Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection

Abstract

<jats:sec> <jats:title>OBJECT</jats:title> <jats:p>There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant <jats:italic>IDH1</jats:italic> gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or <jats:italic>IDH1</jats:italic> wild-type oligodendroglial tumors with partial resection.</jats:p></jats:sec>

Relationship between MGMT gene expression and treatment effectiveness and prognosis in glioma

“…For the patients with glioma, the current first line of chemotherapeutics is alkylating agent TMZ and new nitrosourea drugs. Some clinical research has confirmed that the treatment effect of radiotherapy combined with TMZ was better than that of single radiotherapy for patients with glioma who received tumor excision, which can increase the survival rate of patients from 10 to 26% and improve disease prognosis (15). …”

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017

“…5,9,27,29 Remarkably, further analysis showed that these molecular subgroups could be distinguished based on only a handful of molecular features, including mutation of IDH1 or IDH2 (IDH-mut) and 1p19q-codel, biomarkers independently verified by many studies as hallmarks for distinguishing molecular subgroups in grade II/III glioma. [4][5][6][7]9,13,28,[30][31][32][33][34][35][36][37][38][39] Using these markers alone, most grade II/III tumors can be divided into 3 molecular subtypes: (1) mutation of either IDH1 or IDH2 with 1p19q codeleted (IDH-mut+1p19q-codel), (2) IDH-mut without deletion of 1p or 19q (1p19q intact) or with isolated deletion of 1p or 19q, and (3) no mutation of IDH1 or IDH2 (IDH-wt). 5 Multiple studies have shown that codeletion of 1p and 19q is strongly associated with IDH-mut, such that 1p19q codeletion in IDH-wt tumors is rare.…”

“…Numerous large studies of patients with brain tumors have shown that among grade II/III gliomas, 1p19q-codel is significantly correlated with improved PFS and OS. 4,6,7,9,10,13,30,32,41,42 Many of these studies used heterogenous populations treated with a variety of approaches, but a few showed statistically significant correlation between 1p19q-codel and outcome within a population of patients who received the same treatment. The independent prognostic value of 1p19q status was also confirmed through multivariate analyses from multiple studies in patients with grade II/III glioma.…”

“…4,9,10,42,43 Numerous large studies, including many multivariate analyses, all found that IDH-mut is significantly associated with improved OS in patients with grade II/III glioma. 4,5,7,[9][10][11][12][13]27,28,32,34,35,37,41,43,44 Analyses within single-treatment arms showed that the IDH status is prognostic for outcome across a variety of postoperative adjuvant options. For example, in the NOA-04 phase III randomized trial in newly diagnosed anaplastic gliomas, IDH-mut was associated with improved PFS, time to treatment failure, and OS in each of the 3 treatment arms: standard radiation therapy (RT; n=160); combination therapy with procarbazine, lomustine, and vincristine (PCV RT upon progression; n=78); and temozolomide (TMZ; RT upon progression; n=80).…”

Editorial: The management of low-grade glioma in adults

“…9 In both LGG subsets, radiotherapy (RT) did not clearly correlate with an OS or PFS advantage. Utilizing results from their retrospective cohort study, these au-thors highlight the predictors of OS and progression-free survival (PFS).…”