keine solche QPL erhielten. Die aufkl{\"a}renden {\"A}rzte/ {\"A}rztinnen wussten jeweils nicht, welche Patient:innen zuvor eine QPL erhalten hatten. Nach dem Aufkl{\"a}rungsgespr{\"a}ch f{\"u}llten beide Gruppen von Teilnehmer:innen dann einen Fragebogen aus, mit Hilfe dessen nach Addition der einzelnen Fragewerte zu einem Summen-Score das Maß an Empowerment gemessen werden sollte. Hierbei konnte gezeigt werden, dass sich der Mittelwert des Summen-Scores signifikant zwischen der Interventionsgruppe (M=21,7; SE=0,22; SD=2,65) und der Kontrollgruppe (M=20,8; SE=0,26; SD=3,08) bei einem Signifikanzlevel von alpha=0,05 und einer Effektgr{\"o}ße von d=0,29 (r=0,16): t(277)=2,71; p=0,007, 95\% CI [-1,61, -0,26] unterschied. Außerdem konnte beim Vergleich der einzelnen Fragen des Auswertungsbogens selbst bei 4 von 8 Frageitems ein signifikanter Unterschied zwischen Interventionsgruppe und Kontrollgruppe gezeigt werden. Hierbei handelte es sich um Fragen, die den Fokus auf die relationale, also die beziehungsorientierte Komponente des Aufkl{\"a}rungsgespr{\"a}chs legten, im Gegensatz zu den Fragen, die den Fokus auf den reinen Zuwachs von Informationen, also die informative Komponente des Aufkl{\"a}rungsgespr{\"a}chs legten. Somit kann abschließend von einem signifikanten Effekt der Intervention, dem Gebrauch einer QPL, in Bezug auf das Konstrukt Empowerment bei Krebspatient:innen ausgegangen werden. Mit der QPL konnte ein einfaches, gut durchf{\"u}hrbares Instrument in den klinischen Alltag der Strahlenambulanz des Universit{\"a}tsklinikums W{\"u}rzburg implementiert werden, das von einem Großteil der Patient:innen gut angenommen und als hilfreich bewertet wurde.  }, subject = {Krebskranker}, language = {de} } @article{TamihardjaLawrenzLutyjetal.2022, author = {Tamihardja, J{\"o}rg and Lawrenz, Ingulf and Lutyj, Paul and Weick, Stefan and Guckenberger, Matthias and Polat, B{\"u}lent and Flentje, Michael}, title = {Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer}, series = {Strahlentherapie und Onkologie}, volume = {198}, journal = {Strahlentherapie und Onkologie}, number = {8}, doi = {10.1007/s00066-022-01953-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325055}, pages = {735-743}, year = {2022}, abstract = {Purpose Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. Methods From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (D\(_{Mean}\)). Combined treatment was delivered as 46 Gy (D\(_{Mean}\)) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D\(_{90\\%}\)). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). Results The estimated 10-year bRFS was 82.0\% vs. 76.4\% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9\% vs. 87.0\% (p = 0.195) and the 10-year OS was 65.7\% vs. 68.9\% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6\% vs. 19.2\% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1\% vs. 5.0\% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2\% vs. 3.6\% (p = 0.401) and GI toxicity in 1.0\% vs. 0.3\% (p = 0.249), respectively. Conclusion Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.}, language = {en} } @article{GrabenbauerFlentje2022, author = {Grabenbauer, Felix and Flentje, Michael}, title = {Salvage-Bestrahlung der Prostataloge: Mitbestrahlung der regionalen LK und Bedeutung der ADT}, series = {Strahlentherapie und Onkologie}, volume = {198}, journal = {Strahlentherapie und Onkologie}, number = {12}, doi = {10.1007/s00066-022-02001-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325047}, pages = {1119-1121}, year = {2022}, abstract = {No abstract available.}, language = {de} } @article{ShirakashiSisarioTabanetal.2023, author = {Shirakashi, Ryo and Sisario, Dmitri and Taban, Danush and Korsa, Tessa and Wanner, Sophia B. and Neubauer, Julia and Djuzenova, Cholpon S. and Zimmermann, Heiko and Sukhorukov, Vladimir L.}, title = {Contraction of the rigor actomyosin complex drives bulk hemoglobin expulsion from hemolyzing erythrocytes}, series = {Biomechanics and Modeling in Mechanobiology}, volume = {22}, journal = {Biomechanics and Modeling in Mechanobiology}, number = {2}, doi = {10.1007/s10237-022-01654-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325107}, pages = {417-432}, year = {2023}, abstract = {Erythrocyte ghost formation via hemolysis is a key event in the physiological clearance of senescent red blood cells (RBCs) in the spleen. The turnover rate of millions of RBCs per second necessitates a rapid efflux of hemoglobin (Hb) from RBCs by a not yet identified mechanism. Using high-speed video-microscopy of isolated RBCs, we show that electroporation-induced efflux of cytosolic ATP and other small solutes leads to transient cell shrinkage and echinocytosis, followed by osmotic swelling to the critical hemolytic volume. The onset of hemolysis coincided with a sudden self-propelled cell motion, accompanied by cell contraction and Hb-jet ejection. Our biomechanical model, which relates the Hb-jet-driven cell motion to the cytosolic pressure generation via elastic contraction of the RBC membrane, showed that the contributions of the bilayer and the bilayer-anchored spectrin cytoskeleton to the hemolytic cell motion are negligible. Consistent with the biomechanical analysis, our biochemical experiments, involving extracellular ATP and the myosin inhibitor blebbistatin, identify the low abundant non-muscle myosin 2A (NM2A) as the key contributor to the Hb-jet emission and fast hemolytic cell motion. Thus, our data reveal a rapid myosin-based mechanism of hemolysis, as opposed to a much slower diffusive Hb efflux.}, language = {en} } @article{AndratschkeAlheidAllgaeueretal.2018, author = {Andratschke, N. and Alheid, H. and Allg{\"a}uer, M. and Becker, G. and Blanck, O. and Boda-Heggemann, J. and Brunner, T. and Duma, M. and Gerum, S. and Guckenberger, M. and Hildebrandt, G. and Klement, R. J. and Lewitzki, V. and Ostheimer, C. and Papachristofilou, A. and Petersen, C. and Schneider, T. and Semrau, R. and Wachter, S. and Habermehl, D.}, title = {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}, series = {BMC Cancer}, volume = {18}, journal = {BMC Cancer}, doi = {10.1186/s12885-018-4191-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221116}, year = {2018}, abstract = {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. Conclusion After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.}, language = {en} } @article{KlementAbbasiSengerAdebahretal.2019, author = {Klement, Rainer J. and Abbasi-Senger, N. and Adebahr, S. and Alheid, H. and Allgaeuer, M. and Becker, G. and Blanck, O. and Boda-Heggemann, J. and Brunner, T. and Duma, M. and Eble, M. J. and Ernst, I. and Gerum, S. and Habermehl, D. and Hass, P. and Henkenberens, C. and Hildebrandt, G. and Imhoff, D. and Kahl, H. and Klass, N. D. and Krempien, R. and Lewitzki, V. and Lohaus, F. and Ostheimer, C. and Papachristofilou, A. and Petersen, C. and Rieber, J. and Schneider, T. and Schrade, E. and Semrau, R. and Wachter, S. and Wittig, A. and Guckenberger, M. and Andratschke, N.}, title = {The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5362-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325877}, year = {2019}, abstract = {Background The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.}, language = {en} } @article{WegenerHerzogSauer2020, author = {Wegener, Sonja and Herzog, Barbara and Sauer, Otto A.}, title = {Detector response in the buildup region of small MV fields}, series = {Medical Physics}, volume = {47}, journal = {Medical Physics}, number = {3}, doi = {10.1002/mp.13973}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214228}, pages = {1327-1339}, year = {2020}, abstract = {Purpose: The model used to calculate dose distributions in a radiotherapy treatment plan relies on the data entered during beam commissioning. The quality of these data heavily depends on the detector choice made, especially in small fields and in the buildup region. Therefore, it is necessary to identify suitable detectors for measurements in the buildup region of small fields. To aid the understanding of a detector's limitations, several factors that influence the detector signal are to be analyzed, for example, the volume effect due to the detector size, the response to electron contamination, the signal dependence on the polarity used, and the effective point of measurement chosen. Methods: We tested the suitability of different small field detectors for measurements of depth dose curves with a special focus on the surface-near area of dose buildup for fields sized between 10 × 10 and 0.6 × 0.6 cm\(^{2}\). Depth dose curves were measured with 14 different detectors including plane-parallel chambers, thimble chambers of different types and sizes, shielded and unshielded diodes as well as a diamond detector. Those curves were compared with depth dose curves acquired on Gafchromic film. Additionally, the magnitude of geometric volume corrections was estimated from film profiles in different depths. Furthermore, a lead foil was inserted into the beam to reduce contaminating electrons and to study the resulting changes of the detector response. The role of the effective point of measurement was investigated by quantifying the changes occurring when shifting depth dose curves. Last, measurements for the small ionization chambers taken at opposing biasing voltages were compared to study polarity effects. Results: Depth-dependent correction factors for relative depth dose curves with different detectors were derived. Film, the Farmer chamber FC23, a 0.13 cm\(^{3}\) scanning chamber CC13 and a plane-parallel chamber PPC05 agree very well in fields sized 4 × 4 and 10 × 10 cm\(^{2}\). For most detectors and in smaller fields, depth dose curves differ from the film. In general, shielded diodes require larger corrections than unshielded diodes. Neither the geometric volume effect nor the electron contamination can account for the detector differences. The biggest uncertainty arises from the positioning of a detector with respect to the water surface and from the choice of the detector's effective point of measurement. Depth dose curves acquired with small ionization chambers differ by over 15\% in the buildup region depending on sign of the biasing voltage used. Conclusions: A scanning chamber or a PPC40 chamber is suitable for fields larger than 4 × 4 cm\(^{2}\). Below that field size, the microDiamond or small ionization chambers perform best requiring the smallest corrections at depth as well as in the buildup region. Diode response changes considerably between the different types of detectors. The position of the effective point of measurement has a huge effect on the resulting curves, therefore detector specific rather than general shifts of half the inner radius of cylindrical ionization chambers for the effective point of measurement should be used. For small ionization chambers, averaging between both polarities is necessary for data obtained near the surface.}, language = {en} } @article{WeickBreuerRichteretal.2020, author = {Weick, Stefan and Breuer, Kathrin and Richter, Anne and Exner, Florian and Str{\"o}hle, Serge-Peer and Lutyj, Paul and Tamihardja, J{\"o}rg and Veldhoen, Simon and Flentje, Michael and Polat, B{\"u}lent}, title = {Non-rigid image registration of 4D-MRI data for improved delineation of moving tumors}, series = {BMC Medical Imaging}, volume = {20}, journal = {BMC Medical Imaging}, doi = {10.1186/s12880-020-00439-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229271}, year = {2020}, abstract = {Background To increase the image quality of end-expiratory and end-inspiratory phases of retrospective respiratory self-gated 4D MRI data sets using non-rigid image registration for improved target delineation of moving tumors. Methods End-expiratory and end-inspiratory phases of volunteer and patient 4D MRI data sets are used as targets for non-rigid image registration of all other phases using two different registration schemes: In the first, all phases are registered directly (dir-Reg) while next neighbors are successively registered until the target is reached in the second (nn-Reg). Resulting data sets are quantitatively compared using diaphragm and tumor sharpness and the coefficient of variation of regions of interest in the lung, liver, and heart. Qualitative assessment of the patient data regarding noise level, tumor delineation, and overall image quality was performed by blinded reading based on a 4 point Likert scale. Results The median coefficient of variation was lower for both registration schemes compared to the target. Median dir-Reg coefficient of variation of all ROIs was 5.6\% lower for expiration and 7.0\% lower for inspiration compared with nn-Reg. Statistical significant differences between the two schemes were found in all comparisons. Median sharpness in inspiration is lower compared to expiration sharpness in all cases. Registered data sets were rated better compared to the targets in all categories. Over all categories, mean expiration scores were 2.92 +/- 0.18 for the target, 3.19 +/- 0.22 for nn-Reg and 3.56 +/- 0.14 for dir-Reg and mean inspiration scores 2.25 +/- 0.12 for the target, 2.72 +/- 215 0.04 for nn-Reg and 3.78 +/- 0.04 for dir-Reg. Conclusions In this work, end-expiratory and inspiratory phases of a 4D MRI data sets are used as targets for non-rigid image registration of all other phases. It is qualitatively and quantitatively shown that image quality of the targets can be significantly enhanced leading to improved target delineation of moving tumors.}, language = {en} } @article{PolatWohllebenKosmalaetal.2022, author = {Polat, B{\"u}lent and Wohlleben, Gisela and Kosmala, Rebekka and Lisowski, Dominik and Mantel, Frederick and Lewitzki, Victor and L{\"o}hr, Mario and Blum, Robert and Herud, Petra and Flentje, Michael and Monoranu, Camelia-Maria}, title = {Differences in stem cell marker and osteopontin expression in primary and recurrent glioblastoma}, series = {Cancer Cell International}, volume = {22}, journal = {Cancer Cell International}, issn = {1475-2867}, doi = {10.1186/s12935-022-02510-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301240}, year = {2022}, abstract = {Background Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells. Methods Paired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan-Meier analysis, a possible association with overall survival by marker expression was investigated. Results Sixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08). Conclusions Most of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.}, language = {en} } @article{WegenerSauer2019, author = {Wegener, Sonja and Sauer, Otto A.}, title = {The effective point of measurement for depth-dose measurements in small MV photon beams with different detectors}, series = {Medical Physics}, volume = {46}, journal = {Medical Physics}, number = {11}, doi = {10.1002/mp.13788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206148}, pages = {5209-5215}, year = {2019}, abstract = {Purpose: The effective point of measurement (EPOM) of cylindrical ionization chambers differs from their geometric center. The exact shift depends on chamber construction details, above all the chamber size, and to some degree on the field-size and beam quality. It generally decreases as the chamber dimensions get smaller. In this work, effective points of measurement in small photon fields of a range of cylindrical chambers of different sizes are investigated, including small chambers that have not been studied previously. Methods: In this investigation, effective points of measurement for different ionization chambers (Farmer type, scanning chambers, micro-ionization chambers) and solid state detectors were determined by measuring depth-ionization curves in a 6 MV beam in field sizes between 2 9 2 cm2 and 10 9 10 cm2 and comparing those curves with curves measured with plane-parallel chambers. Results: It was possible to average the results to one shift per detector, as the results were sufficiently independent of the studied field sizes. For cylindrical ion chambers, shifts of the EPOM were determined to be between 0.49 and 0.30 times the inner chamber radius from the reference point. Conclusions: We experimentally confirmed the previously reported decrease of the EPOM shift with decreasing detector size. Highly accurate data for a large range of detectors, including new very small ones, were determined. Thus, small chambers noticeably differ from the 0.5-times to 0.6-times the inner chamber radius recommendations in current dosimetry protocols. The detector-individual EPOMs need to be considered for measurements of depth-dose curves.}, language = {en} } @article{WegenerSchindhelmSauer2022, author = {Wegener, Sonja and Schindhelm, Robert and Sauer, Otto A.}, title = {Implementing corrections of isocentric shifts for the stereotactic irradiation of cerebral targets: Clinical validation}, series = {Journal of Applied Clinical Medical Physics}, volume = {23}, journal = {Journal of Applied Clinical Medical Physics}, number = {5}, doi = {10.1002/acm2.13577}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312906}, year = {2022}, abstract = {Purpose: Any Linac will show geometric imprecisions, including non-ideal alignment of the gantry, collimator and couch axes, and gantry sag or wobble. Their angular dependence can be quantified and resulting changes of the dose distribution predicted (Wack, JACMP 20(5), 2020). We analyzed whether it is feasible to correct geometric shifts during treatment planning. The successful implementation of such a correction procedure was verified by measurements of different stereotactic treatment plans. Methods: Isocentric shifts were quantified for two Elekta Synergy Agility Linacs using the QualiForMed ISO-CBCT+ module, yielding the shift between kV and MV isocenters, the gantry flex and wobble as well as the positions of couch and collimator rotation axes. Next, the position of each field's isocenter in the Pinnacle treatment planning system was adjusted accordingly using a script. Fifteen stereotactic treatment plans of cerebral metastases (0.34 to 26.53 cm3) comprising 9-11 beams were investigated; 54 gantry and couch combinations in total. Unmodified plans and corrected plans were measured using the Sun Nuclear SRS-MapCHECK with the Stereophan phantom and evaluated using gamma analysis. Results: Geometric imprecisions, such as shifts of up to 0.8 mm between kV and MV isocenter, a couch rotation axis 0.9 mm off the kV isocente,r and gantry flex with an amplitude of 1.1 mm, were found. For eight, mostly small PTVs D98 values declined more than 5\% by simulating these shifts. The average gamma (2\%/2 mm, absolute, global, 20\% threshold) was reduced from 0.53 to 0.31 (0.32 to 0.30) for Linac 1 (Linac 2) when including the isocentric corrections. Thus, Linac 1 reached the accuracy level of Linac 2 after correction. Conclusion: Correcting for Linac geometric deviations during the planning process is feasible and was dosimetrically validated. The dosimetric impact of the geometric imperfections can vary between Linacs and should be assessed and corrected where necessary.}, language = {en} } @article{DjuzenovaFiedlerMemmeletal.2019, author = {Djuzenova, Cholpon S. and Fiedler, Vanessa and Memmel, Simon and Katzer, Astrid and Sisario, Dmitri and Brosch, Philippa K. and G{\"o}hrung, Alexander and Frister, Svenja and Zimmermann, Heiko and Flentje, Michael and Sukhorukov, Vladimir L.}, title = {Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5517-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200290}, pages = {299}, year = {2019}, abstract = {Background Most tumor cells show aberrantly activated Akt which leads to increased cell survival and resistance to cancer radiotherapy. Therefore, targeting Akt can be a promising strategy for radiosensitization. Here, we explore the impact of the Akt inhibitor MK-2206 alone and in combination with the dual PI3K and mTOR inhibitor PI-103 on the radiation sensitivity of glioblastoma cells. In addition, we examine migration of drug-treated cells. Methods Using single-cell tracking and wound healing migration tests, colony-forming assay, Western blotting, flow cytometry and electrorotation we examined the effects of MK-2206 and PI-103 and/or irradiation on the migration, radiation sensitivity, expression of several marker proteins, DNA damage, cell cycle progression and the plasma membrane properties in two glioblastoma (DK-MG and SNB19) cell lines, previously shown to differ markedly in their migratory behavior and response to PI3K/mTOR inhibition. Results We found that MK-2206 strongly reduces the migration of DK-MG but only moderately reduces the migration of SNB19 cells. Surprisingly, MK-2206 did not cause radiosensitization, but even increased colony-forming ability after irradiation. Moreover, MK-2206 did not enhance the radiosensitizing effect of PI-103. The results appear to contradict the strong depletion of p-Akt in MK-2206-treated cells. Possible reasons for the radioresistance of MK-2206-treated cells could be unaltered or in case of SNB19 cells even increased levels of p-mTOR and p-S6, as compared to the reduced expression of these proteins in PI-103-treated samples. We also found that MK-2206 did not enhance IR-induced DNA damage, neither did it cause cell cycle distortion, nor apoptosis nor excessive autophagy. Conclusions Our study provides proof that MK-2206 can effectively inhibit the expression of Akt in two glioblastoma cell lines. However, due to an aberrant activation of mTOR in response to Akt inhibition in PTEN mutated cells, the therapeutic window needs to be carefully defined, or a combination of Akt and mTOR inhibitors should be considered.}, language = {en} } @article{ZimmermannRichterWeicketal.2022, author = {Zimmermann, Marcus and Richter, Anne and Weick, Stefan and Exner, Florian and Mantel, Frederick and Diefenhardt, Markus and Fokas, Emmanouil and Kosmala, Rebekka and Flentje, Michael and Polat, B{\"u}lent}, title = {Acute toxicities of patients with locally advanced rectal cancer treated with intensified chemoradiotherapy within the CAO/ARO/AIO-12 trial: comparing conventional versus VMAT planning at a single center}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-25647-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301255}, year = {2022}, abstract = {In locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is regarded as standard treatment. We assessed acute toxicities in patients receiving conventional 3D-conformal radiotherapy (3D-RT) and correlated them with dosimetric parameters after re-planning with volumetric modulated arc therapy (VMAT). Patients were randomized within the multicenter CAO/ARO/AIO-12 trial and received 50.4 Gy in 28 fractions and simultaneous chemotherapy with fluorouracil and oxaliplatin. Organs at risk (OAR) were contoured in a standardized approach. Acute toxicities and dose volume histogram parameters of 3D-RT plans were compared to retrospectively calculated VMAT plans. From 08/2015 to 01/2018, 35 patients with LARC were treated at one study center. Thirty-four patients were analyzed of whom 1 (3\%) was UICC stage II and 33 (97\%) patients were UICC stage III. Grade 3 acute toxicities occurred in 5 patients (15\%). Patients with acute grade 1 cystitis (n = 9) had significantly higher D\(_{mean}\) values for bladder (29.4 Gy vs. 25.2 Gy, p < 0.01) compared to patients without bladder toxicities. Acute diarrhea was associated with small bowel volume (grade 2: 870.1 ccm vs. grade 0-1: 647.3 ccm; p < 0.01) and with the irradiated volumes V5 to V50. Using VMAT planning, we could reduce mean doses and irradiated volumes for all OAR: D\(_{mean}\) bladder (21.9 Gy vs. 26.3 Gy, p < 0.01), small bowel volumes V5-V45 (p < 0.01), D\(_{mean}\) anal sphincter (34.6 Gy vs. 35.6 Gy, p < 0.01) and D\(_{mean}\) femoral heads (right 11.4 Gy vs. 25.9 Gy, left 12.5 Gy vs. 26.6 Gy, p < 0.01). Acute small bowel and bladder toxicities were dose and volume dependent. Dose and volume sparing for all OAR could be achieved through VMAT planning and might result in less acute toxicities.}, language = {en} } @article{Prieto‐GarciaHartmannReisslandetal.2020, author = {Prieto-Garcia, Cristian and Hartmann, Oliver and Reissland, Michaela and Braun, Fabian and Fischer, Thomas and Walz, Susanne and Sch{\"u}lein-V{\"o}lk, Christina and Eilers, Ursula and Ade, Carsten P. and Calzado, Marco A. and Orian, Amir and Maric, Hans M. and M{\"u}nch, Christian and Rosenfeldt, Mathias and Eilers, Martin and Diefenbacher, Markus E.}, title = {Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells}, series = {EMBO Molecular Medicine}, volume = {12}, journal = {EMBO Molecular Medicine}, number = {4}, doi = {10.15252/emmm.201911101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218303}, year = {2020}, abstract = {The transcription factor ∆Np63 is a master regulator of epithelial cell identity and essential for the survival of squamous cell carcinoma (SCC) of lung, head and neck, oesophagus, cervix and skin. Here, we report that the deubiquitylase USP28 stabilizes ∆Np63 and maintains elevated ∆NP63 levels in SCC by counteracting its proteasome-mediated degradation. Impaired USP28 activity, either genetically or pharmacologically, abrogates the transcriptional identity and suppresses growth and survival of human SCC cells. CRISPR/Cas9-engineered in vivo mouse models establish that endogenous USP28 is strictly required for both induction and maintenance of lung SCC. Our data strongly suggest that targeting ∆Np63 abundance via inhibition of USP28 is a promising strategy for the treatment of SCC tumours.}, language = {en} } @phdthesis{Warm2023, author = {Warm, Tobias Dominik}, title = {Einstellung von Pflegeheimbewohnenden zur vorausschauenden Versorgungsplanung}, doi = {10.25972/OPUS-32373}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323739}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Hintergrund: Aufgrund des demographischen Wandels nimmt der Anteil der Pflegebed{\"u}rftigen in Deutschland zu. Aktuelle Erhebungen zeigen, dass der Einzug in station{\"a}re Pflegeeinrichtungen erst in h{\"o}herem Lebensalter und bei steigenden Komorbidit{\"a}ten erfolgt, womit ein erh{\"o}hter Bedarf an medizinischer und pflegerischer Versorgung einhergeht. Ziele der Studie: Durch die Befragung der Pflegeheimbewohnenden sollten Erkenntnisse {\"u}ber eine bereits erfolgte Vorsorgedokumentation und deren Versorgungsw{\"u}nsche am Lebensende gewonnen werden. Methodik: Es wurde eine multizentrische, explorative Beobachtungsstudie als Vollerhebung in elf bayerischen Pflegeeinrichtungen durchgef{\"u}hrt. Die Datenerhebung erfolgte vor Ort durch den Promovierenden mittels eines standardisierten Fragebogens im Zeitraum von April 2018 bis Mai 2019. Im Zuge der statistischen Auswertung wurden deskriptive Statistiken erstellt, Gruppenunterschiede wurden zweiseitig mittels Fisher-Exakt-Test auf Unabh{\"a}ngigkeit hin {\"u}berpr{\"u}ft und paarweise Gruppenvergleiche durch bin{\"a}re logistische Regression durchgef{\"u}hrt. Ergebnisse: Von 1207 wurden 269 (22,3 \%) Pflegeheimbewohnende in die Studie eingeschlossen. Von den Studienteilnehmenden hatten sich 55 \% bereits intensiver mit dem eigenen Sterben auseinandergesetzt. 50,9 \% der Pflegeheimbewohnenden w{\"u}nschten im Falle einer zum Tode f{\"u}hrenden Erkrankung eine alleinige pflegerische und medizinische Versorgung in der Einrichtung. 19,7 \% w{\"u}nschten in diesem Fall eine Klinikeinweisung, aber den Verzicht auf Anwendung invasiver Therapiemaßnahmen. Ein Wunschsterbeort lag bei 65,4 \% der Pflegeheimbewohnenden vor. Von diesen w{\"u}nschten 76,7 \% in der Pflegeeinrichtung zu versterben. 71,7 \% der Pflegeheimbewohnenden w{\"u}nschten, nicht allein zu versterben. {\"U}ber ihre Versorgungsw{\"u}nsche hatten bereits 45,7 \% aller Studienteilnehmenden eine andere Person, mehrheitlich die eigenen Angeh{\"o}rigen, informiert. 49,1 \% der Pflegeheimbewohnenden w{\"u}nschten sich eine Erfassung der Versorgungsw{\"u}nsche direkt bei Einzug in die Einrichtung. In 63,6 \% der F{\"a}lle lag mindestens ein schriftliches Vorsorgedokument vor. Eine Patientenverf{\"u}gung hatten 45,5 \%, eine Vorsorgevollmacht 46,5 \% der Pflegeheimbewohnenden verfasst. Schlussfolgerungen: Pflegeheimbewohnende haben mehrheitlich konkrete Vorstellungen f{\"u}r ihre Versorgung am Lebensende. Die vorhandenen Versorgungsw{\"u}nsche sollten auf Wunsch der Pflegeheimbewohnenden erfasst werden, um eine entsprechende Versorgung auch im Falle einer eintretenden Einwilligungsunf{\"a}higkeit zu erm{\"o}glichen. Der Zeitpunkt der Erfassung der Versorgungsw{\"u}nsche sollte im Hinblick auf das steigende Lebensalter bei Einzug in deutsche Pflegeeinrichtungen und auf die altersbedingt steigende Rate an kognitiven Einschr{\"a}nkungen m{\"o}glichst fr{\"u}hzeitig gew{\"a}hlt werden. Hierbei stellen Konzepte der vorausschauenden Versorgungsplanung eine M{\"o}glichkeit dar, um einen Dialog zwischen den beteiligten Akteuren zu erm{\"o}glichen.}, subject = {Versorgungsplanung}, language = {de} } @article{WegenerSauer2018, author = {Wegener, Sonja and Sauer, Otto A.}, title = {Electrometer offset current due to scattered radiation}, series = {Journal of Applied Clinical Medical Physics}, volume = {19}, journal = {Journal of Applied Clinical Medical Physics}, number = {6}, doi = {10.1002/acm2.12458}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176137}, pages = {274-281}, year = {2018}, abstract = {Relative dose measurements with small ionization chambers in combination with an electrometer placed in the treatment room ("internal electrometer") show a large dependence on the polarity used. While this was observed previously for percent depth dose curves (PDDs), the effect has not been understood or preventable. To investigate the polarity dependence of internal electrometers used in conjunction with a small-volume ionization chamber, we placed an internal electrometer at a distance of 1 m from the isocenter and exposed it to different amounts of scattered radiation by varying the field size. We identified irradiation of the electrometer to cause a current of approximately -1 pA, regardless of the sign of the biasing voltage. For low-sensitivity detectors, such a current noticeably distorts relative dose measurements. To demonstrate how the current systematically changes PDDs, we collected measurements with nine ionization chambers of different volumes. As the chamber volume decreased, signal ratios at 20 and 10 cm depth (M20/M10) became smaller for positive bias voltage and larger for negative bias voltage. At the size of the iba CC04 (40 mm\(^{3}\)) the difference of M20/M10 was around 1\% and for the smallest studied chamber, the iba CC003 chamber (3 mm\(^{3}\)), around 7\% for a 10 × 10 cm² field. When the electrometer was moved further from the source or shielded, the additional current decreased. Consequently, PDDs at both polarities were brought into alignment at depth even for the 3 mm\(^{3}\) ionization chamber. The apparent polarity effect on PDDs and lateral beam profiles was reduced considerably by shielding the electrometer. Due to normalization the effect on output values was low. When measurements with a low-sensitivity probe are carried out in conjunction with an internal electrometer, we recommend careful monitoring of the particular setup by testing both polarities, and if deemed necessary, we suggest shielding the electrometer.}, language = {en} } @article{RabevanOorschotJentschke2020, author = {Rabe, A. and van Oorschot, B. and Jentschke, E.}, title = {Suizidalit{\"a}t bei Krebspatienten}, series = {Der Onkologe}, volume = {26}, journal = {Der Onkologe}, issn = {Suizidalit{\"a}t bei Krebspatienten}, doi = {10.1007/s00761-020-00712-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232401}, pages = {163-168}, year = {2020}, abstract = {Hintergrund Die Diagnose Krebs und ihre Behandlung kann eine große Belastung f{\"u}r die Betroffenen darstellen. Neben k{\"o}rperlichen Beschwerden kann auch die Psyche in Mitleidenschaft gezogen werden. Fehlt es an entsprechenden Bew{\"a}ltigungsstrategien, kann der selbstbestimmte Tod als einziger Ausweg erscheinen. Ziel und Fragestellung Die vorliegende {\"U}bersichtsarbeit zur Suizidalit{\"a}t bei Krebspatienten befasst sich mit einem Thema, das in der Forschung und Praxis in Deutschland nur wenig Aufmerksamkeit findet. Material und Methoden Eine themenbezogene Literaturrecherche stellt die Basis der Arbeit dar. Ergebnisse Todesw{\"u}nsche unter Krebspatienten sind nicht selten und k{\"o}nnen Suizidgedanken/-absichten beinhalten. Psychische Beschwerden, insbesondere Hoffnungslosigkeit und Depression, sind ernstzunehmende Risikofaktoren. Das Erkennen einer hohen psychischen Belastung/von Todesw{\"u}nschen ist ein wichtiger Aspekt f{\"u}r die Suizidpr{\"a}vention. F{\"u}r die Praxis empfiehlt sich zun{\"a}chst die Verwendung von Frageb{\"o}gen. Bei auff{\"a}lligen Werten muss die Suizidalit{\"a}t proaktiv in einem pers{\"o}nlichen Gespr{\"a}ch exploriert werden. Betroffene sind meist ambivalent bez{\"u}glich ihrer Entscheidung f{\"u}r oder gegen das Leben. Dies stellt eine große Chance f{\"u}r Interventionen dar. Schlussfolgerungen Suizidalit{\"a}t kann verhindert werden, wenn die hohe Belastung erkannt wird. Bereits das Gespr{\"a}ch zwischen Arzt und Patient {\"u}ber Todesw{\"u}nsche kann eine erste Entlastung darstellen.}, language = {de} } @phdthesis{Zehner2024, author = {Zehner, Leonie Constanze}, title = {Evaluierung der Rezidivbestrahlung des Prostatakarzinoms}, doi = {10.25972/OPUS-35123}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351230}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Es erfolgte eine Evaluierung von Bestrahlungsdaten aus der Strahlentherapie der Universit{\"a}tsklinik W{\"u}rzburg von 435 Patienten mit biochemischen oder klinischen Rezidiv des Prostatakarzinoms. Der prim{\"a}re Endpunkt war das biochemisch rezidivfreie {\"U}berleben. Sekund{\"a}re Endpunkte waren das Auftreten von Fernmetastasen und das Versterben der Patienten. Zudem wurde der Einfluss patienten-, tumor-, und behandlungsspezifischer Faktoren {\"u}berpr{\"u}ft.}, subject = {Prostata}, language = {de} } @article{DietzschBraesigkSeideletal.2022, author = {Dietzsch, Stefan and Braesigk, Annett and Seidel, Clemens and Remmele, Julia and Kitzing, Ralf and Schlender, Tina and Mynarek, Martin and Geismar, Dirk and Jablonska, Karolina and Schwarz, Rudolf and Pazos, Montserrat and Weber, Damien C. and Frick, Silke and Gurtner, Kristin and Matuschek, Christiane and Harrabi, Semi Ben and Gl{\"u}ck, Albrecht and Lewitzki, Victor and Dieckmann, Karin and Benesch, Martin and Gerber, Nicolas U. and Obrecht, Denise and Rutkowski, Stefan and Timmermann, Beate and Kortmann, Rolf-Dieter}, title = {Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma—an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial}, series = {Strahlentherapie und Onkologie}, volume = {198}, journal = {Strahlentherapie und Onkologie}, number = {3}, issn = {0179-7158}, doi = {10.1007/s00066-021-01822-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307812}, pages = {282-290}, year = {2022}, abstract = {Purpose In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost. Patients and methods A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly. Results Of 65 initial TB plan proposals, 27 (41.5\%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5\%) TB plans. In 25 (38.5\%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity. Conclusion In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed.}, language = {en} } @article{LisowskiHartrampfHasenaueretal.2023, author = {Lisowski, Dominik and Hartrampf, Philipp E. and Hasenauer, Natalie and Nickl, Vera and Monoranu, Camelia-Maria and Tamihardja, J{\"o}rg}, title = {Complete loss of E-cadherin expression in a rare case of metastatic malignant meningioma: a case report}, series = {BMC Neurology}, volume = {23}, journal = {BMC Neurology}, doi = {10.1186/s12883-023-03450-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357996}, year = {2023}, abstract = {Background Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis. Case presentation We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment. Conclusions E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.}, language = {en} } @article{DiefenhardtMartinLudmiretal.2022, author = {Diefenhardt, Markus and Martin, Daniel and Ludmir, Ethan B. and Fleischmann, Maximilian and Hofheinz, Ralf-Dieter and Ghadimi, Michael and Kosmala, Rebekka and Polat, B{\"u}lent and Friede, Tim and Minsky, Bruce D. and R{\"o}del, Claus and Fokas, Emmanouil}, title = {Development and validation of a predictive model for toxicity of neoadjuvant chemoradiotherapy in rectal cancer in the CAO/ARO/AIO-04 phase III trial}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {18}, issn = {2072-6694}, doi = {10.3390/cancers14184425}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288081}, year = {2022}, abstract = {Background: There is a lack of predictive models to identify patients at risk of high neoadjuvant chemoradiotherapy (CRT)-related acute toxicity in rectal cancer. Patient and Methods: The CAO/ARO/AIO-04 trial was divided into a development (n = 831) and a validation (n = 405) cohort. Using a best subset selection approach, predictive models for grade 3-4 acute toxicity were calculated including clinicopathologic characteristics, pretreatment blood parameters, and baseline results of quality-of-life questionnaires and evaluated using the area under the ROC curve. The final model was internally and externally validated. Results: In the development cohort, 155 patients developed grade 3-4 toxicities due to CRT. In the final evaluation, 15 parameters were included in the logistic regression models using best-subset selection. BMI, gender, and emotional functioning remained significant for predicting toxicity, with a discrimination ability adjusted for overfitting of AUC 0.687. The odds of experiencing high-grade toxicity were 3.8 times higher in the intermediate and 6.4 times higher in the high-risk group (p < 0.001). Rates of toxicity (p = 0.001) and low treatment adherence (p = 0.007) remained significantly different in the validation cohort, whereas discrimination ability was not significantly worse (DeLong test 0.09). Conclusion: We developed and validated a predictive model for toxicity using gender, BMI, and emotional functioning. Such a model could help identify patients at risk for treatment-related high-grade toxicity to assist in treatment guidance and patient participation in shared decision making.}, language = {en} } @article{TamihardjaZehnerHartrampfetal.2022, author = {Tamihardja, J{\"o}rg and Zehner, Leonie and Hartrampf, Philipp and Lisowski, Dominik and Kneitz, Susanne and Cirsi, Sinan and Razinskas, Gary and Flentje, Michael and Polat, B{\"u}lent}, title = {Salvage nodal radiotherapy as metastasis-directed therapy for oligorecurrent prostate cancer detected by positron emission tomography shows favorable outcome in long-term follow-up}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {15}, issn = {2072-6694}, doi = {10.3390/cancers14153766}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286064}, year = {2022}, abstract = {Simple Summary Patients, who suffer from oligorecurrent prostate cancer with limited nodal involvement, may be offered positron emission tomography (PET)-directed salvage nodal radiotherapy to delay disease progression. This current analysis aimed to access salvage radiotherapy for nodal oligorecurrent prostate cancer with simultaneous integrated boost to PET-involved lymph nodes as metastasis-directed therapy. A long-term oncological outcome was favorable after salvage nodal radiotherapy and severe toxicity rates were low. Androgen deprivation therapy plays a major role in recurrent prostate cancer management and demonstrates a positive influence on the rate of biochemical progression in patients receiving salvage nodal radiotherapy. The present long-term analysis may help clinicians identify patients who would benefit from salvage nodal radiotherapy and androgen deprivation therapy, as a multimodal treatment strategy for oligorecurrent prostate cancer. Abstract Background: The study aimed to access the long-term outcome of salvage nodal radiotherapy (SNRT) in oligorecurrent prostate cancer. Methods: A total of 95 consecutive patients received SNRT for pelvic and/or extrapelvic nodal recurrence after prostate-specific membrane antigen (PSMA) or choline PET from 2010 to 2021. SNRT was applied as external beam radiotherapy with simultaneous integrated boost up to a median total dose of 62.9 Gy (EQD2\(_{1.5Gy}\)) to the recurrent lymph node metastases. The outcome was analyzed by cumulative incidence functions with death as the competing risk. Fine-Gray regression analyses were performed to estimate the relative hazards of the outcome parameters. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (v5.0). The results are as follows: the median follow-up was 47.1 months. The five-year biochemical progression rate (95\% CI) was 50.1\% (35.7-62.9\%). Concomitant androgen deprivation therapy (ADT) was adminstered in 60.0\% of the patients. The five-year biochemical progression rate was 75.0\% (42.0-90.9\%) without ADT versus 35.3\% (19.6-51.4\%) with ADT (p = 0.003). The cumulative five-year late grade 3 GU toxicity rate was 2.1\%. No late grade 3 GI toxicity occured. Conclusions: Metastasis-directed therapy through SNRT for PET-staged oligorecurrent prostate cancer demonstrated a favorable long-term oncologic outcome. Omittance of ADT led to an increased biochemical progression.}, language = {en} } @article{LisowskiLutyjAbazarietal.2023, author = {Lisowski, Dominik and Lutyj, Paul and Abazari, Arya and Weick, Stefan and Traub, Jan and Polat, B{\"u}lent and Flentje, Michael and Kraft, Johannes}, title = {Impact of Radiotherapy on Malfunctions and Battery Life of Cardiac Implantable Electronic Devices in Cancer Patients}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {19}, issn = {2072-6694}, doi = {10.3390/cancers15194830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358008}, year = {2023}, abstract = {Purpose: This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. Methods: From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. Results: Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8\%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0-64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0-3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0-1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2\%). Depending on the national guidelines, 1-9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. Conclusion: Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised.}, language = {en} } @article{HuflageKunzHendeletal.2023, author = {Huflage, Henner and Kunz, Andreas Steven and Hendel, Robin and Kraft, Johannes and Weick, Stefan and Razinskas, Gary and Sauer, Stephanie Tina and Pennig, Lenhard and Bley, Thorsten Alexander and Grunz, Jan-Peter}, title = {Obesity-related pitfalls of virtual versus true non-contrast imaging — an intraindividual comparison in 253 oncologic patients}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {9}, issn = {2075-4418}, doi = {10.3390/diagnostics13091558}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313519}, year = {2023}, abstract = {Objectives: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. Materials and Methods: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m\(^2\)) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m\(^2\) (n = 110), pre-obese: 25-29.9 kg/m\(^2\) (n = 73), and obese: >30 kg/m\(^2\) (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. Results: While arterial contrast phases in DECT were associated with a higher CTDI\(_{vol}\) than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R\(^2\) = 0.738) and SECT (R\(^2\) = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1\%) compared with non-obese (0\%) and pre-obese patients (4.1\%). Conclusion: DECT facilitates a 30.8\% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients.}, language = {en} } @article{MemmelSisarioZimmermannetal.2020, author = {Memmel, Simon and Sisario, Dmitri and Zimmermann, Heiko and Sauer, Markus and Sukhorukov, Vladimir L. and Djuzenova, Cholpon S. and Flentje, Michael}, title = {FocAn: automated 3D analysis of DNA repair foci in image stacks acquired by confocal fluorescence microscopy}, series = {BMC Bioinformatics}, volume = {21}, journal = {BMC Bioinformatics}, doi = {10.1186/s12859-020-3370-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229023}, year = {2020}, abstract = {Background Phosphorylated histone H2AX, also known as gamma H2AX, forms mu m-sized nuclear foci at the sites of DNA double-strand breaks (DSBs) induced by ionizing radiation and other agents. Due to their specificity and sensitivity, gamma H2AX immunoassays have become the gold standard for studying DSB induction and repair. One of these assays relies on the immunofluorescent staining of gamma H2AX followed by microscopic imaging and foci counting. During the last years, semi- and fully automated image analysis, capable of fast detection and quantification of gamma H2AX foci in large datasets of fluorescence images, are gradually replacing the traditional method of manual foci counting. A major drawback of the non-commercial software for foci counting (available so far) is that they are restricted to 2D-image data. In practice, these algorithms are useful for counting the foci located close to the midsection plane of the nucleus, while the out-of-plane foci are neglected. Results To overcome the limitations of 2D foci counting, we present a freely available ImageJ-based plugin (FocAn) for automated 3D analysis of gamma H2AX foci in z-image stacks acquired by confocal fluorescence microscopy. The image-stack processing algorithm implemented in FocAn is capable of automatic 3D recognition of individual cell nuclei and gamma H2AX foci, as well as evaluation of the total foci number per cell nucleus. The FocAn algorithm consists of two parts: nucleus identification and foci detection, each employing specific sequences of auto local thresholding in combination with watershed segmentation techniques. We validated the FocAn algorithm using fluorescence-labeled gamma H2AX in two glioblastoma cell lines, irradiated with 2 Gy and given up to 24 h post-irradiation for repair. We found that the data obtained with FocAn agreed well with those obtained with an already available software (FoCo) and manual counting. Moreover, FocAn was capable of identifying overlapping foci in 3D space, which ensured accurate foci counting even at high DSB density of up to similar to 200 DSB/nucleus. Conclusions FocAn is freely available an open-source 3D foci analyzer. The user-friendly algorithm FocAn requires little supervision and can automatically count the amount of DNA-DSBs, i.e. fluorescence-labeled gamma H2AX foci, in 3D image stacks acquired by laser-scanning microscopes without additional nuclei staining.}, language = {en} } @article{TamihardjaZehnerHartrampfetal.2022, author = {Tamihardja, J{\"o}rg and Zehner, Leonie and Hartrampf, Philipp E. and Cirsi, Sinan and Wegener, Sonja and Buck, Andreas K. and Flentje, Michael and Polat, B{\"u}lent}, title = {Dose-escalated salvage radiotherapy for macroscopic local recurrence of prostate cancer in the prostate-specific membrane antigen positron emission tomography era}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {19}, issn = {2072-6694}, doi = {10.3390/cancers14194956}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290302}, year = {2022}, abstract = {Simple Summary Prostate cancer often relapses after initial radical prostatectomy, and salvage radiotherapy offers a second chance of cure for relapsed patients. Modern imaging techniques, especially prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), enable radiation oncologists to target radiotherapy at the involved sites of disease. In a group of patients, PSMA PET/CT imaging can detect a macroscopic local recurrence with or without locoregional lymph node metastasis. In these cases, an escalation of the radiotherapy dose is often considered for controlling the visible tumor mass. As the evidence for dose-escalated salvage radiotherapy for macroscopic recurrent prostate cancer after PSMA PET/CT imaging is still limited, we address this topic in the current analysis. We found that the outcome of patients with dose-escalated salvage radiotherapy for macroscopic prostate cancer recurrence is encouragingly favorable, while the toxicity is very limited. Abstract Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2\%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3-72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). Results: The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1\% (95\% CI: 81.1-97.8\%) and the three-year metastasis-free survival rate reached 96.2\% (95\% CI: 91.2-100.0\%). The cumulative three-year late grade 3 GU toxicity rate was 3.4\%. No late grade 3 GI toxicity occurred. Conclusions: Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates.}, language = {en} } @article{LisowskiTroemelLutyjetal.2022, author = {Lisowski, Dominik and Tr{\"o}mel, Jannik and Lutyj, Paul and Lewitzki, Victor and Hartrampf, Philipp E. and Polat, B{\"u}lent and Flentje, Michael and Tamihardja, J{\"o}rg}, title = {Health-related quality of life and clinical outcome after radiotherapy of patients with intracranial meningioma}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-24192-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301233}, year = {2022}, abstract = {This retrospective, single-institutional study investigated long-term outcome, toxicity and health-related quality of life (HRQoL) in meningioma patients after radiotherapy. We analyzed the data of 119 patients who received radiotherapy at our department from 1997 to 2014 for intracranial WHO grade I-III meningioma. Fractionated stereotactic radiotherapy (FSRT), intensity modulated radiotherapy (IMRT) or radiosurgery radiation was applied. The EORTC QLQ-C30 and QLQ-BN20 questionnaires were completed for assessment of HRQoL. Overall survival (OS) for the entire study group was 89.6\% at 5 years and 75.9\% at 10 years. Local control (LC) at 5 and 10 years was 82.4\% and 73.4\%, respectively. Local recurrence was observed in 22 patients (18.5\%). Higher grade acute and chronic toxicities were observed in seven patients (5.9\%) and five patients (4.2\%), respectively. Global health status was rated with a mean of 59.9 points (SD 22.3) on QLQ-C30. In conclusion, radiotherapy resulted in very good long-term survival and tumor control rates with low rates of severe toxicities but with a deterioration of long-term HRQoL.}, language = {en} } @article{TamihardjaSchortmannLawrenzetal.2021, author = {Tamihardja, J{\"o}rg and Schortmann, Max and Lawrenz, Ingulf and Weick, Stefan and Bratengeier, Klaus and Flentje, Michael and Guckenberger, Matthias and Polat, B{\"u}lent}, title = {Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, issn = {0179-7158}, doi = {10.1007/s00066-020-01678-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232509}, pages = {124-132}, year = {2021}, abstract = {Purpose Evaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer. Methods Between 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95). Results Median follow-up was 61.8 months. The 5‑year biochemical relapse-free survival (bRFS) was 85.4\% for all patients and 93.3, 87.4, and 79.4\% for low-, intermediate-, and high-risk disease, respectively. The 5‑year prostate cancer-specific survival (PSS) was 94.8\% for all patients and 98.7, 98.9, 89.3\% for low-, intermediate-, and high-risk disease, respectively. The 5‑year and 10-year overall survival rates were 83.8 and 66.3\% and the 5‑year and 10-year freedom from distant metastasis rates were 92.2 and 88.0\%, respectively. Cumulative 5‑year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1\% of the patients, respectively. Cumulative 5‑year late grade 3 GU/GI toxicity occurred in 4.0/1.2\%. Conclusion Moderately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity.}, language = {en} } @article{RichterWegenerBreueretal.2021, author = {Richter, Anne and Wegener, Sonja and Breuer, Kathrin and Razinskas, Gary and Weick, Stefan and Exner, Florian and Bratengeier, Klaus and Flentje, Michael and Sauer, Otto and Polat, B{\"u}lent}, title = {Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems}, series = {Radiation Oncology}, volume = {16}, journal = {Radiation Oncology}, doi = {10.1186/s13014-021-01942-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265704}, year = {2021}, abstract = {Background To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans. Methods For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom. Results The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3\%/2 mm) with 100\% points passing and ArcCheck QA (3\%/2 mm) with 99.5\%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans. Conclusions For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.}, language = {en} } @article{BratengeierHerzogWegeneretal.2017, author = {Bratengeier, Klaus and Herzog, Barbara and Wegener, Sonja and Holubyev, Kostyantyn}, title = {Finer leaf resolution and steeper beam edges using a virtual isocentre in concurrence to PTV-shaped collimators in standard distance - a planning study}, series = {Radiation Oncology}, volume = {12}, journal = {Radiation Oncology}, number = {88}, doi = {10.1186/s13014-017-0826-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157543}, year = {2017}, abstract = {Purpose: Investigation of a reduced source to target distance to improve organ at risk sparing during stereotactic irradiation (STX). Methods: The authors present a planning study with perfectly target-volume adapted collimator compared with multi-leaf collimator (MLC) at reduced source to virtual isocentre distance (SVID) in contrast to normal source to isocentre distance (SID) for stereotactic applications. The role of MLC leaf width and 20-80\% penumbra was examined concerning the healthy tissue sparing. Several prescription schemes and target diameters are considered. Results: Paddick's gradient index (GI) as well as comparison of the mean doses to spherical shells at several distances to the target is evaluated. Both emphasize the same results: the healthy tissue sparing in the high dose area around the planning target volume (PTV) is improved at reduced SVID ≤ 70 cm. The effect can be attributed more to steeper penumbra than to finer leaf resolution. Comparing circular collimators at different SVID just as MLC-shaped collimators, always the GI was reduced. Even MLC-shaped collimator at SVID 70 cm had better healthy tissue sparing than an optimal shaped circular collimator at SID 100 cm. Regarding penumbra changes due to varying SVID, the results of the planning study are underlined by film dosimetry measurements with Agility™ MLC. Conclusion: Penumbra requires more attention in comparing studies, especially studies using different planning systems. Reduced SVID probably allows usage of conventional MLC for STX-like irradiations.}, language = {en} } @article{DjuzenovaFischerKatzeretal.2021, author = {Djuzenova, Cholpon S. and Fischer, Thomas and Katzer, Astrid and Sisario, Dmitri and Korsa, Tessa and Streussloff, Gudrun and Sukhorukov, Vladimir L. and Flentje, Michael}, title = {Opposite effects of the triple target (DNA-PK/PI3K/mTOR) inhibitor PI-103 on the radiation sensitivity of glioblastoma cell lines proficient and deficient in DNA-PKcs}, series = {BMC Cancer}, volume = {21}, journal = {BMC Cancer}, doi = {10.1186/s12885-021-08930-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265826}, year = {2021}, abstract = {Background: Radiotherapy is routinely used to combat glioblastoma (GBM). However, the treatment efficacy is often limited by the radioresistance of GBM cells. Methods: Two GBM lines MO59K and MO59J, differing in intrinsic radiosensitivity and mutational status of DNA-PK and ATM, were analyzed regarding their response to DNA-PK/PI3K/mTOR inhibition by PI-103 in combination with radiation. To this end we assessed colony-forming ability, induction and repair of DNA damage by gamma H2AX and 53BP1, expression of marker proteins, including those belonging to NHEJ and HR repair pathways, degree of apoptosis, autophagy, and cell cycle alterations. Results: We found that PI-103 radiosensitized MO59K cells but, surprisingly, it induced radiation resistance in MO59J cells. Treatment of MO59K cells with PI-103 lead to protraction of the DNA damage repair as compared to drug-free irradiated cells. In PI-103-treated and irradiated MO59J cells the foci numbers of both proteins was higher than in the drug-free samples, but a large portion of DNA damage was quickly repaired. Another cell line-specific difference includes diminished expression of p53 in MO59J cells, which was further reduced by PI-103. Additionally, PI-103-treated MO59K cells exhibited an increased expression of the apoptosis marker cleaved PARP and increased subG1 fraction. Moreover, irradiation induced a strong G2 arrest in MO59J cells (similar to 80\% vs. similar to 50\% in MO59K), which was, however, partially reduced in the presence of PI-103. In contrast, treatment with PI-103 increased the G2 fraction in irradiated MO59K cells. Conclusions: The triple-target inhibitor PI-103 exerted radiosensitization on MO59K cells, but, unexpectedly, caused radioresistance in the MO59J line, lacking DNA-PK. The difference is most likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to less apoptosis as compared to drug-free MO59J cells and enhanced survival via partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via a yet unknown mechanism.}, language = {en} } @article{TamihardjaCirsiKessleretal.2021, author = {Tamihardja, J{\"o}rg and Cirsi, Sinan and Kessler, Patrick and Razinskas, Gary and Exner, Florian and Richter, Anne and Polat, B{\"u}lent and Flentje, Michael}, title = {Cone beam CT-based dose accumulation and analysis of delivered dose to the dominant intraprostatic lesion in primary radiotherapy of prostate cancer}, series = {Radiation Oncology}, volume = {16}, journal = {Radiation Oncology}, doi = {10.1186/s13014-021-01933-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265656}, year = {2021}, abstract = {Background Evaluation of delivered dose to the dominant intraprostatic lesion (DIL) for moderately hypofractionated radiotherapy of prostate cancer by cone beam computed tomography (CBCT)-based dose accumulation and target coverage analysis. Methods Twenty-three patients with localized prostate cancer treated with moderately hypofractionated prostate radiotherapy with simultaneous integrated boost (SIB) between December 2016 and February 2020 were retrospectively analyzed. Included patients were required to have an identifiable DIL on bi-parametric planning magnetic resonance imaging (MRI). After import into the RayStation treatment planning system and application of a step-wise density override, the fractional doses were computed on each CBCT and were consecutively mapped onto the planning CT via a deformation vector field derived from deformable image registration. Fractional doses were accumulated for all CBCTs and interpolated for missing CBCTs, resulting in the delivered dose for PTV\(_{DIL}\), PTV\(_{Boost}\), PTV, and the organs at risk. The location of the index lesions was recorded according to the sector map of the Prostate Imaging Reporting and Data System (PIRADS) Version 2.1. Target coverage of the index lesions was evaluated and stratified for location. Results In total, 338 CBCTs were available for analysis. Dose accumulation target coverage of PTV\(_{DIL}\), PTV\(_{Boost}\), and PTV was excellent and no cases of underdosage in D\(_{Mean}\), D_95\%, D_02\%, and D_98\% could be detected. Delivered rectum D\(_{Mean}\) did not significantly differ from the planned dose. Bladder mean DMean was higher than planned with 19.4 ± 7.4 Gy versus 18.8 ± 7.5 Gy, p < 0.001. The penile bulb showed a decreased delivered mean DMean with 29.1 ± 14.0 Gy versus 29.8 ± 14.4 Gy, p < 0.001. Dorsal DILs, defined as DILs in the posterior medial peripheral zone of the prostate, showed a significantly lower delivered dose with a mean DMean difference of 2.2 Gy (95\% CI 1.3-3.1 Gy, p < 0.001) compared to ventral lesions. Conclusions CBCT-based dose accumulation showed an adequate delivered dose to the dominant intraprostatic lesion and organs at risk within planning limits. Cautious evaluation of the target coverage for index lesions adjacent to the rectum is warranted to avoid underdosage.}, language = {en} } @article{FischerHartmannReisslandetal.2022, author = {Fischer, Thomas and Hartmann, Oliver and Reissland, Michaela and Prieto-Garcia, Cristian and Klann, Kevin and Pahor, Nikolett and Sch{\"u}lein-V{\"o}lk, Christina and Baluapuri, Apoorva and Polat, B{\"u}lent and Abazari, Arya and Gerhard-Hartmann, Elena and Kopp, Hans-Georg and Essmann, Frank and Rosenfeldt, Mathias and M{\"u}nch, Christian and Flentje, Michael and Diefenbacher, Markus E.}, title = {PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy}, series = {Cell \& Bioscience}, volume = {12}, journal = {Cell \& Bioscience}, issn = {2045-3701}, doi = {10.1186/s13578-022-00778-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299865}, year = {2022}, abstract = {Background Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy. Results We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model. Conclusion PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.}, language = {en} } @article{RichterExnerBratengeieretal.2019, author = {Richter, Anne and Exner, Florian and Bratengeier, Klaus and Polat, B{\"u}lent and Flentje, Michael and Weick, Stefan}, title = {Impact of beam configuration on VMAT plan quality for Pinnacle\(^3\)Auto-Planning for head and neck cases}, series = {Radiation Oncology}, volume = {14}, journal = {Radiation Oncology}, doi = {10.1186/s13014-019-1211-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200301}, pages = {12}, year = {2019}, abstract = {Background The purpose of this study was to compare automatically generated VMAT plans to find the superior beam configurations for Pinnacle3 Auto-Planning and share "best practices". Methods VMAT plans for 20 patients with head and neck cancer were generated using Pinnacle3 Auto-Planning Module (Pinnacle3 Version 9.10) with different beam setup parameters. VMAT plans for single (V1) or double arc (V2) and partial or full gantry rotation were optimized. Beam configurations with different collimator positions were defined. Target coverage and sparing of organs at risk were evaluated based on scoring of an evaluation parameter set. Furthermore, dosimetric evaluation was performed based on the composite objective value (COV) and a new cross comparison method was applied using the COVs. Results The evaluation showed a superior plan quality for double arcs compared to one single arc or two single arcs for all cases. Plan quality was superior if a full gantry rotation was allowed during optimization for unilateral target volumes. A double arc technique with collimator setting of 15° was superior to a double arc with collimator 60° and a two single arcs with collimator setting of 15° and 345°. Conclusion The evaluation showed that double and full arcs are superior to single and partial arcs in terms of organs at risk sparing even for unilateral target volumes. The collimator position was found as an additional setup parameter, which can further improve the target coverage and sparing of organs at risk.}, language = {en} } @article{BratengeierHolubyevWegener2019, author = {Bratengeier, Klaus and Holubyev, Kostyantyn and Wegener, Sonja}, title = {Steeper dose gradients resulting from reduced source to target distance—a planning system independent study}, series = {Journal of Applied Clinical Medical Physics}, volume = {20}, journal = {Journal of Applied Clinical Medical Physics}, number = {1}, doi = {10.1002/acm2.12490}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177424}, pages = {89-100}, year = {2019}, abstract = {Purpose: To quantify the contribution of penumbra in the improvement of healthy tissue sparing at reduced source-to-axis distance (SAD) for simple spherical target and different prescription isodoses (PI). Method: A TPS-independent method was used to estimate three-dimensional (3D) dose distribution for stereotactic treatment of spherical targets of 0.5 cm radius based on single beam two-dimensional (2D) film dosimetry measurements. 1 cm target constitutes the worst case for the conformation with standard Multi-Leaf Collimator (MLC) with 0.5 cm leaf width. The measured 2D transverse dose cross-sections and the profiles in leaf and jaw directions were used to calculate radial dose distribution from isotropic beam arrangement, for both quadratic and circular beam openings, respectively. The results were compared for standard (100 cm) and reduced SAD 70 and 55 cm for different PI. Results: For practical reduction of SAD using quadratic openings, the improvement of healthy tissue sparing (HTS) at distances up to 3 times the PTV radius was at least 6\%-12\%; gradient indices (GI) were reduced by 3-39\% for PI between 40\% and 90\%. Except for PI of 80\% and 90\%, quadratic apertures at SAD 70 cm improved the HTS by up to 20\% compared to circular openings at 100 cm or were at least equivalent; GI were 3\%-33\% lower for reduced SAD in the PI range 40\%-70\%. For PI = 80\% and 90\% the results depend on the circular collimator model. Conclusion: Stereotactic treatments of spherical targets delivered at reduced SAD of 70 or 55 cm using MLC spare healthy tissue around the target at least as good as treatments at SAD 100 cm using circular collimators. The steeper beam penumbra at reduced SAD seems to be as important as perfect target conformity. The authors argue therefore that the beam penumbra width should be addressed in the stereotactic studies.}, language = {en} } @phdthesis{Haeckel2017, author = {H{\"a}ckel, Annalena}, title = {Implementierung und Umsetzbarkeit eines Tablet-gest{\"u}tzten Screenings auf Unterst{\"u}tzungsbedarf in der Radioonkologie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154974}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2017}, abstract = {Die Inzidenz und Pr{\"a}valenz von Krebserkrankungen pr{\"a}sentiert sich in den vergangenen Jahren ungebrochen hoch. Durch die stetige Optimierung der Versorgung werden Betroffenen neuartige Optionen offeriert. Moderne Onkotherapie zeichnet sich durch sektoren{\"u}bergreifende Kooperation aus. Diese komplexen Versorgungskonzepte k{\"o}nnen durch innovative Technologien simplifiziert werden. Vorliegende Arbeit er{\"o}rtert die Frage nach der Umsetzbarkeit Tablet-gest{\"u}tzter Screenings in der Routine der Strahlenmedizin. Die Erfassung der ESAS-Items und des Unterst{\"u}tzungsbedarfs erm{\"o}glichte nach dem Vorbild kanadischer Versorgungskonzepte definierte Aussagen zur Qualit{\"a}t der medizinischen Versorgung. Im Rahmen der Studie erhielten Tumorpatienten vor der perkutanen Radiotherapie (T1) ein Tablet-gest{\"u}tztes Symptom-Screening. Das Tablet-Screening wurde von den Teilnehmern bez{\"u}glich Bedienung und Nutzerfreundlichkeit evaluiert. Nach Abschluss der Radiotherapie erfolgte eine telefonische Nachbefragung der Teilnehmer (T2). Insgesamt partizipierten 332 Krebspatienten am Tablet-Screening. 79 potentielle Studienprobanden nahmen nicht teil. Als Hauptursachen zeigten sich fehlende Zeit (21,5\%), die Teilnahme an sonstigen Studien (20,3\%) und zu hohe psychische Belastungen (17,7\%). Der Anteil der Screening-Teilnehmer mit fundierten Vorkenntnissen im Umgang mit Tablet-PCs (15,7\%) war gering. Probanden mit Tablet-Vorerfahrungen waren signifikant j{\"u}nger als Unerfahrene. Anwendung und Nutzerfreundlichkeit erlangte hohe Zustimmung. Die wenigen (21,7\%) Bef{\"u}rworter konventioneller Stift-Papier-Frageb{\"o}gen waren signifikant {\"a}lter. 219 Screening-Teilnehmer stellten ihre ausgewerteten Symptom-Frageb{\"o}gen weiteren Auswertungen zur Verf{\"u}gung. Der Performance-Status wurde von Patient und Mediziner eher divergent bewertet (ĸ=0,254). Von T1 zu T2 nahm der Anteil positiv gescreenter Probanden ab. Kurativpatienten markierten bei den ESAS-Items M{\"u}digkeit, Kurzatmigkeit und Sonstiges signifikante Symptomverbesserungen. Bei Palliativpatienten zeigte Kurzatmigkeit signifikante Verbesserung, Depressionen hingegen signifikante Verschlechterung. Der schw{\"a}chste Unterst{\"u}tzungsbedarf (23,3\%) wurde beim ,,Bedarf an Informationen beim Erstellen von Patientenverf{\"u}gungen'' registriert. Die BUKA-Studie konnte die Chancen Tablet-gest{\"u}tzter Befragungen in der Routine der Radioonkologie darstellen. Das Screening markierte durchg{\"a}ngig positive Bewertungen sowie große Akzeptanz. Die positiven Ergebnisse deckten sich mit denen anderer Studien bez{\"u}glich EDV-gest{\"u}tzter Datenerhebung. Die oftmals nicht ausreichendende Zeit zur Studienteilnahme war jedoch nicht auf eine zu zeitintensive Bedienung von Tablet-PCs zur{\"u}ckzuf{\"u}hren. Die Anzahl der Screening-Items sollte der kurzen Wartezeit der Strahlenambulanz angepasst werden. EDV-Screenings sollten dar{\"u}ber hinaus zuk{\"u}nftig bereits von zuhause absolviert werden. Die zunehmende Technisierung des Alltags l{\"a}sst den Anteil PC-erfahrener Patienten weiter ansteigen. Die Einf{\"u}hrung EDV-gest{\"u}tzter Versionen bietet eine effektive M{\"o}glichkeit des Patienten-Monitoring als Grundlage multidisziplin{\"a}rer onkologischer Versorgung. Infolge der zunehmenden PC-gest{\"u}tzten Verarbeitung hochsensibler Patientendaten ist die Gew{\"a}hrleistung vollkommener Datensicherheit dringend notwendig. Im Gegensatz zu anderen Arbeiten pr{\"a}sentierte das Studienkollektiv {\"u}berwiegend Kurativpatienten mit gutem Allgemeinzustand. Trotz geringerer Symptombelastung konnten auch hier die positiven Effekte der Radiotherapie dargestellt werden. Der hohe Unterst{\"u}tzungsbedarf erschien oftmals dem mangelnden medizinischen Verst{\"a}ndnis der Betroffenen geschuldet. Kurativpatienten {\"a}ußerten deutlich mehr Interesse aktiv an der Therapie teilzuhaben. Palliativpatienten erschienen durch das {\"U}bermaß an Therapien entkr{\"a}ftet.}, subject = {Screening}, language = {de} } @phdthesis{Maier2023, author = {Maier, Marco}, title = {Therapiezieleinsch{\"a}tzung von palliativ bestrahlten Patienten bei Erstvorstellung in der Radioonkologie}, doi = {10.25972/OPUS-32111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321119}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {In der vorliegenden Arbeit wurden die H{\"a}ufigkeit und m{\"o}gliche Pr{\"a}diktoren f{\"u}r eine {\"u}beroptimistische Therapiezieleinsch{\"a}tzung von palliativ bestrahlten onkologischen Patienten der Klinik und Poliklinik f{\"u}r Strahlentherapie des Universit{\"a}tsklinikum W{\"u}rzburg untersucht. Dazu wurden die Frage zur Therapiezieleinsch{\"a}tzung, die Integrated Palliative Care Outcome Scale (IPOS), das Distress-Thermometer und das Fatigue-Screening aus dem Patientenselbsteinsch{\"a}tzungsbogen, den die Patienten routinem{\"a}ßig vor dem {\"a}rztlichen Erstgespr{\"a}ch erhalten, sowie soziodemographische und krankheitsbezogene Daten aus der elektronischen Patientenakte analysiert (Untersuchungszeitraum 05/2018-05/2019). Die Einsch{\"a}tzung des Therapieziels galt als {\"u}beroptimistisch, wenn ein Patient f{\"a}lschlicherweise von dem Behandlungsziel „Heilung" ausging. Von einer realistischen Therapiezieleinsch{\"a}tzung wurde ausgegangen, wenn ein Patient von der Nichtheilbarkeit seiner Krebserkrankung ausging. Insgesamt wurden Daten von 283 Patienten ausgewertet, davon 133 Frauen (47\%) und 150 M{\"a}nner (53\%). Das mittlere Alter lag bei 66,7 Jahren (Spannweite 30-95 Jahre). Die drei h{\"a}ufigsten Tumorentit{\"a}ten waren Lungen- (26,9\%), Brust- (18,0\%) und Prostatakrebs (10,2\%). 64,7\% (183/283) der Patienten dieser Studie sch{\"a}tzten ihr Therapieziel {\"u}beroptimistisch ein. Es fanden sich statistisch signifikante Zusammenh{\"a}nge (p<0,05) mit einzelnen IPOS-Items, der bisherigen Dauer der Therapie unter palliativer Intention und dem Karnofsky-Index . Die beiden Variablen „Dauer der Therapie unter palliativer Intention" und „Karnofsky-Index" wurden in einer bin{\"a}r logistischen Regression als Pr{\"a}diktoren f{\"u}r eine {\"u}beroptimistische Therapiezieleinsch{\"a}tzung identifiziert. Da die Selbsteinsch{\"a}tzung vor der Erstbegegnung mit dem Strahlentherapeuten erfolgte, bleibt offen, inwieweit die Patienten- und Arzteinsch{\"a}tzung nach dem Aufkl{\"a}rungsgespr{\"a}ch h{\"a}ufiger {\"u}bereinstimmen als in der vorliegenden Studie (35,3\% realistische Therapiezieleinsch{\"a}tzung).}, subject = {Palliativmedizin}, language = {de} } @article{ZetzlRennerPittigetal.2021, author = {Zetzl, Teresa and Renner, Agnes and Pittig, Andre and Jentschke, Elisabeth and Roch, Carmen and van Oorschot, Birgitt}, title = {Yoga effectively reduces fatigue and symptoms of depression in patients with different types of cancer}, series = {Supportive Care in Cancer}, volume = {29}, journal = {Supportive Care in Cancer}, issn = {0941-4355}, doi = {10.1007/s00520-020-05794-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235415}, pages = {2973-2982}, year = {2021}, abstract = {Purpose Examine the effects of an 8-week yoga therapy on fatigue in patients with different types of cancer. Methods A total of 173 cancer patients suffering from mild to severe fatigue were randomly allocated to yoga intervention (n = 84) (IG) versus waitlist control group (CG) (n = 88). Yoga therapy consisted of eight weekly sessions with 60 min each. The primary outcome was self-reported fatigue symptoms. Secondary outcomes were symptoms of depression and quality of life (QoL). Data were assessed using questionnaires before (T0) and after yoga therapy for IG versus waiting period for CG (T1). Results A stronger reduction of general fatigue (P = .033), physical fatigue (P = .048), and depression (P < .001) as well as a stronger increase in QoL (P = .002) was found for patients who attended 7 or 8 sessions compared with controls. Within the yoga group, both higher attendance rate and lower T0-fatigue were significant predictors of lower T1-fatigue (P ≤ .001). Exploratory results revealed that women with breast cancer report a higher reduction of fatigue than women with other types of cancer (P = .016) after yoga therapy. Conclusion The findings support the assumption that yoga therapy is useful to reduce cancer-related fatigue, especially for the physical aspects of fatigue. Women with breast cancer seem to benefit most, and higher attendance rate results in greater reduction of fatigue. Trial registration German Clinical Trials Register DRKS00016034}, language = {en} } @article{RadeloffRamosTiradoHaddadetal.2021, author = {Radeloff, Katrin and Ramos Tirado, Mario and Haddad, Daniel and Breuer, Kathrin and M{\"u}ller, Jana and Hochmuth, Sabine and Hackenberg, Stephan and Scherzad, Agmal and Kleinsasser, Norbert and Radeloff, Andreas}, title = {Superparamagnetic iron oxide particles (VSOPs) show genotoxic effects but no functional impact on human adipose tissue-derived stromal cells (ASCs)}, series = {Materials}, volume = {14}, journal = {Materials}, number = {2}, issn = {1996-1944}, doi = {10.3390/ma14020263}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222970}, year = {2021}, abstract = {Adipose tissue-derived stromal cells (ASCs) represent a capable source for cell-based therapeutic approaches. For monitoring a cell-based application in vivo, magnetic resonance imaging (MRI) of cells labeled with iron oxide particles is a common method. It is the aim of the present study to analyze potential DNA damage, cytotoxicity and impairment of functional properties of human (h)ASCs after labeling with citrate-coated very small superparamagnetic iron oxide particles (VSOPs). Cytotoxic as well as genotoxic effects of the labeling procedure were measured in labeled and unlabeled hASCs using the MTT assay, comet assay and chromosomal aberration test. Trilineage differentiation was performed to evaluate an impairment of the differentiation potential due to the particles. Proliferation as well as migration capability were analyzed after the labeling procedure. Furthermore, the labeling of the hASCs was confirmed by Prussian blue staining, transmission electron microscopy (TEM) and high-resolution MRI. Below the concentration of 0.6 mM, which was used for the procedure, no evidence of genotoxic effects was found. At 0.6 mM, 1 mM as well as 1.5 mM, an increase in the number of chromosomal aberrations was determined. Cytotoxic effects were not observed at any concentration. Proliferation, migration capability and differentiation potential were also not affected by the procedure. Labeling with VSOPs is a useful labeling method for hASCs that does not affect their proliferation, migration and differentiation potential. Despite the absence of cytotoxicity, however, indications of genotoxic effects have been demonstrated.}, language = {en} } @article{ZetzlPittigRenneretal.2021, author = {Zetzl, Teresa and Pittig, Andre and Renner, Agnes and van Oorschott, Birgitt and Jentschke, Elisabeth}, title = {Yoga therapy to reduce fatigue in cancer: effects of reminder e-mails and long-term efficacy}, series = {Supportive Care in Cancer}, volume = {29}, journal = {Supportive Care in Cancer}, number = {12}, issn = {1433-7339}, doi = {10.1007/s00520-021-06345-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268415}, pages = {7725-7735}, year = {2021}, abstract = {Objective To examine the efficacy of reminder e-mails to continue yoga therapy on practice frequency and fatigue in cancer patients and long-term effects of yoga on fatigue, depression, and quality of life. Methology One hundred two cancer patients who completed an 8-week yoga therapy were randomly allocated to two groups: reminder (N = 51) vs. no-reminder group (N = 51). After completing yoga therapy, the reminder group received weekly e-mails for 24 weeks, which reminded them of practicing yoga, whereas the no-reminder group did not. Primary outcomes were fatigue and practice frequency, and long-term outcomes were fatigue, depression, and quality of life. Data were assessed using questionnaires after yoga therapy (T1) and 6 months after completing yoga therapy (T2). Result A significantly stronger reduction of general (p = 0.038, d = 0.42) and emotional fatigue (p = 0.004, d = 0.59) and a higher increase of practice frequency (p = 0.015, d = 0.52) between T1 and T2 were found for the reminder group compared to the no-reminder group. In the mediation model, practice frequency as a mediator partially explained the changes in emotional fatigue (indirect effect B =  - 0.10). Long-term effects of yoga therapy regarding fatigue, depression, and quality of life were found (F > 7.46, p < 0.001, d > 0.54). Conclusion Weekly reminder e-mails after yoga therapy can positively affect general and emotional fatigue and help cancer patients with fatigue establish a regular yoga practice at home. However, higher practice frequency did not lead to higher physical or cognitive fatigue improvement, suggesting other factors that mediate efficacy on physical or cognitive fatigue, such as mindfulness or side effects of therapy.}, language = {en} } @article{TamihardjaRazinskasExneretal.2021, author = {Tamihardja, J{\"o}rg and Razinskas, Gary and Exner, Florian and Richter, Anne and Kessler, Patrick and Weick, Stefan and Kraft, Johannes and Mantel, Frederick and Flentje, Michael and Polat, B{\"u}lent}, title = {Comparison of treatment plans for hypofractionated high-dose prostate cancer radiotherapy using the Varian Halcyon and the Elekta Synergy platforms}, series = {Journal of Applied Clinical Medical Physics}, volume = {22}, journal = {Journal of Applied Clinical Medical Physics}, number = {9}, doi = {10.1002/acm2.13380}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260722}, pages = {262-270}, year = {2021}, abstract = {Purpose To compare radiotherapy plans between an O-ring and a conventional C-arm linac for hypofractionated high-dose prostate radiotherapy in terms of plan quality, dose distribution, and quality assurance in a multi-vendor environment. Methods Twenty prostate cancer treatment plans were irradiated on the O-ring Varian Halcyon linac and were re-optimized for the C-arm Elekta Synergy Agility linac. Dose-volume histogram metrics for target coverage and organ at risk dose, quality assurance, and monitor units were retrospectively compared. Patient-specific quality assurance with ion chamber measurements, gamma index analysis, and portal dosimetry was performed using the Varian Portal Dosimetry system and the ArcCHECK® phantom (Sun Nuclear Corporation). Prostate-only radiotherapy was delivered with simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) in 20 fractions of 2.5/3.0 Gy each. Results For both linacs, target coverage was excellent and plan quality comparable. Homogeneity in PTVBoost was high for Synergy as well as Halcyon with a mean homogeneity index of 0.07 ± 0.01 and 0.05 ± 0.01, respectively. Mean dose for the organs at risk rectum and bladder differed not significantly between the linacs but were higher for the femoral heads and penile bulb for Halcyon. Quality assurance showed no significant differences in terms of ArcCHECK gamma pass rates. Median pass rate for 3\%/2 mm was 99.3\% (96.7 to 99.8\%) for Synergy and 99.8\% (95.6 to 100\%) for Halcyon. Agreement between calculated and measured dose was high with a median deviation of -0.6\% (-1.7 to 0.8\%) for Synergy and 0.2\% (-0.6 to 2.3\%) for Halcyon. Monitor units were higher for the Halcyon by approximately 20\% (p < 0.001). Conclusion Hypofractionated high-dose prostate cancer SIB VMAT on the Halcyon system is feasible with comparable plan quality in reference to a standard C-arm Elekta Synergy linac.}, language = {en} } @phdthesis{Cirak2019, author = {Cirak, Marianne}, title = {Sedierung am Lebensende auf der Palliativstation}, doi = {10.25972/OPUS-17965}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179651}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Retrospektive Analyse von 181 Patienten, die im Zeitraum vom 01.02.2015 bis zum 31.03.2016 auf der Palliativstation des Universit{\"a}tsklinikums W{\"u}rzburg verstorben sind. Es wurde die palliative Sedierungstherapie untersucht unter folgenden Gesichtspunkten: Erfolgte sie leitliniengerecht (waren die Symptome therapierefrakt{\"a}r bzw. wurde eine proportionale Sedierung durchgef{\"u}hrt)? Wie l{\"a}sst sich die palliative Sedierungstherapie von aktiver Sterbehilfe abgrenzen? Welchen Einfluss hat das Delir? Welche Qualit{\"a}t hatte die Dokumentation? Die Autorin kommt zu dem Schluss, dass die palliative Sedierungstherapie ein wichtiges Instrument ist zur Symptomlinderung am Lebensende. Es ist auch eine sichere Therapiemaßnahme, solange sie leitliniengerecht durchgef{\"u}hrt wird. Die palliative Sedierungstherapie auf der Palliativstation der Universit{\"a}tsklinik W{\"u}rzburg konnte als leitliniengerecht best{\"a}tigt werden. Das Delir war mit einer signifikant l{\"a}ngeren Sedierungsdauer verbunden und Patienten mit Delir wiesen signifikant mehr Risikofaktoren f{\"u}r Delir auf. Der Erhebung von Risikofaktoren und der fr{\"u}hzeitigen Erkennung des Delirs kommen damit eine besondere Bedeutung zu. Eine korrekte Dokumentation ist aus rechtlichen Gesichtspunkten und aus Respekt vor dem Selbstbestimmungsrecht des Patienten sehr wichtig, hier gab es Verbesserungspotential. Eine Empfehlung zur strukturierten Durchf{\"u}hrung der palliativen Sedierungstherapie wurde von der Autorin entwickelt.}, subject = {Palliative Sedierung}, language = {de} } @article{WackExnerWegeneretal.2020, author = {Wack, Linda J. and Exner, Florian and Wegener, Sonja and Sauer, Otto A.}, title = {The impact of isocentric shifts on delivery accuracy during the irradiation of small cerebral targets — Quantification and possible corrections}, series = {Journal of Applied Clinical Medical Physics}, volume = {21}, journal = {Journal of Applied Clinical Medical Physics}, number = {5}, doi = {10.1002/acm2.12854}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218146}, pages = {56-64}, year = {2020}, abstract = {Purpose To assess the impact of isocenter shifts due to linac gantry and table rotation during cranial stereotactic radiosurgery on D\(_{98}\), target volume coverage (TVC), conformity (CI), and gradient index (GI). Methods Winston-Lutz (WL) checks were performed on two Elekta Synergy linacs. A stereotactic quality assurance (QA) plan was applied to the ArcCHECK phantom to assess the impact of isocenter shift corrections on Gamma pass rates. These corrections included gantry sag, distance of collimator and couch axes to the gantry axis, and distance between cone-beam computed tomography (CBCT) isocenter and treatment beam (MV) isocenter. We applied the shifts via script to the treatment plan in Pinnacle 16.2. In a planning study, isocenter and mechanical rotation axis shifts of 0.25 to 2 mm were applied to stereotactic plans of spherical planning target volumes (PTVs) of various volumes. The shifts determined via WL measurements were applied to 16 patient plans with PTV sizes between 0.22 and 10.4 cm3. Results ArcCHECK measurements of a stereotactic treatment showed significant increases in Gamma pass rate for all three measurements (up to 3.8 percentage points) after correction of measured isocenter deviations. For spherical targets of 1 cm3, CI was most severely affected by increasing the distance of the CBCT isocenter (1.22 to 1.62). Gradient index increased with an isocenter-collimator axis distance of 1.5 mm (3.84 vs 4.62). D98 (normalized to reference) dropped to 0.85 (CBCT), 0.92 (table axis), 0.95 (collimator axis), and 0.98 (gantry sag), with similar but smaller changes for larger targets. Applying measured shifts to patient plans lead to relevant drops in D\(_{98}\) and TVC (7\%) for targets below 2 cm\(^3\) treated on linac 1. Conclusion Mechanical deviations during gantry, collimator, and table rotation may adversely affect the treatment of small stereotactic lesions. Adjustments of beam isocenters in the treatment planning system (TPS) can be used to both quantify their impact and for prospective correction of treatment plans.}, language = {en} } @phdthesis{SeyboldEpting2019, author = {Seybold-Epting, Vera}, title = {Klinische Qualit{\"a}tsindikatoren f{\"u}r die Versorgung von Patienten mit fortgeschrittenen und metastasierten Pankreastumoren am Lebensende}, doi = {10.25972/OPUS-18117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181174}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Zusammenfassung: Laut Robert Koch-Institut wird in den kommenden Jahren die Anzahl der Menschen, die an Pankreaskarzinom erkranken werden, zunehmen. Dies h{\"a}ngt vor allem mit unseren Lebensbedingungen und dem zunehmendem {\"A}lterwerden der Gesellschaft zusammen. Die Diagnose und Therapie von Pankreastumoren stellt einen erheblichen Einschnitt in die Lebensqualit{\"a}t der Patienten dar, ver- bunden mit einer hohen Symptombelastung. Ziel vorliegender retrospektiver Studie war es, die Versorgung am Lebensende von Patienten mit fortgeschrittenem oder metastasiertem Pankreaskarzinom anhand von Qualit{\"a}tsindikatoren nach Craig C. Earle zu {\"u}berpr{\"u}fen und daraus optimierte Entscheidungsalgorithmen zu generieren. Hierzu untersuchten wir die Daten von insgesamt 202 Patienten. Zur Beantwortung der Fragestellung diente ein daf{\"u}r erstellter Dokumentationsbogen, mit dem die Daten erhoben wurden. Das Patientenkollektiv teilte sich auf in Patienten, die im Comprehensive Cancer Center (CCC) des Uniklinikums W{\"u}rzburg in den Jahren von 2010 bis 2014 vorstellig wurden und Patienten, die am Klinikum Magdeburg in den Jahren 2005 bis 2014 behandelt wurden. Wir unterteilten das Patientengut zus{\"a}tzlich in 132 prim{\"a}r metastasierte Prim{\"a}rf{\"a}lle (UICC-Stadium IV) und in 53 Rezidivf{\"a}lle (UICC-Stadium I-IV). Ebenso verglichen wir die Gruppen mit und ohne Kontakt zu Palliativangeboten. Das Patientenkollektiv setzte sich aus 74 Frauen und 126 M{\"a}nnern zusammen (bei zwei F{\"a}llen fehlte die Geschlechtsangabe) mit einem durchschnittlichen Alter von 68,8 Jahren zum Zeitpunkt der Diagnose. Der Allgemeinzustand wurde mit dem Karnofsky-Index erfasst und lag bei den meisten Patienten zum Diagnosezeitpunkt bei 90 oder 100. Die meisten Patienten befanden sich schon in einem fortgeschrittenen Zustand der Erkrankung, welches sich an der hohen Anzahl des UICC-Stadium IV erkennen l{\"a}sst (n = 132). 42,1 \% (n = 85) der Patienten hatten Kontakt zu Palliativangeboten. Der {\"u}berwiegende Teil der Patienten hatte mehr als 3 Tage vor Tod Kontakt zu Palliativangeboten (77,7 \%). Es war uns nicht m{\"o}glich einen statistisch signifikanten Zusammenhang zwischen tumorspezifischer Therapie (Chemotherapie und / oder Bestrahlung) in den letzten 14 Lebenstagen und SPV-Kontakt < 3 Tagen herzustellen. Der Grund war die geringe Anzahl der F{\"a}lle. Es gab keinen Patient, der unter 3 Tagen Kontakt zu Palliativangeboten hatte und bestrahlt wurde. Lediglich ein Patient erhielt noch eine Chemotherapie. Bei Patienten, die keinen Kontakt zu Palliativangeboten hatten, erhielten immerhin sechs noch eine Chemotherapie und f{\"u}nf eine Bestrahlung in den letzten 14 Lebenstagen. Die Hauptbeschwerden im Palliativkonsil, die von den Patienten aus W{\"u}rzburg genannt wurden, bezogen sich haupts{\"a}chlich auf k{\"o}rperliche Beschwerden, wie z. B. M{\"u}digkeit, Verschlechterung des Allgemeinzustandes, Schlafst{\"o}rungen und Fieber. Gefolgt von Depressionen, Angst, Sorgen und Problemen mit der Nahrungsaufnahme, Appetitst{\"o}rungen, {\"U}belkeit sowie Erbrechen. Die h{\"a}ufigsten Probleme und Komplikationen in den letzten 6 Monaten bis 30 Tagen vor Tod waren bei den W{\"u}rzburger Patienten mit Palliativkonsil das Auftreten eines Verschlußikterus`, Ver{\"a}nderung des Blutbildes oder An{\"a}mie, gefolgt von Ileus, {\"U}belkeit oder Erbrechen und Peritonealkarzinose mit symptomatischem Aszites. In den letzten 30 Tagen vor Tod beliefen sich die h{\"a}ufigsten Komplikationen der W{\"u}rzburger Patienten auf Nieren- und Leberversagen, ur{\"a}misches Koma, metabolische Azidose, Blutungen, Ileus, {\"U}belkeit oder Erbrechen und Peritonealkarzinose mit symptomatischem Aszites. Eine Patientenverf{\"u}gung besaßen 54,4 \% der W{\"u}rzburger Patienten mit Palliativkonsil. Bei den W{\"u}rzburger Patienten ohne Palliativkonsil waren es 50,0 \%. Eine Vorsorgevollmacht oder das Vorliegen eines Notfallplans gab es nur in ganz wenigen F{\"a}llen. Ein großer Anteil der Patienten hatte einen Aufenthalt in der Notaufnahme in den letzten 6 Monaten vor Tod. Bei zwei und mehr Aufenthalten sank die Anzahl stark ab. Gleiches gilt f{\"u}r die Aufenthalte in der Notaufnahme oder auf der Intensivstation in den letzten 30 Lebenstagen. Bei der Datenerhebung wurde nicht differenziert, ob der Aufenthalt vor oder nach der 1. Kontaktaufnahme zustande. Es wurde nur die Tatsache festgehalten, dass ein Kontakt bestand. Dies bedeutet, dass nicht heraus zu lesen ist, inwieweit die Palliativmedizin in diese Entscheidung mit einbezogen wurde. Die gesch{\"a}tzte mediane {\"U}berlebenszeit des W{\"u}rzburger Patientenkollektivs betrug 6,9 Monate. In den Jahren 2010 und 2011 zusammen genommen lag die mediane {\"U}berlebenszeit bei 6,2 Monaten. Nach Gr{\"u}ndung des palliativmedizinischen Dienstes (PMD) an der Uniklinik W{\"u}rzburg lag im Jahr 2012 und 2013 zusammen genommen die mediane {\"U}berlebenszeit bei 8,3 Monaten. Die Frauen {\"u}berlebten die M{\"a}nner um 2,7 Monate. Die Patienten mit Palliativkonsil {\"u}berlebten die Patienten ohne Palliativkonsil um zwei Monate. Bereits nach 12 Monaten waren sowohl bei den Patienten mit und ohne Palliativkonsil in unserer Studie {\"u}ber die H{\"a}lfte verstorben. Nach 24 Monaten lebten vom W{\"u}rzburger Patientenkollektiv nur noch f{\"u}nf Patienten. Die Kriterien von Craig C. Earle sind nicht {\"u}berall erreicht worden. Die Anzahl der Patienten mit Kontakt zu Palliativangeboten k{\"o}nnte h{\"o}her sein (42,1 \%). Die Anzahl der Patienten, die weniger als 3 Tage vor Tod Kontakt zu Palliativangeboten hatten, ist erfreulich niedrig (8,2 \%). Die Anzahl der F{\"a}lle, in denen die Umstellung oder der Start einer neuen tumorspezifischen Therapie in den letzten 30 Lebenstagen stattfand, ist noch viel zu hoch (7,1 \%). Hier wurden die Vorgaben von Craig C. Earle um ein vierfaches {\"u}berstiegen bei den Patienten mit Kontakt zu Palliativangeboten. Bei der tumorspezifischen Therapie in den letzten 14 Lebenstagen lag die Anzahl der Patienten mit Kontakt zu Palliativangeboten auch wieder erfreulich niedrig (4,7 \% f{\"u}r Chemotherapie; 1,2 \% f{\"u}r Bestrahlung). Grunds{\"a}tzlich l{\"a}sst sich durch das kleine Patientenkollektiv keine endg{\"u}ltige Aussage in dieser Studie bez{\"u}glich der Effektivit{\"a}t der palliativen Versorgung treffen. In der vorliegenden Studie konnten zum Teil keine statistische Signifikanz nachgewiesen werden. In Zusammenschau aller Ergebnisse dieser Arbeit zeigt sich, dass die Therapie am Lebensende immer wieder neu evaluiert und an die sich ver{\"a}ndernde Situation angepasst werden muss. Maßnahmen zur Linderung von erwarteten Symptome oder Komplikationen sollten im Vorfeld besprochen werden. Dies bedeu- tet, dass bei der Therapiewahl verschiedene klinische Parameter und jeder Patient individuell ber{\"u}cksichtigt werden sollte. Nach wie vor stellt sich die Herausforderung, die Lebensqualit{\"a}t der Tumorpatienten objektivierbar zu machen. Auch hier zeigt sich in der Literatur, dass das rechtzeitige Miteinbeziehen der Palliativmedizin viele Vorteile mit sich bringt. Es zeigt sich h{\"a}ufig eine k{\"u}rzere Hospitalisationsrate, bessere Linderung der Symptome, eine Kosteneffizienz, eine Verl{\"a}ngerung der {\"U}berlebenszeit und eine verminderte Stressbelastung auch bei Hinterbliebenen. Um festzustellen, an welchen Stellen Qualit{\"a}tsverbesserungsmaßnahmen n{\"o}tig sind, kann ein Vergleich der tats{\"a}chlichen Qualit{\"a}t (Ist-Werte) mit den Soll-Vorgaben Hinweise im klinischen Alltag geben. Hierzu k{\"o}nnte ein systematisches Belastungs- und Symptomscreening dienen, um die richtigen Patienten zum passenden Zeitpunkt zu identifizieren. Moderne Palliativmedizin umfasst somit nicht nur die Versorgung unheilbar kranker Menschen am Lebensende, sondern kann zunehmend als wichtiger Aspekt auch in der interdisziplin{\"a}ren Versorgung verstanden werden.}, subject = {Earle-Kriterien}, language = {de} } @article{KraftWeickBreueretal.2022, author = {Kraft, Johannes and Weick, Stefan and Breuer, Kathrin and Lutyj, Paul and Bratengeier, Klaus and Exner, Florian and Richter, Anne and Tamihardja, J{\"o}rg and Lisowski, Dominik and Polat, B{\"u}lent and Flentje, Michael}, title = {Treatment plan comparison for irradiation of multiple brain metastases with hippocampal avoidance whole brain radiotherapy and simultaneous integrated boost using the Varian Halcyon and the Elekta Synergy platforms}, series = {Radiation Oncology}, volume = {17}, journal = {Radiation Oncology}, doi = {10.1186/s13014-022-02156-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301221}, year = {2022}, abstract = {No abstract available.}, language = {en} } @phdthesis{Huflage2022, author = {Huflage, Henner}, title = {Die stereotaktische Bestrahlung von Lungenmetastasen am Universit{\"a}tsklinikum W{\"u}rzburg im Zeitraum von November 1997 bis September 2012}, doi = {10.25972/OPUS-25762}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257620}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Die vorliegende Arbeit untersucht die stereotaktische Bestrahlung von Lungenmetastasen am Universit{\"a}tsklinikum W{\"u}rzburg im Zeitraum von 1997 bis 2012. In diesem Zeitraum wurden am Institut f{\"u}r Strahlentherapie der Universit{\"a}tsklinik W{\"u}rzburg 102 Patienten bestrahlt. Es sollen Einflussfaktoren auf die wesentlichen Endpunkte lokale Kontrolle, systemische Kontrolle und das {\"U}berleben identifiziert werden. Die Arbeit zeigt, dass die stereotaktische Bestrahlung eine nebenwirkungsarme und effektive Therapie von Lungenmetastasen darstellt und soll einen Beitrag dazu leisten, die Einfl{\"u}sse und Ergebnisse der stereotaktischen Bestrahlung zu objektivieren und zus{\"a}tzliches Datenmaterial f{\"u}r zuk{\"u}nftige Studien liefern. Das untersuchte Kollektiv der Universit{\"a}tsklinik W{\"u}rzburg geh{\"o}rt zum Zeitpunkt der Studie zu den gr{\"o}ßten in den auf diesem Gebiet durchgef{\"u}hrten Single-Center-Studien.}, subject = {Strahlentherapie}, language = {de} } @phdthesis{Lawrenz2020, author = {Lawrenz, Ingulf}, title = {Die moderat hypofraktionierte Bestrahlung des lokalisierten Prostatakarzinoms : Ergebnisse f{\"u}r das tumorspezifische und klinische Outcome nach moderater Hypofraktionerung in intensit{\"a}tsmodulierter Technik}, doi = {10.25972/OPUS-19960}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199605}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Die m{\"a}ßig hypofraktionierte Strahlentherapie des lokalisierten Prostatakarzinoms Wir haben retrospektiv die ersten 150 konsekutiven Patienten analysiert, die mit einer prim{\"a}ren Strahlentherapie in IMRT bei lokalisiertem Prostatakrebs behandelt wurden. Alle Patienten hatten ein histologisch gesichertes Prostatakarzinom und wurden von Urologen zur kurativen Bestrahlung {\"u}berwiesen. Nach der CT-basierter Planung wurden alle Patienten mit einer intensit{\"a}tsmodulierten Strahlenthera (IMRT) unter Verwendung der SIB-Technik (Simultan Integrierter Boost) behandelt. Die applizierten Dosen betrugen 74 Gy (n = 41) und 76,2 Gy (n = 109) in 32 und 33 Fraktionen. Die Behandlung von Beckenlymphknoten (46 Gy) wurde bei 41 Hochrisikopatienten durchgef{\"u}hrt. Die Behandlung wurde unter Verwendung einer integrierten Cone-Beam-CT (IGRT) durchgef{\"u}hrt. Die Toxizit{\"a}t wurde mit CTCAE 3.0 bewertet. Das biochemische Rezidiv wurde gem{\"a}ß der Phoenix-Definition von Nadir + 2 ng / ml definiert. Wir analysierten die gastrointestinale Toxizit{\"a}t (GI), die urogenitale Toxizit{\"a}t (GU) und das Freedom From Biochemichal Failure (FFBF). Ergebnisse: Das mediane Follow-Up der Patienten betrug 50 Monate. Mehr als 80\% der Patienten waren w{\"a}hrend der Nachbeobachtung frei von gastrointestinaler Toxizit{\"a}t. Es gab keinen Trend zu erh{\"o}hten GI-Toxizit{\"a}tsraten im zeitlichen Verlauf. Bei 85\% unserer Patienten wurde innerhalb von 6 Wochen nach der Behandlung eine akute Urogenitaltoxizit{\"a}t vom Grad 1-2 beobachtet. Die meisten Patienten erholten sich von einer akuten GU-Toxizit{\"a}t. Es gab einen kontinuierlichen Anstieg des GU-Toxizit{\"a}tsgrades ≥2 mit <10\% nach 6 bis 12 Monaten auf 22,4\% nach 60 Monaten. Die GU-Toxizit{\"a}t 3. Grades lag w{\"a}hrend der Nachuntersuchung unter 5\%. FFBF betrug 82\% f{\"u}r alle Patienten. Nach Risikogruppen betrug FFBF 88\%, 80\% und 78\% f{\"u}r das niedrige, mittlere und hohe Risiko. Schlussfolgerung: Nach moderat hypofraktionierter Strahlentherapie des Prostatakarzinoms beobachteten wir niedrige GI-Toxizit{\"a}tsraten sowie ein g{\"u}nstiges FFBF. Die GU-Toxizit{\"a}tsraten lagen innerhalb der international berichteten Ergebnisse bei gleichwertiger Behandlung. Die konformale IMRT-Planung und die genaue IGRT haben m{\"o}glicherweise zu diesen Ergebnissen beigetragen.}, subject = {Prostatakrebs}, language = {de} } @phdthesis{Fleischmann2021, author = {Fleischmann, Carolin}, title = {Eine Analyse der Verlegungen von der Palliativstation in die station{\"a}re Hospizversorgung: Ist der Einsatz von Prognosescores hilfreich?}, doi = {10.25972/OPUS-21973}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219731}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Hintergrund: Die zeitgerechte Integration des Entlassmanagements ist ein wesentlicher Bestandteil des umfassenden Therapiekonzepts auf Palliativstation. Speziell zur Entlassung in ein station{\"a}res Hospiz sollte die verbleibende {\"U}berlebenszeit gegen den Benefit eines stressbehafteten Versorgungswechsels diskutiert werden. Ziel der Studie: Aus der Vielzahl der vorhandenen und international validierten palliativmedizinischen Prognosescores wurden f{\"u}r diese Studie die Palliative Performance Scale (PPS) und der Palliative Prognostic Index (PPI) ausgew{\"a}hlt. Ziel war erstens die {\"U}berpr{\"u}fung ihrer Anwendbarkeit auf eine deutsche Palliativpopulation. Zweitens wurden sie neben Symptomen der Terminalphase auf ihre F{\"a}higkeit zur Kurzzeitprognose getestet, um Patienten mit kurzer {\"U}berlebenszeit in der station{\"a}ren Hospizversorgung nach Entlassung identifizieren zu k{\"o}nnen. Methodik: Am Zentrum f{\"u}r Palliativmedizin des Universit{\"a}tsklinikums W{\"u}rzburg wurden retrospektiv PPS, PPI, ausgew{\"a}hlte Symptome der Sterbephase sowie die {\"U}berlebensdauer bei 112 Patienten erhoben, die von 2012 bis 2016 in ein Hospiz entlassen worden waren. Mittels ANOVA und Kaplan-Meier-Statistik wurden {\"U}berlebensdauer und H{\"o}he der Prognosescores in Beziehung gesetzt und Risikogruppen gebildet. Zur Identifizierung von Risikopatienten mit einer Hospizverweildauer ≤ 7 Tagen wurden diese mit der Gruppe der Langverweiler (> 7 Tage) hinsichtlich H{\"o}he der PPS, des PPI und das Vorhandensein von Terminalsymptomen verglichen. Ergebnisse: Mittels ANOVA und Kaplan-Meier-Kurven konnte die signifikante Korrelation zwischen H{\"o}he des Prognosescores und der {\"U}berlebenszeit f{\"u}r die untersuchte Kohorte belegt werden. Risikopatienten mit einer Hospizverweildauer ≤ 7 Tagen wiesen einen signifikant niedrigeren PPS (40 \% vs. 50 \%) respektive einen h{\"o}heren PPI-Wert (6,5 vs. 4,5 P.) als die Langverweiler auf. Die Terminalsymptome Dysphagie und eine reduzierte orale Nahrungsaufnahme waren unter Risikopatienten h{\"a}ufiger vertreten. Schlussfolgerung: Die Prognosef{\"a}higkeit der palliativmedizinischen Prognosescores PPS und PPI konnte f{\"u}r die untersuchte Kohorte belegt werden. Eine Kurzzeitprognose erwies sich allerdings aufgrund der geringen Trennsch{\"a}rfe der Cut-Off-Werte als praxisuntauglich. Sie k{\"o}nnen dennoch in speziellen F{\"a}llen als Orientierungshilfe im Entlassmanagement dienen.}, subject = {Prognosesch{\"a}tzung}, language = {de} } @phdthesis{Cronauer2021, author = {Cronauer, Julian}, title = {Die prim{\"a}re Tele- und Brachytherapie des lokal fortgeschrittenen Zervixkarzinoms - Auswertung der W{\"u}rzburger Daten}, doi = {10.25972/OPUS-21693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216937}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Strahlentherapie des Zervixkarzinoms untergliedert sich in die Teletherapie von extrakorporal und die Brachytherapie von intrauterin und intravaginal. W{\"a}hrend in Bezug auf die Teletherapie international standardisierte Therapieschemata bestehen, fehlen diese bei der Brachytherapie. In W{\"u}rzburg wurde ein Therapieregime von 3x8,5 Gy gew{\"a}hlt, w{\"a}hrend in anderen Therapierzentren mit z.B. 4x7 Gy oder 5x6 Gy bestrahlt wurde. Somit wurden in W{\"u}rzburg deutlich h{\"o}heren Einzeldosen appliziert. Ziel der Arbeit war es, das in W{\"u}rzburg angewandte Fraktionierungsschema auf Vertr{\"a}glichkeit und Effektivit{\"a}t zu {\"u}berpr{\"u}fen. In die Studie eingeschlossen wurden 74 Patientinnen, die zwischen Februar 1999 und September 2014 bei gesichertem Zervixkarzinom einer prim{\"a}ren Radiochemotherapie unterzogen wurden. In einem medianen Follow-Up von 48 Monaten wurden Nebenwirkungen an Blase und Rektum sowie lokale und region{\"a}re Rezidive und Fernmetastasen erhoben. Bei neun Patientinnen (12,2\%) wurde am Rektum eine Sp{\"a}tnebenwirkung vom Grad III oder IV nach CTCAE festgestellt, an der Blase wurde dies bei drei Patientinnen (4,8\%) gefunden. Bei zwei (2,7\%) Patientinnen fand sich ein lokaler, bei drei Patientinnen (4\%) ein region{\"a}rer Progress. 19 Patientinnen (25,66\%) entwickelten Fernmetastasen. Es zeigte sich zusammenfassend, dass es im Rahmen des angewandten Therapieschemas zu einer im internationalen Vergleich sehr guten lokalen Kontrolle kam bei vor allem am Rektum leicht erh{\"o}hten h{\"o}hergradigen Nebenwirkungsraten. Mittels moderner bildgest{\"u}tzter IMRT- und Brachytherapie-Planung werden sich diese Toxizit{\"a}ten in Zukunft weiter reduzieren lassen.}, subject = {Geb{\"a}rmutterhalskrebs}, language = {de} } @phdthesis{Hess2021, author = {Heß, Sebastian}, title = {Externe Validierung eines Prognose-Scores f{\"u}r Patienten mit Hirnmetastasen basierend auf extrakraniellen Faktoren}, doi = {10.25972/OPUS-24362}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243622}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Patienten mit Hirnmetastasen weisen eine limitierte Prognose auf. Um diese Prognose besser absch{\"a}tzen zu k{\"o}nnen, wurden verschiedene Prognosescores entwickelt. Der EC-Score ist ein sehr einfach bestimmbarer Summenscore basierend auf extrakraniellen Faktoren. In dieser retrospektiven Arbeit wurden 538 Patientenf{\"a}lle inkludiert, die im Zeitraum 10/1998 bis 11/2017 eine Bestrahlung ihrer Hirnmetastasen am Uniklinikum W{\"u}rzburg erhalten haben. Der EC-Score konnte bei 173 der Patientenf{\"a}lle ausgewertet werden. Zus{\"a}tzlich wurden die bereits etablierten DS-GPA- und RPA-Score am eigenen Patientenkollektiv angewendet und mit dem EC-Score verglichen. Im Ergebnis stellt diese Arbeit eine wichtige unabh{\"a}ngige externe Validierung des EC-Scores dar. Der Score erm{\"o}glicht es, Patienten sicher zu identifizieren, welche nicht von einer Bestrahlung ihrer Hirnmetastasen profitieren w{\"u}rden.}, subject = {Hirnmetastase}, language = {de} } @phdthesis{Troemel2020, author = {Tr{\"o}mel, Jannik}, title = {Die strahlentherapeutische Behandlung von Meningeomen an der Klinik f{\"u}r Strahlentherapie des Universit{\"a}tsklinikums W{\"u}rzburg von 1994 bis 2014: Klinische Ergebnisse}, doi = {10.25972/OPUS-19995}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199956}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Es wurden die Daten von 119 Meningeompatienten hinsichtlich der lokalen Kontrolle sowie des Gesamt{\"u}berlebens und deren Einflussfaktoren untersucht, um dieses Kollektiv hinsichtlich des Therapieerfolges an der Klinik und Poliklinik f{\"u}r Strahlentherapie der Universit{\"a}t W{\"u}rzburg auszuwerten. Ferner wurden die akuten und chronischen Nebenwirkungen der Strahlenbehandlung erfasst. Dar{\"u}ber hinaus wurden die Fragebogen QLQ-C30 sowie -BN20 zur Evaluation der Lebensqualit{\"a}t nach der Strahlenbehandlung analysiert. Die Strahlenbehandlung zeigte sich im Rahmen des Follow-Ups von 5,4 Jahren als gr{\"o}ßtenteils effektive und sichere Behandlungsmethode. Aufgeschl{\"u}sselt nach den WHO-Graden lagen die lokalen Kontrollraten bei 93,3\% (ohne Histologie), 91,2\% (WHO-Grad I), 66,7\% (WHO-Grad II) sowie 53,1\% (WHO-Grad III) nach f{\"u}nf Jahren. Nach zehn Jahren lagen die Raten bei 82,0\% (ohne Histologie), 91,2\% (WHO-Grad I), 46,7\% (WHO-Grad II) sowie 42,5\% (WHO-Grad III). In der multivariaten Analyse zeigte sich ein grenzwertig signifikanter Unterschied der lokalen Kontrolle f{\"u}r die Histologie (p = 0,050), sowie deutliche Signifikanz zwischen benignen und malignen Meningeomen. Das Gesamt{\"u}berleben lag nach f{\"u}nf Jahren bei 89,6\% sowie nach zehn Jahren bei 75,9\%. Signifikante Einflussfaktoren in der multivariaten Analyse waren die Histologie sowie die Gr{\"o}ße des GTV. Die Rate an medizinisch signifikanten (CTCAE ≥3) akuten und chronischen Nebenwirkungen war niedrig (5,9\% bzw. 4,2\%) und vergleichbar mit den Daten der Literatur. Die Arbeit liefert erstmalig Lebensqualit{\"a}tsdaten mittels der Fragebogen der EORTC an einem reinen Meningeomkollektiv, bei dem alle Patienten eine Strahlenbehandlung erhielten. Diese zeigen schlechtere Werte im Vergleich zur Normalbev{\"o}lkerung. Ebenso weisen sie auf eine Verschlechterung der Lebensqualit{\"a}t im Laufe der Tumorbehandlung hin. Dies ist allerdings aufgrund des einmaligen Messzeitpunktes und des fehlenden Vergleichskollektivs weder auf die Operation, noch auf die Bestrahlung kausal zur{\"u}ckf{\"u}hrbar. Um den genauen Stellenwert der Strahlentherapie im Therapieregime der Meningeome abh{\"a}ngig von der Histologie beurteilen zu k{\"o}nnen sowie diese Ergebnisse zu verifizieren und zu festigen, sind aufwendige prospektive Studien n{\"o}tig. Diese werden zum Teil aktuell durchgef{\"u}hrt. Regelm{\"a}ßige Kontrollen der Lebensqualit{\"a}t sowie der Nebenwirkungen sollen erhoben und ausgewertet werden, um die Auswirkungen der Therapie m{\"o}glichst allumfassend darstellen zu k{\"o}nnen.}, subject = {Meningeom}, language = {de} } @phdthesis{Lutyj2020, author = {Lutyj, Paul}, title = {Modulation der Strahlensensibilit{\"a}t mittels alleiniger sowie kombinierter PI3K/mTOR-Inhibierung im Glioblastommodell: die Rolle des PTENs}, doi = {10.25972/OPUS-21015}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-210159}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Den aktuellen Forschungsgegenstand dieser Arbeit bildet der in Glioblastomen h{\"a}ufig {\"u}beraktivierte PI3K/AKT/mTOR-Signalweg. Eine entscheidende Rolle bei der Aktivierung des Signalwegs spielt das Tumorsuppressorprotein PTEN. Ein mutiertes PTEN sorgt f{\"u}r die zuvor genannte {\"U}beraktivierung des PI3K/AKT/mTOR-Signalwegs und korreliert mit einer Radioresistenz. In der vorliegenden Arbeit wurde die strahlensensibilisierende Wirkung des neuartigen dualen PI3K/mTOR-Inhibitors NVP-BEZ235 an zwei humanen Glioblastomzelllinien mit unterschiedlichem PTEN-Status (GaMG: PTEN wt und U373-MG: PTEN mut) analysiert. Vergleichend dazu erfolgten Untersuchungen mit dem mTOR-Inhibitor Rapamycin und dem PI3K-Inhibitor LY294002. Untersucht wurden die Auswirkungen auf die Zellproliferation, die Strahlensensibilit{\"a}t, das Proteinexpressionsmuster, die Zellzyklusverteilung, die Induktion und Reparaturf{\"a}higkeit des DNS-Schadens sowie die Einleitung des programmierten Zelltods. U373-MG stellte sich im Vergleich zu GaMG als die strahlensensiblere Zelllinie heraus. Des Weiteren konnte gezeigt werden, dass die mTOR-Inhibition durch NVP-BEZ235, unabh{\"a}ngig vom PTEN-Status, f{\"u}r die Einflussnahme auf Proliferation und Proteintranslation vordergr{\"u}ndig ist. Es kam zu keinen radiosensibilisierenden Effekten durch Zugabe von NVP-BEZ235, Rapamycin und LY294002 24 Stunden vor Bestrahlung, was auf das Ausbleiben eines erh{\"o}hten DNA-Schadens und einer verz{\"o}gerten DNA-Reparatur, einen G1-Arrest und der Aktivierung des PI3K-Signalwegs zum Zeitpunkt der Bestrahlung sowie der Unterdr{\"u}ckung der Apoptose zur{\"u}ckzuf{\"u}hren ist. Trotz Ausbleiben radiosensibilisierender Effekt, konnte durch die Testsubstanzen eine starke zytostatische Wirkung gezeigt werden.}, subject = {Strahlensensibilit{\"a}t}, language = {de} } @article{MeyerScherzadMoratinetal.2019, author = {Meyer, Till Jasper and Scherzad, Agmal and Moratin, Helena and Gehrke, Thomas Eckert and Killisperger, Julian and Hagen, Rudolf and Wohlleben, Gisela and Polat, B{\"u}lent and Dembski, Sofia and Kleinsasser, Norbert and Hackenberg, Stephan}, title = {The radiosensitizing effect of zinc oxide nanoparticles in sub-cytotoxic dosing is associated with oxidative stress in vitro}, series = {Materials}, volume = {12}, journal = {Materials}, number = {24}, issn = {1996-1944}, doi = {10.3390/ma12244062}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193897}, pages = {4062}, year = {2019}, abstract = {Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP\(_{20 nm}\) and ZnO-NP\(_{100 nm}\) was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) was observed in a concentration of 10 µg/mL or 1 µg/mL respectively in 30 µg/mL of ZnO-NP\(_{20 nm}\) or 20 µg/mL of ZnO-NP\(_{100 nm}\) in FB. The addition of 1, 5, or 10 µg/mL ZnO-NP\(_{20 nm}\) or ZnO-NP\(_{100 nm}\) significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP\(_{100 nm}\) increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP\(_{20 nm}\). ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP\(_{100 nm}\), an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect.}, language = {en} } @phdthesis{Kunz2022, author = {Kunz, Andreas Steven}, title = {Vergleich von 3D-konformaler und intensit{\"a}tsmodulierter Strahlentherapie beim nicht-kleinzelligen Bronchialkarzinom}, doi = {10.25972/OPUS-25339}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-253399}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Die vorliegende Arbeit soll dazu dienen, die Strahlentherapie bei Patienten mit histologisch gesichertem, nicht-kleinzelligen Bronchialkarzinom nach 3D-konformalem sowie intensit{\"a}tsmoduliertem Schema anhand definierter Outcome-Parameter und ihrer Nebenwirkungsraten zu vergleichen. Insgesamt wurde f{\"u}r diese monozentrisch durchgef{\"u}hrte Studie mit retrospektivem Design ein Kollektiv aus 111 Patienten/-innen untersucht. Anhand des untersuchtem Kollektivs konnte gezeigt werden, dass beide Therapieverfahren bez{\"u}glich der {\"U}berlebensraten und der Rezidiv- bzw. Metastasierungsh{\"a}ufigkeit im Rahmen des beobachteten Studienzeitraums miteinander vergleichbar sind. Auch f{\"u}r die H{\"a}ufigkeit akuter Therapie-assoziierter Nebenwirkungen konnte kein signifikanter Unterschied zwischen den beiden Bestrahlungstechniken nachgewiesen werden; dagegen trat eine chronische Strahlenpneumonitis h{\"a}ufiger in der Patientengruppe auf, die prim{\"a}r eine 3D-CRT erhalten hatte.}, subject = {Nicht-kleinzelliges Bronchialkarzinom}, language = {de} } @phdthesis{Koegl2022, author = {K{\"o}gl, Katharina Anna Edith}, title = {Analyse des Qualit{\"a}tsindikators Reduktion Schmerz und des Qualit{\"a}tsindikators Opioide und Laxantien der S3-Leitlinie Palliativmedizin f{\"u}r Patienten mit einer nicht heilbaren Krebserkrankung}, doi = {10.25972/OPUS-25491}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254919}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Hintergrund: Die Qualit{\"a}tsindikatoren „QI2: Reduktion Schmerz" und „QI 3: Opiate und Laxantien" der S3-Leitlinie „Palliativmedizin f{\"u}r Patienten mit einer nicht heilbaren Krebserkrankung" von 2015 wurden pilotiert und hinsichtlich ihrer Erhebbarkeit, Eindeutigkeit und Vergleichbarkeit evaluiert. Damit sollte die Routinetauglichkeit der Qualit{\"a}tsindikatoren {\"u}berpr{\"u}ft und ein Beitrag zu deren Weiterentwicklung geleistet werden. Methodik: Die Qualit{\"a}tsindikatoren wurden retrospektiv f{\"u}r die Patientinnen und Patienten der Palliativstation des Universit{\"a}tsklinikums W{\"u}rzburg der Jahre 2015 und 2018 mit der Hauptdiagnose einer nicht heilbaren Krebserkrankung ausgewertet. Aufbauend auf den Vorgaben der S3-LL Palliativ Langversion 1.0 2015 wurde der Qualit{\"a}tsindikator Reduktion Schmerz (QI RS) f{\"u}r den gesamten Zeitraum des station{\"a}ren Aufenthalts erhoben. Der Qualit{\"a}tsindikator Opioide und Laxantien wurde am 3. Tag des station{\"a}ren Aufenthalts (QI OL T1) und am 3. Tag vor station{\"a}rer Entlassung (QI OL T2) erhoben. Ergebnisse: Bei 78,5\% der Grundgesamtheit wurden moderate bis starke Schmerzen dokumentiert und f{\"u}r den QI RS eingeschlossen (419/534). Die Datengrundlage des QI RS war f{\"u}r die eingeschlossenen F{\"a}lle vollst{\"a}ndig, da Schmerzanamnesen im Schmerzassessment der pflegerischen Dokumentation integriert sind: Unter den eingeschlossenen F{\"a}llen lag nach den Kriterien des QI RS bei insgesamt 73,5\% (308/419) eine dokumentierte Schmerzreduktion vor. Bei 26,5\% aller eingeschlossenen F{\"a}lle (111/419) lag nach den Kriterien des QI RS keine dokumentierte Schmerzreduktion vor. Unter jenen F{\"a}llen lag der Anteil der station{\"a}r Verstorbenen bei 64,0\% (71/111). Es lag ein signifikanter Zusammenhang zwischen dem Fehlen einer dokumentierten Schmerzreduktion und dem Versterben vor (p<0,05). 73,4\% (392/534) der Grundgesamtheit wurden f{\"u}r den QI OL T1 eingeschlossen, da eine Therapie mit Opioiden an T1 dokumentiert war. 75,8\% (405/534) der Grundgesamtheit wurde f{\"u}r den QI OL T2 eingeschlossen, da eine Therapie mit Opioiden an T2 dokumentiert war. Aufgrund der Vollst{\"a}ndigkeit der Routinedokumentation konnte die Auswertung des QI OL T1 bzw. des QI OL T2 bei allen eingeschlossenen F{\"a}llen vorgenommen werden: Am 3. Tag des station{\"a}ren Aufenthalts lag der Anteil dokumentierter Laxantien bei Opioidtherapie mit 57,9\% (227/392) etwas h{\"o}her als am 3. Tag vor station{\"a}rer Entlassung mit 53,8\% dokumentierter Laxantien bei Opioidtherapie (218/405). Unter den F{\"a}llen ohne Laxantien bei Opioidtherapie an T1 verstarben mit 58,8\% (97/165) weniger als unter den F{\"a}llen ohne Laxantien bei Opioidtherapie an T2 mit 67,4\% (126/187). Es zeigt sich sowohl f{\"u}r den QI OL T1 als auch f{\"u}r den QI OL T2 ein signifikanter Zusammenhang zwischen dem Fehlen dokumentierter Laxantien bei Opioidtherapie und dem Versterben (p<0,001). Schlussfolgerung: Die vorliegende Studie belegt die Sinnhaftigkeit der Evaluation von Qualit{\"a}tsindikatoren f{\"u}r die Palliativversorgung. Exemplarisch zeigt die Erhebung des Qualit{\"a}tsindikators Opioide und Laxantien in der Sterbephase, dass regelm{\"a}ßig von der Leitlinienempfehlung abgewichen wird. In der Erweiterten S3-LL Palliativ Langversion 2.0 von 2019 wurde der genaue Erhebungszeitpunkt des „QI2: Reduktion Schmerz" pr{\"a}zisiert: Eingeschlossen f{\"u}r die Erhebung sind nun alle Patienten mit starkem bzw. mittleren Schmerz „bei station{\"a}rer Aufnahme".}, subject = {Tumor}, language = {de} } @phdthesis{Lotter2020, author = {Lotter, Christina Theresa}, title = {Beurteilung einer tumorspezifischen Therapie durch Patientinnen/Patienten mit fortgeschrittenen Tumorerkrankungen in Abw{\"a}gung von Lebensverl{\"a}ngerung und Lebensqualit{\"a}t: Evaluierung und Identifikation assoziierter Variablen}, doi = {10.25972/OPUS-21369}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213699}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Hintergrund: Die Diagnose einer fortgeschrittenen Tumorerkrankung bedingt den Beginn eines komplexen Entscheidungsfindungsprozesses mit dem Ziel, unter Einbezug des betroffenen Patienten, seinen Angeh{\"o}rigen und dem behandelnden multiprofessionellen Team, realistische gemeinsame Therapieziele zu finden. Das Wissen um die aktuellen Patientenpr{\"a}ferenzen ist dabei unerl{\"a}sslich. Ziel dieser Studie war es, die Einstellung von Patienten mit fortgeschrittenen Tumorerkrankungen zur Inanspruchnahme von tumorspezifischer Therapie in Abh{\"a}ngigkeit von ihrer individuellen Pr{\"a}ferenz f{\"u}r Lebensverl{\"a}ngerung oder Lebensqualit{\"a}t zu untersuchen und Variablen zu identifizieren, die mit dieser Pr{\"a}ferenz in Zusammenhang stehen. Methode: In die prospektive klinische Beobachtungsstudie wurden zwischen 03.08.2015 und 23.03.2016 konsekutiv 92 von 522 gescreenten Patienten mit fortgeschrittenen Tumorerkrankungen eingeschlossen, die durch den palliativmedizinischen Dienst (PMD) am Universit{\"a}tsklinikum W{\"u}rzburg mitbetreut wurden. Die Patientenpr{\"a}ferenzen bez{\"u}glich Lebensverl{\"a}ngerung und Lebensqualit{\"a}t wurden mittels des Lebensqualit{\"a}t- und Lebenszeitfragebogen (Laryionava et al., 2014) erhoben und die Ergebnisse wurden unter Einsatz nicht-parametrischer Tests auf Assoziation mit diversen patienten- und krankheitsbezogenen Variablen {\"u}berpr{\"u}ft. Ergebnisse: Die Patienten unterscheiden sich in ihrer grundlegenden Pr{\"a}ferenz f{\"u}r Lebensverl{\"a}ngerung oder Lebensqualit{\"a}t: Ein gutes Drittel (37.0 \%) sprach sich ungeachtet einer m{\"o}glichen Beeintr{\"a}chtigung der Lebensqualit{\"a}t f{\"u}r den Einsatz tumorspezifischer Therapien mit dem Ziel der Lebensverl{\"a}ngerung aus, w{\"a}hrend ein weiteres Drittel (37.0 \%) der Patienten angab, Lebensqualit{\"a}t zu pr{\"a}ferieren und ein best-supportive-care-Konzept auch bei mutmaßlicher Einschr{\"a}nkung der Lebenszeit zu bevorzugen. Das verbleibende knappe Drittel (26.0 \%) der Patienten verblieb in Abw{\"a}gung von Lebensverl{\"a}ngerung und Lebensqualit{\"a}t ambivalent, pr{\"a}ferierte also entweder sowohl Lebensverl{\"a}ngerung als auch Lebensqualit{\"a}t (12.0 \%) oder zeigte f{\"u}r keines der beiden angebotenen Therapieziele eine Pr{\"a}ferenz (14.0 \%). Die Pr{\"a}ferenz f{\"u}r Lebensverl{\"a}ngerung war statistisch signifikant mit der Krankheitsselbsteinsch{\"a}tzung als heilbar (X2 (4, N = 92) = 8.20; p = .001), dem Leben in Gemeinschaft (X2 (2, N = 92) = 6.97; p = .031) und der Bereitschaft zur Ber{\"u}cksichtigung von Angeh{\"o}rigenw{\"u}nschen bei der Therapiezielfindung (rs (90) = .44; p < .001) assoziiert. Patienten, die nach Lebensqualit{\"a}t strebten, hielten ihre Krankheit f{\"u}r lebensbedrohlich (X2 (2, N = 92) = 6.07; p = .048) bzw. nicht-heilbar (X2 (4, N = 92) = 8.20; p = .001), zeigten eine Pr{\"a}ferenz f{\"u}r Therapiezielfindung ohne Einbezug von Angeh{\"o}rigenw{\"u}nschen (rs (90) = - .33; p = .001) und berichteten Hoffnungsverlust im Kampf gegen die Krankheit (p = .013). Patienten, die das Gef{\"u}hl hatten, ihre Angeh{\"o}rigen h{\"a}tten ihre Erkrankung nicht akzeptiert (X2 (2, N = 92) = 7.01; p = .030) und Patienten, die alleine lebten (X2 (2, N = 92) = 6.97; p = .031) blieben signifikant h{\"a}ufiger ambivalent. 41.3 \% der im Rahmen dieser Studie befragten Patienten mit fortgeschrittenen Tumorerkrankungen und objektiv infauster Prognose (medianes {\"U}berleben nach Studieneinschluss: 42 Tage), stuften ihre Krankheit als nicht lebensbedrohlich ein. 34.8 \% der Befragten gingen von der Heilbarkeit ihrer Erkrankung aus. Schlussfolgerung: Die Einstellung zu Lebensverl{\"a}ngerung und Lebensqualit{\"a}t ist individuell, ver{\"a}ndert sich dynamisch im Krankheitsverlauf und unterliegt zudem dem Einfluss diverser Variablen. Insbesondere eine realistische Krankheitsselbsteinsch{\"a}tzung durch die Patienten erscheint relevant, um beiderseits zufriedenstellende, sinnvolle Therapiekonzepte entwickeln zu k{\"o}nnen. Sinnvoll erscheint ein fr{\"u}h im Krankheitsverlauf implementierter, kontinuierlich aufrechterhaltener Gespr{\"a}chsprozess, mit dem Ziel, bereits kurz nach Diagnose einer Erkrankung deren schlechtesten oder bestm{\"o}glichen Verlauf zu thematisieren und regelm{\"a}ßig die aktuelle Situation zu reevaluieren, um in der Folge m{\"o}glichst realit{\"a}tsbasierte und aktuelle Patientenpr{\"a}ferenzen erheben zu k{\"o}nnen. Der Lebensqualit{\"a}t- und Lebenszeitfragebogen eignet sich aufgrund des hohen Zeitaufwandes und der psychischen Belastung der Patienten eher f{\"u}r eine initiale, einmalige Pr{\"a}ferenzerhebung. T{\"a}gliche Erhebungen, beispielsweise im Rahmen der Arztvisite, k{\"o}nnten mittels einfacher visueller Analogskalen (vgl. Douglas et al. 2018) erfolgen und als Grundlage f{\"u}r die Therapiekonzeptdiskussion in w{\"o}chentlichen interdisziplin{\"a}ren Visiten dienen. Dieser Ansatz sollte weiter auf Umsetzbarkeit und Wirksamkeit untersucht werden.}, subject = {Lebensqualit{\"a}t}, language = {de} } @article{RichterWeickKriegeretal.2017, author = {Richter, Anne and Weick, Stefan and Krieger, Thomas and Exner, Florian and Kellner, Sonja and Polat, B{\"u}lent and Flentje, Michael}, title = {Evaluation of a software module for adaptive treatment planning and re-irradiation}, series = {Radiation Oncology}, volume = {12}, journal = {Radiation Oncology}, number = {205}, doi = {10.1186/s13014-017-0943-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158711}, year = {2017}, abstract = {Background: The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow. Methods: The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed. Results: The Dynamic Planning Tool was used in 20\% of treated patients per year for both approaches nearly equally (42\% plan adaptation and 58\% re-irradiation). Most cases were assessed for the thoracic body region (51\%) followed by pelvis (21\%) and head and neck cases (10\%). The sub-group evaluation showed that unintended plan adaptation was performed in 38\% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4-35 days) was observed. PTV changed by 12 ± 12\% on average (maximum change 42\%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases. Conclusion: The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to consider the pretreatment dose, to adapt the actual treatment schema more specifically and to review the accumulated dose.}, language = {en} } @article{HartmannReisslandMaieretal.2021, author = {Hartmann, Oliver and Reissland, Michaela and Maier, Carina R. and Fischer, Thomas and Prieto-Garcia, Cristian and Baluapuri, Apoorva and Schwarz, Jessica and Schmitz, Werner and Garrido-Rodriguez, Martin and Pahor, Nikolett and Davies, Clare C. and Bassermann, Florian and Orian, Amir and Wolf, Elmar and Schulze, Almut and Calzado, Marco A. and Rosenfeldt, Mathias T. and Diefenbacher, Markus E.}, title = {Implementation of CRISPR/Cas9 Genome Editing to Generate Murine Lung Cancer Models That Depict the Mutational Landscape of Human Disease}, series = {Frontiers in Cell and Developmental Biology}, volume = {9}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2021.641618}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230949}, year = {2021}, abstract = {Lung cancer is the most common cancer worldwide and the leading cause of cancer-related deaths in both men and women. Despite the development of novel therapeutic interventions, the 5-year survival rate for non-small cell lung cancer (NSCLC) patients remains low, demonstrating the necessity for novel treatments. One strategy to improve translational research is the development of surrogate models reflecting somatic mutations identified in lung cancer patients as these impact treatment responses. With the advent of CRISPR-mediated genome editing, gene deletion as well as site-directed integration of point mutations enabled us to model human malignancies in more detail than ever before. Here, we report that by using CRISPR/Cas9-mediated targeting of Trp53 and KRas, we recapitulated the classic murine NSCLC model Trp53fl/fl:lsl-KRasG12D/wt. Developing tumors were indistinguishable from Trp53fl/fl:lsl-KRasG12D/wt-derived tumors with regard to morphology, marker expression, and transcriptional profiles. We demonstrate the applicability of CRISPR for tumor modeling in vivo and ameliorating the need to use conventional genetically engineered mouse models. Furthermore, tumor onset was not only achieved in constitutive Cas9 expression but also in wild-type animals via infection of lung epithelial cells with two discrete AAVs encoding different parts of the CRISPR machinery. While conventional mouse models require extensive husbandry to integrate new genetic features allowing for gene targeting, basic molecular methods suffice to inflict the desired genetic alterations in vivo. Utilizing the CRISPR toolbox, in vivo cancer research and modeling is rapidly evolving and enables researchers to swiftly develop new, clinically relevant surrogate models for translational research.}, language = {en} } @article{OorschotIshiiKusomotoetal.2020, author = {Oorschot, Birgitt van and Ishii, Koji and Kusomoto, Yuko and Zetzl, Theresa and Roch, Carmen and Mettenleiter, Andreas and Ozawa, Hiroko and Flentje, Michael}, title = {Anxiety, depression and psychosocial needs are the most frequent concerns reported by patients: preliminary results of a comparative explorative analysis of two hospital-based palliative care teams in Germany and Japan}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02186-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235675}, pages = {1481-1489}, year = {2020}, abstract = {In the partnership between the medical departments of W{\"u}rzburg University, Germany, and Nagasaki University, Japan, palliative care is a relevant topic. The aim of the study was to perform a comparative analysis of the hospital-based palliative care teams in W{\"u}rzburg (PCT-W) and Nagasaki (PCT-N). Survey of staff composition and retrospective analysis of PCT patient charts in both PCTs were conducted. Patients self-assessed their symptoms in PCT-W and in Radiation Oncology W{\"u}rzburg (RO-W). The (negative) quality indicator 'percentage of deceased hospitalised patients with PCT contact for less than 3 days before death' (Earle in Int J Qual Health Care 17(6):505-509, 2005) was analysed. Both PCTs follow a multidisciplinary team approach. PCT-N saw 410 cancer patients versus 853 patients for PCT-W (22.8\% non-cancer patients). The Eastern Cooperative Oncology Group Performance Status at first contact with PCT-N was 3 or 4 in 39.3\% of patients versus 79.0\% for PCT-W. PCT-N was engaged in co-management longer than PCT-W (mean 20.7 days, range 1-102 versus mean 4.9 days, range 1-48). The most frequent patient-reported psychological symptom was anxiety (family anxiety: 98.3\% PCT-W and 88.7\% RO-W, anxiety 97.9\% PCT-W and 85.9\% RO-W), followed by depression (98.2\% PCT-W and 80.3\% RO-W). In 14 of the 148 deceased patients, PCT-N contact was initiated less than 3 days before death (9.4\%) versus 121 of the 729 deceased PCT-W patients (16.6\%). Psychological needs are highly relevant in both Germany and Japan, with more than 85\% anxiety and depression in patients in the Japanese IPOS validation study (Sakurai in Jpn J Clin Oncol 49(3):257-262, 2019). This should be taken into account when implementing PCTs.}, language = {en} } @phdthesis{Grabenbauer2021, author = {Grabenbauer, Felix}, title = {Radiosensibilisierung humaner Tumorzelllinien unterschiedlicher Entit{\"a}ten durch den MEK-Inhibitor PD184352 allein oder in Kombination mit dem HSP90-Inhibitor NVP-AUY922: Einfluss der Behandlungsschemas}, doi = {10.25972/OPUS-23979}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239790}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Das Targeting des MEK-Proteins in Krebszellen f{\"u}hrt in der Regel zu einer erworbenen Resistenz gegen MEK-Inhibitoren und zur Aktivierung des {\"u}berlebenswichtigen Proteins Akt. Da sowohl MEK als auch Akt Clienten des Hsp90-Chaperonsystems sind, untersucht die vorliegende Arbeit die Reaktionen von bestrahlten Lungenkarzinom- (A549) und Glioblastom- (SNB19) Zelllinien auf eine kombinierte MEK- und Hsp90-Hemmung. Unerwarteterweise verbesserte der 24 h vor der Bestrahlung verabreichte MEK-Inhibitor PD184352 das Zell{\"u}berleben durch Hochregulation von MEK und Erk1/2, aber auch von Akt. Im Gegensatz dazu reduzierte PD184352, das 1 h vor der Bestrahlung zugegeben wurde, die Expression von Erk stark und regulierte Akt in beiden Zelllinien nicht hoch. Als Ergebnis verst{\"a}rkte der MEK-Inhibitor die radiosensibilisierende Wirkung des Hsp90-Inhibitors NVP-AUY922 in Glioblastomzellen (SNB19).}, subject = {Strahlenbiologie}, language = {de} } @article{HechtMeierZimmeretal.2018, author = {Hecht, Markus and Meier, Friedegund and Zimmer, Lisa and Polat, B{\"u}lent and Loquai, Carmen and Weishaupt, Carsten and Forschner, Andrea and Gutzmer, Ralf and Utikal, Jochen S. and Goldinger, Simone M. and Geier, Michael and Hassel, Jessica C. and Balermpas, Panagiotis and Kiecker, Felix and Rauschenberg, Ricarda and Dietrich, Ursula and Clemens, Patrick and Berking, Carola and Grabenbauer, Gerhard and Schadendorf, Dirk and Grabbe, Stephan and Schuler, Gerold and Fietkau, Rainer and Distel, Luitpold V. and Heinzerling, Lucie}, title = {Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients}, series = {British Journal of Cancer}, volume = {118}, journal = {British Journal of Cancer}, doi = {10.1038/bjc.2017.489}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227970}, pages = {785-792}, year = {2018}, abstract = {Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients. Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi). Results: The median duration of BRAFi treatment interruption prior to radiotherapy was 4 days and lasted for 17 days. Median OSRT and OSBRAFi in the entire cohort were 9.8 and 12.6 months in the interrupted group and 7.3 and 11.5 months in the concomitant group (P=0.075/P=0.217), respectively. Interrupted vemurafenib treatment with a median OSRT and OSBRAFi of 10.1 and 13.1 months, respectively, was superior to concomitant vemurafenib treatment with a median OSRT and OSBRAFi of 6.6 and 10.9 months (P=0.004/P=0.067). Interrupted dabrafenib treatment with a median OSRT and OSBRAFi of 7.7 and 9.8 months, respectively, did not differ from concomitant dabrafenib treatment with a median OSRT and OSBRAFi of 9.9 and 11.6 months (P=0.132/P=0.404). Median local control of the irradiated area did not differ in the interrupted and concomitant BRAFi treatment groups (P=0.619). Skin toxicity of grade ≥2 (CTCAE) was significantly increased in patients with concomitant vemurafenib compared to the group with treatment interruption (P=0.002). Conclusions: Interruption of vemurafenib treatment during radiation was associated with better survival and less toxicity compared to concomitant treatment. Due to lower number of patients, the relevance of treatment interruption in dabrafenib treated patients should be further investigated. The results of this analysis indicate that treatment with the BRAFi vemurafenib should be interrupted during radiotherapy. Prospective studies are desperately needed.}, language = {en} } @phdthesis{Dalkmann2024, author = {Dalkmann, Theresa}, title = {Evaluierung prognostischer und pr{\"a}diktiver Biomarker beim neoadjuvant vorbehandelten Rektumkarzinom}, doi = {10.25972/OPUS-36336}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363368}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Fragestellung. Osteopontin (OPN) kann im Blut nachgewiesen werden und wird bei vielen Tumorentit{\"a}ten exprimiert, wie auch der Tyrosinkinaserezeptor c-Met und sein Ligand, das Zytokin Hepatocyte Growth Factor (HGF). In der vorliegenden Arbeit untersuchten wir die prognostische und pr{\"a}diktive Wertigkeit der Plasmakonzentrationen von OPN, c-Met und HGF bei Patienten mit lokal fortgeschrittenem Rektumkarzinom (LARC). Methodik. Das Plasma von 63 Patienten mit LARC wurde untersucht. Die Blutentnahmen (EDTA-Plasma) erfolgten vor Therapiebeginn sowie im Verlauf. Die Plasmaspiegel von OPN, c-Met und HGF wurden mittels Enzyme-Linked Immunosorbent Assay analysiert. Die Konzentrationen wurden auf eine Korrelation mit den klinischen Parametern untersucht. Ergebnisse. 68 Patienten wurden neoadjuvant mit einer Radiochemotherapie behandelt, 63 Blutproben wurden untersucht. Initial befanden sich nach UICC 14 Patienten in Stadium II, 47 in Stadium III und 7 in Stadium IV. Das mediane Follow-Up betrug 29,87 Monate. 20 der 68 Patienten (29,4 \%) verstarben, 19 entwickelten Fernmetastasen. OPN korrelierte signifikant mit dem {\"U}berleben (p=0,001). OPN-Werte korrelierten mit dem pT-Stadium (R:0,445 p=0,018) und dem pUICC-Stadium (R:0,412 p=0,018), sowie mit dem Auftreten von Fernmetastasen (R:0,271 p=0,031). Eine Korrelation zwischen OPN und dem Therapieansprechen konnte gezeigt werden: pathologisch komplette Remission (pCR) (R:0,379 p=0,001), NAR-Score (R:0,373 p=0,015), TRG (R:0,380 p=0,020). Die logistische Regressionsanalyse ergab eine Pr{\"a}diktivit{\"a}t OPNs f{\"u}r pCR (OR:0,990 p=0,009), NAR-Score (OR:1,008 p=0,007), TRG (OR:0,459 p=0,008). C-Met und HGF korrelierten nicht mit dem {\"U}berleben. F{\"u}r c-Met und HGF ergab sich keine Korrelation zu initialen klinischen Daten und Therapieansprechen. Die logistische Regression ergab keinen pr{\"a}diktiven Wert. Schlussfolgerung. Die Plasmakonzentration von OPN besitzt prognostische und pr{\"a}diktive Wertigkeit beim LARC. Die Konzentrationen von c-Met und HGF sind nicht prognostisch f{\"u}r das {\"U}berleben oder pr{\"a}diktiv f{\"u}r das Therapieansprechen.}, subject = {Biomarker}, language = {de} } @article{GreberPolatFlentjeetal.2019, author = {Greber, Johannes and Polat, B{\"u}lent and Flentje, Michael and Bratengeier, Klaus}, title = {Properties of the anisotropy of dose contributions: A planning study on prostate cases}, series = {Medical Physics}, volume = {46}, journal = {Medical Physics}, doi = {10.1002/mp.13308}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228237}, pages = {419-425}, year = {2019}, abstract = {Purpose To characterize the static properties of the anisotropy of dose contributions for different treatment techniques on real patient data (prostate cases). From this, we aim to define a class of treatment techniques with invariant anisotropy distribution carrying information of target coverage and organ-at-risk (OAR) sparing. The anisotropy presumably is a helpful quantity for plan adaptation problems. Methods The anisotropy field is analyzed for different intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques for a total of ten planning CTs of prostate cases. Primary irradiation directions ranged from 5 to 15. The uniqueness of anisotropy was explored: In particular, the anisotropy distribution inside the planning treatment volume (PTV) and in its vicinity was investigated. Furthermore, deviations of the anisotropy under beam rotations were explored by direct plan comparison as an indicating the susceptibility of each planned technique to changes in the geometric plan configuration. In addition, plan comparisons enabled the categorization of treatment techniques in terms of their anisotropy distribution. Results The anisotropy profile inside the PTV and in the transition between OAR and PTV is independent of the treatment technique as long as a sufficient number of beams contribute to the dose distribution. Techniques with multiple beams constitute a class of almost identical and technique-independent anisotropy distribution. For this class of techniques, substructures of the anisotropy are particularly pronounced in the PTV, thus offering good options for applying adaptation rules. Additionally, the techniques forming the mentioned class fortunately allow a better OAR sparing at constant PTV coverage. Besides the characterization of the distribution, a pairwise plan comparison reveals each technique's susceptibility to deviations which decreases for an increasing number of primary irradiation directions. Conclusions Techniques using many irradiation directions form a class of almost identical anisotropy distributions which are assumed to provide a basis for improved adaptation procedures. Encouragingly, these techniques deliver quite invariant anisotropy distributions with respect to rotations correlated with good plan qualities than techniques using few gantry angles. The following will be the next steps toward anisotropy-based adaptation: first, the quantification of anisotropy regarding organ deformations; and second, establishing the interrelation between the anisotropy and beam shaping.}, language = {en} }