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Rieber J.,University of Heidelberg | Rieber J.,Heidelberg Institute of Radiation Oncology | Deeg A.,University of Heidelberg | Deeg A.,Heidelberg Institute of Radiation Oncology | And 18 more authors.
Lung Cancer | Year: 2016

Purpose: Current guidelines recommend postoperative radiation therapy (PORT) for incompletely resected non-small cell lung cancer (NSCLC). However, there is still a paucity of evidence for this approach. Hence, we analyzed survival in 78 patients following radiotherapy for incompletely resected NSCLC (R1) and investigated prognostic factors. Patients and methods: All 78 patients with incompletely resected NSCLC (R1) received PORT between December 2001 and September 2014. The median total dose for PORT was 60. Gy (range 44-68. Gy). The majority of patients had locally advanced tumor stages (stage IIA (2.6%), stage IIB (19.2%), stage IIIA (57.7%) and stage IIIB (20.5%)). 21 patients (25%) received postoperative chemotherapy. Results: Median follow-up after radiotherapy was 17.7 months. Three-year overall (OS), progression-free (PFS), local (LPFS) and distant progression-free survival (DPFS) rates were 34.1, 29.1, 44.9 and 51.9%, respectively. OS was significantly prolonged at lower nodal status (pN0/1) and following dose-escalated PORT with total radiation doses >54. Gy (p = 0.012, p = 0.013). Furthermore, radiation doses >54. Gy significantly improved PFS, LPFS and DPFS (p = 0.005; p = 0.050, p = 0.022). Interestingly, survival was neither significantly influenced by R1 localization nor by extent (localized vs. diffuse). Multivariate analyses revealed lower nodal status and radiation doses >54.0. Gy as the only independent prognostic factors for OS (p = 0.021, p = 0.036). Conclusion: For incompletely resected NSCLC, PORT is used for improving local tumor control. Local progression is still the major pattern of failure. Radiation doses >54 Gy seem to support improved local control and were associated with better OS in this retrospective study. © 2015.


Rieber J.,University of Heidelberg | Rieber J.,Heidelberg Institute of Radiation Oncology | Streblow J.,University of Heidelberg | Streblow J.,Heidelberg Institute of Radiation Oncology | And 28 more authors.
Lung Cancer | Year: 2016

Objectives: The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control. Materials and methods: All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5 Gy (range 3.0-33.0 Gy) in a median number of 3 fractions (range 1-13). Results: After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p = 0.006). Conclusion: SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach. © 2016 Elsevier Ireland Ltd.


Rieber J.,University of Heidelberg | Rieber J.,Heidelberg Institute of Radiation Oncology | Tonndorf-Martini E.,University of Heidelberg | Tonndorf-Martini E.,Heidelberg Institute of Radiation Oncology | And 16 more authors.
Strahlentherapie und Onkologie | Year: 2016

Background: Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques. Materials and methods: Between November 2014 and June 2015, 21 consecutive patients with 25 brain metastases were treated with stereotactic radiosurgery (SRS) in FFF mode. Brain metastases received dose-fractionation schedules of 1 × 20 Gy or 1 × 18 Gy, delivered to the conformally enclosing 80 % isodose. Three patients with critically localized or large (>3 cm) brain metastases were treated with 6 × 5 Gy. Plan quality and efficiency were evaluated by analyzing conformity, dose gradients, dose to healthy brain tissue, treatment delivery time, and number of monitor units. FFF plans were compared to those using the FF method, and early clinical outcome and toxicity were assessed. Results: FFF mode resulted in significant reductions in beam-on time (p < 0.001) and mean brain dose (p = 0.001) relative to FF-mode comparison plans. Furthermore, significant improvements in dose gradients and sharper dose falloffs were found for SRS in FFF mode (−1.1 %, −29.6 %; p ≤ 0.003), but conformity was slightly superior in SRS in FF mode (−1.3 %; p = 0.001). With a median follow-up time of 5.1 months, 6‑month overall survival was 63.3 %. Local control was observed in 24 of 25 brain metastases (96 %). Conclusion: SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity. © 2016 Springer-Verlag Berlin Heidelberg


Rief H.,University of Heidelberg | Katayama S.,University of Heidelberg | Bruckner T.,University of Heidelberg | Rieken S.,University of Heidelberg | And 8 more authors.
Trials | Year: 2015

Background: Stereotactic body radiation therapy (SBRT)using intensity-modulated radiotherapy (IMRT) can be a safe modality for treating spinal bone metastasis with enhanced targeting accuracy and an effective method for achieving good tumor control and a rigorous pain response. Methods/design: This is a single-center, prospective randomized controlled trial to evaluate pain relief after RT and consists of two treatment groups with 30 patients in each group. One group will receive single-fraction intensity-modulated RT with 1×24 Gy, and the other will receive fractionated RT with 10×3 Gy. The target parameters will be measured at baseline and at 3 and 6 months after RT. Discussion: The aim of this study is to evaluate pain relief after RT in patients with spinal bone metastases by means of two different techniques: stereotactic body radiation therapy and fractionated RT. The primary endpoint is pain relief at the 3-month time-point after RT. Secondly, quality of life, fatigue, overall and bone survival, and local control will be assessed. Trial registration: ClinicalTrials.gov identifier NCT02358720(June 2, 2015). © Rief et al.


Sterzing F.,University of Heidelberg | Sterzing F.,German Cancer Research Center | Sterzing F.,Heidelberg Institute of Radiation Oncology | Kratochwil C.,University of Heidelberg | And 13 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2016

Purpose: Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of [68Ga]Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning. Methods: A cohort of 57 patients with prostate cancer scanned with 68Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with 68Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified. Results: 68Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed. Conclusion: The presented imaging technique of 68Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer. © 2015, Springer-Verlag Berlin Heidelberg.


Rieber J.G.,University of Heidelberg | Rieber J.G.,Heidelberg Institute of Radiation Oncology | Kessel K.A.,University of Heidelberg | Kessel K.A.,Heidelberg Institute of Radiation Oncology | And 9 more authors.
Acta Oncologica | Year: 2015

Curative treatment of pediatric cancer not only focuses on long-term survival, but also on reducing treatment-related side effects. Advantages of particle therapy are mainly due to their physical ability of significantly reducing integral dose. Methods: Between January 2009 and December 2012, we treated 83 pediatric patients (aged 21 and younger) at the Heidelberg Ion Therapy Center at University Hospital of Heidelberg (HIT). In total 56 patients (67%) received proton irradiation, while 25 (30%) patients were treated with carbon ions (C12). Two patients received both treatments (3%). Treatment toxicity was analyzed retrospectively and documented according to the CTCAE/RTOG classification. In a second step, treatment toxicity from ion therapy was analyzed in comparison to treatment toxicity during photon irradiation of a comparable historical group of 19 pediatric patients. Results: In all patients, particle therapy was tolerated well (median follow-up time 3.7 months), children (20 patients) with at least two follow-up visits showed a median follow-up time of 10.2 months. During the first two months patients mainly suffered from radiogenic skin reaction (63%), mucositis (30%), headache and dizziness (35%) as well as nausea and vomiting (13%). Severe toxicity reaction (grade II-IV) was only seen in patients who had intensive simultaneous chemotherapy or who had undergone several operations in the irradiated area before radiotherapy (18%). Treatment toxicity during ion therapy was comparable to treatment toxicity from photon irradiation of a historical group. Conclusions: In comparison to conventional therapy, patients with particle therapy do not suffer from increased acute treatment-related toxicity during the first months. More experience with particle therapy will be needed during the next years to help to thoroughly evaluate the high potential of ion therapy. © 2015 Informa Healthcare.


Rieber J.,University of Heidelberg | Rieber J.,Heidelberg Institute of Radiation Oncology | Schmitt J.,University of Heidelberg | Schmitt J.,Heidelberg Institute of Radiation Oncology | And 20 more authors.
European Journal of Medical Research | Year: 2015

Background: There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non-small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC. Methods: Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan-Meier method. Results: Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages. Conclusion: In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI. © 2015 Rieber et al.


Dokic I.,German Cancer Research Center | Dokic I.,Heidelberg Ion Therapy Center | Dokic I.,Heidelberg Institute of Radiation Oncology | Niklas M.,German Cancer Research Center | And 22 more authors.
Frontiers in Oncology | Year: 2015

Development of novel approaches linking the physical characteristics of particles with biological responses are of high relevance for the field of particle therapy. In radiobiology, the clonogenic survival of cells is considered the gold standard assay for the assessment of cellular sensitivity to ionizing radiation. Toward further development of next generation biodosimeters in particle therapy, cell-fluorescent ion track hybrid detector (Cell-FIT-HD) was recently engineered by our group and successfully employed to study physical particle track information in correlation with irradiation-induced DNA damage in cell nuclei. In this work, we investigated the feasibility of Cell-FIT-HD as a tool to study the effects of clinical beams on cellular clonogenic survival. Tumor cells were grown on the fluorescent nuclear track detector as cell culture, mimicking the standard procedures for clonogenic assay. Cell-FIT-HD was used to detect the spatial distribution of particle tracks within colony-initiating cells. The physical data were associated with radiation-induced foci as surrogates for DNA double-strand breaks, the hallmark of radiation-induced cell lethality. Long-term cell fate was monitored to determine the ability of cells to form colonies. We report the first successful detection of particle traversal within colony-initiating cells at subcellular resolution using Cell-FIT-HD. © 2015 Dokic, Niklas, Zimmermann, Mairani, Seidel, Krunic, Jäkel, Debus, Greilich and Abdollahi.

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