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Tryptophan PET-defined gross tumor volume offers better coverage of initial progression than standard MRI-based planning in glioblastoma patients

  • Original Research
  • Published:
Journal of Radiation Oncology

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 + AMT was 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 + AMT than with GTVAMT alone (p = 0.068). Addition of 5 mm concentric margin around GTVMRI, GTVAMT, and GTVMRI + AMT would have completely covered the initial progression volume in 14, 57, and 71 % of the patients, respectively.

Conclusion

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.

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Abbreviations

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography

AMT:

Alpha-[11C]methyl-l-tryptophan

SUV:

Standardized uptake volume

CI:

Concordance index

GTV:

Gross tumor volume

CTV:

Clinical target volume

PTV:

Planning target volume

LAT1:

l-type amino acid transporter

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Acknowledgments

The study was partially supported by a grant from the National Cancer Institute (R01 CA123451 to CJ). The authors are thankful to Geoffrey Barger, MD who performed the clinical follow-up of the patients after postsurgical chemoradiation. Also, the authors are also thankful to Janet Barger, RN; Melissa Burkett, CNMT; Jane Cornett, RN; Anna DeBoard, RN; Kelly Forcucci, RN; Cathie Germain, MA; Carole Klapko, CNMT; Mei-li Lee, MS; Xin Lu, MS; Marcia Lodej, RN; Andrew Mosqueda, CNMT; Karen Nichols, NP; Galina Rabkin, CNMT; and Angela Wigeluk, CNMT for their assistance in patient recruitment, scheduling, and preparation, as well as for their technical assistance in performing the PET studies. Finally, the authors are grateful to Pulak Chakraborty, PhD and Hancheng Cai, PhD for the reliable radiosynthesis of the PET radiotracer.

Compliance with ethical guidelines

This retrospective series does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Barbara Ann Karmanos Cancer Center, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI, 48201, USA

    Michael Christensen, Michael Snyder & Harold Kim

  2. Departments of Pediatrics and Neurology, Wayne State University School of Medicine, Detroit, MI, USA

    David Olayinka Kamson & Csaba Juhász

  3. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Michael Christensen, Michael Snyder, Harold Kim, Natasha L. Robinette, Sandeep Mittal & Csaba Juhász

  4. PET Center and Translational Imaging Laboratory, Children’s Hospital of Michigan, Detroit, MI, USA

    David Olayinka Kamson & Csaba Juhász

  5. Department of Radiology, Wayne State University School of Medicine, Detroit, MI, USA

    Natasha L. Robinette

  6. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA

    Sandeep Mittal

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  1. Michael Christensen
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  2. David Olayinka Kamson
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  7. Csaba Juhász
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Correspondence to Michael Christensen.

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Christensen, M., Kamson, D.O., Snyder, M. et al. Tryptophan PET-defined gross tumor volume offers better coverage of initial progression than standard MRI-based planning in glioblastoma patients. J Radiat Oncol 3, 131–138 (2014). https://doi.org/10.1007/s13566-013-0132-5

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  • DOI: https://doi.org/10.1007/s13566-013-0132-5

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