Positron emission tomography (PET) for prediction of glioma histology: protocol for an individual-level data meta-analysis of test performance

Abstract

IntroductionGliomas, the most commonly diagnosed primary brain tumours, are associated with varied survivals based, in part, on their histological subtype. Therefore, accurate pretreatment tumour grading is essential for patient care and clinical trial design.Methods and analysisWe will perform an individual-level data meta-analysis of published studies to evaluate the ability of different types of positron emission tomography (PET) to differentiate high from low-grade gliomas. We will search PubMed and Scopus from inception through 30 July 2017 with no language restriction and full-text evaluation of potentially relevant articles. We will choose studies that assess PET using 18-Fludeoxyglucose (18F-FDG), l-[Methyl-()11C]Methionine (11C-MET), 18F-Fluoro-Ethyl-Tyrosine (18F-FET) or (18)F-Fluorothymidine (18F-FLT)for grading, verified with histological confirmation. We will include both prospective and retrospective studies. Bias will be assessed by two reviewers with the Quality Assessment of Diagnostic Accuracy Studies-2 tool and as per method described by Deeks et al.Ethics and disseminationEthics approval was not applicable, as this is a meta-analytic study. Results of the analysis will be submitted for publication in a peer-reviewed journal.PROSPERO registration number CRD42017078649.

Multiple positron emission tomography tracers for use in the classification of gliomas according to the 2016 World Health Organization criteria

“…Previous reports evaluating multiple PET tracers were based on systematic reviews based on the meta-analyses of published studies, and few reports evaluated multiple PET tracers used in the same patient. 18–20 Furthermore, no report to date has evaluated the utility of multiple PET tracers including 18 F-FMISO. The systematic reviews of published meta-analyses related to PET were based on the glioma classification according to WHO grades II, III, and IV and did not conform to the 2016 WHO classification of gliomas.…”

Modern surgical management of incidental gliomas

“…Interestingly, there’s evidence suggesting the epileptogenic nature of 2HG as higher tissue concentrations of it have been associated with preoperative seizures in glioma patients [ 40 ]. Positron emission tomography (PET) imaging provides valuable insight about tumor metabolism and PET can be combined with radiolabeled particles such as O-(2–18F-fluoroethyl)- l -tyrosine (18F-FET), and 6-fluoro- l -DOPA(FDOPA) to guide glioma detection during biopsy or resection [ 41 , 42 ]. LGGs are typically hypometabolic on PET with 18F-fluorodeoxyglucose compared to HGGs; however, PET with amino acid uptake of 18F-FET is noted to be increased in two-thirds of LGGs and is therefore utilized to distinguish LGGs from HGGs [ 7 ].…”

“…LGGs are typically hypometabolic on PET with 18F-fluorodeoxyglucose compared to HGGs; however, PET with amino acid uptake of 18F-FET is noted to be increased in two-thirds of LGGs and is therefore utilized to distinguish LGGs from HGGs [ 7 ]. The metabolic information obtained with PET can be combined with the morphological characteristics acquired from MRI to improve histological grading and accurately perform targeted biopsies [ 41 ].…”

“…PET imaging with 18F-FET has shown to help differentiate gliomas from other tumors. In LGGs with increased uptake of 18F-FET, studies have shown it may be suggestive of increased diagnosis accuracy for malignant progression compared to MRI This technique could not only improve diagnosis of potential LGGs are a higher risk for malignant transformation, but also enhance histologic diagnosis obtained during biopsy or resection Proton magnetic resonance (MR) spectroscopy ( 1 H-MRSI) [ 7 , 10 , 37 ] Diagnostic imaging for iLGGs Proton MR spectroscopy is another physiologic and metabolic imaging modality that offers more information about tumor activity than conventional MRI by assessing the distribution of cellular metabolite levels Several studies have reported 1 H-MRSI can serve as an aid in detecting LGG tumor progression by evaluating for cellular metabolite levels that are characteristically found in LGGs, but not HGGs, such as choline (CHO) peak due to increased membrane synthesis or low N-acetylaspartate (NAA), and no presence of lactate or lipids Specifically, studies have noted that a decreased NAA-CHO ratio potentially may be used as a technique to identify early LGG dedifferentiation and transformation to higher malignancy tumors Intraoperative magnetic resonance imaging (iMRI) [ 7 , 40 ] Biopsy or resection of iLGGs iMRI is a continuous imaging technique that allows for intraoperative imaging to evaluate progress of tumor resection iMRI is well-documented in the literature as a useful technology in LGG surgery that can help safely achieve maximal EOR in an efficient and cost-effective manner Studies have demonstrated this modality has improved EOR, decreased damage to functional brain regions, and better survival outcomes in glioma surgery Intraoperative fluorescence-guided microscopy with 5-amino-levulinic acid (5-ALA) [ 7 , 38 , 40 , 41 ] Biopsy or resection of iLGGs This novel imaging method offers enhanced intraoperative visualization of LGG tissue with the aid of 5-ALA induced fluorescence compared to traditional white-light microscopy While 5-ALA tool has less visible fluorescence in LGGs compared to HGGs, it is still a valuable approach that has potential to be combined with newer techniques such as quantitative fluorescence, intraoperative confocal microscopy, and FLIM of PpIX to improve patient outcomes While this technique is now routinely incorporated to visualize HGGs during resection, recent studies highlight this modality’s potential to overcome brain shift and effectively identify intratumoral regions of anaplastic foci in LG...…”

Editorial: Differentiating brain cancers and glioblastoma through imaging methodologies

“…As summarized in the Mini Review by Hooper and Ginat and others [e.g., ( 1 , 4 , 5 )], no single imaging technique has been proven to be successful in this aim, whereas a combination of imaging modalities, such as e.g., 18 F-FDG PET and multiparametric magnetic resonance (MR) imaging (MRI), improve the detection, staging and differentiation of brain tumors. Quantitative radiomics of multiparametric MRI with or without the inclusion of brain MR spectroscopy further the finer differentiation of brain tumors as well as glioma or GBM subtypes, with the goal of personalizing tumor treatment ( 1 , Hooper and Ginat ; Vallee et al.…”