Heidelberger Ionenstrahl Therapiezentrum HIT

Heidelberg, Germany

Heidelberger Ionenstrahl Therapiezentrum HIT

Heidelberg, Germany
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Combs S.E.,University of Heidelberg | Bauer J.,Heidelberger Ionenstrahl Therapiezentrum HIT | Unholtz D.,Heidelberger Ionenstrahl Therapiezentrum HIT | Kurz C.,Heidelberger Ionenstrahl Therapiezentrum HIT | And 5 more authors.
BMC Cancer | Year: 2012

Background: The purpose of this clinical study is to investigate the clinical feasibility and effectiveness of offline Positron-Emission-Tomography (PET) quality assurance for promoting the accuracy of proton and carbon ion beam therapy.Methods/Design: A total of 240 patients will be recruited, evenly sampled among different analysis groups including tumors of the brain, skull base, head and neck region, upper gastrointestinal tract including the liver, lower gastrointestinal tract, prostate and pelvic region. From the comparison of the measured activity with the planned dose and its corresponding simulated activity distribution, conclusions on the delivered treatment will be inferred and, in case of significant deviations, correction strategies will be elaborated.Discussion: The investigated patients are expected to benefit from this study, since in case of detected deviations between planned and actual treatment delivery a proper intervention (e.g., correction) could be performed in a subsequent irradiation fraction. In this way, an overall better treatment could be achieved than without any in-vivo verification. Moreover, site-specific patient-population information on the precision of the ion range at HIT might enable improvement of the CT-range calibration curve as well as safe reduction of the treatment margins to promote enhanced treatment plan conformality and dose escalation for full clinical exploitation of the promises of ion beam therapy.Trial Registration: NCT01528670. © 2012 Combs et al; licensee BioMed Central Ltd.


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 | Habermehl D.,University of Heidelberg | Ganten T.,University of Heidelberg | Schmidt J.,University of Heidelberg | And 5 more authors.
BMC Cancer | Year: 2011

Background: Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months.Radiation therapy is a treatment alternative, however, high local doses are required for long-term local control. However, due to the relatively low radiation tolerance of liver normal tissue, even using stereotactic techniques, delivery of sufficient doses for successful local tumor control has not be achieved to date.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed.Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with HCC.Methods/Design: In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control.Primary endpoint is toxicity, secondary endpoint is progression-free survival and response.Discussion: The Prometheus-01 trial ist the first trial evaluating carbon ion radiotherapy delivered by intensity-modulated rasterscanning for the treatment of HCC. Within this Phase I dose escalation study, the optimal dose of carbon ion radiotherapy will be determined.Trial registration: NCT 01167374. © 2011 Combs et al; licensee BioMed Central Ltd.


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.


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 | Burkholder I.,University of Heidelberg | Edler L.,University of Heidelberg | Rieken S.,University of Heidelberg | And 7 more authors.
BMC Cancer | Year: 2010

Background: Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective.Methods Design: In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy.Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival.Discussion: The Cinderella trial is the first study to evaluate carbon ion radiotherapy for recurrent gliomas, and to compare this treatment to photon FSRT in a randomized setting using an ion beam delivered by intensity modulated rasterscanning.Trial Registration: NCT01166308. © 2010 Combs et al; licensee BioMed Central Ltd.


Combs S.E.,University of Heidelberg | Edler L.,University of Heidelberg | Burkholder I.,StaBiL | Rieken S.,University of Heidelberg | And 7 more authors.
BMC Cancer | Year: 2010

Background: Treatment standard for patients with atypical or anaplastic meningioma is neurosurgical resection. With this approach, local control ranges between 50% and 70%, depending on resection status. A series or smaller studies has shown that postoperative radiotherapy in this patient population can increase progression-free survival, which translates into increased overall survival. However, meningiomas are known to be radioresistant tumors, and radiation doses of 60 Gy or higher have been shown to be necessary for tumor control.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.First data obtained within the Phase I/II trial performed at GSI in Darmstadt on carbon ion radiotherapy for patients with high-risk meningiomas has shown safety, and treatment results are promising.Methods/design: The Phase II-MARCIE-Study will evaluate a carbon ion boost applied to the macroscopic tumor in conjunction with photon radiotherapy in patients with atypical menigiomas after incomplete resection or biopsy.Primary endpoint is progression-free survival, secondary endpoints are overall survival, safety and toxicity.Discussion: Based on published data on the treatment of atypical meningiomas with carbon ions at GSI, the present study will evaluate this treatment concept in a larger patient population and will compare outcome to current standard photon treatment. © 2010 Combs et al; licensee BioMed Central Ltd.


Combs S.E.,University of Heidelberg | Kieser M.,University of Heidelberg | Rieken S.,University of Heidelberg | Habermehl D.,University of Heidelberg | And 7 more authors.
BMC Cancer | Year: 2010

Background: Treatment standard for patients with primary glioblastoma (GBM) is combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to a total dose of 60 Gy using photons. Using this treatment regimen, overall survival could be extended significantly however, median overall survival is still only about 15 months.Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.First Japanese Data on the evaluation of carbon ion radiation therapy showed promising results in a small and heterogeneous patient collective.Methods/Design: In the current Phase II-CLEOPATRA-Study a carbon ion boost will be compared to a proton boost applied to the macroscopic tumor after surgery at primary diagnosis in patients with GBM applied after standard radiochemotherapy with TMZ up to 50 Gy. In the experimental arm, a carbon ion boost will be applied to the macroscopic tumor up to a total dose of 18 Gy E in 6 fractions at a single dose of 3 Gy E. In the standard arm, a proton boost will be applied up to a total dose 10 Gy E in 5 single fractions of 2 Gy E.Primary endpoint is overall survival, secondary objectives are progression-free survival, toxicity and safety.Discussion: The Cleopatra Trial is the first study to evaluate the effect of carbon ion radiotherapy within multimodality treatment of primary glioblastoma in a randomized trial comparing this innovative treatment of the treatment standard, consisitng of photon radiotherapy in combination with temozolomide. © 2010 Combs et al; licensee BioMed Central Ltd.

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