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Genetic Abnormality Predicts Benefit from Treatment for a Rare Brain Tumor

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A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

This abnormality is characterized by the simultaneous deletion of the short arm of chromosome 1 and long arm of chromosome 19.

The presence of the chromosomal abnormality was associated with substantially better prognosis and marked improvements in survival in a treatment program of combined chemotherapy and radiation therapy compared to radiation therapy alone.

Oligodendrogliomas are characterized by tumors that form in the nerve tissue of the brain. The study was supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

In the trial, 286 patients with aggressive oligodendrogliomas were randomly assigned to study groups of equal size to receive radiotherapy alone or radiotherapy plus PCV chemotherapy, which includes the drugs procarbazine, lomustine and vincristine.

Tumor tissue from all patients was collected and stored for genetic tests. The analysis was performed when about half of the patients had been followed for just over 11 years.

Oligodendrogliomas occur primarily in adults, and the average age at diagnosis is 35. The tumors comprise 9.4 percent of all primary brain and central nervous system tumors.

For the entire study population, the median overall survival time for patients receiving radiotherapy alone or radiotherapy plus PCV chemotherapy was similar.

However, the 126 patients with 1p19q co-deleted tumors had much longer median survival times than the 135 patients whose tumors did not carry the 1p19q co-deletion: 8.7 years versus 2.7 years.

This observation suggests that patients whose tumors contain the chromosomal abnormality will live substantially longer than patients whose tumors don't carry it, regardless of treatment.

Even more impressive, however, was the finding that 1p19q co-deletion predicted the benefit from adding chemotherapy to radiotherapy.

Patients with 1p19q co-deleted tumors who received PCV chemotherapy plus radiotherapy (59 patients) had a median overall survival time of 14.7 years, compared with only 7.3 years for patients with co-deleted tumors who received radiotherapy alone (67 patients).

Patients whose tumors did not have the chromosomal abnormality did not show an improvement in survival from the addition of chemotherapy.

The study, known as RTOG 9402, was led by the Radiation Therapy Oncology Group (RTOG) with the participation of the North Central Cancer Treatment Group, the National Cancer Institute of Canada Clinical Trials Group, the Eastern Cooperative Oncology Group, and SWOG (formerly the Southwest Oncology Group).

"The Radiation Therapy Oncology Group and other participating cooperative groups are to be congratulated for conducting this randomized clinical trial in a rare form of brain tumor that took many years," said Jeffrey Abrams, M.D., associate director, Cancer Therapy Evaluation Program, NCI.

Abrams continued, "Their persistence and dedication was rewarded as this genetic abnormality has a powerful effect on survival, and the results will change how patients with this disease are treated. This clinical trial also highlights the necessity for collecting tumor tissue for genetic studies to define more precisely the patients who benefit most from specific therapies."