Bent, Martin J. van den

Abstract The finding that most grades II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and deletional analysis of cyclin-dependent kinase inhibitor 2A and 2B. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing, and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein.

Abstract The treatment of newly diagnosed oligodendroglioma has been revolutionized in the past decade by multiple studies demonstrating that the addition of chemotherapy to radiation therapy results in a significant survival benefit. While the most direct evidence comes from clinical trials that utilized PCV, a chemotherapy regimen consisting of procarbazine, CCNU (lomustine), and vincristine, there is circumstantial evidence suggesting that the oral agent temozolomide (TMZ), which is both better tolerated and logistically simpler than PCV, may also be effective. The lack of currently available direct comparative data for PCV vs TMZ results in a diversity of practice. In this article, Ruff and Buckner argue for PCV as part of the standard-of-care regimen for newly diagnosed anaplastic oligodendroglioma, while Geurts and van den Bent defend the use of TMZ.

2057 Background: The optimal role of chemotherapy and radiation (RT) in adult low-grade glioma (LGG, WHO grade 1 & 2) is unclear. We conducted a systematic review and study-level meta-analysis of the literature on overall survival (OS) and progression free survival (PFS) in patients with LGG. Methods: Pubmed was queried with MeSH terms. All comparative studies of adults with newly diagnosed, supratentorial LGG were included. Comparisons of interest were OS and PFS at 2, 5, and 10 years in chemotherapy versus no chemotherapy and early RT versus delayed or no RT. Data were extracted from studies and synthesized with a random effects model. Quality of evidence was determined by American Academy of Neurology criteria and further analysis was performed, separating high quality (class I and II) from low quality (class III and IV) evidence. Numbers needed to treat (NNT) were determined from the risk difference. Results: 1531 articles were screened; 18 studies were included. Chemotherapy was not associated with a significant survival advantage compared to control. However, an analysis of high quality data revealed a survival advantage at 10 years associated with chemotherapy compared to control with NNT 5 (relative risk death chemo vs control 0.69 [0.56-0.86] p = 0.0006). Furthermore, NNT to prevent one progression with chemotherapy at 5 and 10 years was 6 and 3, respectively. Early RT was not associated with an OS advantage compared to control. However, early RT had progression benefit at all time points, with NNT of 10, 6, and 5 at 2, 5, and 10 years. Conclusions: Further study will be needed to confirm the optimal role of chemotherapy and RT. Caution must be used in interpretation as much of the literature consists of low-quality studies. [Table: see text]

2025 Background: Low-grade gliomas (LGG) account for 17-22% of all primary brain tumors. Optimal surgical management consists of optimum safe resection with the goal of complete resection. We performed a systematic review and meta-analysis to quantify the association of extent of resection with likelihood of survival, expressing our results in numbers needed to treat (NNT). Methods: A systematic review and study-level meta-analysis to determine the association of resection with overall survival and progression-free survival in newly diagnosed, supratentorial LGG in adults was performed by querying PubMed. Data were extracted to compare gross total resection (GTR) to subtotal resection (STR) and STR to biopsy (Bx) to determine relative risks (RR) of death and progression at 2, 5, and 10 years. Data were analyzed using a random effects model. NNT were calculated from significant comparisons and rounded up to the nearest whole number. Quality of evidence was determined by American Academy of Neurology criteria. Results: The systematic review resulted in 283 potential studies. Ultimately 29 studies were included in at least one comparison. There were no high quality (class I and II) or prospective studies discovered in the review. Comparing GTR to STR, RR with 95% confidence intervals (CI) of death at 2, 5, and 10 years, and NNT to avoid one death at 2, 5, and 10 years (GTR vs. STR) were 0.29 [0.17-0.52, p < 0.0001, NNT 17], 0.39 [0.29-0.51, p < 0.00001, NNT 6], and 0.50 [0.35-0.70, p < 0.0001 NNT 4]. RR and NNT for progression (GTR vs. STR) at 2, 5, and 10 years were 0.37 [0.24-0.57, p < 0.0001 NNT 7], 0.50 [0.39-0.64, p < 0.0001 NNT 4], and 0.67 [0.53-0.84, p = 0.0005 NNT 4]. Comparing STR to Bx, RR of death at 2, 5, and 10 years were 0.55 [0.34-0.88, p = 0.01 NNT 10], 0.9 [0.61-1.34], and 0.95 [0.73-1.23]. Conclusions: Increasing resection thresholds appear to be associated with improved overall and progression free survival, but the body of literature consists of low quality studies. Prospective studies are required to explore whether extent of resection matters or whether resectable tumors share a favorable biology associated with better outcome.

Abstract Background Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. Methods A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. Results Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. Conclusions Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.