title: Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume.
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.
authors.affiliation: Department of Radiation Oncology, University Hospital RWTH Aachen, Aachen, Germany. marc.piroth@helios-kliniken.de.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany. marc.piroth@helios-kliniken.de.|Department of Radiation Oncology, HELIOS University Hospital Wuppertal, Witten/Herdecke University, Wuppertal, Germany. marc.piroth@helios-kliniken.de.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Piroth
authors.affiliation: Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.|Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.affiliation: Department of Radiation Oncology, University Hospital RWTH Aachen, Aachen, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pinkawa
authors.affiliation: Department of Radiation Oncology, University Hospital RWTH Aachen, Aachen, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.|Department of Radiation Oncology, HELIOS University Hospital Wuppertal, Witten/Herdecke University, Wuppertal, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Holy
authors.affiliation: Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoffels
authors.affiliation: Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ermert
authors.affiliation: Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany.|Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: N Jon
authors.initials: NJ
authors.lastname: Shah
authors.affiliation: Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany.|Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
authors.affiliation: Department of Radiation Oncology, University Hospital RWTH Aachen, Aachen, Germany.|Jülich-Aachen Research Alliance (JARA) - Section JARA-Brain, Research Center Jülich, Jülich, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eble
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000378:metabolism; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000592:standards*; D012189:Retrospective Studies; D047368:Tumor Burden; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C117289:O-(2-fluoroethyl)tyrosine; D019275:Radiopharmaceuticals; D014443:Tyrosine
keywords: FET-PET; Glioblastoma; Radiochemotherapy; Relapse patterns; Target volume definition