Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M−P− in 16%, M−P+ in 32%, M+P+ in 46% and M+P− in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

[1]  J. Martí-Climent,et al.  Quantitative volumetric analysis of gliomas with sequential MRI and 11C-methionine PET assessment: patterns of integration in therapy planning , 2012, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  Abhishek Kumar,et al.  Comparative diagnostic accuracy of contrast-enhanced MRI and 18F-FDOPA PET-CT in recurrent glioma , 2013, European Radiology.

[3]  J. Sarkaria,et al.  The role of LAT1 in 18F-DOPA uptake in malignant gliomas , 2012, Journal of Neuro-Oncology.

[4]  W. Ng,et al.  Re-do Craniotomy for Recurrent Grade IV Glioblastomas: Impact and Outcomes from the National Neuroscience Institute Singapore. , 2016, World neurosurgery.

[5]  John O. Prior,et al.  Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis. , 2016, Neuro-oncology.

[6]  E. Shaw,et al.  Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  A. Jemal,et al.  Cancer statistics, 2016 , 2016, CA: a cancer journal for clinicians.

[8]  C. Belka,et al.  Recurrence pattern analysis after re-irradiation with bevacizumab in recurrent malignant glioma patients , 2014, Radiation oncology.

[9]  B. Meyer,et al.  Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. , 2016, Neuro-oncology.

[10]  Val J Lowe,et al.  Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. , 2013, Neuro-oncology.

[11]  B A Kall,et al.  Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. , 1987, Journal of neurosurgery.

[12]  Marie Blonski,et al.  Correlation of SUV-Derived Indices With Tumoral Aggressiveness of Gliomas in Static 18F-FDOPA PET: Use in Clinical Practice , 2015, Clinical nuclear medicine.

[13]  J. Cairncross,et al.  Corticosteroid-induced magnetic resonance imaging changes in patients with recurrent malignant glioma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Irène Buvat,et al.  Evaluation of Quantitative Criteria for Glioma Grading With Static and Dynamic 18F-FDopa PET/CT , 2013, Clinical nuclear medicine.

[15]  Fred H. Hochberg,et al.  Assumptions in the radiotherapy of glioblastoma , 1980, Neurology.

[16]  J. Buckner,et al.  Changes in presentation, treatment, and outcomes of adult low-grade gliomas over the past fifty years. , 2013, Neuro-oncology.

[17]  Rebecca L. Siegel Mph,et al.  Cancer statistics, 2016 , 2016 .

[18]  T. Cascino,et al.  Response criteria for phase II studies of supratentorial malignant glioma. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Thomas C. Chen,et al.  Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. , 2015, JAMA.

[20]  W. Hall,et al.  Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas. , 1999, International journal of radiation oncology, biology, physics.

[21]  J. Uhm Hypofractionated Stereotactic Radiation Therapy: An Effective Therapy for Recurrent High-Grade Gliomas , 2011 .

[22]  R. Floris,et al.  Factors affecting ¹⁸F FDOPA standardized uptake value in patients with primary brain tumors after treatment. , 2015, Nuclear medicine and biology.

[23]  Wei Chen,et al.  18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  K. Wallner,et al.  Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. , 1989, International journal of radiation oncology, biology, physics.

[25]  Branislav Jeremic,et al.  L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. , 2005, International journal of radiation oncology, biology, physics.

[26]  Rajeev Kumar,et al.  Can (18)F-FDOPA PET/CT predict survival in patients with suspected recurrent glioma? A prospective study. , 2014, European journal of radiology.

[27]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[28]  Thomas Czech,et al.  Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[29]  N. Dowson,et al.  Increasing feasibility and utility of (18)F-FDOPA PET for the management of glioma. , 2015, Nuclear medicine and biology.

[30]  P. Box Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression , 2005 .

[31]  J. Uhm Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group , 2010 .

[32]  Peter Nakaji,et al.  An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. , 2014, Journal of neurosurgery.

[33]  R. Laing,et al.  Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. , 1997, International journal of radiation oncology, biology, physics.

[34]  W. Burchert,et al.  3-O-Methyl-6-[18F]fluoro-l-DOPA and its evaluation in brain tumour imaging , 2003, European Journal of Nuclear Medicine and Molecular Imaging.