TY - JOUR A1 - Bratengeier, Klaus A1 - Herzog, Barbara A1 - Wegener, Sonja A1 - Holubyev, Kostyantyn T1 - Finer leaf resolution and steeper beam edges using a virtual isocentre in concurrence to PTV-shaped collimators in standard distance – a planning study JF - Radiation Oncology N2 - 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. KW - radiotherapy KW - multi-leaf collimator KW - stereotactic irradiation KW - robotic table motion KW - planning study KW - virtual isocentre Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157543 VL - 12 IS - 88 ER - TY - JOUR A1 - Bratengeier, Klaus A1 - Holubyev, Kostyantyn T1 - Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation? JF - Medical Physics N2 - Purpose: To suggest a definition of dose deposition anisotropy for the purpose of ad hoc adaptation of intensity modulated arc therapy (IMRT) and volumetric arc therapy (VMAT), particularly in the vicinity of important organs at risk (OAR), also for large deformations. Methods: Beam's-eye-view (BEV) based fluence warping is a standard adaptation method with disadvantages for strongly varying OAR shapes. 2-Step-adaptation overcomes these difficulties by a deeper analysis of the 3D properties of adaptation processes, but requires separate arcs for every OAR to spare, which makes it impractical for cases with multiple OARs. The authors aim to extend the 2-Step method to arbitrary intensity modulated plan by analyzing the anisotropy of dose contributions. Anisotropy was defined as a second term of Fourier transformation of gantry angle dependent dose contributions. For a cylindrical planning target volume (PTV) surrounding an OAR of varying diameter, the anisotropy and the dose-normalized anisotropy were analyzed for several scenarios of optimized fluence distributions. 2-Step adaptation to decreasing and increasing OAR diameter was performed, and compared to a usual fluence based adaptation method. For two clinical cases, prostate and neck, the VMAT was generated and the behavior of anisotropy was qualitatively explored for deformed organs at risk. # Results: Dose contribution anisotropy in the PTV peaks around nearby OARs. The thickness of the "anisotropy wall" around OAR increases for increasing OAR radius, as also does the width of 2-Step dose saturating fluence peak adjacent to the OAR K. Bratengeier et al., "A comparison between 2-Step IMRT and conventional IMRT planning," Radiother. Oncol. 84, 298-306 (2007)]. Different optimized beam fluence profiles resulted in comparable radial dependence of normalized anisotropy. As predicted, even for patient cases, anisotropy was inflated even more than increasing diameters of OAR. Conclusions: For cylindrically symmetric cases, the dose distribution anisotropy defined in the present work implicitly contains adaptation-relevant information about 3D relationships between PTV and OAR and degree of OAR sparing. For more complex realistic cases, it shows the predicted behavior qualitatively. The authors claim to have found a first component for advancing a 2-Step adaptation to a universal adaptation algorithm based on the BEV projection of the dose anisotropy. Further planning studies to explore the potential of anisotropy for adaptation algorithms using phantoms and clinical cases of differing complexity will follow. KW - modulated arc therapy KW - 2-step IMRT KW - radiation-therapy KW - online adaption KW - prostate-cancer KW - plans KW - IMAT KW - tracking KW - radiotherapy KW - adaption KW - IMRT KW - VMAT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186833 VL - 43 IS - 11 ER - TY - JOUR A1 - Bratengeier, Klaus A1 - Holubyev, Kostyantyn A1 - Wegener, Sonja T1 - Steeper dose gradients resulting from reduced source to target distance—a planning system independent study JF - Journal of Applied Clinical Medical Physics N2 - 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. KW - radiotherapy KW - stereotactic irradiation KW - penumbra KW - leaf width KW - virtual isocenter Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177424 VL - 20 IS - 1 ER - TY - JOUR A1 - Drozd, Valentina M. A1 - Saenko, Vladimir A. A1 - Brenner, Alina V. A1 - Drozdovitch, Vladimir A1 - Pashkevich, Vasilii I. A1 - Kudelsky, Anatoliy V. A1 - Demidchik, Yuri E. A1 - Branovan, Igor A1 - Shiglik, Nikolay T1 - Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role? JF - PLoS One N2 - One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (I-131) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the I-131-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer. KW - analysis KW - areas KW - power-station accident KW - iodine nutrition KW - skin hemagioma KW - pooled KW - risk KW - children KW - radiation KW - exposure KW - radiotherapy Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141863 VL - 10 IS - 9 ER - TY - JOUR A1 - El Majdoub, Faycal A1 - Hunsche, Stefan A1 - Igressa, Alhadi A1 - Kocher, Martin A1 - Sturm, Volker A1 - Maarouf, Mohammad T1 - Stereotactic LINAC-Radiosurgery for Glomus Jugulare Tumors: A Long-Term Follow-Up of 27 Patients JF - PLoS ONE N2 - Background The optimal treatment of glomus jugulare tumors (GJTs) remains controversial. Due to the critical location, microsurgery still provides high treatment-related morbidity and a decreased quality of life. Thus, we performed stereotactical radiosurgery (SRS) for the treatment of GJTs and evaluated the long-term outcome. Methods Between 1991 and 2011, 32 patients with GJTs underwent SRS using a linear accelerator (LINAC) either as primary or salvage therapy. Twenty-seven patients (median age 59.9 years, range 28.7-79.9 years) with a follow-up greater than five years (median 11 years, range 5.3-22.1 years) were selected for retrospective analysis. The median therapeutic single dose applied to the tumor surface was 15 Gy (range 11-20 Gy) and the median tumor volume was 9.5 ml (range 2.8-51 ml). Results Following LINAC-SRS, 10 of 27 patients showed a significant improvement of their previous neurological complaints, whereas 12 patients remained unchanged. Five patients died during follow-up due to old age or other, not treatment-related reasons. MR-imaging showed a partial remission in 12 and a stable disease in 15 patients. No tumor progression was observed. The actuarial overall survival rates after five, ten and 20 years were 100%, 95.2% and 79.4%, respectively. Conclusions Stereotactic LINAC-Radiosurgery can achieve an excellent long-term tumor control beside a low rate of morbidity in the treatment of GJTs. It should be considered as an alternative therapy regime to surgical resection or fractionated external beam radiation either as primary, adjuvant or salvage therapy. KW - gamma knife radiosurgery KW - accelerator based radiosurgery KW - radiation therapy KW - temporal bone KW - skull base KW - surgery KW - paragangliomas KW - management KW - radiotherapy KW - head Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151717 VL - 10 IS - 6 ER - TY - JOUR A1 - Fischer, Thomas A1 - Hartmann, Oliver A1 - Reissland, Michaela A1 - Prieto-Garcia, Cristian A1 - Klann, Kevin A1 - Pahor, Nikolett A1 - Schülein-Völk, Christina A1 - Baluapuri, Apoorva A1 - Polat, Bülent A1 - Abazari, Arya A1 - Gerhard-Hartmann, Elena A1 - Kopp, Hans-Georg A1 - Essmann, Frank A1 - Rosenfeldt, Mathias A1 - Münch, Christian A1 - Flentje, Michael A1 - Diefenbacher, Markus E. T1 - PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy JF - Cell & Bioscience N2 - 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. KW - PTEN KW - ATM KW - IR KW - NSCLC KW - radiotherapy KW - cancer KW - DNA-PK KW - PI3K Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299865 SN - 2045-3701 VL - 12 ER - TY - JOUR A1 - Gaab, Christine A1 - Adolph, Jonas E. A1 - Tippelt, Stephan A1 - Mikasch, Ruth A1 - Obrecht, Denise A1 - Mynarek, Martin A1 - Rutkowski, Stefan A1 - Pfister, Stefan M. A1 - Milde, Till A1 - Witt, Olaf A1 - Bison, Brigitte A1 - Warmuth-Metz, Monika A1 - Kortmann, Rolf-Dieter A1 - Dietzsch, Stefan A1 - Pietsch, Torsten A1 - Timmermann, Beate A1 - Sträter, Ronald A1 - Bode, Udo A1 - Faldum, Andreas A1 - Kwiecien, Robert A1 - Fleischhack, Gudrun T1 - Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 Study JF - Cancers N2 - Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9–16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7–10.0) and 18.5 months (CI: 13.6–23.5), respectively. Early relapses/progressions (<18 months, n = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, n = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, n = 47/93) which was 34.8%. Intraventricular (n = 43) as well as high-dose chemotherapy (n = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients' survival. KW - medulloblastoma KW - refractory KW - recurrent KW - children KW - chemotherapy KW - surgery KW - radiotherapy KW - re-irradiation KW - intraventricular therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254809 SN - 2072-6694 VL - 14 IS - 3 ER - TY - THES A1 - Glüer, Wibke T1 - Kosmetische Ergebnisse nach Bestrahlung bei Brusterhaltender Therapie des Mammakarzinoms T1 - Cosmetic results following radiation and breast-conserving therapy N2 - Ziel: Auswirkungen der strahlentherapeutischen Vorgehensweise, insbesondere der lokalen Dosisaufsättigung 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 Universitätsfrauenklinik und der Klinik und Poliklinik für Strahlentherapie der Universität Würzburg 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 Tuorbettaufsättigung (20Gy), entweder als interstitieller Boost mit Ir-192 (77 Prozent) oder als Elektronenboost (16 Prozent). Ergebnisse: Die Überlebensrate betrug nach 5 und 10 Jahren 88 bzw. 73 Prozent. Die lokoregionäre Kontrollrate betrug nach 5 und 10 Jahren 90 und 75 Prozent. Es konnte kein statistisch signifikanter Zusammenhang mit der Art der angewandten Tumorbettaufsättigung 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 gewählten Boostart. N2 - Purpose: Effect of radiotherapy, especially of the type of boost on the late cosmetic outcome and frequency of recurrences after breast-conserving therapy. Methods and materials: 451 patients, treated between 1984-1994 in the Universitätsfrauenklinik and the Klinik und Poliklinik für Strahlentherapie der Universität Würzburg, with evaluable records for cosmetic outcome were analyzed retrospectively. Therapy: All patients had a tumor excision and axillary dissection followed by radiation therapy. The entire breast received an external beam dose of 50Gy. A boost dose of 20Gy to the tumor bed was given with an Ir-192 implant (77 per cent) or with electron beam therapy (16 per cent). Results: The 5- and 10- year survival rates were 88 and 73 per cent. The 5- and 10 year locoregional control rates were 90 and 75 per cent. There were no statistically significant differences wether implant or electron beam were used. 61 Prozent of patients obtained a good or excellent cosmetic result, and no statistically significant differences in cosmetic outcome were seen regardless which of the two methods of therapy was applied. KW - Brustkrebs KW - Strahlentherapie KW - Kosmetik KW - lokale Dosisaufsättigung KW - breast cancer KW - radiotherapy KW - cosmetic KW - boost Y1 - 2000 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-452 ER - TY - JOUR A1 - Henke, Erik A1 - Nandigama, Rajender A1 - Ergün, Süleyman T1 - Extracellular matrix in the tumor microenvironment and its impact on cancer therapy JF - Frontiers in Molecular Biosciences N2 - Solid tumors are complex organ-like structures that consist not only of tumor cells but also of vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differs significantly from that in normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence malignancy and growth of the tumor but also its response toward therapy. Understanding the particularities of the ECM in solid tumor is necessary to develop approaches to interfere with its negative effect. In this review, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radio-, chemo-, and immunotherapy. Finally, we will discuss the various strategies to target and modify the tumor ECM and how they could be utilized to improve response to therapy. KW - extracellular matrix KW - cancer therapy KW - drug transport KW - immunotherapy KW - chemotherapy (CH) KW - radiotherapy KW - tumor microenvironment KW - ECM Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199341 SN - 2296-889X VL - 6 IS - 160 ER - TY - JOUR A1 - Kandels, Daniela A1 - Pietsch, Torsten A1 - Bison, Brigitte A1 - Warmuth‐Metz, Monika A1 - Thomale, Ulrich‐Wilhelm A1 - Kortmann, Rolf‐Dieter A1 - Timmermann, Beate A1 - Hernáiz Driever, Pablo A1 - Witt, Olaf A1 - Schmidt, René A1 - Gnekow, Astrid K. T1 - Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low‐grade glioma patients—Report from the German SIOP‐LGG 2004 cohort JF - International Journal of Cancer N2 - First‐line treatment of pediatric low‐grade glioma using surgery, radio‐ or chemotherapy fails in a relevant proportion of patients. We analyzed efficacy of subsequent surgical and nonsurgical therapies of the German cohort of the SIOP‐LGG 2004 study (2004‐2012, 1558 registered patients; median age at diagnosis 7.6 years, median observation time 9.2 years, overall survival 98%/96% at 5/10 years, 15% neurofibromatosis type 1 [NF1]). During follow‐up, 1078/1558 patients remained observed without (n = 217), with 1 (n = 707), 2 (n = 124) or 3 to 6 (n = 30) tumor volume reductions; 480/1558 had 1 (n = 332), 2 (n = 80), 3 or more (n = 68) nonsurgical treatment‐lines, accompanied by up to 4 tumor‐reductive surgeries in 215/480; 265/480 patients never underwent any neurosurgical tumor volume reduction (163/265 optic pathway glioma). Patients with progressing tumors after first‐line adjuvant treatment were at increased risk of suffering further progressions. Risk factors were young age (<1 year) at start of treatment, tumor dissemination or progression within 18 months after start of chemotherapy. Progression‐free survival rates declined with subsequent treatment‐lines, yet remaining higher for patients with NF1. In non‐NF1‐associated tumors, vinblastine monotherapy vs platinum‐based chemotherapy was noticeably less effective when used as second‐line treatment. Yet, for the entire cohort, results did not favor a certain sequence of specific treatment options. Rather, all can be aligned as a portfolio of choices which need careful balancing of risks and benefits. Future molecular data may predict long‐term tumor biology. KW - chemotherapy KW - pediatric low‐grade glioma KW - progression KW - radiotherapy KW - surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216130 VL - 147 IS - 12 SP - 3471 EP - 3489 ER -