RTOG reveals practice-changing marker for brain tumor treatment

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An analysis of clinical trial results performed by the Radiation Therapy Oncology Group (RTOG) demonstrated that a chromosomal abnormality has definitive prognostic and predictive value for managing the treatment of adult patients with pure and mixed anaplastic oligodendrogliomas. "These are exciting and practice-changing results," said Walter J. Curran, Jr., MD, RTOG group chair and executive director of the Winship Cancer Institute of Emory University in Atlanta, in a statement.

The abnormality—specifically, the absence (co-deletion) of chromosomes 1p and 19q—indicates treatment and outcome in patients with the rare brain tumor, according to the RTOG statement.

The presence of the chromosomal abnormality was associated with a substantially better prognosis and near-doubling of median survival time when treatment with combined chemotherapy and radiation therapy was compared to treatment with radiation therapy alone.

The RTOG 9402 trial A Phase III Intergroup Randomized Comparison of Radiation Alone vs. Pre-Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas was conducted with four other National Cancer Institute (NCI)-supported cooperative groups.

Trial participants had a pathologically confirmed pure or mixed anaplastic oligodendroglioma and were randomly assigned into one of two treatment arms. The 148 participants randomized to arm 1 were treated with combined chemotherapy and radiation therapy (RT), and the 143 participants randomized to arm 2 were treated with RT alone.

Previous RTOG 9402 study results reported with a minimum follow-up time of three years in the Journal of Clinical Oncology in June 2006 showed no survival benefit for patients treated with early chemotherapy plus RT over RT alone. Although a significant impact on median progression-free survival time was realized (2.6 years versus 1.7 years for RT alone), the regimen was associated with significantly more adverse side effects. The study authors also reported that study participants in both arms whose tumor lacked chromosomes 1p and 19q had longer median survival times as compared with participants without these deletions (greater than 7 years vs. 2.8 years, respectively). This led the study authors to conclude "tumors with 1p and 19q co-deletion are less aggressive or more responsive to chemotherapy or both."

A recent analysis undertaken of the RTOG 9402 data (at a median study participant follow-up time of 11 years) is planned for submission to the 2012 American Society of Clinical Oncology Annual Meeting in June in Chicago. However, due to the finding's significance for patient care, the group reported results in advance of submission.

The abstract reported for the 126 study participants with 1p and 19q co-deletion the median survival time of 59 participants randomized to the chemotherapy and RT arm was much longer than the 67 participants randomized to the RT alone arm (14.7 years vs. 7.3 years). For study participants whose tumors contained only one deletion (either 1p or 19q) or no deletions, no difference was found in median survival time between the two treatment arms (2.6 years vs. 2.7 years).

"The profound association between improved outcome for patients who lack the 1p and 19q chromosomes and were treated with chemotherapy and radiation therapy has significant implications for patients with anaplastic oligodendrogliomas. We now have unequivocal evidence the chromosomal structure of 1p and 19q co-deletion can be used as a marker to determine which patients will benefit from combined chemotherapy and radiation therapy," said J. Gregory Cairncross, MD, head of the department of clinical neurosciences at the University of Calgary, Alberta, Canada.

Oligodendrogliomas are uncommon tumors that represent approximately 4 percent of all brain tumors. Mixed oligodendrogliomas (those also containing astrocytic elements) account for 1 percent of all brain tumors. Pure and mixed oligodendrogliomas that contain anaplastic (malignant) cells typically grow more rapidly than non-anaplastic tumors.