Anaplastic glioma: current treatment and management

Abstract

Anaplastic glioma (AG) is divided into three morphology-based groups (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) as well as three molecular groups (glioma-CpG island methylation phenotype [G-CIMP] negative, G-CIMP positive non-1p19q codeleted tumors and G-CIMP positive codeleted tumors). The RTOG 9402 and EORTC 26951 trials established radiotherapy plus (procarbazine, lomustine, vincristine) chemotherapy as the standard of care in 1p/19q codeleted AG. Uni- or non-codeleted AG are currently best treated with radiotherapy only or alkylator-based chemotherapy only as determined by the NOA-04 trial. Maturation of NOA-04 and results of the currently accruing studies, CODEL (for codeleted AG) and CATNON (for uni or non-codeleted AG), will likely refine current up-front treatment recommendations for AG.

Keywords:

• 1p/19q codeletion
• anaplastic glioma
• ATRX
• bevacizumab
• chemotherapy
• IDH1
• MGMT promoter methylation
• molecular biomarkers
• nitrosourea
• radiotherapy
• temozolomide

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Anaplastic glioma (AG) represent 6–15% of all newly diagnosed of primary brain tumors [1,2].

• The WHO 2007 classification is prone to high interobservator discordance between the three morphology-based groups of AG [7,24–27].

• Molecular biomarkers add diagnostic, prognostic and predictive value to the current morphological classification of AG and increasingly influence treatment. Recognized as useful in the management of AG are the molecular biomarkers of IDH mutation, 1p/19q codeletion, MGMT promoter methylation and ATRX mutation.

• AG can be robustly divided into three main molecular groups based on genome wide DNA methylation and copy-number alterations independent of histology: G-CIMP-negative tumors, which molecularly resemble GB, G-CIMP-negative, non-codeleted tumors and G-CIMP-positive, codeleted tumors [25].

• The NOA-04 trial confirmed the non-inferiority of alkylator-based CT versus RT only as first-line treatment of AG [11].

• The RTOG 9402 and EORTC 26951 trials established RT + PCV as the standard of care in 1p/19q codeleted AG [7,9,10].

• Uni- or non-codeleted AG based on the NOA-04 trial are treated with RT only followed by observation and chemotherapy at progression. Alternatively, these tumors may be treated with alkylator-based chemotherapy only followed by observation and RT only at progression [82]. Combined chemoradiotherapy is currently not established as the standard of care for non-codeleted tumors [20,56,82,111].

• The risk of RT-associated neurotoxicity, in particular cognitive impairment, remains a challenge particularly in the 1p9qcodeleted subset of AG due in part to long survival. The mature results of NOA-04 and the results of CODEL and CATNON trials will further determine the best up-front treatment strategy in AG.

• Although not approved for recurrent AG, bevacizumab, alone, represents a therapeutic option after failure of RT and alkylating CT or because of intolerance to chemotherapy [7,56,110,138–142].

Notes