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Heidelberg, Germany

Combs S.E.,University of Heidelberg | Welzel T.,University of Heidelberg | Habermehl D.,University of Heidelberg | Rieken S.,University of Heidelberg | And 5 more authors.
Acta Oncologica | Year: 2013

Purpose. To evaluate early treatment results and toxicity in patients with meningiomas treated with particle therapy. Material and methods. Seventy patients with meningiomas were treated with protons (n = 38) or carbon ion radiotherapy (n = 26). Median age was 49 years. Median age at treatment was 55 years, 24 were male (34%), and 46 were female (66%). Histology was benign meningioma in 26 patients (37%), atypical in 23 patients (33%) and anaplastic in four patients (6%). In 17 patients (24%) with skull base meningiomas diagnosis was based on the typical appearance of a meningioma. For benign meningiomas, total doses of 52.2-57.6 GyE were applied with protons. For high-grade lesions, the boost volume was 18 GyE carbon ions, with a median dose of 50 GyE applied as highly conformal radiation therapy. Nineteen patients were treated as re-irradiation. Treatment planning with MRI and 68-Ga-DOTATOC-PET was evaluated. Results. Very low rates of side effects developed, including headaches, nausea and dizziness. No severe treatment-related toxicity was observed. Local control for benign meningiomas was 100%. Five of 27 patients (19%) developed tumor recurrence during follow-up. Of these, four patients had been treated as re-irradiation for recurrent high-risk meningiomas. Actuarial local control after re-irradiation of high-risk meningiomas was therefore 67% at six and 12 months. In patients treated with primary radiotherapy, only one of 13 patients (8%) developed tumor recurrence 17 months after radiation therapy (photon and carbon ion boost). Conclusion. Continuous prospective follow-up and development of novel study concepts are required to fully exploit the long-term clinical data after particle therapy for meningiomas. To date, it may be concluded that when proton therapy is available, meningioma patients can be offered a treatment at least comparable to high-end photon therapy. © 2013 Informa Healthcare.

Steidl P.,Helmholtz Center for Heavy Ion Research | Steidl P.,Siemens AG | Haberer T.,Heidelberg Ion Therapy Center | Durante M.,Helmholtz Center for Heavy Ion Research | And 2 more authors.
Physics in Medicine and Biology | Year: 2013

Gating is one option for radiotherapy of tumours that move intrafractionally due to respiration. Delays of the motion monitoring system can lead to a shift of the gating window and thus slightly shifted dose distributions. We studied the delay of two motion monitoring systems which use the motion of the chest wall as surrogate for tumour motion. Delays and their dosimetric influence were determined against a precise motion acquisition system in a phantom study. The measurement data were supplemented by dedicated simulations of the experimental setup. Finally, the dosimetric influence for patient treatments was estimated for a lung tumour case using the extreme situation of a radiosurgery setting with a single field. We determined delays of 132 ± 18 ms and 103 ± 22 ms for the two systems. There was no significant difference between beam start and beam stop delay. Even for delays of 200 ms the dosimetric influence in a single-field radiosurgery setting is moderate (V95 = 96.5%, V107 = 8.5%, D5-D95 = 13%). We conclude, that the delay of the motion monitoring system should be part of the commissioning process for gated treatments. The dosimetric impact should be studied in detail prior treatments with a scanned ion beam. © 2013 Institute of Physics and Engineering in Medicine.

Abdollahi A.,United Medical Systems | Abdollahi A.,Heidelberg Ion Therapy Center | Folkman J.,Vascular Biology Program
Drug Resistance Updates | Year: 2010

Within three decades, anti-angiogenic therapy has rapidly evolved into an integral component of current standard anti-cancer treatment. Anti-angiogenic therapy has fulfilled a number of its earlier proposed promises. The universality of this approach is demonstrated by the broad spectrum of malignant and benign tumor entities, as well as non-neoplastic diseases, that are currently treated with anti-angiogenic agents. In contrast to tumor cell targeting therapies, the development of acquired drug resistance (e.g., via mutations in growth factor receptor signaling genes) has not been described yet for the principal target of anti-angiogenic therapy-the tumor endothelium. Moreover, the tumor endothelium has emerged as a critical target of conventional cancer therapies, such as chemotherapy and radiotherapy. The presumption that tumor growth and metastasis are angiogenesis-dependent implies that the number of potential targets of an anti-cancer therapy could be reduced to those that stimulate the angiogenesis process. Therefore, the set of endogenous angiogenesis stimulants might constitute an "Achilles heel" of cancer. Direct targeting of tumor endothelium via, e.g., endogenous angiogenesis inhibitors poses another promising but clinically less explored therapeutic strategy. Indeed, the majority of current anti-angiogenic approaches block the activity of a single or at most a few pro-angiogenic proteins secreted by tumor cells or the tumor stroma. Based on our systems biology work on the angiogenic switch, we predicted that the redundancy of angiogenic signals might limit the efficacy of anti-angiogenic monotherapies. In support of this hypothesis, emerging experimental evidence suggests that tumors may become refractory or even evade the inhibition of a single pro-angiogenic pathway via compensatory upregulation of alternative angiogenic factors. Here, we discuss current concepts and propose novel strategies to overcome tumor evasion of anti-angiogenic therapy. We believe that early detection of tumors, prediction of tumor evasive mechanisms and rational design of anti-angiogenic combinations will direct anti-angiogenic therapy towards its ultimate goal-the conversion of cancer to a dormant, chronic, manageable disease. © 2009 Elsevier Ltd. All rights reserved.

Adeberg S.,University of Heidelberg | Bostel T.,University of Heidelberg | Konig L.,University of Heidelberg | Welzel T.,University of Heidelberg | And 4 more authors.
Radiation Oncology | Year: 2014

Objective: Long-term survival is rare in patients with glioblastoma (GBM). We set out to determine prognostic factors for patients with favorable and poor prognosis in regard of tumor localization to the subventricular zone (SZV).Methods: We reviewed the clinical records, pre-operative and post-operative MRI imaging of 50 LTS long-term survivors (LTS) (> 3 years) and 50 short-term survivors (STS) (< 1 year) with glioblastoma. These groups were matched for clinical characteristics being consistently associated with prolonged or shortened survival. All patients had undergone initial surgery or biopsy to confirm GBM diagnosis followed by radio- or chemoradiotherapy.Results: LTS had a median progression-free survival PFS of 25, 4 months (2, 3-97, 8 months) and overall-survival (OS) of 55, 9 months (38, 2-98, 6 months) compared to STS who had a significantly lower PFS of 4, 2 months (1, 4-10, 2 months) and OS of 6, 6 months (2, 2-11, 6 months) (each p < 0,001).Survival analysis showed that age under 60 years (p < 0,001), total resection status (p < 0,001) and tumor localization without SVZ contact (p = 0,05) were significant factors for prolonged survival.Conclusion: Our findings underline that survival in GBM patients is heterogeneous and influenced by multiple factors. This study confirms that tumor location with regard to the SVZ is significantly associated with survival. © 2014 Adeberg et al.; licensee BioMed Central Ltd.

Jensen A.D.,INF | Nikoghosyan A.,INF | Ellerbrock M.,Heidelberg Ion Therapy Center | Ecker S.,Heidelberg Ion Therapy Center | And 2 more authors.
Radiotherapy and Oncology | Year: 2011

Background: Treatment of surgically unresectable recurrence in the head and neck region remains a therapeutic problem with the only curative option being a second course of radiation with a tumouricidal dose. We report initial toxicity and efficacy of charged particle therapy in this situation. Methods: Treatment-related side-effects of patients treated with charged particle beams for recurrent tumours of the head and neck were prospectively collected and patient data was retrospectively analysed with regard to toxicity and efficacy of the treatment according to CTCAE v. 4.03 and RECIST. Results: Treatment was tolerated well without any severe acute toxicity. In non-chordoma/chondrosarcoma patients, overall response rate was 53.3% at 8 weeks post RT. 4/5 chordoma/chondrosarcoma patients showed no signs of further tumour progression. Conclusion: Initial experience of re-irradiation with scanned particle beams in recurrent tumours of the head and neck seems feasible and encouraging. Further follow-up is needed to investigate potential late effects. © 2011 Elsevier Ireland Ltd. All rights reserved.

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