title: Tryptophan PET-defined gross tumor volume offers better coverage of initial progression than standard MRI-based planning in glioblastoma patients.
abstract: OBJECTIVE
  Glioblastoma is an infiltrative malignancy that tends to extend beyond the MRI-defined tumor volume. We utilized positron emission tomography (PET) imaging with the radiotracer alpha-[11C]methyl-L -tryptophan (AMT) to develop a reliable high-risk gross tumor volume (HR-GTV) method for delineation of glioblastoma. AMT can detect solid tumor mass and tumoral brain infiltration by increased tumoral tryptophan transport and metabolism via the immunosuppressive kynurenine pathway.
  
  
  METHODS
  We reviewed all patients in our database with histologically proven glioblastoma who underwent preoperative AMT-PET scan prior to surgery and chemoradiation. Treated radiotherapy volumes were derived from the simulation CT with MRI fusion. High-GTV with contrast enhanced T1-weighted MRI alone (GTVMRI) was defined as the postoperative cavity plus any residual area of enhancement on postcontrast T1-weighted images. AMT-PET images were retrospectively fused to the simulation CT, and a high-risk GTVs generated by both AMT-PET alone (GTVAMT) was defined using a threshold previously established to distinguish tumor tissue from peritumoral edema. A composite volume of MRI and AMT tumor volume was also created (combination of MRI fused with AMT-PET data; GTVMRI+AMT). In patients with definitive radiographic progression, follow-up MRI demonstrating initial tumor progression was fused with the pretreatment images and a progression volume was contoured. The coverage of the progression volume by GTVMRI, GTVAMT, and GTVMRI+AMTwas determined and compared using the Wilcoxon's signed-rank test.
  
  
  RESULTS
  Eleven patients completed presurgical AMT-PET scan, seven of whom had progressive disease after initial therapy. GTVMRI(mean, 50.2 cm3) and GTVAMT(mean, 48.9 cm3) were not significantly different. Mean concordance index of the volumes was 39±15 %. Coverage of the initial recurrence volume by HR-GTVMRI(mean, 52 %) was inferior to both GTVAMT(mean, 68 %;p=0.028) and GTVMRI+AMT(mean 73 %;p=0.018). The AMT-PET-exclusive coverage was up to 41 % of the recurrent volume. There was a tendency towards better recurrence coverage with GTVMRI+AMTthan with GTVAMTalone (p=0.068). Addition of 5 mm concentric margin around GTVMRI, GTVAMT, and GTVMRI+AMTwould have completely covered the initial progression volume in 14, 57, and 71 % of the patients, respectively.
  
  
  CONCLUSIONS
  We found that a GTV defined by AMT-PET produced similar volume, but superior recurrence coverage than the treated standard MRI-determined volume. A prospective study is necessary to fully determine the usefulness of AMT-PET for volume definition in glioblastoma radiotherapy planning.
authors.affiliation: Department of Radiation Oncology, Barbara Ann, Karmanos Cancer Center, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Christensen
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, Detroit, MI, USA. PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: David Olayinka
authors.initials: DO
authors.lastname: Kamson
authors.affiliation: Department of Radiation Oncology, Barbara Ann, Karmanos Cancer Center, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.affiliation: Department of Radiation Oncology, Barbara Ann, Karmanos Cancer Center, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Kim
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA. Department of Radiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Robinette
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Departments of Pediatrics and Neurology, Wayne State University School of Medicine, Detroit, MI, USA. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA. PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Juhász
keywords: GTV; MRI; PET; Radiation therapy; Recurrence coverage; Tryptophan; Volumetry