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

Hyperfractionated concomitant boost proton radiotherapy for supratentorial glioblastoma multiforme

Meeting Abstract

  • K. Tsuboi - Proton Medical Research Center, University of Tsukuba, Tsukuba, Japan
  • M. Mizumoto - Proton Medical Research Center, University of Tsukuba, Tsukuba, Japan
  • T. Tsurubuchi - Neurological Surgery, University of Tsukuba, Tsukuba, Japan
  • T. Yamamoto - Neurological Surgery, University of Tsukuba, Tsukuba, Japan
  • T. Okumura - Proton Medical Research Center, University of Tsukuba, Tsukuba, Japan
  • H. Sakurai - Proton Medical Research Center, University of Tsukuba, Tsukuba, Japan
  • T. Sakae - Proton Medical Research Center, University of Tsukuba, Tsukuba, 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. Doc09ptcog210

DOI: 10.3205/09ptcog210, URN: urn:nbn:de:0183-09ptcog2107

Veröffentlicht: 24. September 2009

© 2009 Tsuboi et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: In this study the safety and efficacy of postoperative hyperfractionated concomitant boost proton beam (PB) radiotherapy for supratentorial glioblastoma multiforme (GBM) were prospectively evaluated. In addition, the chronological changes of gadolinium-enhanced volume (EV) on MRI and immuno histochemical changes on tumor tissue were analyzed to clarify the features of the MRI-change observed after this PB radiotherapy protocol.

Material and methods: Twenty patients with histologically-confirmed supratentorial GBM met the following criteria: (1) KPS was >60; (2) the diameter of the enhanced area before radiotherapy was <4 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. T2-high area (CTV3) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hours later, 250 MeV proton beams were delivered to the enhanced area plus 10 mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions), and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to CTV1 was 96.6 GyE. ACNU (80 mg/m2) was administered in the 1st and 4th weeks. Among these patients, 7 patients who underwent second surgery due to increase of EV after this PB radiotherapy were enrolled to the further analysis in which the EV on MRI were measured and their tumor specimens were analyzed by immunohistochemical examinations targeting Ki67, apoptosis, autophagy, vascular endothelial growth factor (VEGF) and CD133.

Results: Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression free survival rates were 45.0% and 15.5%, respectively. The median MRI-change free survival was 11.2 months. Volumetric study of the 6 cases with intra-field MRI-change demonstrated transient decrease or stabilization of EV while 1 case with extra-field recurrence showed continuous increase of EV. Histopathological examinations on the specimens taken after PB radiotherapy demonstrated reactive inflammatory changes and degenerated tumor cells. Immunohistochemical studies revealed that Ki67 positivity decreased significantly while apoptosis and autophagy increased moderately. Also, the VEGF expressions and CD133 positive cells increased relatively in tumor tissues taken at second surgery.

Conclusions: Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size is well-considered. The increase of EV on MRI could be "pseudo-progression" however these phenomenon and eventual true-progression from survived tumor stem cells were probably sequential. Further studies are warranted to pursue the possibility to control border region recurrences.