期刊论文详细信息
Radiation Oncology
Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts
Stephanie E Combs1  Jürgen Debus1  Oliver Jaekel2  Thomas Haberer2  Daniel Habermehl1  Stefan Rieken3 
[1] Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany;Heavy Ion Therapy Center, University Hospital of Heidelberg, Im Neuenheimer Feld 450, 69120 Heidelberg, Germany;Department of Radiation Oncology, Neuro-Radiation Oncology Research Group, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
关键词: Toxicity;    Particle therapy;    Meningioma;    Glioma;   
Others  :  1160875
DOI  :  10.1186/1748-717X-7-41
 received in 2011-11-26, accepted in 2012-03-21,  发布年份 2012
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【 摘 要 】

Background

Particle irradiation was established at the University of Heidelberg 2 years ago. To date, more than 400 patients have been treated including patients with primary brain tumors. In malignant glioma (WHO IV) patients, two clinical trials have been set up-one investigating the benefit of a carbon ion (18 GyE) vs. a proton boost (10 GyE) in addition to photon radiotherapy (50 Gy), the other one investigating reirradiation with escalating total dose schedules starting at 30 GyE. In atypical meningioma patients (WHO °II), a carbon ion boost of 18 GyE is applied to macroscopic tumor residues following previous photon irradiation with 50 Gy.

This study was set up in order to investigate toxicity and response after proton and carbon ion therapy for gliomas and meningiomas.

Methods

33 patients with gliomas (n = 26) and meningiomas (n = 7) were treated with carbon ion (n = 26) and proton (n = 7) radiotherapy. In 22 patients, particle irradiation was combined with photon therapy. Temozolomide-based chemotherapy was combined with particle therapy in 17 patients with gliomas. Particle therapy as reirradiation was conducted in 7 patients. Target volume definition was based upon CT, MRI and PET imaging. Response was assessed by MRI examinations, and progression was diagnosed according to the Macdonald criteria. Toxicity was classified according to CTCAE v4.0.

Results

Treatment was completed and tolerated well in all patients. Toxicity was moderate and included fatigue (24.2%), intermittent cranial nerve symptoms (6%) and single episodes of seizures (6%). At first and second follow-up examinations, mean maximum tumor diameters had slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. Nine glioma patients suffered from tumor relapse, among these 5 with infield relapses, causing death in 8 patients. There was no progression in any meningioma patient.

Conclusions

Particle radiotherapy is safe and feasible in patients with primary brain tumors. It is associated with little toxicity. A positive response of both gliomas and meningiomas, which is suggested in these preliminary data, must be evaluated in further clinical trials.

【 授权许可】

   
2012 Rieken et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352:987-996.
  • [2]Walker MD, Green SB, Byar DP, et al.: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 1980, 303:1323-1329.
  • [3]Walker MD, Strike TA, Sheline GE: An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 1979, 5:1725-1731.
  • [4]Mizoe JE, Tsujii H, Hasegawa A, et al.: Phase I/II clinical trial of carbon ion radiotherapy for malignant gliomas: combined X-ray radiotherapy, chemotherapy, and carbon ion radiotherapy. Int J Radiat Oncol Biol Phys 2007, 69:390-396.
  • [5]Combs SE, Hartmann C, Nikoghosyan A, et al.: Carbon ion radiation therapy for high-risk meningiomas. Radiother Oncol 95:54-59.
  • [6]Combs SE, Burkholder I, Edler L, et al.: Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: the CINDERELLA trial. BMC Cancer 10:533.
  • [7]Combs SE, Edler L, Burkholder I, et al.: Treatment of patients with atypical meningiomas Simpson grade 4 and 5 with a carbon ion boost in combination with postoperative photon radiotherapy: the MARCIE trial. BMC Cancer 10:615.
  • [8]Combs SE, Kieser M, Rieken S, et al.: Randomized Phase II study Evaluating a Carbon Ion Boost applied after Combined Radiochemotherapy with Temozolomide versus a Proton Boost after Radiochemotherapy with Temozolomide in Patients with Primary Glioblastoma-The CLEOPATRA Trial. BMC Cancer 10:478.
  • [9]Combs SE, Ellerbrock M, Haberer T, et al.: Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients. Acta Oncol 49:1132-1140.
  • [10]Combs SE, Kalbe A, Nikoghosyan A, et al.: Carbon ion radiotherapy performed as re-irradiation using active beam delivery in patients with tumors of the brain, skull base and sacral region. Radiother Oncol 98:63-67.
  • [11]Rieken S, Habermehl D, Nikoghosyan A, et al.: Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at The Heidelberg Ion Therapy Center Using The Raster Scanning Technique. Int J Radiat Oncol Biol Phys
  • [12]Combs SE, Kieser M, Rieken S, et al.: Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial. BMC Cancer 10:478.
  • [13]Fitzek MM, Thornton AF, Rabinov JD, et al.: Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg 1999, 91:251-260.
  • [14]Mizumoto M, Tsuboi K, Igaki H, et al.: Phase I/II trial of hyperfractionated concomitant boost proton radiotherapy for supratentorial glioblastoma multiforme. Int J Radiat Oncol Biol Phys 77:98-105.
  • [15]Boskos C, Feuvret L, Noel G, et al.: Combined proton and photon conformal radiotherapy for intracranial atypical and malignant meningioma. Int J Radiat Oncol Biol Phys 2009, 75:399-406.
  • [16]Pichler R, Dunzinger A, Wurm G, et al.: Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance? Eur J Nucl Med Mol Imaging 37:1521-1528.
  • [17]Floeth FW, Pauleit D, Sabel M, et al.: 18F-FET PET differentiation of ring-enhancing brain lesions. J Nucl Med 2006, 47:776-782.
  • [18]Mahasittiwat P, Mizoe JE, Hasegawa A, et al.: l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: impact on results of carbon ion radiotherapy. Int J Radiat Oncol Biol Phys 2008, 70:515-522.
  • [19]Grosu AL, Astner ST, Riedel E, et al.: An Interindividual Comparison of O-(2- [(18)F]Fluoroethyl)-L-Tyrosine (FET)- and L-[Methyl-(11)C]Methionine (MET)-PET in Patients With Brain Gliomas and Metastases. Int J Radiat Oncol Biol Phys
  • [20]Grosu AL, Weber WA, Riedel E, et al.: L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys 2005, 63:64-74.
  • [21]Gehler B, Paulsen F, Oksuz MO, et al.: [68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning. Radiat Oncol 2009, 4:56. BioMed Central Full Text
  • [22]Milker-Zabel S, Zabel-du Bois A, Henze M, et al.: Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET. Int J Radiat Oncol Biol Phys 2006, 65:222-227.
  • [23]Kraft G: The radiobiological and physical basis for radiotherapy with protons and heavier ions. Strahlenther Onkol 1990, 166:10-13.
  • [24]Combs SE, Bohl J, Elsasser T, et al.: Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines. Int J Radiat Biol 2009, 85:126-137.
  • [25]Combs SE, Schulz-Ertner D, Debus J, et al.: Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients with Atypical and Anaplastic Meningiomas. Int J Radiat Oncol Biol Phys 2011, 81(5):1415-1421.
  • [26]Gudjonsson O, Blomquist E, Nyberg G, et al.: Stereotactic irradiation of skull base meningiomas with high energy protons. Acta Neurochir (Wien) 1999, 141:933-940.
  • [27]Hug EB, Muenter MW, Archambeau JO, et al.: Conformal proton radiation therapy for pediatric low-grade astrocytomas. Strahlenther Onkol 2002, 178:10-17.
  • [28]Wenkel E, Thornton AF, Finkelstein D, et al.: Benign meningioma: partially resected, biopsied, and recurrent intracranial tumors treated with combined proton and photon radiotherapy. Int J Radiat Oncol Biol Phys 2000, 48:1363-1370.
  • [29]Noel G, Bollet MA, Calugaru V, et al.: Functional outcome of patients with benign meningioma treated by 3D conformal irradiation with a combination of photons and protons. Int J Radiat Oncol Biol Phys 2005, 62:1412-1422.
  • [30]Miyatake S, Tamura Y, Kawabata S, et al.: Boron neutron capture therapy for malignant tumors related to meningiomas. Neurosurgery 2007, 61:82-90. discussion 90-81
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