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Peer-reviewedCC BY-NC-ND 4.0Translational Cancer Research

Diagnostic accuracy of PET/CT parameters for noninvasive prediction of isocitrate dehydrogenase mutation status in glioma: a systematic review and meta-analysis

  1. 1Department of Neurosurgery, Shanxi Provincial People’s Hospital, Shanxi Medical University, Taiyuan, China
  2. 2Department of Clinical Medicine, Shanxi Medical University, Taiyuan, China
  3. 3Department of Forensic Medicine, Shanxi Medical University, Taiyuan, China

Abstract

Background: Noninvasive prediction of isocitrate dehydrogenase (IDH) mutation status may facilitate the preoperative characterization of gliomas. However, the diagnostic performance of positron emission tomography/computed tomography (PET/CT) parameters may vary according to the radiotracer used, cutoff thresholds, reference standards, and patient populations. These differences may increase the uncertainty in the clinical interpretation and application of PET/CT parameters. This study systematically evaluated the diagnostic accuracy of quantitative PET/CT parameters for the noninvasive prediction of IDH mutation status in glioma.

Methods: A systematic search of Web of Science, PubMed, the Cochrane Library, and Embase was conducted from database inception to November 5, 2024, with an updated search conducted on August 20, 2026. Eligible studies were diagnostic accuracy studies evaluating quantitative PET/CT parameters for predicting IDH mutation status in glioma, with IDH status determined using pathological and/or molecular reference standards. Data were independently extracted by two reviewers. Diagnostic performance was assessed using sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio, and the area under the summary receiver operating characteristic (SROC) curve (AUC). Threshold-effect, subgroup, and meta-regression analyses were performed where appropriate. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.

Results: Fourteen studies involving 1,205 patients were included, comprising 655 patients with IDH-wild-type gliomas and 550 with IDH-mutant gliomas. All included studies were retrospective. The included studies evaluated multiple PET tracers and seven quantitative parameters: time to peak (TTP), tumor-to-normal tissue ratio (T/N ratio), maximum standardized uptake value (SUVmax), maximum tumor-to-background ratio (TBRmax), mean tumor-to-background ratio (TBRmean), metabolic tumor volume (MTV), and slope. Diagnostic performance varied across PET parameters. TTP showed a pooled SEN of 0.72, SPE of 0.81, and AUC of 0.84, whereas the T/N ratio showed a SEN of 0.66, SPE of 0.86, and AUC of 0.81. SUVmax demonstrated the highest SEN (0.90), with an SPE of 0.58 and an AUC of 0.90. Threshold-effect analysis indicated significant threshold effects for TBRmean and MTV. The QUADAS-2 assessment identified no studies at high risk of bias, although some concerns remained regarding the index test and reference standard domains. Exploratory meta-regression analyses found no significant associations between diagnostic performance and country, glioma grade, tracer type, or reference standard.

Conclusions: PET/CT demonstrates potential as a noninvasive tool for predicting IDH mutation status in glioma. TTP, the T/N ratio, and SUVmax exhibited relatively favorable diagnostic performance. However, their clinical applicability remains uncertain due to heterogeneity across studies, variable diagnostic thresholds, and limitations of the included studies. Further prospective studies are warranted to validate these findings.

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BibTeX
@article{zhao2026diagnostic,
  title = {{Diagnostic accuracy of PET/CT parameters for noninvasive prediction of isocitrate dehydrogenase mutation status in glioma: a systematic review and meta-analysis}},
  author = {Xulu Zhao and Yiran Chen and Zhi Zhang and Zhenping Ge and Ziyang Ren and Tao Hu},
  journal = {Translational Cancer Research},
  year = {2026},
  month = sep,
  doi = {10.21037/tcr-2026-1228},
  url = {https://doi.org/10.21037/tcr-2026-1228},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Diagnostic accuracy of PET/CT parameters for noninvasive prediction of isocitrate dehydrogenase mutation status in glioma: a systematic review and meta-analysis
AU  - Xulu Zhao
AU  - Yiran Chen
AU  - Zhi Zhang
AU  - Zhenping Ge
AU  - Ziyang Ren
AU  - Tao Hu
PY  - 2026
DA  - 2026/09/28
JO  - Translational Cancer Research
DO  - 10.21037/tcr-2026-1228
UR  - https://doi.org/10.21037/tcr-2026-1228
AB  - Background: Noninvasive prediction of isocitrate dehydrogenase (IDH) mutation status may facilitate the preoperative characterization of gliomas. However, the diagnostic performance of positron emission tomography/computed tomography (PET/CT) parameters may vary according to the radiotracer used, cutoff thresholds, reference standards, and patient populations. These differences may increase the uncertainty in the clinical interpretation and application of PET/CT parameters. This study systematically evaluated the diagnostic accuracy of quantitative PET/CT parameters for the noninvasive prediction of IDH mutation status in glioma.  Methods: A systematic search of Web of Science, PubMed, the Cochrane Library, and Embase was conducted from database inception to November 5, 2024, with an updated search conducted on August 20, 2026. Eligible studies were diagnostic accuracy studies evaluating quantitative PET/CT parameters for predicting IDH mutation status in glioma, with IDH status determined using pathological and/or molecular reference standards. Data were independently extracted by two reviewers. Diagnostic performance was assessed using sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio, and the area under the summary receiver operating characteristic (SROC) curve (AUC). Threshold-effect, subgroup, and meta-regression analyses were performed where appropriate. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.  Results: Fourteen studies involving 1,205 patients were included, comprising 655 patients with IDH-wild-type gliomas and 550 with IDH-mutant gliomas. All included studies were retrospective. The included studies evaluated multiple PET tracers and seven quantitative parameters: time to peak (TTP), tumor-to-normal tissue ratio (T/N ratio), maximum standardized uptake value (SUVmax), maximum tumor-to-background ratio (TBRmax), mean tumor-to-background ratio (TBRmean), metabolic tumor volume (MTV), and slope. Diagnostic performance varied across PET parameters. TTP showed a pooled SEN of 0.72, SPE of 0.81, and AUC of 0.84, whereas the T/N ratio showed a SEN of 0.66, SPE of 0.86, and AUC of 0.81. SUVmax demonstrated the highest SEN (0.90), with an SPE of 0.58 and an AUC of 0.90. Threshold-effect analysis indicated significant threshold effects for TBRmean and MTV. The QUADAS-2 assessment identified no studies at high risk of bias, although some concerns remained regarding the index test and reference standard domains. Exploratory meta-regression analyses found no significant associations between diagnostic performance and country, glioma grade, tracer type, or reference standard.  Conclusions: PET/CT demonstrates potential as a noninvasive tool for predicting IDH mutation status in glioma. TTP, the T/N ratio, and SUVmax exhibited relatively favorable diagnostic performance. However, their clinical applicability remains uncertain due to heterogeneity across studies, variable diagnostic thresholds, and limitations of the included studies. Further prospective studies are warranted to validate these findings.
SN  - 2218-676X
SN  - 2219-6803
ER  -