TY - JOUR A1 - Steinmann, Diana A1 - Paelecke-Habermann, Yvonne A1 - Geinitz, Hans A1 - Aschoff, Raimund A1 - Bayerl, Anja A1 - Bölling, Tobias A1 - Bosch, Elisabeth A1 - Bruns, Frank A1 - Eichenseder-Seiss, Ute A1 - Gerstein, Johanna A1 - Gharbi, Nadine A1 - Hagg, Juliane A1 - Hipp, Matthias A1 - Kleff, Irmgard A1 - Müller, Axel A1 - Schäfer, Christof A1 - Schleicher, Ursula A1 - Sehlen, Susanne A1 - Theodorou, Marilena A1 - Wypior, Hans-Joachim A1 - Zehentmayr, Franz A1 - van Oorschot, Birgitt A1 - Vordermark, Dirk T1 - Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases JF - BMC Cancer N2 - Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information. KW - breast cancer KW - brain tumours KW - survival KW - validation KW - symptoms KW - EORTC-QLQ-C15-PAL KW - EORTC-BN20 KW - whole-brain radiotherapy KW - partitioning analysis RPA KW - cancer patients KW - lung cancer KW - prognostic index KW - radiation oncology KW - clinical trials Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135254 VL - 12 IS - 283 ER - TY - JOUR A1 - Hardcastle, Nicholas A1 - Tomé, Wolfgang A. A1 - Cannon, Donald M. A1 - Brouwer, Charlotte L. A1 - Wittendorp, Paul W. H. A1 - Dogan, Nesrin A1 - Guckenberger, Matthias A1 - Allaire, Stéphane A1 - Mallya, Yogish A1 - Kumar, Prashant A1 - Oechsner, Markus A1 - Richter, Anne A1 - Song, Shiyu A1 - Myers, Michael A1 - Polat, Bülent A1 - Bzdusek, Karl T1 - A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy JF - Radiation Oncology N2 - Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27% (12/44) of the GTVs required major edits. Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician. KW - intensity-modulated radiotherapy KW - megavoltage computed-tomography KW - cancer KW - variability KW - strategies KW - risk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134756 VL - 7 IS - 90 ER - TY - JOUR A1 - Said, Harun M. A1 - Polat, Buelent A1 - Stein, Susanne A1 - Guckenberger, Mathias A1 - Hagemann, Carsten A1 - Staab, Adrian A1 - Katzer, Astrid A1 - Anacker, Jelena A1 - Flentje, Michael A1 - Vordermark, Dirk T1 - Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells JF - World Journal of Clinical Oncology N2 - AIM: To study short dsRNA oligonucleotides (siRNA) as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1 (NDRG1) gene induced under different physiological conditions (Normoxia and hypoxia) modulating NDRG1 transcription, mRNA stability and translation. METHODS: A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 x 10(7) cells, nuclear extracts were prepared according to previous protocols. The pSUPER-NDRG1 vectors were designed, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on -actin and hypoxia-inducible factor (HIF)-1 mRNA sequences in GenBank. NDRG1 mRNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia (P < 0.05 was considered significant). RESULTS: siRNA- and iodoacetate (IAA)-mediated downregulation of NDRG1 mRNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results. CONCLUSION: NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it can represent a potential target for tumor treatment in human glioblastoma. The siRNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays. KW - Strahlentherapie KW - brain cancer KW - radiotherapy KW - human cancer diseases KW - Short dsRNA oligonucleotides KW - N-Myc down regulated gene 1 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123385 VL - 3 IS - 7 ER - TY - THES A1 - Assenbrunner, Bernadette T1 - Palliative hypofraktionierte Bestrahlung bei nicht kleinzelligem Bronchialkarzinom T1 - Palliative hypofractionated radiotherapy in non-small cell lung cancer N2 - Für die palliative Bestrahlung des NSCLC stehen mehrere, sehr unterschiedliche hypofraktionierte Behandlungsschemata zur Verfügung. Prospektive Studien in der Vergangenheit konnten keine Überlegenheit für eines dieser Regime zeigen. Ziel vorliegender retrospektiver Arbeit war es, die Effektivität der Radiatio mit 13 bis 15 Fraktionen zu 3 Gy zu überprüfen. Hierzu untersuchten wir die Daten von 57 Patienten, die sich in den Jahren 2006 bis 2008 in der Strahlentherapie der Universitätsklinik Würzburg einer solchen Therapie unterzogen. Das Patientengut unterteilten wir für die Untersuchung in zwei Gruppen M0 und M1, deren Prognose wir unterschiedlich einschätzten. Der Einteilung lag das Vorhandensein von Fernmetastasen zu Behandlungsbeginn zugrunde. Das Gesamtüberleben war für Patienten der M0-Gruppe signifikant besser und lag für M1-Patienten in einem zu erwartenden Bereich. 17,5% unserer Patienten lebten 18 Monate oder länger. Welche Ursachen hinter diesem prolongierten Überleben stehen könnten, blieb jedoch weitgehend unklar. Für das Gesamtüberleben 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, führten zu keinen signifikanten bzw. widersprüchlichen Ergebnissen. Hierzu zählten insbesondere der Charlson comorbidity score und das Alter. Für die Höhe der Gesamtdosis und die Größe des PTV wurde interessanterweise kein Einfluss auf das Überleben nachgewiesen. Die lokale Kontrolle war von diesen beiden Variablen ebenfalls unabhängig. Ein systemischer Progress trat bei unseren Patienten tendenziell früher 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 Akuttoxizitäten, insbesondere Ösophagitiden, relativ häufig. N2 - There are several different hypofractionated schedules in palliative radiation therapy for non-small cell lung cancer. Recent prospective studies could not demonstrate superiority of one of these schedules. The aim of the present retrospective paper was to evaluate the efficacy of a radiation therapy with 13 to 15 fractions at 3 Gy. Therefore we analyzed data of 57 patients who underwent such a radiation therapy at the university hospital of Würzburg between 2006 and 2008. Patients were divided into two different groups (M0 and M1, based on the presence of distant metastases) with expected unequal prediction. Overall survival was significant better in M0-patients and was 11.7 months for M1-patients. 17,5% of our patients survived 18 months or longer. The reasons of this prolonged survival remained unclear. Stage of disease, performance status and chemotherapy turned out to be prognostic factors in survival - as known from literature. Other factors, which we supposed to have an influence, like Charlson comorbidity score and patients' age generated no significant respectively disputed results. There was neither a correlation between total dose and overall survival nor between planning target volume and overall survival. Local control was also independent of these variables. Systemic progress occurred rather earlier than local progress. Performance status was not influenced negatively by radiation. Acute toxicities - particularly oesophagitis- were rather frequent but we did not observe any severe infection. KW - Nicht-kleinzelliges Bronchialkarzinom KW - hypofraktionierte KW - Bestrahlung KW - palliativ KW - nicht kleinzelliges Bronchialkarzinom Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-90159 ER - TY - THES A1 - Saur, Gabriella-Sofie T1 - Klinische Ergebnisse und Lebensqualität nach neoadjuvanter Radiochemotherapie von Rektumkarzinomen T1 - Clinical outcomes and life-qualiy after long-course radiochemotherapy for locally advanced rectal cancer N2 - 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 Therapiemodalitäten, 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 Gesamtüberleben sprechen die Ergebnisse für 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 für diese beiden Therapiemodalitäten abgeleitet werden. N2 - The standard therapy for local advanced rectal cancer in UICC stadium II and III consists of neoadjuvant radio(chemo)therapy followed by surgical intervention. In this connection the two therapy regiments on the one hand a short term radiotherapy (5x5 Gy) followed by surgery and on the other hand a long term radiotherapy (28x1,8 Gy) with a free interval of 4-6 weeks till surgery are differentiated. Looking at the frequency of local relapses and overall survival the results of the long term radiotherapy are superior to the results of short term radiotherapy. Nevertheless there are clinical situations in which the use of short term radiotherapy can be indicated. In consequence there has to be a well differentiated indication-defining process for choosing the right therapy. KW - Rektumkarzinom KW - Langzeitradiochemotherapie KW - Lebensqualität KW - rectal cancer KW - long-course radiochemotherapy KW - life-quality Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78562 ER - TY - THES A1 - Gabor, Manuela T1 - Die stereotaktische Bestrahlung von Lungentumoren – Klinische Ergebnisse dieser innovativen Behandlungsmethode an der Universitätsklinik Würzburg von 1997 bis 2007 T1 - The stereotactic body radiation therapy of lung tumors - Clinical results of this innovative treatment at the University Hospital of Würzburg 1997-2007 N2 - Ziel dieser retrospektiven Arbeit war es, die Daten von Patienten, die stereotaktisch aufgrund eines Lungentumors (NSCLC, Lungenmetastasen und Rezidiven) bestrahlt wurden, hinsichtlich des Therapieerfolges auszuwerten. Hierfür wurden die Unterlagen von 148 Patienten der Klinik und Poliklinik für Strahlentherapie der Universität Würzburg bezüglich der lokalen und systemischen Kontrolle, des Überlebens und der strahlenbedingten Nebenwirkungen untersucht. Für die Analyse wurden die Patienten in zwei Gruppen unterteilt. Die erste Gruppe bestand aus 40 Patienten mit 41 NSCLC im frühen Stadium (Stadium I und T3N0M0). In der zweiten Gruppe wurden 108 Patienten mit 25 NSCLC im fortgeschrittenen (Stadium III) und metastasierten Stadium sowie Patienten mit 111 Lungenmetastasen und zehn Rezidiven zusammengefasst. Die Bestrahlung erfolgte je nach Lage und Größe des Tumors mit Bestrahlungsdosen zwischen 6 und 26 Gy in einer bis acht Fraktionen, wobei die biologisch effektive Dosis appliziert auf das PTV zwischen 24 und 94 Gy lag. Die mediane Nachsorgedauer betrug 14 Monate. Bei der Betrachtung des lokalen Tumoransprechens zeigten sich in beiden Gruppen gute Ergebnisse mit lokalen Kontrollraten nach drei Jahren von jeweils 84%. In der statistischen Analyse wurde deutlich, dass eine lokale Tumorkontrolle sehr stark mit der Höhe der verabreichten Bestrahlungsdosis korreliert. So wurden mit BED > 80 Gy signifikant bessere Ergebnisse erzielt als mit BED < 80 Gy. Dementsprechend konnte auch mit den hochdosierten Bestrahlungsschemata (1 x 26 Gy auf 80% und 3 x 12,5 Gy auf 65%) eine bessere Kontrolle erreicht werden. In der ersten Gruppe der NSCLC im frühen Stadium waren die CTV und PTV der Tumoren, die lokal kontrolliert blieben signifikant kleiner, als die CTV und PTV der Tumoren, die lokal rezidivierten. Die systemische Kontrollrate fiel in der ersten Gruppe besser aus als in der zweiten Gruppe. Nach drei Jahren lagen die Werte entsprechend bei 36% und 16%. In der Gruppe der NSCLC im frühen Stadium erwies sich die Größe des bestrahlten Volumens als Faktor, der die systemische Kontrolle beeinflusst, wobei systemisch kontrollierte Patienten ein signifikant kleineres CTV und PTV hatten. Die Überlebensraten der Patienten lagen in der Gruppe 1 und 2 nach drei Jahren bei 32% und 17%. Sowohl der Leistungszustand vor Behandlungsbeginn als auch die Größe des bestrahlten Volumens beeinflussten das Überleben der Patienten. In der Gruppe 2 zeigte sich außerdem, dass ein hochdosiertes Bestrahlungsschema vorteilhaft für die Überlebensdauer eines Patienten ist. Da 46% der Todesursachen in der Gruppe 1 auf Begleiterkrankungen zurückzuführen waren, fiel folglich auch das tumorspezifische Überleben mit 51% nach drei Jahren deutlich besser aus als das Gesamtüberleben. Die Faktoren, die ein tumorspezifisches Überleben begünstigten, waren in Gruppe 1 das Alter und die Größe des bestrahlten Volumens. In der Gruppe 2 wirkte sich noch zusätzlich die Höhe der Bestrahlungsdosis signifikant auf das CSS aus. Das krankheitsfreie Überleben in der Gruppe 1 lag nach drei Jahren bei 23% und unterschied sich signifikant zwischen den einzelnen Tumorhistologien, wobei Patienten mit einem Adeno-CA am längsten krankheitsfrei überlebten. Außerdem hatten Patienten mit einem krankheitsfreien Überleben im Median kleinere CTV und PTV als Patienten, die während der Nachsorge verstarben oder nicht kontrolliert blieben. Die Gruppe 2 erreichte nach drei Jahren eine DFS-Rate von 8%. Die Rate an strahleninduzierten Nebenwirkungen fiel insgesamt gering aus. Schwere Nebenwirkungen ≥ Grad 3 traten in der Gesamtgruppe zu einem Anteil von 1,4% auf. Es zeigten sich jeweils eine Grad 3 und eine Grad 5 Nebenwirkung in der Gruppe 2 nach mehr als sechs Monaten nach Bestrahlung. Leichte akute und späte Nebenwirkungen ≤ Grad 2 konnten bei 42,5% der Patienten in der Gruppe 1 und bei 39,7% der Patienten der Gruppe 2 beobachtet werden. Weder die Höhe der BED noch die Größe des bestrahlten Volumens konnten mit dem Auftreten einer Nebenwirkung und deren Schweregrad in Verbindung gebracht werden. Insgesamt lässt sich festhalten, dass die stereotaktische Bestrahlung eine effektive und sichere Therapiemethode zur Bestrahlung von Lungenherden darstellt. Wird die stereotaktische Bestrahlung in kurativer Intention eingesetzt, sollte darauf geachtet werden, dass eine ausreichend hohe Bestrahlungsdosis Anwendung findet, um eine lokale Tumorkontrolle zu erzielen. N2 - The aim of this retrospective study was to analyze the data of patients with lung tumors who were treated with stereotactic body radiation therapy in terms of treatment success. For this purpose the records of 148 patients of the Clinic of Radiotherapy at the University of Würzburg were examined with regard to the local and systemic control, survival and radiation-related side effects. For analysis, the patients were divided into two groups. The first group consisted of 40 patients with 41 early stage NSCLC (Stage I and T3N0M0). In the second group 108 patients with 25 advanced NSCLC (Stage III and IV), patients with 111 lung metastasis and ten recurrences were combined. The irradiation protocoll depended on tumor location and size. Doses of 6-26 Gy in one to eight fractions were applied, the biologically effective dose to the PTV was 24-94 Gy. The median follow-up duration was 14 months. In both groups good results were achieved considering the local tumor response, with local control rates after three years of 84%. In the statistical analysis, local tumor control was very strongly correlated with the amount of radiation dose administered. With a BED > 80 Gy better results were obtained than with BED < 80 Gy. A better local control was also achieved with the high-dose irradiation regimens (1 x 26 Gy to 80% and 3 x 12.5 Gy to 65%). In the first group of early stage NSCLC the CTV and PTV of locally controlled tumors were significantly smaller than the CTV and PTV of tumors that recurred locally. In the first group a better systemic controll rate was achieved than in the second group. After three years, the values ​​were correspondingly 36% and 16%. In the group of early stage NSCLC the size of the irradiated volume proved to be a factor influencing the systemic control, wherein systemically controlled patients had a significantly smaller CTV and PTV. The survival rates in group 1 and 2 after three years were 32% and 17%. In both groups the performance state prior to the start of treatment and the size of the irradiated volume affected the survival. In Group 2 a high dose radiation scheme was advantageous for the survival. The tumor specific survival in Group 1 was significantly better than the overall survival. The factors favoring a tumor-specific survival were age and size of the irradiated volume in group 1. In Group 2 the amount of radiation dose seemed to be a significant effect on the CSS. After three years the disease-free survival in group 1 was 23% and significantly different between the individual tumor histologies. In addition, patients who survived disease-free had a smaller CTV and PTV. Group 2 achieved a DFS rate of 8% after three years. Radiation-induced side effects were rare. In the entire group serious adverse effects ≥ Grade 3 occurred in 1.4%. There were one Grade 3 and Grade 5 adverse event in group 2 after more than six months after irradiation. Slight acute and late side effects ≤ Grade 2 were observed in 42.5% of patients in Group 1 and in 39.7% of patients in Group 2. Neither the size nor the BED of the irradiated volume could be associated with the occurrence of a side effect and its severity. Overall, it can be stated that the stereotactic body radiation therapy is an effective and safe method for the treatment of lung tumors. If the stereotactic radiation is used in curative intent, it should be ensured that a sufficiently high radiation dose is applied to achieve local tumor control. KW - Lungentumor KW - Bestrahlung KW - NSCLC KW - Lungenmetastase KW - Lungentumor KW - stereotaktische Bestrahlung KW - NSCLC KW - Lungenmetastase KW - Lung tumor KW - stereotactic body radiation therapy KW - NSCLC KW - lung metastasis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78298 ER - TY - JOUR A1 - Li, Xiang A1 - Samnick, Samuel A1 - Lapa, Constantin A1 - Israel, Ina A1 - Buck, Andreas K. A1 - Kreissl, Michael C. A1 - Bauer, Wolfgang T1 - 68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors N2 - Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N0,N00,N000-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors. Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed. Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation. Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions. KW - Medizin KW - Atherosclerotic plaque KW - 68Ga-DOTATATE KW - Somatostatin receptor KW - Cardiovascular risk factors KW - Macrophage Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76231 ER - TY - JOUR A1 - Guckenberger, Matthias A1 - Hawkins, Maria A1 - Flentje, Michael A1 - Sweeney, Reinhart A. T1 - Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial N2 - 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 KW - Medizin KW - Phase II trial KW - Spinal metastasis KW - Pain KW - Radiosurgery KW - Stereotactic body radiotherapy Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75853 ER - TY - JOUR A1 - Guckenberger, Matthias A1 - Alexandrow, Nikolaus A1 - Flentje, Michael T1 - Radiotherapy alone for stage I-III low grade follicular lymphoma: long-term outcome and comparison of extended field and total nodal irradiation N2 - Background: To analyze long-term results of radiotherapy alone for stage I-III low grade follicular lymphoma and to compare outcome after extended field irradiation (EFI) and total nodal irradiation (TNI). Methods and materials: Between 1982 and 2007, 107 patients were treated with radiotherapy alone for low grade follicular lymphoma at Ann Arbor stage I (n = 50), II (n = 36) and III (n = 21); 48 and 59 patients were treated with EFI and TNI, respectively. The median total dose in the first treatment series of the diaphragmatic side with larger lymphoma burden was 38 Gy (25 Gy – 50 Gy) and after an interval of median 30 days, a total dose of 28 Gy (12.6 Gy – 45 Gy) was given in the second treatment series completing TNI. Results: After a median follow-up of 14 years for living patients, 10-years and 15-years overall survival (OS) were 64% and 50%, respectively. Survival was not significantly different between stages I, II and III. TNI and EFI resulted in 15-years OS of 65% and 34% but patients treated with TNI were younger, had better performance status and higher stage of disease compared to patients treated with EFI. In multivariate analysis, only age at diagnosis (p<0.001, relative risk [RR] 1.06) and Karnofsky performance status (p = 0.04, RR = 0.96) were significantly correlated with OS. Freedom from progression (FFP) was 58% and 56% after 10-years and 15-years, respectively. Recurrences outside the irradiated volume were significantly reduced after TNI compared to EFI; however, increased rates of in-field recurrences and extra-nodal out-of-field recurrence counterbalanced this effect resulting in no significant difference in FFP between TNI and EFI. In univariate analysis, FFP was significantly improved in stage I compared to stage II but no differences were observed between stages I/II and stage III. In multivariate analysis no patient or treatment parameter was correlated with FFP. Acute toxicity was significantly increased after TNI compared to EFI with a trend to increased late toxicity as well. Conclusions: Radiotherapy alone for stage I and II follicular lymphoma resulted in long-term OS with high rates of disease control; no benefit of TNI over EFI was observed. For stage III follicular lymphoma, TNI achieved promising OS and FFP and should be considered as a potentially curative treatment option. KW - Medizin KW - Follicular lymphoma KW - Total nodal irradiation KW - Extended field irradiation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75702 ER - TY - JOUR A1 - Sweeney, Reinhart A. A1 - Seubert, Benedikt A1 - Stark, Silke A1 - Homann, Vanessa A1 - Müller, Gerd A1 - Flentje, Michael A1 - Guckenbeger, Matthias T1 - Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors N2 - Background: To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors. Materials and methods: Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results. Results: Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs. Conclusions: Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability. KW - Medizin KW - Lung cancer KW - Image-guidance KW - Cone-beam CT KW - Inter-observer variability KW - Respiration correlated imaging Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75698 ER -