Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma

Tom, Martin C.; Park, Deborah Y.J.; Yang, Kailin; Leyrer, C.M.; Wei, Wei; Xing, Jia; Varra, Vamsi; Yu, Jennifer; Chao, Samuel T.; Balagamwala, E.H.; Suh, John H.; Vogelbaum, Michael A.; Barnett, Gene H.; Prayson, Richard A.; Stevens, Glen; Peereboom, David M.; Ahluwalia, Manmeet; Murphy, Erin S.

doi:10.1016/j.ijrobp.2019.08.025

Cited by 50 publications

(62 citation statements)

References 12 publications

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“…The median time to MT in the present study was 5.1 years, which correlates well with previous reports in which it ranged from 2.7 to 5.4 years. 16,17 Previously identified prognostic factors for MT include older age, male sex, multiple tumor locations, tumor size $5 cm, adjuvant temozolomide, presence of residual tumor, astrocytoma histology, and IDH wild-type. [16][17][18] However, in our study, none of these factors were helpful in making the diagnosis of MT.…”

Section: Discussionmentioning

confidence: 99%

MRS as an Aid to Diagnose Malignant Transformation in Low-Grade Gliomas with Increasing Contrast Enhancement

Toh¹,

Castillo

Wei

et al. 2020

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Increased contrast enhancement has been used as a marker of malignant transformation in lowgrade gliomas. This marker has been found to have limited accuracy because many low-grade gliomas with increased contrast enhancement remain grade II. We aimed to investigate whether MR spectroscopy can contribute to the diagnosis of malignant transformation in low-grade gliomas with increased contrast enhancement. MATERIALS AND METHODS: Patients with low-grade gliomas who had contemporaneous MR spectroscopy and histopathology for tumor regions with increased contrast enhancement between 2004 and 2015 were retrospectively reviewed. Clinical data collected were sex and age, Karnofsky Performance Scale, histologic subtypes, isocitrate dehydrogenase 1 mutation status, disease duration, adjuvant therapy, and post-radiation therapy duration. Imaging data collected were contrast-enhancement size, whole-tumor size, MR spectroscopy metabolite ratios, and tumor grades of regions with increased contrast enhancement. Diagnostic values of these factors on malignant transformation of low-grade gliomas were statistically analyzed. RESULTS: A total of 86 patients with 96 MR spectroscopy studies were included. Tumor grades associated with increased contrast enhancement were grade II (n ¼ 42), grade III (n ¼ 27), and grade IV (n ¼ 27). On multivariate analysis, the NAA/Cho ratio was the only significant factor (P , .001; OR, 7.1; 95% CI, 3.2-16.1) diagnostic of malignant transformation. With 0.222 as the cutoff value, the sensitivity, specificity, and accuracy of NAA/Cho for diagnosing malignant transformation were 94.4%, 83.3%, and 89.6%, respectively. CONCLUSIONS: MR spectroscopy complements conventional MR imaging in the diagnosis of malignant transformation in a subgroup of low-grade gliomas with increased contrast enhancement. ABBREVIATIONS: LGG ¼ low-grade glioma; MT ¼ malignant transformation; WHO ¼ World Health Organization L ow-grade gliomas (LGGs) are grade II World Health Organization (WHO) primary brain tumors, accounting for 14.6% of gliomas in population-based studies. 1 LGGs may remain clinically and radiographically stable for years after initial diagnosis and treatment. However, at an unpredictable time, some may show MR imaging features suggestive of disease progression, eg,

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Section: Discussionmentioning

confidence: 99%

MRS as an Aid to Diagnose Malignant Transformation in Low-Grade Gliomas with Increasing Contrast Enhancement

Toh¹,

Castillo

Wei

et al. 2020

AJNR Am J Neuroradiol

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“…Low-grade gliomas (LGGs) mainly refer to grade 2 by the WHO grading system and are relatively uncommon, constituting approximately 10% of all primary brain tumors in adults [ 1 , 2 ]. Although often considered as “benign”, over half of these patients will develop tumor progression within 5 years and the rate of progression-free survival (PFS) at 10 years was 21–51% [ 3 , 4 ]. Treatment options for LGGs include surgery, radiotherapy (RT), and/or chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

High-dose radiotherapy in newly diagnosed low-grade gliomas with nonmethylated O(6)-methylguanine-DNA methyltransferase

Liu

Wang

et al. 2021

Radiat Oncol

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Background Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethylation (MGMT-non-pM) have a particularly short survival and are great resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM. Methods 268 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005–2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariate analysis were performed using the Cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose–response on MGMT status defined subtypes was analyzed. Results On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas(p = 0.002 and p = 0.005), high-dose RT (> 54 Gy) (p = 0.021 and p = 0.029) and 1p/19q codeletion (p < 0.001 and p = 0.001). On multivariate analysis, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.47; 95%CI, 0.22–0.98; p = 0.045; and HR, 0.44; 95%CI, 0.21–0.96; p = 0.038, respectively) and PFS (HR, 0.48; 95%CI, 0.26–0.90; p = 0.022; and HR, 0.51; 95%CI, 0.26–0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.56; 95%CI, 0.32–0.96; p = 0.036) and PFS (HR, 0.58; 95%CI, 0.35–0.96; p = 0.033) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype. Conclusions High-dose RT (> 54 Gy) is an independently protective factor for LGGs and is associated with improved survival in patients with MGMT-non-pM.

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“…Low-grade gliomas (LGGs) mainly refers grade II by the WHO grading system and are relatively uncommon, constituting approximately 10% of all primary brain tumors in adults [1][2]. Although often considered as "benign", over half of these patients will develop tumor progression within 5 years and the rate of progression-free survival (PFS) at 10 years was 21-51% [3][4]. Therefore, postoperative radiotherapy (RT) is frequently utilized after surgical resection.…”

Section: Introductionmentioning

confidence: 99%

High-dose Radiotherapy in Newly Diagnosed Low-grade Gliomas with Nonmethylated O6-methylguanine-DNA Methyltransferase

Liu

Wang

et al. 2021

Preprint

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Background: Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethyaltion (MGMT-non-pM) have a particularly short survival and are greatly resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM.Methods: 269 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005-2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariable analyses were performed using the cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose-response on MGMT status defined subtypes was analyzed.Results: On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas（p = 0.002 and p = 0.005）, high-dose RT (> 54 Gy) （p = 0.017 and p = 0.023） and 1p/19q codeletion （p <0.001 and p = 0.001）. On multivariable analyses, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.44; 95%CI, 0.21-0.92; p = 0.029; and HR, 0.43; 95%CI, 0.20-0.90; p = 0.025, respectively) and PFS (HR, 0.48; 95%CI, 0.27-0.90; p = 0.021; and HR, 0.52; 95%CI, 0.27-0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.55; 95%CI, 0.32-0.93; p = 0.026) and PFS (HR, 0.57; 95%CI, 0.35-0.93; p = 0.026) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype.Conclusions: High-dose RT (> 54 Gy) is an independently protective factor for LGGs and associated with improved survival in patients with MGMT-non-pM.

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Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma

Cited by 50 publications

References 12 publications

MRS as an Aid to Diagnose Malignant Transformation in Low-Grade Gliomas with Increasing Contrast Enhancement

MRS as an Aid to Diagnose Malignant Transformation in Low-Grade Gliomas with Increasing Contrast Enhancement

High-dose radiotherapy in newly diagnosed low-grade gliomas with nonmethylated O(6)-methylguanine-DNA methyltransferase

High-dose Radiotherapy in Newly Diagnosed Low-grade Gliomas with Nonmethylated O6-methylguanine-DNA Methyltransferase

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