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

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 T_1-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.

SUBMITTER: Fan Z

PROVIDER: S-EPMC7244074 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Fan Ziwen Z Liu Yukun Y Li Shaowu S Liu Xing X Jiang Tao T Wang Yinyan Y Wang Lei L

Aging 20200509 9

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 T<sub>2</sub>-weighted and contrast-enhancement T<sub>1-</sub>weighted magnetic resonance images (MRIs). Tumor growth rates were calculated based on tumor volume and diameter using various methods. The association of biomarkers ...[more]

PMID: 32388499

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Project description:PurposeThis prospective clinical trial investigated sodium (23Na) MRI at 7 Tesla (T) field strength as biomarker for tumor extent, isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation in glioma patients.Methods28 glioma patients underwent 23Na MRI on a 7T scanner (Siemens Healthcare, Erlangen, Germany) parallel to standard 3T MRI before chemoradiation. Areas of Gadolinium-contrast enhancement (gdce), non-enhancing T2-hyperintensity (regarded as edema), necrosis, and normal-appearing white matter (nawm) were segmented on 3T MRI imaging and were co-registered with the 23Na images. The median total 23Na concentrations of all areas were compared by pairwise t-tests. Furthermore, areas of gdce and edema were merged to yield the whole tumor area without necrosis. Subsequently, the difference in median of the 23Na concentration of this whole tumor area was compared between IDH-mutated and IDH wild-type gliomas as well as MGMT methylated and MGMT not-methylated glioblastomas using Whitney-Mann U-tests. All p-values were corrected after the Bonferroni-Holm procedure.ResultsThe 23Na concentration increased successively from nawm to necrotic areas (mean ± sd: nawm = 37.84 ± 5.87 mM, edema = 54.69 ± 10.64 mM, gdce = 61.72 ± 12.95 mM, necrosis = 81.88 ± 17.53 mM) and the concentrations differed statistically significantly between all regarded areas (adjusted p-values for all pairwise comparisons < 0.05). Furthermore, IDH-mutated gliomas showed significantly higher 23Na concentrations than IDH wild-type gliomas (median [interquartile range]: IDH wild-type = 52.37 mM [45.98 - 58.56 mM], IDH mutated = 65.02 mM [58.87-67.05 mM], p = 0.039). Among the glioblastomas, there was a trend towards increased 23Na concentration in MGMT methylated tumors that did not reach statistical significance (median [interquartile range]: MGMT methylated = 57.59 mM [50.70 - 59.17 mM], MGMT not methylated = 48.78 mM [45.88 - 53.91 mM], p = 1.0).Conclusions23Na MRI correlates with the IDH mutation status and could therefore enhance image guidance towards biopsy sites as wells as image-guided surgery and radiotherapy. Furthermore, the successive decrease of 23Na concentration from central necrosis to normal-appearing white matter suggests a correlation with tumor infiltration.

Project description:BackgroundLower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials.MethodsIn this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model.ResultsThe pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (-15.24% /180 days, 95% CI: [-21.37%, -8.62%]) (P < 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108).ConclusionIn this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.

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

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

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