gms | German Medical Science

48th Meeting of the Particle Therapy Co-Operative Group

Particle Therapy Co-Operative Group (PTCOG)

28.09. - 03.10.2009, Heidelberg

The Effectiveness of Combining Temozolomide with Carbon Ion Radiotherapy for Glioblastomas: In vitro and In vivo study

Meeting Abstract

  • Y. Yoshida - Gunma University Heavy Ion Medical Center, Gunma, Japan
  • S. Ishiuchi - Department of Neurosurgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
  • H. Katoh - Gunma University Heavy Ion Medical Center, Gunma, Japan
  • H. Kiyohara - National Institute of Radiological Sciences, Chiba, Japan
  • Y. Suzuki - Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan
  • S. Katoh - National Institute of Radiological Sciences, Chiba, Japan
  • T. Ohno - Gunma University Heavy Ion Medical Center, Gunma, Japan
  • T. Nakano - Gunma University Heavy Ion Medical Center, Gunma, Japan

PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09ptcog230

DOI: 10.3205/09ptcog230, URN: urn:nbn:de:0183-09ptcog2303

Published: September 24, 2009

© 2009 Yoshida et al.
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Outline

Text

Background: Glioblastoma (GB) is one of the most common and the most malignant tumor occurring in the central nervous system. GB is notorious for highly growth and invasive behavior and makes the surgical intervention ineffective. Recently, though there are many reports about the effectiveness of carbon ion radiotherapy (CRT), little is known about effects of CRT for GB. In addition, the almost of GB patients has not satisfied with treatment of the CRT alone for GB. Temodar (temozolomide: TMZ) is a cytotoxic alkylating agent which has shown an activity in the anaplastic glioma and GB. Combining TMZ with radiotherapy followed by maintenance TMZ has been reported to improve outcome compared with radiotherapy alone, and this treatment is currently considered as the standard treatment for GB. Hence, in this study, we investigated the effectiveness of TMZ with CRT for GB.

Materials and Methods: In vitro and In vivo study was used human glioblastoma cell lines CGNH-PM and/or U-87MG. Human glioblastoma cell suspensions were injected subcutaneously or intracerebrally into the flank or cerebrum of 4- to 5-week-old nude mice. TMZ was administered intraperitoneally once 5 days after tumor inoculation. The mice were exposed to irradiation within an hour after the drug administration. Carbon ion irradiation (CIR) was performed with a single dose at the NIRS. X-ray irradiation was carried in parallel with CIR.

Results: In vitro study, TMZ showed an additive effect in combination with CIR in clonogenicity of both cells. TMZ had an effect on increasing the frequency of apoptosis in both cells. However, TMZ had no significant enhancement of suppression of migration rate in both cells. In vivo study, the tumor growth of the irradiated group at CIR of 0.5, 1, 2 and 3 Gy was decreased to 92.2%, 66.3%, 35.6% and 31.0% respectively compared with the control (non treatment) group at 26 days after tumor inoculation. Comparable results were observed in X- irradiated mice, and the relative biological effectiveness (RBE) for the tumor growth delay was 2.7. Subsequently, the tumor growth was measured in the group which was treated with CIR + TMZ. The tumor growth of the group treated with 1 Gy CIR + 4 mg/kg TMZ was decreased to 50.1% compared to the irradiated group at 1 Gy CIR. MIB-1 index was significantly decreased by treatment of CIR + TMZ. Mice did not show any behavioral and weight changes in all recruited groups.

Conclusion: Growth reduction was significantly potentiated by CIR and TMZ combined treatment compared to that treated with either of them alone, though the problem of invasiveness still remains. These results suggest that the addition of TMZ may be a promising treatment when combined with CRT of GB.