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Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors

From J.K. Douglas Laboratories (C.W., K.A.J., D.F.) and Clatterbridge Centre for Oncology (B.H., D.H.), Clatterbridge Hospital, Bebington, Wirral; and Walton Centre for Neurology and Neurosurgery (M.D.J., T.S., J.B., P.C.W.) and Department of Neurological Science (M.D.J., D.G.d.P., P.C.W.), University of Liverpool, UK.

Address correspondence and reprint requests to Dr. C. Walker, J.K. Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, UK CH63 4JY; e-mail: carol.walker{at}ccrt.nhs.uk

Background: The –1p/–19q genotype has been associated with prolonged survival and chemosensitivity in oligodendroglial neoplasms, but the predictive and prognostic significance of genotype in the routine clinic is not established.

Methods: The authors investigated allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation in a cohort representative of clinical practice at their center (50 primary, 26 recurrent cases) given PCV chemotherapy between 2000 and 2003 and compared with response and outcome following PCV.

Results: 1p/19q loss was found in 12/19 OII, 10/23 OAII, 11/13 OIII, and 6/21 OAIII. Response, seen in 92% with 1p/19q loss, was associated with the –1p/–19q genotype (Fisher exact: p < 0.001) regardless of WHO grade or whether primary or recurrent. 1p/19q loss was an independent prognostic factor associated with longer progression-free (PFS) and overall survival (OS) (Cox regression: PFS and OS p < 0.001), with greater impact on PFS than OS in primary tumors, and OS at recurrence. 17p13 loss and p53 mutation were associated with poor prognosis in recurrent tumors and chromosome 10 loss was associated with short PFS and OS in primary tumors. Histologic subtype did not influence outcome in tumors of equivalent genotype. Genotype had greater association with response and outcome than conventional clinical factors. A total of 29% with intact 1p/19q and a variety of genetic or clinicopathologic characteristics responded in association with increased PFS and OS.

Conclusions: The –1p/–19q genotype predicted response and favorable outcome following PCV chemotherapy corroborating genetic analysis to guide routine clinical management. However, some cases with intact 1p/19q also had clinical benefit.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the June 13 issue to find the title link for this article.

Supported by Clatterbridge Cancer Research Trust (C.W., D.F., K.J.) and the Walton Neurosciences Fund (M.J.).

Disclosure: The authors report no conflicts of interest.

Received March 24, 2005. Accepted in final form March 2, 2006.

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