TY - JOUR A1 - Sabel, Magnus A1 - Fleischhack, Gudrun A1 - Tippelt, Stephan A1 - Gustafsson, Göran A1 - Doz, François A1 - Kortmann, Rolf A1 - Massimino, Maura A1 - Navajas, Aurora A1 - von Hoff, Katja A1 - Rutkowski, Stefan A1 - Warmuth-Metz, Monika A1 - Clifford, Steven C. A1 - Pietsch, Torsten A1 - Pizer, Barry A1 - Linnering, Birgitta T1 - Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study JF - Journal of Neurooncology N2 - The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 +/- 2 % and 78 +/- 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. > 5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 +/- 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour. KW - High-dose chemotherapy KW - Childhood medulloblastoma KW - Adolescents KW - Primitive neuroectodermal KW - Tumors KW - Recurrent medulloblastoma KW - Childrens-cancer KW - Phase-II KW - Trial KW - Therapy KW - Reirradiation KW - Medulloblastoma KW - Relapse KW - Survival KW - Treatment KW - Clinical trial KW - Chemotherapy KW - Radiotherapy KW - Paediatric KW - Secondary tumours Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187498 VL - 129 IS - 3 ER - TY - THES A1 - Wolfschmidt, Franziska T1 - Radio- und/oder Chemotherapie-induzierte Ototoxizität bei Kindern mit Medulloblastom im Alter von 4 bis 21 Jahren, die im Rahmen der Studie HIT 2000 - AB 4 mit postoperativer normofraktionierter bzw. hyperfraktionierter Bestrahlung und anschließender Erhaltungschemotherapie behandelt wurden T1 - Radiation and/or Chemotherapy induced Ototoxicity in Children with Medulloblastoma N2 - Radio- und/oder Chemotherapie-induzierte Ototoxizität bei Kindern mit Medulloblastom im Alter von 4 bis 21 Jahren, die im Rahmen der Studie HIT 2000 – AB 4 mit postoperativer normofraktionierter bzw. hyperfraktionierter Bestrahlung und anschließender Erhaltungschemotherapie behandelt wurden. N2 - Radiation and/or chemotherapy induced ototoxicity in children with medulloblastoma aged 4 to 21 years treated within the study HIT 2000 - AB 4 with postoperative normofractionated or hyperfractionated radiation and following maintenance chemotherapy. KW - Ototoxizität KW - Cisplatin KW - Ototoxizität KW - Cisplatin KW - Medulloblastom KW - HIT KW - Hörverlust KW - Radiotherapie KW - Ototoxicity KW - Medulloblastoma KW - Radiotherapy KW - HIT KW - Hearing Impairment KW - Cisplatin Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73144 ER - TY - THES A1 - Heilmann, Katrin Monika T1 - Pulmonale Strahlenreaktion und Tumoransprechen nach stereotaktischer Bestrahlung von Lungentumoren : Eine computertomographische Verlaufsbeobachtung T1 - Pulmonary injury and tumor response after stereotactic body radiation therapy. Results of a follow-up CT study N2 - Die hypofraktionierte stereotaktische Bestrahlung erlaubt eine präzise hochdosierte und kleinvolumige Radiotherapie umschriebender Raumforderungen mit Tumorkontrollen größer 90% bei peripheren Lungentumoren. Berichtet wird über 70 Patienten mit 86 pulmonalen Läsionen in der Lunge (35 Bronchialkarzinome NSCLC, 51 Metastasen), die zwischen 1997 und 2005 an der Klinik für Strahlentherapie (Universität Würzburg) stereotaktisch bestrahlt wurden. Die Patienten wurden hypofraktioniert mit 3 x 10-12,5 Gy oder mit 1 x 26 Gy (Einzeitbestrahlung) therapiert. Die Morpholgie der pulmonalen Strahlenreaktion sowie deren zeitlicher Verlauf wurden ebenso wie das Tumoransprechen anhand von 346 Verlauf-CTs qualitativ und semiquantitativ ausgewertet. In der Diskussion wurden diese Ergebnisse mit Publikationen zu diesem Thema nach konventioneller Bestrahlung verglichen. Es zeigte sich eine günstiges Verhältnis zwischen Tumorwirksamkeit und Strahlenpneumonitis. N2 - The purpose was to evaluate the CT morphological pattern of tumor response and pulmonary injury after stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC) and pulmonary metastases. Seventy patients (lesions n = 86) with pulmonary metastases (n = 51) or primary early stage NSCLC (n = 35) were analyzed. Patients were treated with hypofractionated SBRT (3 x 10-12,5 Gy; n = 53) or with radiosurgery (1 x 26 Gy; n = 33). The pattern and sequence of pulmonary injury and of tumor response was evaluated in 346 follow-up CT studies, 4.7 on average. No pulmonary reaction was observed in most patients six weeks after treatment. Spotted-streaky condensations were characteristic between three and six months. Dense consolidation and retraction started after nine months. At twelve months complete response was seen in 43% and the differentiation of residual tumor from pulmonary reaction was not possible in 33%. KW - Strahlentherapie KW - Strahlentherapie KW - stereotaktische Bestrahlung KW - Lunge KW - Strahlenpneumonitis KW - Radiotherapy KW - stereotactic body radiation therapy KW - lung KW - radiation pneumonitis Y1 - 2007 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-26452 ER - TY - JOUR T1 - Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials JF - Lancet Oncology N2 - Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21.4% for NACT versus 15.9% for adjuvant chemotherapy (5.5% increase [95% CI 2.4-8.6]; rate ratio 1.37 [95% CI 1.17-1.61]; p = 0.0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38.2% for NACT vs 38.0% for adjuvant chemotherapy; rate ratio 1.02 [95% CI 0.92-1.14]; p = 0.66), breast cancer mortality (34.4% vs 33.7%; 1.06 [0.95-1.18]; p = 0.31), or death from any cause (40.9% vs 41.2%; 1.04 [0.94-1.15]; p = 0.45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. Copyright (c) The Author(s). Published by Elsevier Ltd. KW - Stimulating factor KW - Therapy KW - Methotrexate KW - Radiotherapy KW - Survival KW - Surgery Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227782 VL - 19 IS - 1 ER - TY - THES A1 - Trömel, Jannik T1 - Die strahlentherapeutische Behandlung von Meningeomen an der Klinik für Strahlentherapie des Universitätsklinikums Würzburg von 1994 bis 2014: Klinische Ergebnisse T1 - Radiotherapeutic treatment of meningiomas at the Department of Radiotherapy of the University Hospital of Wuerzburg from 1994 to 2014: clinical results N2 - Es wurden die Daten von 119 Meningeompatienten hinsichtlich der lokalen Kontrolle sowie des Gesamtüberlebens und deren Einflussfaktoren untersucht, um dieses Kollektiv hinsichtlich des Therapieerfolges an der Klinik und Poliklinik für Strahlentherapie der Universität Würzburg auszuwerten. Ferner wurden die akuten und chronischen Nebenwirkungen der Strahlenbehandlung erfasst. Darüber hinaus wurden die Fragebogen QLQ-C30 sowie -BN20 zur Evaluation der Lebensqualität nach der Strahlenbehandlung analysiert. Die Strahlenbehandlung zeigte sich im Rahmen des Follow-Ups von 5,4 Jahren als größtenteils effektive und sichere Behandlungsmethode. Aufgeschlüsselt 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 fünf 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 für die Histologie (p = 0,050), sowie deutliche Signifikanz zwischen benignen und malignen Meningeomen. Das Gesamtüberleben lag nach fünf Jahren bei 89,6% sowie nach zehn Jahren bei 75,9%. Signifikante Einflussfaktoren in der multivariaten Analyse waren die Histologie sowie die Größe 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 Lebensqualitätsdaten mittels der Fragebogen der EORTC an einem reinen Meningeomkollektiv, bei dem alle Patienten eine Strahlenbehandlung erhielten. Diese zeigen schlechtere Werte im Vergleich zur Normalbevölkerung. Ebenso weisen sie auf eine Verschlechterung der Lebensqualität 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 zurückführbar. Um den genauen Stellenwert der Strahlentherapie im Therapieregime der Meningeome abhängig von der Histologie beurteilen zu können sowie diese Ergebnisse zu verifizieren und zu festigen, sind aufwendige prospektive Studien nötig. Diese werden zum Teil aktuell durchgeführt. Regelmäßige Kontrollen der Lebensqualität sowie der Nebenwirkungen sollen erhoben und ausgewertet werden, um die Auswirkungen der Therapie möglichst allumfassend darstellen zu können. N2 - The data of 119 meningioma patients were examined with regard to local control as well as overall survival and their influencing factors in order to evaluate this collective with regard to therapy success at the Clinic and Polyclinic for Radiotherapy of the University of Wuerzburg. Furthermore, the acute and chronic side effects of this radiation treatment were recorded. In addition, the questionnaires QLQ-C30 and -BN20 were analysed to evaluate the quality of life after radiation treatment. The radiation treatment proved to be a largely effective and safe treatment method during the follow-up of 5.4 years. Broken down by WHO grade, local control rates were 93.3% (without histology), 91.2% (WHO grade I), 66.7% (WHO grade II) and 53.1% (WHO grade III) after five years. After ten years the rates were 82.0% (without histology), 91.2% (WHO grade I), 46.7% (WHO grade II) and 42.5% (WHO grade III). The multivariate analysis showed a borderline significant difference in local control for histology (p = 0.050), as well as clear significance between benign and malignant meningiomas. Overall survival was 89.6% after five years and 75.9% after ten years. Significant influencing factors in the multivariate analysis were histology and the size of the GTV. The rate of clinically significant (CTCAE ≥3) acute and chronic adverse events was low (5.9% and 4.2%, respectively) and comparable to the data in the literature. This work provides for the first time quality of life data using the EORTC questionnaires on a collective with just meningioma patients, in which all patients received radiation treatment. These show worse values compared to the normal population. They also indicate a deterioration in quality of life during tumor treatment. However, due to the unique measurement time and the lack of a comparative collective, this cannot be causally attributed to either the surgery or the radiation treatment. Extensive prospective studies are necessary to assess the exact role of radiotherapy in the treatment regime of meningiomas depending on the histology and to verify and consolidate these results. Some of these studies are currently being conducted. Regular controls of the quality of life as well as the side effects should be collected and evaluated in order to be able to present the effects of the therapy as comprehensively as possible. KW - Meningeom KW - Strahlentherapie KW - Lebensqualität KW - Nebenwirkung KW - Bestrahlung KW - Radiotherapy KW - Meningioma KW - Quality of Life KW - Adverse Events KW - Nebenwirkungen Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199956 ER - TY - THES A1 - Stommel, Jörg T1 - Das follikuläre Non-Hodgkin-Lymphom - retrospektive Analyse aus einer strahlentherapeutischen Klinik T1 - The Follicular Non-Hodgkin's Lymphoma - Retrospective Study of the Department of Radiotherapy N2 - Das follikuläre Non-Hodgkin Lymphom macht 20-30% aller NHL aus. Seit Jahren wird weltweit eine steigende Inzidenz festgestellt. In Deutschland wird von einer Inzidenz von ca. 7-10/100.000/Jahr ausgegangen. Damit erkranken pro Jahr wesentlich mehr Patienten am follikulären Lymphom als am Hodgkin-Lymphom. In dieser retrospektiven Studie wurden die Daten von 89 Patienten mit follikulärem Non-Hodgkin-Lymphom ausgewertet, die zwischen 1985 und 2000 in der Klinik und Poliklinik für Strahlentherapie der Universität Würzburg im Rahmen der Primärtherapie bestrahlt wurden. Die Mehrzahl der Patienten befand sich in den klinischen Stadien I und II (67,4%) nach der Ann-Arbor-Klassifikation. 27 Patienten (30,3%) erhielten eine „Total Nodale Bestrahlung“, 49 (55,1%) wurden mit der „Extended-Field-Technik“ behandelt und 13 (14,6%) wurden mit der „Involved-Field-Technik“ bestrahlt. Nach Behandlung konnte bei 73 Patienten (82,0%) Vollremission erreicht werden. Partialremission wurde bei zwölf Patienten (13,5%) erzielt, zur Progression kam es viermal (4,5%). Bei 25 Patienten (28,1% aller Patienten) trat ein Rezidiv des NHL auf, wobei der Mittelwert des rezidivfreien Intervalls 3,3 Jahre betrug. Bei drei Patienten (3/25, 12,0%) lagen die Rezidivlokalisationen ausschließlich innerhalb des Bestrahlungsfeldes. Bei 17 Patienten (17/25, 68,0%) rezidivierten Regionen, die außerhalb des primären Bestrahlungsfeldes lagen. Bei fünf Patienten (5/25, 20,0%) ließen sich sowohl Rezidive „infield“ als auch „outfield“ nachweisen. Die Überlebenswahrscheinlichkeit nach Kaplan-Meier betrug für alle Patienten nach zwei Jahren 97% und nach fünf Jahren 81%. Nach zehn Jahren ergab sich eine ÜR von 61%. Ungünstige prognostische Faktoren bezüglich der Überlebensrate waren Alter >60 Jahre, fortgeschrittenes Stadium, Lymphknotenbefall beidseits des Zwerchfells, extranodaler Befall, Knochenmarkbefall, erniedrigter Hb-Wert und modifizierter Karnofsky-Index >2. Die unterschiedlichen Bestrahlungstechniken („Total Nodale Bestrahlung“, „Extended-Field“, „Involved-Field“) hatten keinen signifikanten Einfluss auf die Überlebensrate oder das rezidivfreie Intervall. Allerdings zeigte sich der Trend zu einer höheren Rezidivfreiheit bei ausgedehnter Bestrahlung. Ebenso konnte kein Vorteil der adjuvanten Chemotherapie gegenüber der alleinigen Strahlentherapie für die Überlebensrate und das rezidivfreie Intervall festgestellt werden, was die Wichtigkeit der Radiatio bei der Behandlung des follikulären Lymphoms unterstreicht. N2 - Follicular Non-Hodgkin’s Lymphomas account for 20-30% of all Non-Hodgkin’s Lymphomas (NHL). A rising incidence could be seen worldwide over the last years. In Germany the current incidence is approximately 7-10/100,000/year. This means that much more patients suffer from follicular NHL than from Hodgkin’s Lymphoma. In this retrospective study the data of 89 patients with follicular NHL were analysed. All patients were treated primarily with radiotherapy at the Department of Radiotherapy at the University Hospital Wuerzburg/Germany. Most patients were diagnosed in the localised stages I and II according to Ann-Arbor-Classification of NHL. 27 patients (30.3%) underwent a “Total Nodal Radiation”, 49 (55.1%) an “Extended Field Radiotherapy” and 13 (14.6%) an “Involved Field Radiotherapy”. Complete remission was achieved in 73 patients (82.0%), partial remission in 12 patients (13.5%) and progression occurred only in 4 patients (4.5%). 25 Patients (28.1%) relapsed after an average intervall of 3.3 years. In most patients (17 patients, 68.0%) relapses occurred outside the radiation field only, 3 patients (20.0%) suffered relapses within the radiation field, 5 patients (20.0%) showed infield and outfield relapses. The 2-year overall survival for all patients was 97%, the 5-year overall survival 81% and the 10-year overall survival 61%. Poor prognostic factors in terms of overall survival include the following: age >60 years, advanced stage, nodal involvement on both sides of the diaphragm, extranodal involvement, bone marrow involvement, low Haemoglobin and modified Karnofsky Index >2. Different radiation techniques (“Total Nodal Radiation”, “Extended Field Radiotherapy”, “Involved Field Radiotherapy”) did not show any statistical significance in terms of overall survival and relapse free survival. Nevertheless there was a clear trend towards a better relapse free survival in patients treated with extended radiation therapy compared to localised radiation only. The adjuvant chemotherapy did not prove to have any impact on overall survival and relapse free survival compared to single radiotherapy. This underlines the importance of radiotherapy in follicular NHL. KW - Follikuläres Non-Hodgkin-Lymphom KW - Strahlentherapie KW - Follicular Non-Hodgkin's Lymphoma KW - Radiotherapy Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-13348 ER - TY - JOUR A1 - Kreissl, Michael C. A1 - Hänscheid, Heribert A1 - Löhr, Mario A1 - Verburg, Frederik A. A1 - Schiller, Markus A1 - Lassmann, Michael A1 - Reiners, Christoph A1 - Samnick, Samuel S. A1 - Buck, Andreas K. A1 - Flentje, Michael A1 - Sweeney, Reinhart A. T1 - Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma N2 - 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. KW - Medizin KW - PRRT KW - Peptide receptor radionuclide therapy KW - Meningioma KW - Radiotherapy KW - EBRT KW - Combination Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75540 ER - TY - JOUR A1 - von Bueren, André O. A1 - Oehler, Christoph A1 - Shalaby, Tarek A1 - von Hoff, Katja A1 - Pruschy, Martin A1 - Seifert, Burkhardt A1 - Gerber, Nicolas U. A1 - Warmuth-Metz, Monika A1 - Stearns, Duncan A1 - Eberhart, Charles G. A1 - Kortmann, Rolf D. A1 - Rutkowski, Stefan A1 - Grotzer, Michael A. T1 - c-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients JF - BMC Cancer N2 - Background: To study whether and how c-MYC expression determines response to radio-and chemotherapy in childhood medulloblastoma (MB). Methods: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio-and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio-and chemotherapy as examined by neuroradiological imaging. Results: In DAOY -and to a lesser extent in UW228 -cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation-and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio-(14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively). Conclusions: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment. KW - Induced apoptosis KW - Down-regulation KW - Childhood medulloblastoma KW - Melanoma-cells KW - Cisplatin KW - Lines KW - Gene KW - Radiotherapy KW - Fibroblasts KW - Activation Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134185 VL - 11 IS - 74 ER - TY - THES A1 - Kraus, Pia T1 - Behandlungsergebnisse maligner Nasenhaupt- und Nebenhöhlentumore T1 - Therapeutic results of patients with cancer ot the nasal and sinunasal cavities N2 - Ziel der Dissertation ist es, die Behandlungsergebnisse von Patienten mit malignen Nasenhaupt- und Nebenhöhlentumore, die zwischen Februar 1990 bis März 2014 unter kurativer Zielsetzung in der Klinik für Strahlentherapie des Universitätskrankenhauses Würzburg behandelt wurden, zu analysieren. Vor 2007 kam eine 3D-CRT Technik zum Einsatz, danach eine IMRT-Bestrahlung, in primärer oder postoperativer Form. Eine Verminderung der Überlebensrate ergab sich bei hohem Gesamttumorvolumen (>60ml), bei primäre Bestrahlung, bei Infiltration des Subkutangewebes, bei einer Fernmetastasierung im Verlauf und wenn keine komplette Remission erreicht wurde. Eine Verschlechterung der lokalen Tumorkontrolle wurde durch ein hohes Gesamttumorvolumen (>60ml) verursacht. Eine Chemotherapie zog keinen Vorteil in den Überlebenszeiten und der lokalen Tumorkontrolle nach sich. Die postoperative Radiotherapie ist die häufigste und zu bevorzugende Therapiemodalität. N2 - To analyse the therapeutic results of patients with malignant cancer of the nasal an paranasal sinuses is the objective of this thesis. Those patients were treated under curative terms in the department of radiotheray in the university hosptial Würzburg between Febuary 1990 and March 2014. Before 2007 a 3D-CRT technique was used, afterwards a IMRT technique. A reduction of survival rates was produced with large tumor volumes (>60ml), with primary radiation, with infiltration of subcutaneous tissue, with distant metastases and if no complete remission was achieved. Local control rates were downgraded by large tumor volumens (>60ml). No positive effects on local control and overall survival were attained by the application of a chemotherapy. Postoperative radiotherapy is the most common and preferred therapeutic modality. KW - Strahlentherapie KW - Radiotherapy KW - IMRT KW - Nasenhaupthöhlentumore KW - Nasennebenhöhlentumore KW - Gesamttumorvolumen Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160525 ER - TY - JOUR A1 - Lewitzki, Victor A1 - Klement, Rainer J. A1 - Kosmala, Rebekka A1 - Lisowski, Dominik A1 - Flentje, Michael A1 - Polat, Bülent T1 - Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma JF - Radiation Oncology N2 - 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. KW - Brain cancer KW - Glioblastoma KW - High grade glioma KW - Radiotherapy KW - Temozolomide KW - Corticosteroids Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202614 VL - 14 ER -