Current therapeutic approaches to diffuse grade II and III gliomas

Abstract

The 2016 WHO classification of Tumors of the Central Nervous System brought major conceptual and practical changes in the classification of diffuse gliomas, by combining molecular features and histology into ‘integrated’ diagnoses. In diffuse gliomas, molecular profiling has thus become essential for nosological purposes, as well as to plan adequate treatment strategies and identify patients susceptible of target therapy. WHO grade II (low grade) and grade III (anaplastic) diffuse gliomas form a heterogeneous group of neoplasms, also known as ‘lower-grade gliomas’, characterized by a wide range of malignant potential. Molecular profile accounts for this biological diversity, and provides an accurate prognostic stratification of tumors in this group. Treatment strategies in lower-grade gliomas are ultimately based on molecular profile and WHO grade, as well as on patient characteristics such as age and Karnofsky performance status. The purpose of this review is to summarize recent advances in the classification of grade II and III gliomas, synthesize current treatment schemes according to molecular profile and describe ongoing research and future perspectives for the use of target therapies.

Diagnostic performance of 18F‐fluorodeoxyglucose positron emission tomography in the evaluation of glioma

“…An imaging modality (or combination of modalities) with high sensitivity and NPV for high‐grade histology may allow safe observation of patients with negative findings, and modalities with high sensitivity and PPV for high‐grade disease may encourage more aggressive upfront management of patients with adverse prognosis. Surgery may be avoided in patients with imaging indicating low‐grade disease, minimal symptoms and tumours in noneloquent areas . The standard of post‐surgical care in grade II glioma is ‘watch and wait’ unless adverse features (such as astrocytic histology, midline shift, age > 40, lesion > 6 cm) are present .…”

“…Histological analysis via biopsy may also contribute to the accuracy of FDG‐PET/CT seen in our study. Biopsy has the potential to under‐diagnose the grade of a glioma as there can be focal regions of transformation to grade III disease in grade II tumours, and debulking to yield greater tissue for analysis may not be appropriate. When technically possible, biopsy or debulking was directed at any region identified on imaging as suspicious for high‐grade disease.…”

Exploring Novel Molecular Targets for the Treatment of High-Grade Astrocytomas Using Peptide Therapeutics: An Overview

“…Advancements in the comprehension of molecular, cellular and genetic anomalies of various tumors have enabled the development of the "Atlas of Genetics and Cytogenetics in Oncology and Haematology", a database listing several genes and proteins that are relevant for different types of cancer, including diffuse glioma. Some of these have been investigated as potential targets for small molecules or peptide vaccines, while others were specifically addressed with peptidic agents [36][37][38][39]. Peptidic molecules can be used both as monotherapy as well as in combination with standard anti-cancer drugs.…”

Bridging Cancer Biology with the Clinic: Comprehending and Exploiting IDH Gene Mutations in Gliomas

“…In the same context, Lu et al (92) reported on synergistic effects between temozolomide and the PARP inhibitor olaparib, in patients with IDH mutation, providing the possibility to achieve improved cytotoxic effects with minimal use of alkylating agents in order to reduce bone marrow cytotoxicity (109). Based on these results, a phase I trial with the above combination in patients with relapsed glioblastoma recently completed accrual and results are awaited (NCT01390571) (124).…”