Adjuvant treatment of anaplastic oligodendrogliomas and oligoastrocytomas

Anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) are relatively rare brain tumors. They have been traditionally treated with surgery followed by radiotherapy

Two randomized controlled trials (RCTs) have found that, although the addition of procarbazine, lomustine, and vincristine (PCV) chemotherapy to standard treatment does not prolong survival, it does delay progression of these tumors. However, this chemotherapy is associated with many serious side effects. Also, during pathologic examination of these brain tumor specimens, there are specific chromosome deletions which can identify a group of patients with better survival outcomes.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2009 Issue 1, Copyright © 2009 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in (ISSN 1464-780X).
This record should be cited as: Quon H, Abdulkarim B. Adjuvant treatment of anaplastic oligodendrogliomas and oligoastrocytomas. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007104. DOI: 10.1002/14651858.CD007104.

This version first published online: April 16. 2008

Abstract

Background

Anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) are known to be chemosensitive tumors. However, the impact of adding chemotherapy to surgery and radiotherapy has not been studied. Also, the value of chromosome 1p and 19q deletions as prognostic and predictive markers is only beginning to be defined.

Objectives

After surgery, to compare radiotherapy (RT) plus chemotherapy versus RT alone (standard of care) in adults with newly diagnosed AO or mixed AOA. To investigate the prognostic and predictive value of loss of heterozygosity of chromosomes 1p and 19q. Outcomes analyzed include overall survival (OS), progression-free survival (PFS), and treatment toxicity greater than or equal to grade 3.

Search strategy

Cochrane Central Register for Controlled Trials (CENTRAL, Issue 4,2006), MEDLINE (1966 to 2006) and EMBASE (1988 to 2006) were searched. Reference lists from relevant studies were scanned for any additional relevant articles.

Selection criteria

RCTs of adults with AO or mixed AOA comparing surgery plus RT versus surgery plus RT plus chemotherapy were included. No specific chemotherapy regimens were excluded.

Data collection and analysis

Relevant studies were critically appraised and data was extracted. Based on the differences in patient selection with respect to the definition of AO (2 versus 3 high risk anaplastic features) and sequence of treatment (RT and chemotherapy), the results from the two RCTs were not able to be considered for meta-analysis.

Main results

Two RCTs have tested surgery plus RT plus early procarbazine, lomustine, and vincristine (PCV) chemotherapy versus surgery plus RT alone. Neither study observed a survival benefit with the addition of early PCV chemotherapy. However, both studies found a statistically significant increase in PFS associated with the administration of PCV chemotherapy before surgery or after surgery and RT, with the benefit ranging from 10 to 11 months. Co-deletion of chromosomes 1p and 19q identifies a favorable subgroup of tumors with better overall survival outcomes. The predictive value of 1p and 19q co-deletions is less clear with one study observing a longer PFS with chemotherapy, while the other study did not.

Authors' conclusions

Early PCV chemotherapy in addition to standard treatment of surgery and RT does not improve OS in patients with AO or AOA. However, it does improve PFS. It also is associated with significant toxicities. Tumors with 1p and 19q co-deletions are associated with better OS and may indicate a more chemo-responsive tumor.