Pre-operative dual-time-point [F]FET PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study.

in European journal of nuclear medicine and molecular imaging by Dong Yun Lee, Jungsu S Oh, Jeong Won Kim, Minyoung Oh, Seung Jun Oh, Seungjoo Lee, Young-Hoon Kim, Jeong Hoon Kim, Soo Jeong Nam, Sang Woo Song, Jae Seung Kim

TLDR

  • The study shows that [F]FET PET scans can help differentiate genetic changes in glioma patients, which can improve treatment decisions.
  • CDKN2A/B loss and PIK3CA mutation status can be identified using pre-operative dual-time-point [F]FET PET/CT.

Abstract

While [F]FET PET plays a complementary role in glioma imaging, it needs to be more comprehensively understood for improved characterization of glioma prior to surgery given the evolving landscape of molecular neuropathology. Thus, we investigated the utility of pre-operative dual-time-point [F]FET PET in correlation with next-generation sequencing (NGS) data in patients with adult-type diffuse glioma (ADG). Adult patients who were suspected to have primary glioma were prospectively recruited between June 2021 and January 2024. They underwent pre-operative dual-time-point static PET/CT at 20 min (early) and 80 min (delay) after [F]FET injection. Semi-quantitative parameters of the hottest lesion (SUV) of tumour and the hottest lesion-to-normal brain ratio (TBR) were assessed from each summed image. Furthermore, the percentage changes (△) of SUVand TBRbetween two images were calculated. Histopathology of glioma was determined according to the 2021 WHO classification and NGS data. This study investigated a dozen genes in 76 patients, of whom 51 had isocitrate dehydrogenase (IDH)-wild-type glioblastoma, 13 had IDH-mutant astrocytoma, and 12 had IDH-mutant oligodendroglioma. Every tumour was [F]FET-avid having TBRmore than 1.6. Patients with CDKN2A/B loss had significantly higher values of SUV(5.7 ± 1.6 vs. 4.7 ± 1.3, p = 0.004; 5.0 ± 1.4 vs. 4.4 ± 1.2, p = 0.026) and TBR(6.5 ± 1.8 vs. 5.1 ± 1.7, p = 0.001; 5.3 ± 1.5 vs. 4.3 ± 1.3, p = 0.004) in both scans than patients without CDKN2A/B loss, even after adjustment for age, MRI enhancement, tumor grade and type of pathology. Furthermore, patients with PIK3CA mutation (16.2 ± 11.8 vs. 6.7 ± 11.6, p = 0.007) had significantly higher △SUVthan patients without PIK3CA mutation, even after adjustment for age, MRI enhancement, tumor grade, and type of pathology. Among the dozen genes investigated in this prospective study in patients with ADG, we found out that CDKN2A/B loss and PIK3CA mutation status could be differentiated by pre-operative dual-time-point [F]FET PET/CT.

Overview

  • The study investigates the utility of pre-operative dual-time-point [F]FET PET in correlation with next-generation sequencing (NGS) data in patients with adult-type diffuse glioma (ADG).
  • The study included 76 patients, of whom 51 had isocitrate dehydrogenase (IDH)-wild-type glioblastoma, 13 had IDH-mutant astrocytoma, and 12 had IDH-mutant oligodendroglioma.
  • The primary objective of the study is to differentiate CDKN2A/B loss and PIK3CA mutation status by pre-operative dual-time-point [F]FET PET/CT in patients with ADG.

Comparative Analysis & Findings

  • Patients with CDKN2A/B loss had significantly higher values of SUV and TBR than patients without CDKN2A/B loss, both in the early and delay scans.
  • Patients with PIK3CA mutation had significantly higher △SUV than patients without PIK3CA mutation, even after adjusting for other factors.
  • CDKN2A/B loss and PIK3CA mutation status could be differentiated by pre-operative dual-time-point [F]FET PET/CT among the dozen genes investigated in the study.

Implications and Future Directions

  • The study emphasizes the importance of understanding [F]FET PET in glioma imaging and its potential utility in improving characterization of glioma prior to surgery.
  • Future studies should investigate the incorporation of [F]FET PET with other imaging modalities and molecular markers to enhance its diagnostic accuracy.
  • The study highlights the need for further research to validate the findings and explore the applicability of [F]FET PET in other types of gliomas and patient populations.
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