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Habl G.,Heidelberg Institute of Radiation Oncology HIRO | Habl G.,TU Munich | Katayama S.,Heidelberg Institute of Radiation Oncology HIRO | Uhl M.,Heidelberg Institute of Radiation Oncology HIRO | And 6 more authors.
BMC Cancer | Year: 2015

Background: Definitive, percutaneous irradiation of the prostate and the pelvic lymph nodes in high-risk prostate cancer is the alternative to prostatectomy plus lymphadenectomy. To date, the role of whole pelvis radiotherapy (WPRT) has not been clarified especially taking into consideration the benefits of high conformal IMRT (intensity modulated radiotherapy) of complex-shaped target volumes. Methods: From 2009 to 2012, 40 patients of high-risk prostate cancer with an increased risk of microscopic lymph node involvement were enrolled into this prospective phase II trial. Patients received at least two months of antihormonal treatment (AT) before radiotherapy continuing for at least 2years. Helical IMRT (tomotherapy) of the pelvic lymph nodes (51.0Gy) with a simultaneous integrated, moderate hypofractionated boost (single dose of 2.25Gy) to the prostate (76.5Gy) was performed in 34 fractions. PSA levels, prostate-related symptoms and quality of life were assessed at regular intervals for 24months. Results: Of the 40 patients enrolled, 38 finished the treatment as planned. Overall acute toxicity rates were low and no acute grade 3 or 4 gastrointestinal (GI) and genitourinary (GU) toxicity occurred. 21.6% of patients experienced acute grade 2 but no late grade ≥2 GI toxicity. Regarding GU side effects, results showed 48.6% acute grade 2 and 6.4% late grade 2 toxicity. After a median observation time of 23.4months the PLATIN 1 trial can be considered as sufficiently safe meeting the prospectively defined aims of the trial. With 34/37 patients free of a PSA recurrence it shows promising efficacy. Conclusion: Tomotherapy of the pelvic lymph nodes with a simultaneous integrated boost to the prostate can be performed safely and without excessive toxicity. The combined irradiation of both prostate and pelvic lymph nodes seems to be as well tolerated as the irradiation of the prostate alone. Trial registration: Trial Numbers: ARO 2009-05, ClinicalTrials.gov: NCT01903408. © 2015 Habl et al. Source

Gallas R.R.,German Cancer Research Center | Gallas R.R.,Heidelberg Institute of Radiation Oncology HIRO | Hunemohr N.,German Cancer Research Center | Hunemohr N.,Heidelberg Institute of Radiation Oncology HIRO | And 10 more authors.
Zeitschrift fur Medizinische Physik | Year: 2015

With the increasing complexity of external beam therapy "end-to-end" tests are intended to cover every step from therapy planning through to follow-up in order to fulfill the higher demands on quality assurance. As magnetic resonance imaging (MRI) has become an important part of the treatment process, established phantoms such as the Alderson head cannot fully be used for those tests and novel phantoms have to be developed. Here, we present a feasibility study of a customizable multimodality head phantom. It is initially intended for ion radiotherapy but may also be used in photon therapy. As basis for the anthropomorphic head shape we have used a set of patient computed tomography (CT) images. The phantom recipient consisting of epoxy resin was produced by using a 3D printer. It includes a nasal air cavity, a cranial bone surrogate (based on dipotassium phosphate), a brain surrogate (based on agarose gel), and a surrogate for cerebrospinal fluid (based on distilled water). Furthermore, a volume filled with normoxic dosimetric gel mimicked a tumor.The entire workflow of a proton therapy could be successfully applied to the phantom. CT measurements revealed CT numbers agreeing with reference values for all surrogates in the range from 2 HU to 978 HU (120 kV). MRI showed the desired contrasts between the different phantom materials especially in T2-weighted images (except for the bone surrogate). T2-weighted readout of the polymerization gel dosimeter allowed approximate range verification. © 2015. Source

Adeberg S.,University of Heidelberg | Adeberg S.,German Cancer Research Center | Adeberg S.,Heidelberg Institute of Radiation Oncology HIRO | Bernhardt D.,University of Heidelberg | And 19 more authors.
Journal of Neuro-Oncology | Year: 2016

Clinical guidelines for gliosarcoma (GSM) are poorly defined and GSM patients are usually treated in accordance with existing guidelines for glioblastoma (GBM), with maximal surgical resection followed by chemoradiation with temozolomide (TMZ). However, it is not clear yet if GSM patients profit from TMZ therapy and if O6-methylguanine–DNA–methyltransferase (MGMT) promoter methylation is crucial. We retrospectively evaluated 37 patients with histologically proven, primary GSM who had received radiation therapy since the temozolomide era (post-2005). Twenty-five patients (67.6 %) received combined chemoradiation with temozolomide, and 12 cases (32.4 %) received radiation therapy alone. Molecular markers were determined retrospectively. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. All cases were isocitrate dehydrogenase 1 (IDH1) wildtype, MGMT promoter methylation could be observed in 33.3 % of the assessable cases (10/30) and TERT promoter mutation was seen in a high frequency of 86.7 % (26/30). The influence of TMZ therapy on overall survival (OS) was significantly improved compared with cases in which radiation therapy alone was performed (13.9 vs. 9.9 months; p = 0.045), independently of MGMT promoter methylation. The positive effect of TMZ on OS was confirmed in this study’s multivariate analyses (p = 0.04), after adjusting our results for potential confounders. In conclusion, this study demonstrates that concomitant TMZ together with radiation therapy increases GSM-patient survival independent of MGMT promoter methylation. Thus, GSM can be treated in accordance to GBM guidelines. MGMT promoter methylation was infrequent and TERT promoter mutation common without influencing the survival rates. The mechanisms of TMZ effects in GSM are still not fully understood and merit further clinical and molecular-genetic and -biological evaluation. © 2016 Springer Science+Business Media New York Source

Rief H.,University of Heidelberg | Chaudhri N.,Heidelberg Ion Beams Therapy Center | Tonndorf-Martini E.,University of Heidelberg | Bruckner T.,University of Heidelberg | And 8 more authors.
Journal of Applied Clinical Medical Physics | Year: 2015

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiotherapy (SBRT). As target geometry is complex, we compared SBRT plans using step-and-shoot intensity-modulated radiotherapy (IMRT), carbon ion RT, and proton RT. We prepared plans treating cervical, thoracic, and lumbar metastases for three different techniques - IMRT, carbon ion, and proton plans - to deliver a median single 24 Gy fraction such that at least 90% of the planning target volume (PTV) received more than 18 Gy and were compared for PTV coverage, normal organ sparing, and estimated delivery time. PTV coverage did not show significant differences for the techniques, spinal cord dose sparing was lowered with the particle techniques. For the cervical lesion spinal cord maximum dose, dose of 1% (D1), and percent volume receiving 10 Gy (V10Gy) were 11.9 Gy, 9.1 Gy, and 0.5% in IMRT. This could be lowered to 4.3 Gy, 2.5 Gy, and 0% in carbon ion planning and to 8.1 Gy, 6.1 Gy, and 0% in proton planning. Regarding the thoracic lesion no difference was found for the spinal cord. For the lumbar lesion maximum dose, D1 and percent volume receiving 5Gy (V5Gy) were 13.4 Gy, 8.9 Gy, and 8.9% for IMRT; 1.8 Gy, 0.7 Gy, and 0% for carbon ions; and 0 Gy, < 0.01 Gy, and 0% for protons. Estimated mean treatment times were shorter in particle techniques (6-7 min vs. 12-14 min with IMRT). This planning study indicates that carbon ion and proton RT can deliver high-quality PTV coverage for complex treatment volumes that surround the spinal cord. Source

Haefner M.F.,University of Heidelberg | Haefner M.F.,Heidelberg Institute of Radiation Oncology HIRO | Lang K.,University of Heidelberg | Lang K.,Heidelberg Institute of Radiation Oncology HIRO | And 12 more authors.
Journal of Radiation Research | Year: 2015

The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients recieved either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome. © The Author 2015. Source

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