Research Paper Volume 12, Issue 9 pp 7908—7926

Association of tumor growth rates with molecular biomarker status: a longitudinal study of high-grade glioma

Ziwen Fan 1, , Yukun Liu 1, , Shaowu Li 2, , Xing Liu 3, , Tao Jiang 1, 4, , Yinyan Wang 1, 4, *, , Lei Wang 1, *, ,

  • 1 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
  • 2 Department of Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
  • 3 Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
  • 4 Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China
* Equal contribution

received: January 14, 2020 ; accepted: March 31, 2020 ; published: May 9, 2020 ;

https://doi.org/10.18632/aging.103110
How to Cite

Copyright © 2020 Fan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

To determine the association of molecular biomarkers with tumor growth in patients with high-grade gliomas (HGGs), the tumor growth rates and molecular biomarker status in 109 patients with HGGs were evaluated. Mean tumor diameter was assessed on at least two pre-surgical T2-weighted and contrast-enhancement T1-weighted magnetic resonance images (MRIs). Tumor growth rates were calculated based on tumor volume and diameter using various methods. The association of biomarkers with increased or decreased tumor growth was calculated using linear mixed-effects models. HGGs exhibited rapid growth rates, with an equivalent volume doubling time of 63.4 days and an equivalent velocity of diameter expansion of 51.6 mm/year. The WHO grade was an independent clinical factor of eVDEs. TERT promoter mutation C250T and MGMT promoter methylation was significantly associated with tumor growth in univariable analysis but not in multivariable analysis. Molecular groups of IDH1, TERT, and 1p/19q and IDH1 and MGMT were independently associated with tumor growth. In addition, tumor enhanced area had a faster growth rate than a tumor entity in incomplete enhanced HGGs (p = 0.006). Our findings provide crucial information for the prediction of preoperative tumor growth in HGGs, and aided in the decision making for aggressive resection and adjuvant treatment strategies.

Abbreviations

WHO: World Health Organization; MRI: magnetic resonance imaging; CE-T1WI: contrast-enhanced T1-weighted images; T2WI: T2-weighted images; HGGs: high-grade gliomas; AO: anaplastic oligodendroglioma; AA: anaplastic astrocytoma; AG: Anaplastic glioma; NOS: not otherwise specified; VDT: volume-doubling time; eVDT: equivalent VDT; SGR: specific growth rate; MTD: mean tumor diameter; VDE: velocity of diameter expansion; eVDE: equivalent VDE; IDH1: isocitrate dehydrogenase 1; MGMT: O-6-methylguanine-DNA methyltransferase; TERT: telomerase reverse transcriptase; ATRX: α-thalassemia X-linked intellectual disability; GFAP: primary glial fibrillary acidic protein; Olig-2: oligodendrocyte transcription factor; TOPO2: topoisomerase II; MMP9: matrix metallopeptidase 9; GST-π: glutathione S-transferase π; EGFR: epidermal growth factor receptor; VEGF: vascular endothelial growth factor; PTEN: phosphatase and tensin homolog; Wt: wild-type; Mut: mutation; Mt: methylation; LME: linear mixed-effects models; MSE: mean square error; IQR: interquartile range; CI: confidence interval; SE: standard error; BBB: blood-brain barrier.