@article{KaemmererTribiusCohrsetal.2023,
  author    = {K{\"a}mmerer, Peer W. and Tribius, Silke and Cohrs, Lena and Engler, Gabriel and Ettl, Tobias and Freier, Kolja and Frerich, Bernhard and Ghanaati, Shahram and Gosau, Martin and Haim, Dominik and Hartmann, Stefan and Heiland, Max and Herbst, Manuel and Hoefert, Sebastian and Hoffmann, J{\"u}rgen and H{\"o}lzle, Frank and Howaldt, Hans-Peter and Kreutzer, Kilian and Leonhardt, Henry and Lutz, Rainer and Moergel, Maximilian and Modabber, Ali and Neff, Andreas and Pietzka, Sebastian and Rau, Andrea and Reichert, Torsten E. and Smeets, Ralf and Sproll, Christoph and Steller, Daniel and Wiltfang, J{\"o}rg and Wolff, Klaus-Dietrich and Kronfeld, Kai and Al-Nawas, Bilal},
  title     = {Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1) — a prospective multicentric cohort study},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {6},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15061833},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311024},
  year      = {2023},
  abstract  = {(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.},
  language  = {en}
}
@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}
}
@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{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{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{WiegeringRiedmeierThompsonetal.2022,
  author    = {Wiegering, Verena and Riedmeier, Maria and Thompson, Lester D. R. and Virgone, Calogero and Redlich, Antje and Kuhlen, Michaela and Gultekin, Melis and Yalcin, Bilgehan and Decarolis, Boris and H{\"a}rtel, Christoph and Schlegel, Paul-Gerhardt and Fassnacht, Martin and Timmermann, Beate},
  title     = {Radiotherapy for pediatric adrenocortical carcinoma - Review of the literature},
  series = {Clinical and Translational Radiation Oncology},
  volume    = {35},
  journal   = {Clinical and Translational Radiation Oncology},
  doi       = {10.1016/j.ctro.2022.05.003},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300472},
  pages     = {56-63},
  year      = {2022},
  abstract  = {Background and purpose Pediatric adrenocortical carcinoma (pACC) is a rare disease with poor prognosis. Publications on radiotherapy (RT) are scarce. This review summarizes the current data on RT for pACC and possibly provides first evidence to justify its use in this setting. Materials and methods We searched the PubMed and Embase database for manuscripts regarding RT for pACC. Results We included 17 manuscripts reporting on 76 patients treated with RT, after screening 2961 references and 269 full articles. In addition, we added data of 4 unreported pACC patients treated by co-authors. All reports based on retrospective data. Median age at first diagnosis was 11.1 years (70\% female); 78\% of patients presented with hormonal activity. RT was mostly performed for curative intent (78\%). 88\% of RT were administered during primary therapy. The site of RT was predominantly the local tumor bed (76\%). Doses of RT ranged from 15 to 62 Gy (median 50 Gy). Information on target volumes or fractionation were lacking. Median follow-up was 6,9 years and 64\% of the patients died of disease, with 33\% alive without disease. In 16 of 48 patients with available follow-up data after adjuvant RT (33\%) no recurrence was reported and in 3 of 9 patients palliative RT seemed to induce some benefit for the patient. Conclusions Our first systematic review on RT for pACC provides too few data for any general recommendation, but adjuvant RT in patients with high risk might be considered. International collaborative studies are urgently needed to establish better evidence on the role of RT in this rare malignancy.},
  language  = {en}
}
@article{GaabAdolphTippeltetal.2022,
  author    = {Gaab, Christine and Adolph, Jonas E. and Tippelt, Stephan and Mikasch, Ruth and Obrecht, Denise and Mynarek, Martin and Rutkowski, Stefan and Pfister, Stefan M. and Milde, Till and Witt, Olaf and Bison, Brigitte and Warmuth-Metz, Monika and Kortmann, Rolf-Dieter and Dietzsch, Stefan and Pietsch, Torsten and Timmermann, Beate and Str{\"a}ter, Ronald and Bode, Udo and Faldum, Andreas and Kwiecien, Robert and Fleischhack, Gudrun},
  title     = {Local and systemic therapy of recurrent medulloblastomas in children and adolescents: results of the P-HIT-REZ 2005 Study},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {3},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14030471},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254809},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{TamihardjaLutyjKraftetal.2021,
  author    = {Tamihardja, J{\"o}rg and Lutyj, Paul and Kraft, Johannes and Lisowski, Dominik and Weick, Stefan and Flentje, Michael and Polat, B{\"u}lent},
  title     = {Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis},
  series = {Frontiers in Oncology},
  volume    = {11},
  journal   = {Frontiers in Oncology},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2021.764536},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250992},
  year      = {2021},
  abstract  = {Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90\%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1\%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4\%)/115 (34.0\%)/208 (61.5\%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7\% and 75.9\% for all patients. The estimated 5-year bRFS was 93.3\%, 93.4\% and 79.5\% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5\% and 70.0\%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3\% and 5.0\% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6\%/0.3\%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.},
  language  = {en}
}
@article{HenkeNandigamaErguen2020,
  author    = {Henke, Erik and Nandigama, Rajender and Erg{\"u}n, S{\"u}leyman},
  title     = {Extracellular matrix in the tumor microenvironment and its impact on cancer therapy},
  series = {Frontiers in Molecular Biosciences},
  volume    = {6},
  journal   = {Frontiers in Molecular Biosciences},
  number    = {160},
  issn      = {2296-889X},
  doi       = {10.3389/fmolb.2019.00160},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199341},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{KandelsPietschBisonetal.2020,
  author    = {Kandels, Daniela and Pietsch, Torsten and Bison, Brigitte and Warmuth-Metz, Monika and Thomale, Ulrich-Wilhelm and Kortmann, Rolf-Dieter and Timmermann, Beate and Hern{\´a}iz Driever, Pablo and Witt, Olaf and Schmidt, Ren{\´e} and Gnekow, Astrid K.},
  title     = {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},
  series = {International Journal of Cancer},
  volume    = {147},
  journal   = {International Journal of Cancer},
  number    = {12},
  doi       = {10.1002/ijc.33170},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216130},
  pages     = {3471 -- 3489},
  year      = {2020},
  abstract  = {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.},
  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}
}
@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{BratengeierHolubyev2016,
  author    = {Bratengeier, Klaus and Holubyev, Kostyantyn},
  title     = {Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation?},
  series = {Medical Physics},
  volume    = {43},
  journal   = {Medical Physics},
  number    = {11},
  doi       = {10.1118/1.4963806},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186833},
  pages     = {5826-5834},
  year      = {2016},
  abstract  = {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.},
  language  = {en}
}
@article{DrozdSaenkoBrenneretal.2015,
  author    = {Drozd, Valentina M. and Saenko, Vladimir A. and Brenner, Alina V. and Drozdovitch, Vladimir and Pashkevich, Vasilii I. and Kudelsky, Anatoliy V. and Demidchik, Yuri E. and Branovan, Igor and Shiglik, Nikolay},
  title     = {Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0137226},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141863},
  pages     = {e0137226},
  year      = {2015},
  abstract  = {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.},
  language  = {en}
}
@article{KlaesnerBuchmannGemptetal.2015,
  author    = {Kl{\"a}sner, Benjamin and Buchmann, Niels and Gempt, Jens and Ringel, Florian and Lapa, Constantin and Krause, Bernd Joachim},
  title     = {Early [\(^{18}\)F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0141153},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139549},
  pages     = {e0141153},
  year      = {2015},
  abstract  = {Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [\(^{18}\)F]O-(2-[\(^{18}\)F]-fluoroethyl)-L-tyrosine ([\(^{18}\)F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent preoperative [\(^{18}\)F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [\(^{18}\)F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [\(^{18}\)F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48\%) patients and incomplete resection in 6/25 cases (24\%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [\(^{18}\)F]FET-PET seems to be feasible.},
  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{ElMajdoubHunscheIgressaetal.2015,
  author    = {El Majdoub, Faycal and Hunsche, Stefan and Igressa, Alhadi and Kocher, Martin and Sturm, Volker and Maarouf, Mohammad},
  title     = {Stereotactic LINAC-Radiosurgery for Glomus Jugulare Tumors: A Long-Term Follow-Up of 27 Patients},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0129057},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151717},
  pages     = {e0129057},
  year      = {2015},
  abstract  = {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.},
  language  = {en}
}
@phdthesis{Rosenheim2013,
  author    = {Rosenheim, Eva},
  title     = {Operation und adjuvante Bestrahlung bei Oropharynx- und Mundh{\"o}hlenkarzinomen - Klinische Ergebnisse an der Universit{\"a}t W{\"u}rzburg aus den Jahren 1998 - 2010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139429},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Ergebnisse einer retrospektiven Studie an der Universit{\"a}t W{\"u}rzburg: Patienten und Methoden: In einer retrospektiven Studie wurden Einflussfaktoren auf die Lokoregion{\"a}re Kontrolle, das Gesamt{\"u}berleben und das rezidivfreie {\"U}berleben von 106 Patienten, mit histologisch gesicherten Oropharynxkarzinomen (28 T1, 46 T2, 25 T3 und 7 T4 Tumore, mit lymphatischer Beteiligung in 78 F{\"a}llen), mit uni- und multivariaten Analysen untersucht. Das mediane Alter bei Prim{\"a}rdiagnose betrug 55 Jahre. Es wurde eine mediane Nachbeobachtungszeit 36 Monaten erreicht (zwischen 5 bis 126 Monate). In 18 F{\"a}llen (17\%) konnte der Prim{\"a}rtumor in sano entfernt werden (Sicherheitsabstand > 3mm). In 34 F{\"a}llen (32\%) bestand ein knapper Sicherheitsabstand (definitionsgem{\"a}ß < als 3mm) und in 54 F{\"a}llen (51\%) waren die Resektatr{\"a}nder nicht frei von Tumorzellen (R1 Resektion). Patienten, welche eine Chemotherapie aufgrund des erh{\"o}hten Rezidivrisikos erhielten, machten 24\% (25 Patienten) des Patientenkollektivs aus. Behandlungskonzept Das Tumorbett des Prim{\"a}rtumors und die zervikalen lymphatischen Abflussgebiete erhielten mediane Bestrahlungsdosen von 56 Gy (2 Gy/ Behandlung, 5 Fraktionen pro Woche). Patienten mit R0-Resektion erhielten Bestrahlungsdosen von 56-60Gy. Bei Patienten mit knappen Resektatrand wurde das Tumorbett mit einer h{\"o}heren Dosis von 60-66Gy bestrahlt, R1 Resektionen wurden mit einer Boost-Aufs{\"a}ttigung bis zu einer Gesamtdosis von 66-70 Gy behandelt. Patienten im UICC-Stadium 4, mit erh{\"o}htem Rezidivrisiko, machten 24\% (25 Patienten) des Patientenkollektivs aus. Diese Patienten erhielten je nach Nierenfunktion und Blutbild eine zus{\"a}tzliche Chemotherapie mit Cisplatin (40mg/m² w{\"o}chentlich) in 1-4 Zyklen, sowie eine Boost-Aufs{\"a}ttigung des Tumorbettes bis zu einer Gesamtdosis von 66-70 Gy. Ergebnisse der univariaten Analysen mittels Kaplan-Maier Plot Verfahren: lokoregion{\"a}re Kontrolle Mit einer medianen Nachbeobachtungszeit von 36 Monaten wurde eine 5 Jahres Rezidivfreiheit bei 87\% der Patienten erzielt. Davon wurden 80\% der Rezidive innerhalb der ersten 24 Monate diagnostiziert. Bei Patienten mit R0 Status wurde in 16,7 \% ein Rezidiv diagnostiziert, bei Patienten mit R1 Situation in 17\% und bei Patienten mit knappen Resektatrand wurde nur in 6 \% ein Rezidiv diagnostiziert. Als statistisch signifikanter Einflussfaktor des Rezidiv erwies sich nur das Gesamttumorvolumen. Gesamt{\"u}berlebensrate Es wurde eine 3- und 5- Jahres{\"u}berlebensrate von 75\% und 66\% erreicht. Die 5J{\"U}R bez{\"u}glich der Radikalit{\"a}t der Resektion erreichte bei R0 Resektion 61\%, 71\% bei Patienten mit knappen Resektatrand und 65\% bei R1 Situation. Bei Patienten mit einem T1 Tumorstadium ergab sich eine 5J{\"U}R von 82\%, bei T2 67\%, bei T3 52\% und f{\"u}r Patienten im T4 Stadium ergab sich eine 5J{\"U}R von 43 \%. Patienten mit N0-Status verzeichneten eine 5J{\"U}R von 68\%, mit N1-Status 82\%, N2a,b-Status 68\%, N2c-Status 36\% und N3-Status ergab 43\%. Patienten ohne adjuvante Chemotherapie erzielten eine 5J{\"U}R von 69\% und Patienten, die aufgrund des erh{\"o}hten Rezidivrisikos eine Chemotherapie erhielten, erreichten 56\%. Die Einflussgr{\"o}ße der Rezidiventwicklung erbrachte eine 5J{\"U}R von 13\%, wogegen sie bei Patienten ohne Rezidiv 75\% betrug. Patienten, welche einen 2. Tumor entwickelten, verzeichneten eine 5J{\"U}R von 45\% gegen{\"u}ber 71\% bei Patienten ohne 2.Tumor. Der Vergleich der Bestrahlungsdosen im Tumorbett ergab, dass Patienten mit einer Gesamtdosis unter/gleich 66Gy eine 5J{\"U}R von 71\% erreichten und 62\% bei Gesamtdosen {\"u}ber 66Gy. Die 5J{\"U}R bez{\"u}glich des Tumorvolumens des Prim{\"a}rtumors, inklusive der befallenen Lymphknoten, erbrachte in der ersten Gruppe von unter 10ml Tumorvolumen 77\%, von 10 bis 20ml 83\%, von 20 bis 50ml 52\% und in der vierten Gruppe mit {\"u}ber 50ml Tumorvolumen 33\%. Mit einem Grading von 2 wurde 69\% und mit einem Grading von 3 wurde bei Patienten eine 5J{\"U}R von 61\% berechnet. In der univariaten Analyse mittels des Kaplan-Maier-Plot-Verfahrens, zeigte sich in der 5-Jahres {\"U}berlebenskurve eine Signifikanz der Einflussgr{\"o}ßen Tumorstadium (p-Wert 0,003), Rezidivereignis (p-Wert 0,000), 2.Tumor (p-Wert 0,001) und Tumorvolumen (p-Wert 0,000). Rezidivfreies {\"U}berleben Das rezidivfreie {\"U}berleben betrug nach 3 Jahren 68\% und nach 5 Jahren 64\%. Bez{\"u}glich der Radikalit{\"a}t der Resektion ermittelte man f{\"u}r Patienten mit R0 Resektion nach 5 Jahren ein rezidivfreies {\"U}berleben von 61\%, 71\% bei knappen Resektatrand und 61\% bei R1 Situation. Patienten mit einem T1 Stadium erreichten ein 5 j{\"a}hriges rezidivfreies {\"U}berleben in 82\%, mit T2 Stadium 67\%, mit T3 Stadium 48\% und Patienten im T4 Tumorstadium erzielten 43 \%. Patienten mit N0-Status verzeichneten ein 5 j{\"a}hriges rezidivfreies {\"U}berleben von 64\%, mit N1-Status 82\%, N2a,b-Status 68\%, N2c-Status 27\% und ein N3-Status ergab 43\%. Patienten ohne adjuvante Chemotherapie erreichten in 68\% und Patienten, welche eine Chemotherapie erhielten, erreichten ein 5 j{\"a}hriges rezidivfreies {\"U}berleben in 52\%. Patienten, welche einen 2. Tumor entwickelten, verzeichneten eine 5 j{\"a}hriges rezidivfreies {\"U}berleben von 45\%, gegen{\"u}ber 68\% bei Patienten ohne 2.Tumor. Die Gegen{\"u}berstellung der Bestrahlungsdosen im Tumorbett ergab, dass Patienten mit einer Gesamtdosis unter/gleich 66Gy ein rezidivfreies 5-j{\"a}hriges {\"U}berleben von 69\% erreichten, hingegen Patienten mit mehr als 66Gy Bestrahlungsdosis 60\% erzielten. Das 5 j{\"a}hrige rezidivfreie {\"U}berleben in Bezug auf das Tumorvolumen des Prim{\"a}rtumors, inklusive der befallenen Lymphknoten, erbrachte in der ersten Gruppe von unter 10ml Tumorvolumen 77\%, von 10 bis 20ml 79\%, in der dritten Gruppe von 20 bis 50ml 48\% und in der vierten Gruppe mit {\"u}ber 50ml Tumorvolumen wurde nach 5 Jahren ein rezidivfreies {\"U}berleben von 33\% verzeichnet. Mit einem Grading von 2, wurde 66\% und mit einem Grading von 3 ergaben sich f{\"u}r die Patienten ein 5 j{\"a}hriges rezidivfreies {\"U}berleben von 61\%. In der univariaten Analyse mittels des Kaplan-Maier-Plot-Verfahren, zeigte sich in der Kurve f{\"u}r das 5-j{\"a}hrige rezidivfreie {\"U}berleben, eine Signifikanz der Einflussgr{\"o}ßen Tumorstadium (p-Wert 0,003), Lymphknotenstatus (p-Wert 0,048), Chemotherapie (p-Wert 0,047), 2.Tumor (p-Wert 0,003) und Tumorvolumen (p-Wert 0,000). Ergebnisse der multivarianten Analysen In einer multivariaten Cox-Regressions Analyse erwiesen sich die Einflussgr{\"o}ßen des Tumorstadiums und die Entwicklung eines 2. Tumors, bez{\"u}glich des Gesamt- und des rezidivfreien {\"U}berlebens, als statistisch signifikant. Das Tumorstadium konnte, in Bezug auf das Gesamt{\"u}berleben, eine Signifikanz von 0,015 ermittelt werden. Im Hinblick auf das rezidivfreie {\"U}berleben konnte ihm eine Signifikanz von 0,03 zugeschreiben werden. Die Einflussgr{\"o}ße des 2.Tumors ergab f{\"u}r das Gesamt{\"u}berleben eine Signifikanz von ebenfalls 0,015 und eine Signifikanz von 0,025 bez{\"u}glich des rezidivfreien {\"U}berlebens. Schlussfolgerung: Mit dem Therapiekonzept konnte eine Verbesserung der 5J{\"U}R und des 5-j{\"a}hrigen rezidivfreien {\"U}berlebens erzielt werden. Die Patienten mit knappen Resektatrand wiesen durchweg bessere Ergebnisse auf als Patienten mit R0-Resektion. Als Konsequenz dieser Ergebnisse m{\"u}sste man eine Angleichung des bisherigen Therapiekonzeptes der R0 Patienten an das der knapp resezierten Patienten vornehmen. Bei Patienten mit einem prim{\"a}r erh{\"o}htem Rezidivrisiko, welche eine simultane Radiochemotherapie erhielten, erzielte man mit diesem Therapiekonzept eine Angleichung der 5J{\"U}R an Patienten ohne dieses. Es zeigte sich hierbei in der multivariaten Analyse, sowohl beim Gesamt{\"u}berleben, als auch beim rezidivfreien {\"U}berleben kein statistisch signifikanter Unterschied (Gesamt{\"u}berleben p-Wert 0,064, rezidivfreies {\"U}berleben p-Wert 0,085).},
  subject      = {Oropharynx-Karzinom},
  language  = {de}
}
@article{SaidPolatSteinetal.2012,
  author    = {Said, Harun M. and Polat, Buelent and Stein, Susanne and Guckenberger, Mathias and Hagemann, Carsten and Staab, Adrian and Katzer, Astrid and Anacker, Jelena and Flentje, Michael and Vordermark, Dirk},
  title     = {Inhibition of N-Myc down regulated gene 1 in in vitro cultured human glioblastoma cells},
  series = {World Journal of Clinical Oncology},
  volume    = {3},
  journal   = {World Journal of Clinical Oncology},
  number    = {7},
  doi       = {10.5306/wjco.v3.i7.104},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123385},
  pages     = {104-110},
  year      = {2012},
  abstract  = {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.},
  language  = {en}
}
@article{vanOorschotBeckmannSchulzeetal.2011,
  author    = {van Oorschot, Birgitt and Beckmann, Gabriele and Schulze, Wolfgang and Rades, Dirk and Feyer, Petra},
  title     = {Radiotherapeutic options for symptom control in breast cancer},
  series = {Breast Care},
  volume    = {6},
  journal   = {Breast Care},
  number    = {1},
  issn      = {1661-3791},
  doi       = {10.1159/000324564},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199105},
  pages     = {14-19},
  year      = {2011},
  abstract  = {The majority of breast cancer patients will require radiation therapy at some time during the course of their disease. An estimated 30-50\% of all radiation treatments are of palliative nature, either to alleviate symptoms or prophylactic to prevent deterioration of quality of life due to locally progressive disease. Radiotherapy is a locally effective tool, and typically causes no systemic and mostly mild acute side effects. The following article provides an overview of options and decision-making in palliative radiotherapy for symptom control.},
  language  = {en}
}
@phdthesis{Schramm2008,
  author    = {Schramm, Stefanie},
  title     = {{\"U}berleben und Lebensqualit{\"a}t sprechen f{\"u}r ein konservatives Therapiekonzept bei Patienten mit Magenlymphomen : Ergebnisse einer prospektiven randomisierten Studie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30698},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Gastrointestinale Lymphome des MALT sind heute als eigenst{\"a}ndige Entit{\"a}t anerkannt. Sie zeichnen sich durch morphologische, molekularbiologische, {\"a}tiopathogenetische und biologische Besonderheiten aus, die sie von den nodalen Lymphomen abgrenzen lassen. Im Rahmen der W{\"u}rzburger Multicenterstudie „Gastrointestinale Lymphome II" soll die Frage gekl{\"a}rt werden, ob in den lokalisierten Stadien I und II prim{\"a}rer Magenlymphome unter Ber{\"u}cksichtigung der posttherapeutischen Lebensqualit{\"a}t der operativen oder einer prim{\"a}r konservativen Therapie (Chemo- oder Radiotherapie) Vorzug gegeben werden soll. Von 1998 bis 2002 wurden dazu 49 Patienten mit neu diagnostiziertem niedrig- (n=19) oder hochmalignen (n=30) NHL des Magens in die Studie eingeschlossen. Nach zentraler Randomisierung wurden die Patienten mit low grade NHL der Operation (n=10) oder der Radiotherapie (n=9) zugeteilt. Die Patienten mit high grade NHL erhielten Operation plus Chemotherapie (n=16) oder alleinige Chemotherapie (n=14). Das mediane follow up betrug 74 Monate. Sowohl das operative als auch das konservative Vorgehen zeigten bei beiden Lymphomhistologien {\"u}beraus hohe Remissionsraten in den Stadien EI und EII (CR um 90\%). Unterschiede zwischen den Behandlungsmethoden konnten, evtl. auch bedingt durch die kleinen Gruppengr{\"o}ßen, nicht nachgewiesen werden. Insgesamt verstarben sechs Patienten, die sich in etwa gleichm{\"a}ßig auf die Gruppen verteilten. Die Auswertung der Frageb{\"o}gen zur Lebensqualit{\"a}t ergab gem{\"a}ß SF-36 durchaus hohe Werte zur posttherapeutischen Lebensqualit{\"a}t. Eine Differenzierung der Patienten nach Behandlungsmethode oder Malignit{\"a}tsgrad (low, high grade) war nicht m{\"o}glich. Der Lebensqualit{\"a}tsindex nach Troidl ließ einen pr{\"a}-post-therapeutischen Vergleich zu: Betrachtet man die Kombination von Therapie und Malignit{\"a}tsgrad, so fallen konservativ therapierte Patienten (unabh{\"a}ngig vom Malignit{\"a}tsgrad) durch deutlich ansteigende Lebensqualit{\"a}t auf. Es l{\"a}sst sich festhalten, dass bei prim{\"a}r gastrointestinalen Lymphomen sowohl mit operativem als auch konservativem Vorgehen hohe Remissionsraten erzielt werden k{\"o}nnen. Jedoch sind im Hinblick auf Organerhalt und die h{\"o}here post-therapeutische Lebensqualit{\"a}t die prim{\"a}re Radio- und/oder Chemotherapie dem operativen Vorgehen vorzuziehen.},
  subject      = {Non-Hodgkin-Lymphom},
  language  = {de}
}
@phdthesis{Wirth2008,
  author    = {Wirth, Susanne},
  title     = {Postoperative Strahlentherapie des Prostatakarzinoms in Nordbayern: "Patterns of Care" 1998 - 2000 multizentrische retrospektive Analyse von 134 Patienten in Nordbayern},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34197},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Ziel der vorliegenden Arbeit war die Analyse der Versorgungsstrukturen in der postoperativen Strahlentherapie des Prostatakarzinoms in Nordbayern, um f{\"u}r den Behandlungszeitraum von 1998 bis 2000 Patientenselektion, Behandlungskonzepte und Ergebnisse auf der Ebene eines regionalen Qualit{\"a}tszirkels zu charakterisieren. Hierf{\"u}r wurden die Daten von 134 in kurativer Absicht postoperativ perkutan bestrahlter Patienten aus den strahlentherapeutischen Abteilungen von vier fr{\"a}nkischen Kliniken ausgewertet. Als Endpunkte dieser Patterns of Care Studie wurden das Gesamt{\"u}berleben und die biochemische Kontrolle (ASTRO-Kriterien mit R{\"u}ckdatierung) analysiert. Bei der Datenauswertung wurde evident, dass das untersuchte Patientenkollektiv eine ausgepr{\"a}gte Heterogenit{\"a}t bez{\"u}glich der klinischen Eigenschaften aufweist. Diese Studie offenbart somit, dass die Zuweiser im Untersuchungszeitraum die Patienten anhand unterschiedlicher Kriterien sowohl zur Operation als auch zur postoperativen Strahlentherapie selektierten. So differierten Resektionsgrad sowie initialer PSA-Wert zwischen den beteiligten Zentren signifikant. Wesentlich homogener erschien das Patientengut im Hinblick auf Alter, Gleason-Score sowie den pT- und pN- Stadien. Die vorliegende Analyse dokumentiert dar{\"u}ber hinaus die unterschiedlichen strahlentherapeutischen Konzepte im Untersuchungszeitraum von 1998-2000. Ein signifikanter Unterschied zwischen den Zentren im Behandlungsregime ergab sich in der Zielvolumendefinition, wohingegen die applizierten Gesamtdosen vergleichbar waren. Die mittlere Nachbeobachtungszeit lag insgesamt bei 4,8 Jahren. Die aktuarische biochemische Kontrolle nach 5 Jahren betrug 82,1\%. Sie variierte zwischen den Zentren nicht signifikant von 63,8\% bis 100\%. Bei multivariater Analyse zeigte sich, dass die biochemische Kontrolle mit dem Alter und dem initialen PSA-Wert assoziiert war. Das 5-Jahres-Gesamt{\"u}berleben betrug 93,9\% und variierte ebenfalls nicht signifikant zwischen 88,9\% (Zentrum 3) und 94,7\% (Zentrum 4). Die Erfassung von Akut- und Sp{\"a}ttoxizit{\"a}ten waren nicht Gegenstand der vorliegenden Untersuchung. Die von Zentrum zu Zentrum unterschiedliche Form der Dokumentation von Akutreaktionen w{\"a}hrend der Strahlentherapie sowie die nur in geringem Umfange vorliegenden Angaben zu Sp{\"a}tfolgen der Strahlentherapie ließen eine einheitliche Graduierung sowie eine Vergleichbarkeit von Toxizit{\"a}tsdaten zwischen den Zentren als nicht realistisch erscheinen. Abschließend l{\"a}sst sich festhalten, dass die Daten eine sehr heterogene Indikationsstellung und insbesondere im Hinblick auf die Zielvolumendefinition eine heterogene Durchf{\"u}hrung der postoperativen Strahlentherapie dokumentieren. Dies mag darin mitbegr{\"u}ndet sein, dass zum Untersuchungszeitraum keine einheitlichen Leitlinien f{\"u}r das Prostatakarzinom verf{\"u}gbar waren. Ziele der evidenzbasierten Medizin k{\"o}nnten somit zuk{\"u}nftig sein, Kriterien f{\"u}r eine verbesserte Patientenselektion zu finden und therapeutische Richtlinien in die Praxis zu transferieren. Vielf{\"a}ltige Diskussionen, beispielsweise der Zielvolumendefinition sowie der Therapiealternativen sind gegenw{\"a}rtig am Beginn. Weitere klinische Studien werden initiiert und deren Ergebnisse abgewartet werden m{\"u}ssen, bis validierte Empfehlungen als Standards etabliert werden k{\"o}nnen.},
  subject      = {Prostatakarzinom},
  language  = {de}
}
@phdthesis{Klingelhoeffer2006,
  author    = {Klingelh{\"o}ffer, Christoph},
  title     = {Untersuchung zur Lebensqualit{\"a}t nach neoadjuvanter Chemotherapie und Radiatio bei fortgeschrittenen Larynx- und Hypopharynxkarzinomen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-20134},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Diese Studie stellt die Lebensqualit{\"a}t und den Gesundheitszustand von Patienten mit einem fortgeschrittenen Larynx- oder Hypopharynxkarzinom nach neoadjuvanter Chemotherapie und Radiatio dar. Hierbei wird auf verschiedene Teilbereiche der Auswirkungen dieser Erkrankung eingegangen, die individuell den Grad der Lebensqualit{\"a}t beeinflussen. Die Werte geben die durchschnittliche Meinung des Patientenkollektivs wieder und k{\"o}nnen somit nur gemeinsame Tendenzen hervorbringen. Die Patienten gaben an, nur eine geringe Minderung ihrer Lebensqualit{\"a}t durch die Erkrankung festzustellen. {\"U}ber 60\% des Patientenkollektivs sch{\"a}tzten ihre Lebensqualit{\"a}t bzw. ihren Gesundheitszustand als sehr gut oder nur wenig beeintr{\"a}chtigt ein. Das Patientenkollektiv best{\"a}tigt durch seinen hohen Nikotin- und Alkoholkonsumenten-anteil die Risikofaktoren f{\"u}r diese Erkrankung. Leider konnte der Großteil der Patienten nicht dazu bewegt werden, das Alkoholgenussverhalten zu {\"u}berdenken und es deutlich zu reduzieren. Die Notwendigkeit, den Nikotinkonsum einzuschr{\"a}nken, wurde eher akzeptiert. Im Hinblick auf die alternative operative Entfernung des Prim{\"a}rtumors und damit des Kehlkopfes, war die erneute Entscheidung f{\"u}r die konservative Therapie f{\"u}r die meisten Patienten eindeutig. Auch die Aufkl{\"a}rung wurde in der Regel positiv bewertet. Der hohe Stellenwert einer erhaltenen Kommunikationsf{\"a}higkeit ist f{\"u}r die Patienten der ausschlaggebende Punkt, sich wieder f{\"u}r diese Therapie zu entscheiden. Das Symptom der Xerostomie bereitet den Patienten die gr{\"o}ßten Schwierigkeiten. Die Auswirkung auf andere Bereiche wie verminderte Gleitf{\"a}higkeit der Speisen, schlechterer Prothesensitz und verst{\"a}rkte Zerkleinerung der Speisen sind hier zu ber{\"u}cksichtigen. Eine erh{\"o}hte psychische Belastung ist die Folge, die auch das Sozialleben der Patienten beeinflusst. Dies zeigte sich vor allem in der Frage nach Genuss von Essen in der Gesellschaft. 44 \% vermieden es, in der {\"O}ffentlichkeit zu essen oder schr{\"a}nkten es zumindest stark ein. H{\"a}ufiger traten Ver{\"a}nderungen der Stimme auf. Sie waren vor allem durch Heiserkeit bedingt. Die Betroffenen wurden jedoch dadurch nur im geringen Maße gest{\"o}rt. Einschr{\"a}nkungen in der Kopf- und Armbewegung stellen sich aufgrund der nichtoperativen Therapie als geringf{\"u}giges Problem dar. Dies tr{\"a}gt dazu bei, dass nur wenige Einschr{\"a}nkungen im Bereich Mobilit{\"a}t bzw. Arbeitsf{\"a}higkeit zu verzeichnen waren. Eine geringere Abh{\"a}ngigkeit von den Angeh{\"o}rigen ist die Folge, was die Selbstst{\"a}ndigkeit der Patienten erh{\"a}lt und gleichzeitig psychische Belastungen abbaut. Andere Symptome wie Schmerzen, Kieferklemme, Entz{\"u}ndungen im Mund- und Rachenraum kommen aufgrund der bereits durchschnittlich l{\"a}ngeren Genesungsphase nur selten vor.},
  language  = {de}
}
@phdthesis{Mueller2004,
  author    = {M{\"u}ller, Matthias},
  title     = {Vergleich von in-vitro-Ergebnissen im Mikrokerntest und den klinischen Beobachtungen nach Bestrahlung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-10212},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Hintergrund: Mikrokerne sind Chromosomenfragmente, die nicht in den Hauptkern integriert wurden und im Zytoplasma von proliferierenden Zellen nach ionisierender Strahlung oder Behandlung mit mutagensierenden Substanzen zu finden sind. In vielen F{\"a}llen konnte gezeigt werden, dass die Mikrokernfrequenz als Indikator f{\"u}r den strahleninduzierten Schaden dienen kann. Humane Lymphozyten und Fibroblasten von Patientinnen mit Brustkrebs nach Brusterhaltender Therapie wurden bestrahlt, im Mikrokerntest ausgewertet und die Ergebnisse mit den klinischen Akutreaktionen verglichen. Methode: Beide Zelltypen der 24 Patientinnen mit dem selben Bestrahlungsproceder (50 Gy + 10 Gy Boost) und ohne Chemotherapie wurden untersucht. Die Normalgewebsreaktionen wurden unter Verwendung der RTOG-Kriterien bestimmt. Die Zellen wurden in vitro mit 0-, 1-, 2-Gy-Einmaldosis-Bestrahlung (Lymphozyten) bzw. 0-, 2-, 4-Gy-Einmaldosis-Bestrahlung behandelt, {\"u}ber 72 h kultiviert, auf Objekttr{\"a}gern fixiert und bei 400 - 1000facher Vergr{\"o}ßerung (Fluoreszenzmikroskop) ausgewertet. Die Zellteilung der Lymphozyten wurde mittels Cytochalasin B (Cyt B) inhibiert. Ergebnisse: Es konnte keine signifikante Korrelation der in-vitro-Strahlenempfindlichkeit und den Normalgewebsreaktionen beobachtet werden. Des weiteren wurde kein Zusammenhang zwischen der Strahlenempfindlichkeit der lymphozyten und den Fibroblasten, die vom selben Spender gewonnen wurden, beobachtet. Zusammenfassung: Die Daten unterst{\"u}tzen nicht den Nutzen des Mikrokern-Testes in der Vorhersage von Normalgewebsreaktionen auf die Strahlentherapie bei Malignompatienten.},
  language  = {de}
}
@phdthesis{Popp2003,
  author    = {Popp, Karoline},
  title     = {Die Lagevariabilit{\"a}t des Ring-Stift-Applikators bei der Brachytherapie zur Prim{\"a}rbehandlung des Zervix-Karzinoms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-4947},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Die prim{\"a}re Strahlentherapie des Zervix-Karzinoms unter kurativer Absicht besteht immer aus einer Kombination aus Tele- und Brachytherapie. Aus strahlenbiologischen Gr{\"u}nden ist dabei die Ausblendung des Brachytherapie-Volumens zeitlich vor Beginn oder zumindest vor Abschluß der intrauterinen Bestrahlung erforderlich. Aus diesem Grund ist die prospektive Kenntnis der m{\"o}glichen Variabilit{\"a}t der Applikatorlage und damit der r{\"a}umlichen Dosisverteilung von großer Bedeutung. In der vorliegenden Arbeit wurde daher die Applikatorlage und ihre Variabilit{\"a}t bei 92 Patientinnen mit jeweils f{\"u}nf intrauterinen Bestrahlungen retrospektiv untersucht. Mit Hilfe orthogonaler R{\"o}ntgenaufnahmen von ventral und seitlich wurde die Applikatorlage relativ zu kn{\"o}chernen Referenzstrukturen des Beckens bestimmt. Der Applikatorursprung lag im Mittel 14mm kaudal der H{\"u}ftpfannenebene (55mm kaudal bis 23mm kranial, SD 14mm), 1mm rechts der Beckenmitte (27mm links bis 23mm rechts, SD 6mm) und 26mm dorsal der H{\"u}ftkopfmitte (6-53mm dorsal, SD 8mm). Daraus resultierte eine interindividuelle Lagevariabilit{\"a}t von 78mm in kraniokaudaler Richtung, 50mm in lateraler Richtung und 47mm in ventrodorsaler Richtung. Insgesamt betrug die intraindividuelle Variabilit{\"a}t der Applikatorlage unabh{\"a}ngig von einer bestimmten Applikation im Mittel 14mm (2-36mm, SD 6mm) in kraniokaudaler Richtung, 6mm (2-23mm, SD 3mm) in lateraler Richtung und 10mm (2-34mm, SD 6mm) in ventrodorsaler Richtung. Die erste Brachytherapie-Applikation sollte demnach kurz vor der geplanten Ausblendung des Brachytherapie-Volumens aus dem der Teletherapie erfolgen. Die Gr{\"o}ße des Blockes richtet sich dann nach der Referenzisodose des Applikatorsystems mit einem Sicherheitsabstand von 2 SD in jeder Richtung, d.h. 24mm in kraniokaudaler und 12mm in lateraler Richtung.},
  language  = {de}
}
@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}
}