Dirk Vordermark

Universitätsklinikum Halle (Saale), Halle-on-the-Saale, Saxony-Anhalt, Germany

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Publications (146)633.26 Total impact

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    ABSTRACT: Radiooncological therapies are an integral part of the multimodal oncological treatment concepts in general and abdominal surgery. These include therapeutic approaches with a curative intention such as the neoadjuvant (pre-operative) radiotherapy of locoregionally advanced and/or N+ oesophageal and rectal cancer, definitive combined chemoradiotherapy of locally advanced, unresectable oesophageal cancer or oesophageal tumour lesions of the upper third, definitive radiotherapy of anal cancer (sphincter sparing) and pre- or post-operative radiotherapy of soft tissue sarcoma on the one hand. A yT0 stage achieved as characteristic of a curative effect by radiation in oesophageal and rectal cancer (omitting subsequent surgical intervention, naturally under clinical and imaging-based controls within short-term follow-up intervals) can be considered as a very interesting set-up with regard to its reasonable integration in daily clinical practice, which needs to be further and critically discussed. By integrating radiotherapy in interdisciplinary therapy concepts, improved tumour control and survival rates with clinically acceptable toxicity can be achieved. On the other hand, non-invasive, locally ablative radiooncological therapies such as extracranial stereotactic body radiotherapy constitute an effective and feasible treatment method for liver metastases in oligometastatic colorectal cancer or other tumour entities according to the decisions by the institutional tumour board, offering high local tumour control rates which can be part of multistep, multimodal procedures with curative intention. This review aims at providing an overview for the general and abdominal surgeon, outlining relevant radiooncological treatment aspects in the multimodal cancer therapy with a focus on the treatment of rectal, oesophageal and anal cancer as well as soft tissue sarcoma and hepatic metastases in oligometastatic colorectal cancer. Georg Thieme Verlag KG Stuttgart · New York.
    Zentralblatt fur Chirurgie, Supplement 02/2015; 140(1):83-93. DOI:10.1055/s-0034-1383338
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    ABSTRACT: In very elderly cancer patients, health-related quality of life (HRQOL) is a particularly important issue but has rarely been studied due to a lack of specific instruments and of reference data. We performed a prospective analysis of HRQOL in patients ≥80 years undergoing radiotherapy with the newly validated elderly-specific HRQOL module EORTC QLQ-ELD14. We prospectively assessed HRQOL in n = 50 radiotherapy patients ≥80 years (32 % lung, 20 % gastrointestinal, 8 % each of breast, head and neck, gynecologic cancer) at the start (t1), end (t2), and 6 months after (t3) radiotherapy, using EORTC QLQ-C30 and EORTC QLQ-ELD14. Overall survival was determined in the whole cohort and subgroups. Median overall survival from the start of radiotherapy was 15 months; 1-year and 2-year overall survival rates were 57.1 and 31.0 %, respectively. Eastern Cooperative Oncology Group (ECOG) performance status <2, Charlson comorbidity index ≤6, curative treatment intention, local tumor stage Union Internationale Contre le Cancer (UICC I, II), and total dose >45 Gy were associated with prolonged survival. No significant changes in any HRQOL domain were observed during the course of treatment (t1 to t2). Six months after radiotherapy (t3), a significant and clinically relevant deterioration of HRQOL was seen in EORTC QLQ-C30 for physical function and role function and in EORTC QLQ-ELD14 for future worries, burden of illness, and family support. In radiotherapy patients ≥80 years, HRQOL was maintained until the end of radiotherapy but deteriorated in general and elderly-specific areas thereafter, suggesting a need to develop specific supportive interventions for this age group.
    Supportive Care Cancer 12/2014; DOI:10.1007/s00520-014-2546-z · 2.50 Impact Factor
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    ABSTRACT: Circulating baseline levels of the plasma-protein osteopontin (OPN) have been suggested as a prognostic indicator in chemotherapy and surgery for lung cancer. However, the role of this hypoxia-related protein in radiotherapy of lung cancer is unclear. We previously demonstrated the prognostic effect of baseline OPN plasma levels which was increased by co-detection with other hypoxia-related proteins in the radical radiotherapy of non-small-cell lung cancer (NSCLC). This prospective clinical study investigated whether serial OPN measurements during and after curative-intent radiotherapy for NSCLC provide additional or superior prognostic information. Sixty-nine patients with inoperable NSCLC were prospectively enrolled (55 M0, 14 M1). OPN plasma levels were measured before (t0), at the end (t1) and four weeks after radiotherapy (t2) by ELISA, compared between M0 and M1 patients and correlated with clinicopathological parameters. OPN levels were monitored over time and correlated with prognosis in M0-stage patients treated by radical 66-Gy radiotherapy +/- chemotherapy. Pre-treatment OPN levels were associated with T stage (p = .03), lung function (p = .002), weight loss (p = .01), tumor volume (p = .02) and hemoglobin concentration (p = 04). M1 patients had significantly elevated OPN levels at all time points (p < .001). Patients with increasing OPN levels after radiotherapy had inferior freedom from relapse (p = .008), overall survival (p = .004) and disease-free survival (p = .001) compared to patients with stable or decreasing OPN levels. The risk of relapse in patients with increasing or stable OPN levels after radiotherapy was increased by a factor of 2.9 (p = .01). Patients with increasing post-treatment OPN levels had a 3.1-fold increased risk of death (p = .003). In an exploratory multivariate model, post-treatment OPN level changes but not absolute baseline OPN levels remained an independent prognostic factor for overall survival (p = .002) with a 3.6-fold increased risk of death, as well as N stage (p = .006). Our results suggest that OPN level changes over time, particularly post-treatment, may yield additional prognostic information in curative-intent radiotherapy of NSCLC.
    BMC Cancer 11/2014; 14(1):858. DOI:10.1186/1471-2407-14-858 · 3.32 Impact Factor
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    ABSTRACT: Betulinic acid (BA), a pentacyclic triterpene, represents a new therapeutic substance that has potential benefits for treating glioblastoma. Recently, new strategies for producing BA derivatives with improved properties have evolved. However, few studies have examined the combination of BA or BA derivatives using radiotherapy. The effects of two BA derivatives, NVX-207 and B10, on cellular and radiobiological behavior were analyzed using glioblastoma cell lines (U251MG, U343MG and LN229). Based on IC50 values under normoxic conditions, we detected a 1.3-2.9-fold higher cytotoxicity of the BA derivatives B10 and NVX-207, respectively, compared to BA. Incubation using both BA derivatives led to decreased cell migration, cleavage of PARP and decreased protein expression levels of Survivin. Weak radiation sensitivity enhancement was observed in U251MG cells after treatment with both BA derivatives. The enhancement factors at an irradiation dose of 6 Gy after treatment with 5 µM NVX-207 and 5 µM B10 were 1.32 (p = 0.029) and 1.55 (p = 0.002), respectively. In contrast to BA, neither NVX-207 nor B10 had additional effects under hypoxic conditions. Our results suggest that the BA derivatives NVX-207 and B10 improve the effects of radiotherapy on human malignant glioma cells, particularly under normoxic conditions.
    International Journal of Molecular Sciences 11/2014; 15(11):19777-19790. DOI:10.3390/ijms151119777 · 2.34 Impact Factor
  • Dirk Vordermark
    Journal of Clinical Oncology 09/2014; 32(30). DOI:10.1200/JCO.2014.56.2215 · 17.88 Impact Factor
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    ABSTRACT: The epidermal growth factor receptors, EGFR (HER1) and HER2, have proven prognostic relevance in a variety of human malignancies and both are functionally involved in the molecular pathogenesis of malignant gliomas.
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    ABSTRACT: Sialic acids (Sia) represent negative-charged terminal sugars on most glycoproteins and glycolipids on the cell surface of vertebrates. Aberrant expression of tumor associated sialylated carbohydrate epitopes significantly increases during onset of cancer. Since Sia contribute towards cell migration ( = metastasis) and to chemo- and radiation resistance. Modulation of cellular Sia concentration and composition poses a challenge especially for neuroblastoma therapy, due to the high heterogeneity and therapeutic resistance of these cells. Here we propose that Metabolic Sia Engineering (MSE) is an effective strategy to reduce neuroblastoma progression and metastasis.
    PLoS ONE 08/2014; 9(8):e105403. DOI:10.1371/journal.pone.0105403 · 3.53 Impact Factor
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    ABSTRACT: Almost 500,000 women are newly diagnosed with cervical cancer (CC) every year, the majority from developing countries. There is little information on the survival of these patients. Our primary objective was to evaluate consecutive CC patients presenting over 4 years at the only radiotherapy center in Ethiopia.METHODS: All patients with CC from September 2008 to September 2012 who received radiotherapy and/or surgery were included (without brachytherapy). Vital status was obtained through telephone contact or patient cards.RESULTS: Of 2,300 CC patients, 1,059 patients with standardized treatment were included. At the end of the study, 249 patients had died; surviving patients had a median follow-up of 16.5 months; the 10% and 90% percentiles were 3.0 and 32.7 months, respectively. Mean age was 49 years (21-91 years). The majority of patients presented with International Federation of Gynecology and Obstetrics stage IIb-IIIa (46.7%). Because of progression during the waiting time (median 3.8 months), this proportion declined to 19.3% at the beginning of radiotherapy. The 1- and 2-year overall survival probabilities were 90.4% and 73.6%. If assuming a worst-case scenario (i.e., if all patients not available for follow-up after 6 months had died), the 2-year survival probability would be 45.4%.CONCLUSION: This study gives a thorough 4-year overview of treated patients with CC in Ethiopia. Given the limited treatment availability, a relatively high proportion of patients survived 2 years. More prevention and early detection at all levels of the health care system are needed. Increasing the capacity for external-beam radiation as well as options for brachytherapy would facilitate treatment with curative intention.
    The Oncologist 06/2014; 19(7). DOI:10.1634/theoncologist.2013-0326 · 4.54 Impact Factor
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    ABSTRACT: Human epidermal growth factor receptor 2 (ErbB2) is overexpressed in a variety of human malignancies. Moreover, ErbB2 has been reported to influence cancer patient survival and progression of different tumor entities. However, information regarding the prognostic impact of ErbB2 in soft tissue sarcoma (STS) patients is limited and conflicting. ErbB2 mRNA and protein levels were defined by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), and the prognostic impact of ErbB2 mRNA and protein levels in tumor tissue of 124 soft tissue sarcoma patients were investigated. The median ErbB2 mRNA expression level in tumor tissue was decreased 3.9-fold compared to non-neoplastic surrounding tissue (p = 0.001). Furthermore, an increased ErbB2 mRNA expression level was associated with an improved tumor-specific survival (p = 0.01, log rank test). Multivariate Cox's proportional hazard regression analyses revealed an increased ErbB2 mRNA expression level as an independent favorable prognostic factor for tumor-specific survival of STS patients (n = 124; RR = 3.0; 95 % CI = 1.6-5.7; p < 0.001). In addition, multivariate Cox's proportional hazard regression analyses showed that an increased ErbB2 protein expression level correlated with poorer recurrence-free survival of STS patients (n = 47; RR = 9.9; 95 % CI = 1.7-59.7; p = 0.012), in particular for STS patients who received postoperative radiotherapy (n = 27; RR = 17.9; 95 % CI = 1.3-247.7; p = 0.031). This study suggests an inverse prognostic value of ErbB2 mRNA and protein expression level.
    Strahlentherapie und Onkologie 04/2014; 190(10). DOI:10.1007/s00066-014-0655-8 · 2.73 Impact Factor
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    Anne-Katrin Dumke, Tanja Pelz, Dirk Vordermark
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    ABSTRACT: Anaplastic thyroid cancer (ATC) is an aggressive malignant tumour with a poor prognosis. The median overall survival is described in the literature to be just 6 months, however, in series of selected patients treated by multimodal therapy cases of long-time-survival have been reported. We analyzed the role of radiotherapy and the impact of other therapies and clinical features on survival in patients with ATC. In a retrospective analysis of all patients (n = 40), who presented with histologically proven ATC at a single centre between 1989 and 2008, patient and treatment characteristics with a focus on details of radiotherapy were registered and the survival status determined. 39 of 40 patients received radiotherapy, 80% underwent surgery and 15% had chemotherapy. The median dosis of radiation was 50 Gy (6-60.4 Gy), in 87.5% fractionation was once daily. In 49.4% opposing-field techniques were applied, in 14% 3D-conformal-techniques and 32.5% combinations of both.The median overall survival (OS) was 5 months, 1-year survival 35.2% and 5-year-survival 21.6%. Interestingly, 24.3% survived 2 years or longer. Three factors could be identified as predictors of improved overall survival: absence of lymph node metastasis (N0) (median OS 18.3 months), median dose of radiation of 50 Gy or more (median OS 10.5 months) and the use of any surgery (median OS 10.5 months). Despite the generally poor outcome, the combination of surgery and intensive radiotherapy can result in long-term survival in selected patients with ATC.
    Radiation Oncology 03/2014; 9(1):90. DOI:10.1186/1748-717X-9-90 · 2.36 Impact Factor
  • Klinische Pädiatrie 03/2014; 226(02). DOI:10.1055/s-0034-1371171 · 1.90 Impact Factor
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    ABSTRACT: This clinical study compared four different cases of extensive scalp malignancies treated by intensity-modulated radiation therapy. The merits of coplanar and non-coplanar Step-and-shoot total scalp irradiation techniques were evaluated against the background of the literature. Four patients (angiosarcoma, n=2, cutaneous B-cell non-Hodgkin lymphoma, B-NHL, n=1, mycosis fungoides, n=1) treated between 2008 and 2012 at our institution were retrospectively analyzed. For every patient with executed coplanar plan, a non-coplanar plan and vice versa has been calculated additionally for direct comparison. Three patients underwent limited surgery before radiotherapy. Individual adapted bolus material was used for every patient (helmet). Total scalp dose was 30 Gy (B-NHL, mycosis fungoides) and 50 Gy (angiosarcoma) with fractional doses of 2.0-2.5 Gy (without sequential local boost in three patients). Conformity and homogeneity indexes and dose volume histograms were used for treatment plan comparison. Dose hot spots were higher in coplanar plans (110-128% Dmax). Non-coplanar plans showed a more homogeneous dose distribution (HI = .12 - .17) and superior PTV coverage (88 - 96%). Target dose coverage was 81-117% in non-coplanar and 30-128% in coplanar plans. Coplanar plans yielded a stronger dose gradient across the target (.7-1.6 Gy/mm) compared to non-coplanar plans (.8-1.3 Gy/mm). The most conformal plan was a non-coplanar plan (CI = .7). Mean and maximum brain doses were comparable and showed an almost linear decrease between min. and max. dose. The optic chiasm and brain stem was spared most with non-coplanar plans, mean doses to the lenses ranged between 4 and 8 Gy and were higher in non-coplanar plans as were doses to the optic nerves.Radiotherapy tolerance was acceptable and acute side effects included erythema, scalp pain, alopecia and radiodermatitis which all spontaneously resolved. Two patients accomplished partial response, two patients showed complete response after radiotherapy. Three patients had locally controlled tumors without recurrence until their deaths or at last follow up, one patient had local progression shortly after radiotherapy. Photon-IMRT is an effective and feasible approach to treat extensive scalp malignancies. Non-coplanar beams could increase dose homogeneity and PTV coverage and might reduce doses particularly to the optic chiasm.
    Radiation Oncology 03/2014; 9(1):82. DOI:10.1186/1748-717X-9-82 · 2.36 Impact Factor
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    ABSTRACT: Cardiotoxic and other side effects limit the usefulness of treatments for cancer. This article is based on pertinent articles that were retrieved by a selective search in PubMed and other databases, and on the guidelines of the European Society of Cardiology, the Association of Scientific Medical Societies in Germany, and the European Society of Medical Oncology. Prospective studies have shown that some treatments for cancer are cardiotoxic. The heart damage that they cause can manifest itself as arrhythmia, arterial hypertension, thromboembolism, angina pectoris, myocardial infarction, or heart failure. It has been observed that potentially lethal complications can arise as late as 40 years after treatment of the original cancer. The anthracycline drug doxorubicin, given in a dose of 500 mg/m2 of body surface area, has been found to cause cardiac complications in 4-36% of the patients treated with it. Trastuzumab and epirubicin cause dose-limiting cardiac events in 1.7-5% of patients, depending on the dosage. Paclitaxel causes bradycardia, intracardiac conduction block, or arrhythmia in 0.5% of patients. 18% of patients treated with sunitimib or sorafenib have clinical manifestations relating to the heart (angina pectoris, dyspnea). 5-fluorouracil can cause angina pectoris at the beginning of treatment and rarely causes myocardial infarction. Cardiac radiation therapy, a form of treatment practiced in earlier decades, can cause cardiac complications 20 years after the event. The opportunity to prevent cardiac complications of anthracycline drugs with dexrazoxane is decidedly limited, but initial studies have shown that treatment with beta-blockers and ACE inhibitors lessens the likelihood of cardiotoxic side effects. When cardiac complications arise, the generally applicable rules for the treatment of each type of cardiac problem should be followed. The oncological treatment protocol should be adjusted or switched to one that is less damaging to the heart. Treating physicians need to be thoroughly acquainted with the cardiotoxic effects of anti-cancer drugs so that they can diagnose them early on and avoid jeopardizing the overall success of treatment.
    Deutsches Ärzteblatt International 03/2014; 111(10):161-8. DOI:10.3238/arztebl.2014.0161 · 3.61 Impact Factor
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    ABSTRACT: Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.
    Strahlentherapie und Onkologie 12/2013; 190(3). DOI:10.1007/s00066-013-0484-1 · 2.73 Impact Factor
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    ABSTRACT: The co-incidence of synchronous intraepithelial neoplasia and early stage invasive lung cancer is not a rare phenomenon. The need for curative treatment and the invasive potential of squamous cell pulmonary carcinoma in situ have been a topic of controversy. Surgical resection still remains the treatment of choice. Varieties of endoscopic techniques such as brachytherapy were developed as an alternative to surgery in selected patients. External beam radiation therapy has been used traditionally in combination with endobronchial brachytherapy in the treatment of roentgenographically occult lung cancer, and can be offered for all patients, but is handicapped, because these tumors are radiographically invisible. We report the first case of a pulmonary carcinoma in situ that was successfully treated with stereotactic body radiation therapy.
    Radiation Oncology 09/2013; 8(1):213. DOI:10.1186/1748-717X-8-213 · 2.36 Impact Factor
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    Journal der Deutschen Dermatologischen Gesellschaft 08/2013; 11 Suppl 6:1-116. DOI:10.1111/ddg.12113_suppl · 1.40 Impact Factor
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    Journal der Deutschen Dermatologischen Gesellschaft 08/2013; 11 Suppl 6:1-126. DOI:10.1111/ddg.12113 · 1.40 Impact Factor
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    ABSTRACT: We investigated the role of the hypoxia-associated secreted glycoprotein osteopontin (OPN) in the response of malignant glioma to radiotherapy by characterizing OPN and its splice variants in vitro and in patient material. The effect of siRNA knockdown of OPN splice variants on cellular and radiobiologic behavior was analyzed in U251MG cells using OpnS siRNA (inhibition of all OPN splice variants) and OpnAC siRNA (knockdown only of OPNa and OPNc). OPN and splice variant mRNA levels were quantified in archival material of 41 glioblastoma tumor samples. Plasma OPN was prospectively measured in 33 malignant glioma patients. Inhibition of OPNa and OPNc (OpnAC) reduced clonogenic survival in U251MG cells but did not affect proliferation, migration or apoptosis. Knockdown of all OPN splice variants (OpnS) resulted in an even stronger inhibition of clonogenic survival, while cell proliferation and migration were reduced and rate of apoptosis was increased. Additional irradiation had additive effects with both siRNAs. Plasma OPN increased continuously in malignant glioma patients and was associated with poor survival. OPNb is partially able to compensate the effects of OPNa and OPNc knockdown in U251MG cells. High OPN plasma levels at the end of radiotherapy are associated with poor survival.
    Radiotherapy and Oncology 07/2013; DOI:10.1016/j.radonc.2013.06.036 · 4.86 Impact Factor
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    ABSTRACT: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 ± 5 % after EFRT and 65 ± 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative.
    Strahlentherapie und Onkologie 07/2013; 189(8). DOI:10.1007/s00066-013-0357-7 · 2.73 Impact Factor
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Publication Stats

2k Citations
633.26 Total Impact Points

Institutions

  • 2009–2015
    • Universitätsklinikum Halle (Saale)
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2014
    • Boston University
      • Department of Epidemiology
      Boston, Massachusetts, United States
  • 2008–2014
    • Martin Luther University Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2013
    • OncoRay- Center for Radiation Research in Oncology
      Dresden, Saxony, Germany
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 1999–2012
    • University of Wuerzburg
      • Department of Radiation Oncology
      Würzburg, Bavaria, Germany
  • 2005
    • University Hospital Regensburg
      Ratisbon, Bavaria, Germany
  • 2002–2003
    • Stanford Medicine
      • Division of Radiation and Cancer Biology
      Stanford, California, United States