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

Stephanie E Combs, Lutz Edler, Iris Burkholder, Stefan Rieken, Daniel Habermehl, Oliver Jäkel, Thomas Haberer, Andreas Unterberg, Wolfgang Wick, Jürgen Debus, Renate Haselmann, Stephanie E Combs, Lutz Edler, Iris Burkholder, Stefan Rieken, Daniel Habermehl, Oliver Jäkel, Thomas Haberer, Andreas Unterberg, Wolfgang Wick, Jürgen Debus, Renate Haselmann

Abstract

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 meningiomas 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.

Trial registration: NCT01166321.

Figures

Figure 1
Figure 1
Flow chart of the MARCIE-Study.

References

    1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109. doi: 10.1007/s00401-007-0243-4.
    1. Palma L, Celli P, Franco C, Cervoni L, Cantore G. Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases. Neurosurg Focus. 1997;2:e3. doi: 10.3171/foc.1997.2.4.6.
    1. Kallio M, Sankila R, Hakulinen T, Jaaskelainen J. Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Neurosurgery. 1992;31:2–12. doi: 10.1227/00006123-199207000-00002.
    1. Salazar OM. Ensuring local control in meningiomas. Int J Radiat Oncol Biol Phys. 1988;15:501–504.
    1. Lusis E, Gutmann DH. Meningioma: an update. Curr Opin Neurol. 2004;17:687–692. doi: 10.1097/00019052-200412000-00008.
    1. Milker-Zabel S, Zabel A, Schulz-Ertner D, Schlegel W, Wannenmacher M, Debus J. Fractionated stereotactic radiotherapy in patients with benign or atypical intracranial meningioma: long-term experience and prognostic factors. Int J Radiat Oncol Biol Phys. 2005;61:809–816.
    1. Simon M, Bostrom J, Koch P, Schramm J. Interinstitutional variance of postoperative radiotherapy and follow up for meningiomas in Germany: impact of changes of the WHO classification. J Neurol Neurosurg Psychiatry. 2006;77:767–773. doi: 10.1136/jnnp.2005.077974.
    1. Engenhart-Cabillic R, Farhoud A, Sure U, Heinze S, Henzel M, Mennel HD, Bertalanffy H. Clinicopathologic features of aggressive meningioma emphasizing the role of radiotherapy in treatment. Strahlenther Onkol. 2006;182:641–646. doi: 10.1007/s00066-006-1555-3.
    1. Hoffmann W, Muhleisen H, Hess CF, Kortmann RD, Schmidt B, Grote EH, Bamberg M. Atypical and anaplastic meningiomas--does the new WHO-classification of brain tumours affect the indication for postoperative irradiation? Acta Neurochir (Wien) 1995;135:171–178. doi: 10.1007/BF02187764.
    1. Milosevic MF, Frost PJ, Laperriere NJ, Wong CS, Simpson WJ. Radiotherapy for atypical or malignant intracranial meningioma. Int J Radiat Oncol Biol Phys. 1996;34:817–822.
    1. Smith SJ, Boddu S, Macarthur DC. Atypical meningiomas: WHO moved the goalposts? Br J Neurosurg. 2007;21:588–592. doi: 10.1080/02688690701684246.
    1. Pasquier D, Bijmolt S, Veninga T, Rezvoy N, Villa S, Krengli M, Weber DC, Baumert BG, Canyilmaz E, Yalman D, Szutowicz E, Tzuk-Shina T, Mirimanoff RO. Atypical and malignant meningioma: outcome and prognostic factors in 119 irradiated patients. A multicenter, retrospective study of the rare cancer network. Int J Radiat Oncol Biol Phys. 2008;71:1388–1393.
    1. Hug EB, Devries A, Thornton AF, Munzenride JE, Pardo FS, Hedley-Whyte ET, Bussiere MR, Ojemann R. Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy. J Neurooncol. 2000;48:151–160. doi: 10.1023/A:1006434124794.
    1. Combs SE, Bohl J, Elsaesser T, Weber KJ, Schulz-Ertner D, Debus J, Weyrather WK. Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines. Int J Rad Biol. 2008. in press .
    1. Iwadate Y, Mizoe J, Osaka Y, Yamaura A, Tsujii H. High linear energy transfer carbon radiation effectively kills cultured glioma cells with either mutant or wild-type p53. Int J Radiat Oncol Biol Phys. 2001;50:803–808.
    1. Schulz-Ertner D, Tsujii H. Particle radiation therapy using proton and heavier ion beams. J Clin Oncol. 2007;25:953–964. doi: 10.1200/JCO.2006.09.7816.
    1. Schulz-Ertner D, Nikoghosyan A, Hof H, Didinger B, Combs SE, Jakel O, Karger CP, Edler L, Debus J. Carbon ion radiotherapy of skull base chondrosarcomas. Int J Radiat Oncol Biol Phys. 2007;67:171–177.
    1. Schulz-Ertner D, Karger CP, Feuerhake A, Nikoghosyan A, Combs SE, Jakel O, Edler L, Scholz M, Debus J. Effectiveness of carbon ion radiotherapy in the treatment of skull-base chordomas. Int J Radiat Oncol Biol Phys. 2007;68:449–457.
    1. Milosevic MF, Frost PJ, Laperriere NJ, Wong CS, Simpson WJ. Radiotherapy for atypical or malignant intracranial meningioma. Int J Radiat Oncol Biol Phys. 1996;34:817–822.
    1. Combs SE, Hartmann C, Nikoghosyan A, Jakel O, Karger CP, Haberer T, von Deimling A, Munter MW, Huber PE, Debus J, Schulz-Ertner D. Carbon ion radiation therapy for high-risk meningiomas. Radiother Oncol. 2010;95:54–59. doi: 10.1016/j.radonc.2009.12.029.
    1. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–122.

Source: PubMed

3
Abonneren