Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume

Radiat Oncol. 2016 Jun 24:11:87. doi: 10.1186/s13014-016-0665-z.

Abstract

Background: O-(2-18 F-fluoroethyl)-L-tyrosine-(FET)-PET may be helpful to improve the definition of radiation target volumes in glioblastomas compared with MRI. We analyzed the relapse patterns in FET-PET after a FET- and MRI-based integrated-boost intensity-modulated radiotherapy (IMRT) of glioblastomas to perform an optimized target volume definition.

Methods: A relapse pattern analysis was performed in 13 glioblastoma patients treated with radiochemotherapy within a prospective phase-II-study between 2008 and 2009. Radiotherapy was performed as an integrated-boost intensity-modulated radiotherapy (IB-IMRT). The prescribed dose was 72 Gy for the boost target volume, based on baseline FET-PET (FET-1) and 60 Gy for the MRI-based (MRI-1) standard target volume. The single doses were 2.4 and 2.0 Gy, respectively. Location and volume of recurrent tumors in FET-2 and MRI-2 were analyzed related to initial tumor, detected in baseline FET-1. Variable target volumes were created theoretically based on FET-1 to optimally cover recurrent tumor.

Results: The tumor volume overlap in FET and MRI was poor both at baseline (median 12 %; range 0-32) and at time of recurrence (13 %; 0-100). Recurrent tumor volume in FET-2 was localized to 39 % (12-91) in the initial tumor volume (FET-1). Over the time a shrinking (mean 12 (5-26) ml) and shifting (mean 6 (1-10 mm) of the resection cavity was seen. A simulated target volume based on active tumor in FET-1 with an additional safety margin of 7 mm around the FET-1 volume covered recurrent FET tumor volume (FET-2) significantly better than a corresponding target volume based on contrast enhancement in MRI-1 with a same safety margin of 7 mm (100 % (54-100) versus 85 % (0-100); p < 0.01). A simulated planning target volume (PTV), based on FET-1 and additional 7 mm margin plus 5 mm margin for setup-uncertainties was significantly smaller than the conventional, MR-based PTV applied in this study (median 160 (112-297) ml versus 231 (117-386) ml, p < 0.001).

Conclusions: In this small study recurrent tumor volume in FET-PET (FET-2) overlapped only to one third with the boost target volume, based on FET-1. The shrinking and shifting of the resection cavity may have an influence considering the limited overlap of initial and relapse tumor volume. A simulated target volume, based on FET-1 with 7 mm margin covered 100 % of relapse volume in median and led to a significantly reduced PTV, compared to MRI-based PTVs. This approach may achieve similar therapeutic efficacy but lower side effects offering a broader window to intensify concomitant systemic treatment focusing distant failures.

Keywords: FET-PET; Glioblastoma; Radiochemotherapy; Relapse patterns; Target volume definition.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Chemoradiotherapy*
  • Female
  • Follow-Up Studies
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Prognosis
  • Prospective Studies
  • Radiopharmaceuticals / metabolism
  • Radiotherapy Dosage
  • Radiotherapy Planning, Computer-Assisted / methods
  • Radiotherapy, Image-Guided / methods*
  • Radiotherapy, Intensity-Modulated / standards*
  • Retrospective Studies
  • Tumor Burden
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • O-(2-fluoroethyl)tyrosine
  • Radiopharmaceuticals
  • Tyrosine