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Helmbrecht S.,TU Dresden | Enghardt W.,TU Dresden | Parodi K.,Heidelberger Ionenstrahl Therapiezentrum HIT | Parodi K.,Ludwig Maximilians University of Munich | And 5 more authors.
Medical Physics | Year: 2013

Purpose: Particle Therapy Positron Emission Tomography (PT-PET) is a suitable method for verification of therapeutic dose delivery by measurements of irradiation-induced β+-activity. Due to metabolic processes in living tissue β+-emitters can be removed from the place of generation. This washout is a limiting factor for image quality. The purpose of this study is to investigate whether a washout model obtained by animal experiments is applicable to patient data. Methods: A model for the washout has been developed by Mizuno [Phys. Med. Biol. 48(15), 2269-2281 (2003)]10.1088/0031-9155/48/15/302 and Tomitani [Phys. Med. Biol. 48(7), 875-889 (2003)]10.1088/0031-9155/48/7/305. It is based upon measurements in a rabbit in living and dead conditions. This model was modified and applied to PET data acquired during the experimental therapy project at GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Germany. Three components are expected: A fast one with a half life of 2 s, a medium one in the range of 2-3 min, and a slow component of the order of 2-3 h. Ten patients were selected randomly for investigation of the fast component. To analyze the other two components, 12 one-of-a-kind measurements from a single volunteer patient are available. Results: A fast washout on the time scale of a few seconds was not observed in the patient data. The medium processes showed a mean half life of 155.7 ± 4.6 s. This is in the expected range. Fractions of the activity not influenced by the washout were found. Conclusions: On the time scale of an in-beam or in-room measurement only the medium-time washout processes play a remarkable role. A slow component may be neglected if the measurements do not exceed 20 min after the end of the irradiation. The fast component is not observed due to the low relative blood filled volume in the brain. © 2013 American Association of Physicists in Medicine.

Combs S.E.,University of Heidelberg | Kessel K.,University of Heidelberg | Habermehl D.,University of Heidelberg | Haberer T.,Heidelberger Ionenstrahl Therapiezentrum HIT | And 2 more authors.
Acta Oncologica | Year: 2013

To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods. In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results. Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neurocognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion. The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neurocognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications. © 2013 Informa Healthcare.

Combs S.E.,University of Heidelberg | Combs S.E.,German Cancer Research Center | Hartmann C.,University of Heidelberg | Hartmann C.,German Cancer Research Center | And 13 more authors.
Radiotherapy and Oncology | Year: 2010

Background: We analyzed outcome after a carbon ion boost in combination with precision photon radiation therapy in patients with meningiomas. Patients and methods: Ten patients with meningiomas were treated with carbon ion RT as part of a Phase I/II trial. Carbon ion RT was conducted in conjunction with fractionated stereotactic RT (FSRT) or intensity-modulated RT (IMRT). Eight patients were treated as primary RT, in 2 patients carbon ion RT was performed as re-irradiation. Carbon ion RT was applied with a median dose of 18 Gy E, and photon RT was applied with a median dose of 50.4 Gy. Two patients with a history of former irradiation received 18 Gy E of carbon ion RT and a reduced dose of photon treatment. Results: The median follow-up time was 77 months. Five patients died during follow-up, of which four died of tumor progression. In the group treated in the primary situation, actuarial survival rates after RT were 75% and 63% at 5 and 7 years. After re-irradiation, both patients died at 10 and 67 months, respectively. Actuarial local control rates after primary RT were 86% and 72% at 5 and 7 years. Two patients developed tumor recurrence after re-irradiation, 6 and 67 months after treatment. Conclusion: In conclusion, carbon ion radiation shows promising results in patients with atypical or anaplastic meningiomas. Further evaluation in a larger, prospective study in comparison to proton RT or modern photon RT is needed to corroborate these results. © 2010 Elsevier Ireland Ltd. All rights reserved.

Combs S.E.,University of Heidelberg | Kalbe A.,University of Heidelberg | Nikoghosyan A.,University of Heidelberg | Ackermann B.,Heidelberger Ionenstrahl Therapiezentrum HIT | And 3 more authors.
Radiotherapy and Oncology | Year: 2011

Introduction: To asses carbon ion radiation therapy (RT) performed as re-irradiation in 28 patients with recurrent tumors. Materials and methods: Twenty-eight patients were treated with carbon ion RT as re-irradiation for recurrent chordoma and chondrosarcoma of the skull base (n = 16 and n = 2), one chordoma and one chondrosarcoma of the os sacrum, high-risk meningioma (n = 3), adenoid-cystic carcinoma (n = 4) as well as one SCCHN. All patients were treated using active raster scanning, and treatment planning was performed on CT- and MRI-basis. All patients were followed prospectively during follow-up. Results: In all patients re-irradiation could be applied safely without interruptions. For skull base tumors, local tumor control after re-irradiation was 92% at 24 months and 64% at 36 months. Survival after re-irradiation was 86% at 24 months, and 43% at 60 months. In all three meningiomas treated with C12 for re-irradiation, the tumor recurrence was located within the former RT-field. Two patients developed tumor progression at 6 months, and in one patient the tumor remained stable for 67 months. In patients with head-and-neck tumors, three patients developed local tumor progression at 12, 24 and 29 months after re-irradiation. Median local progression-free survival was 24 months. For sacral tumors, re-irradiation offered palliation with tumor control for 24 and 36 months. Conclusion: Due to the physical characteristics particle therapy offers a new treatment modality in cases with tumor recurrences. With carbon ions, the additional biological benefits may be exploited for long-term tumor control. Further evaluation in a larger patients' cohort will be performed in the future. © 2010 Published by Elsevier Ireland Ltd.

Combs S.E.,University of Heidelberg | Ellerbrock M.,Heidelberger Ionenstrahl Therapiezentrum HIT | Haberer T.,Heidelberger Ionenstrahl Therapiezentrum HIT | Habermehl D.,University of Heidelberg | And 12 more authors.
Acta Oncologica | Year: 2010

The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. In this report we present the first 80 patients treated with proton and carbon ion radiotherapy and describe patient selection, treatment planning and daily treatment for different indications. Patients and methods. Between November 15, 2009 and April 15, 2010, 80 patients were treated at the Heidelberg Ion Therapy Center (HIT) with carbon ion and proton radiotherapy. Main treated indications consisted of skull base chordoma (n=9) and chondrosarcoma (n=18), malignant salivary gland tumors (n=29), chordomas of the sacrum (n=5), low grade glioma (n=3), primary and recurrent malignant astrocytoma and glioblastoma (n=7) and well as osteosarcoma (n=3). Of these patients, four pediatric patients aged under 18 years were treated. Results. All patients were treated using the intensity-modulated rasterscanning technique. Seventy six patients were treated with carbon ions (95%), and four patients were treated with protons. In all patients X-ray imaging was performed prior to each fraction. Treatment concepts were based on the initial experiences with carbon ion therapy at the Gesellschaft fr Schwerionenforschung (GSI) including carbon-only treatments and carbon-boost treatments with photon-IMRT. The average time per fraction in the treatment room per patient was 29 minutes; for irradiation only, the mean time including all patients was 16 minutes. Position verification was performed prior to every treatment fraction with orthogonal X-ray imaging. Conclusion. Particle therapy could be included successfully into the clinical routine at the Department of Radiation Oncology in Heidelberg. Numerous clinical trials will subsequently be initiated to precisely define the role of proton and carbon ion radiotherapy in radiation oncology. © 2010 Informa Healthcare.

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