Institutional Experience of High-Risk, Low-Grade Glioma in the Temozolomide Era

Abstract Background EORTC study 22033–26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Methods Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. Results Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. Conclusion In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.

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Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma

Journal of Clinical Oncology ◽

10.1200/jco.19.02983 ◽

2020 ◽

Vol 38 (29) ◽

pp. 3407-3417 ◽

Cited By ~ 3

Author(s):

Erica H. Bell ◽

Peixin Zhang ◽

Edward G. Shaw ◽

Jan C. Buckner ◽

Geoffrey R. Barger ◽

...

Keyword(s):

High Risk ◽

Low Grade Glioma ◽

Phase Iii ◽

Adjuvant Chemoradiotherapy ◽

Rank Test ◽

Low Grade ◽

Wild Type ◽

450K Array ◽

Significant Difference ◽

Post Hoc

PURPOSE NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375 ) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802. METHODS IDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates. RESULTS Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup. CONCLUSION This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

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(P14) Cost Effectiveness of Radiation and Chemotherapy for High-Risk Low Grade Glioma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2018.02.102 ◽

2018 ◽

Vol 101 (2) ◽

pp. E26

Author(s):

Yushen Qian ◽

Satoshi Maruyama ◽

Haju Kim ◽

Erqi L. Pollom ◽

Kiran A. Kumar ◽

...

Keyword(s):

Cost Effectiveness ◽

High Risk ◽

Low Grade Glioma ◽

Low Grade

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Radiation dose response for supratentorial low-grade glioma—institutional experience and literature review

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(03)00181-3 ◽

2003 ◽

Vol 214 (1-2) ◽

pp. 43-48 ◽

Cited By ~ 6

Author(s):

Simon S. Lo ◽

Walter A. Hall ◽

Kwan H. Cho ◽

Jamie Orner ◽

Chung K. Lee ◽

...

Keyword(s):

Radiation Dose ◽

Literature Review ◽

Dose Response ◽

Low Grade Glioma ◽

Low Grade ◽

Institutional Experience

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Multi Omics Profiling and Clustering Low Grade Glioma Based on Integrated Stress Status

10.21203/rs.3.rs-139591/v1 ◽

2021 ◽

Author(s):

Xiaolin Ren ◽

Xin Chen ◽

Chen Zhu ◽

Anhua Wu

Keyword(s):

Stress Response ◽

High Risk ◽

Malignant Transformation ◽

Immune Cell ◽

High Risk Group ◽

Low Grade Glioma ◽

The Cancer Genome Atlas ◽

Low Grade ◽

Integrated Stress Response ◽

Genome Atlas

Abstract Background: Although the prognosis of low-grade glioma (LGG) is better than that of glioblastoma (GBM), there are still some patients who will develop into high-grade glioma. Integrated stress response contributed to the malignant transformation of tumor. As there is few research focus on the integrated stress status in LGG, it is urgent to profile and re-classify LGG based on integrated stress response (ISR). Methods: Glioma patients were obtained from the Chinese Glioma Genome Atlas ( the Cancer Genome Atlas (TCGA) and GSE16011 cohorts. Statistical 8 analyses were conducted by GraphPad Prism and R language. Results: We quantified four types of integrated stress response respectively. The relationship between the four stress states and the clinical characteristics of LGG was analyzed. Then we re-classified the patients based on these four scores, we found that cluster 1 had the worst prognosis, whereby cluster 3 had the best prognosis. We also established an accurate ISR risk signature to predicting cluster 1. We found that immune response and suppressive immune cell components were more enriched in the high-risk group. We also profiled the genomic difference between low and high risk groups, including the non-missense mutation of drivel genes and the condition of copy number variation (CNV). Conclusion: LGG patients could be divided into four clusters based on the integrated stress status, cluster 1 exhibited malignant transformation trends. ISR signature could reflect the traits of cluster 1 well, high ISR score indicated worse prognosis and enriched inhibitory immune microenvironments.

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Observation versus radiotherapy with or without temozolomide in postoperative WHO grade II high-risk low-grade glioma: a retrospective cohort study

Neurosurgical Review ◽

10.1007/s10143-020-01326-y ◽

2020 ◽

Author(s):

Jingjing Wang ◽

Lvjun Yan ◽

Ping Ai ◽

Yan He ◽

Hui Guan ◽

...

Keyword(s):

Cohort Study ◽

High Risk ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Low Grade Glioma ◽

Low Grade ◽

Who Grade ◽

Grade Ii

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The management of lomustine overdose in malignant glioma patients

Neuro-Oncology Practice ◽

10.1093/nop/npu023 ◽

2014 ◽

Vol 1 (4) ◽

pp. 178-183 ◽

Cited By ~ 1

Author(s):

Hans-Georg Wirsching ◽

Isabel Tritschler ◽

Antonella Palla ◽

Christoph Renner ◽

Michael Weller ◽

...

Keyword(s):

Brain Tumor ◽

High Risk ◽

Malignant Glioma ◽

Standard Of Care ◽

Low Grade Glioma ◽

Anaplastic Oligodendroglioma ◽

Low Grade ◽

Potential Complication ◽

Tumor Patients

Abstract Lomustine is an oral alkylating drug commonly used for brain tumor patients. Recently, the lomustine-containing PCV polychemotherapy regime (procarbazine, CCNU/lomustine, and vincristine) in combination with radiotherapy has become the standard of care for anaplastic oligodendroglioma with 1p/19q codeletion and high-risk low-grade glioma. Here, we review the literature of all reported cases of lomustine overdose, highlight complications by exemplifying a case of inadvertent lomustine overdose, and outline the management of this potential complication of outpatient PCV therapy.

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