Improved Survival in Certain Patients With Primary Brain Tumors

Zosia Chustecka

June 03, 2012

June 3, 2012 (Chicago, Illinois) — Updated results from 2 studies, both with a follow-up of more than 11 years, show a clear survival advantage for a certain group of patients with the rare primary anaplastic oligodendroglial brain tumors.

For patients with tumors that harbor specific deletions of genetic material in chromosomes 1 and 19 (1p/19q codeletions), chemoradiation is the new standard of care, experts reported here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Most patients with these tumors are treated with either radiation or chemotherapy; however, "from this trial, it's clear that combining chemotherapy and radiation can significantly improve survival for certain patients," said Martin van den Bent MD, PhD, professor of neuro-oncology at the Daniel  den Hoed Cancer Center, Erasmus University Medical Center, in Rotterdam, the Netherlands. He was the lead author of 1 of the 2 studies presented.

Anaplastic oligodendroglial tumors account for around 5% to 10% of primary malignant brain tumors, which are diagnosed in about 15,000 people each year in the United States, Dr. van den Bent noted. He and his colleagues found that the 1p/19q codeletion is present in about 25% of patients; the other study found the codeletion in about 40% of patients.

"Not only do we have a better treatment, we also have a genetic marker that can help us determine which patients will benefit, allowing us to personalize treatment for this challenging disease," Dr. van den Bent said.

Clear Survival Advantage

Results were presented from the phase 3 trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC), known as EORTC 26951. It began in 1995, and enrolled 368 newly diagnosed and previously untreated patients. They were randomized to treatment with radiation alone or to the same radiation followed by chemotherapy. Although the study design called for 6 cycles of standard PCV (procarbazine, CCNU [lomustine], and vincristine) chemoradiation, the median number of cycles administered was actually 3, mainly because of toxic effects.

In 2001, the study was amended to test patients for the 1p/19q codeletion; this abnormality was found in 80 of the 300 patients tested.

The updated results, with a follow-up of 140 months, show a clear survival advantage for chemoradiation, with a 25% reduction in the risk for death, Dr. van den Bent reported. Median overall survival was longer with chemoradiation than with radiotherapy alone (42 vs 31 months; P = .018).

This was seen despite a high crossover effect, he noted, where 75% of patients who received radiotherapy alone went on to receive chemoradiation after disease progression.

There was a significant improvement in progression-free survival with chemoradiation, compared with radiotherapy alone (23 vs 13 months; hazard ratio [HR], 0.66; P = .003), he noted.

However, the significant improvement in survival was restricted to the subgroup of patients who had the codeletion. In this subgroup of 80 patients, median overall survival for those treated with chemoradiation has not yet been reached, Dr. van den Bent explained; for those treated with radiotherapy alone, it was 113 months (HR, 0.54; P = .0487).

In contrast, in the subgroup of 224 patients without the codeletion, there was no significant difference in median overall survival in the chemoradiation and radiotherapy groups (21 vs 25 months; HR, 0.82; P = .18).

"It is clear that the codeleted patients benefited the most," Dr. van den Bent concluded.

Confirmatory Results From North America

Confirmatory results from the North American phase 3 RTOG 9402 study were also presented. It began in 1994 and involved 291 previously untreated patients. It also compared radiotherapy alone with the combination of chemotherapy and radiation, but the chemotherapy was given before the radiation.

Results from this study were reported earlier this year by Medscape Medical News. Here at the ASCO meeting, the RTOG 9402 researchers noted that at a follow-up of 11.3 years, in patients treated with chemoradiation, survival improved in those with the codeletion but not in those without the codeletion. For patients with the codeletion, median survival time was 14.7 years in those treated with chemoradiation and 7.3 years in those treated with radiotherapy alone (HR, 0.59; P = .03). In this study, 126 of the 291 patients were found to have the codeletion.

"In this setting, 1p/19q codeletion was both prognostic and predictive, and the early progression-free survival benefit in codeleted cases was a harbinger of longer overall survival," conclude the researchers, headed by Gregory Cairncross, MD, from the University of Calgary in Alberta, Canada.

Two Studies Mirror Each Other

"These 2 studies mirror each other," said Mark Gilbert, MD, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center in Houston, who acted as a discussant.

EORTC 26951 and RTOG 9042 are complementary studies that confirm and validate these findings, he said. Both studies showed improved survival after chemoradiation in patients with anaplastic oligodendroglial tumors with the 1p/19q deletion.

When these studies began, radiotherapy was the standard of care; this is no longer adequate for patients with the codeletion, Dr. Gilbert said.

The existing data now support first-line treatment with chemoradiation for patients with the codeletion, he said.

However, the optimal treatment paradigm has not been established. One trial used chemotherapy before radiation, the other after. Although both used the PCV regimen, this has fallen out of favor in recent years because of toxicity; temozolomide is now widely used instead because it is much better tolerated. An ongoing study known as CODEL is comparing temozolomide plus radiation with temozolomide alone; a third study group that was going to use radiation alone has been dropped, he explained.

Another point for practice is that histology is no longer sufficient. Anaplastic oligodendroglial tumors have a distinctive histologic appearance, with "fried egg" cell morphology and a capillary network that looks like chicken wire, Dr. Gilbert told the audience. These results emphasize the importance of genetic testing to identify patients with the codeletion who have a better prognosis and would benefit from chemoradiation. The codeletion is both predictive and prognostic, he said.

These findings also underscore the importance of prospective tumor sample collection, Dr. Gilbert noted.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstracts 2 and 2008b. Presented June 3, 2012.

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