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CHICAGO -- Whole-brain radiation at about half the standard dose is safe and effective after chemotherapy for patients with primary central nervous system (CNS) lymphoma, researchers are reporting.

In a phase II clinical trial, median progression-free survival (PFS) was nearly 8 years among participants who received radiation treatment at a reduced dose of 23.4 Gy, according to Richard Curry, MD, of Memorial Sloan-Kettering Cancer Center in New York City, and colleagues.

And in that group, the median overall survival hasn't been reached yet, Curry and colleagues will report at the annual meeting of the American Society of Clinical Oncology here.

Primary CNS lymphoma has a median age of onset of about 62 and accounts for about 3% of all primary brain tumors. Because of its diffuse nature, surgery is usually not a treatment option and, for many years, whole-brain radiation alone was used with relatively poor outcomes.

According to the National Cancer Institute, several trials combining radiation and chemotherapy -- usually based on high-dose methotrexate -- have improved outcomes, but at the cost of delayed neurotoxicity.

To try to maintain the benefits and reduce the toxicity, Curry and colleagues treated 52 patients with newly diagnosed disease with a chemotherapy regimen consisting of five cycles of methotrexate, rituximab (Rituxan), procarbazine (Matulane), and vincristine (Oncovin).

Patients who showed a partial response after five cycles received an extra two cycles, and those who achieved a complete response after chemotherapy (five or seven cycles) were given whole-brain radiation at a reduced dose of 23.4 Gy. Others were offered standard radiation at a dose of 45 Gy.

All patients were also given consolidation therapy with cytarabine (Cytosar-U).

The primary endpoint was the rate of PFS at 2 years in patients getting the reduced-dose radiation, but the investigators also explored neuropsychological testing, white matter changes using the Fazekas scale, and the apparent diffusion coefficient on MRI.

They found that 31 of 52 patients (or 59%) had a complete response with induction chemotherapy and received the reduced dose radiation.

The 2-year PFS was 78% and the median PFS was 7.7 years. The median overall survival has not yet been reached after a median follow-up of 6 years.

In the intent-to-treat population of 52 patients, median PFS was 3.3 years and median overall survival was 6.6 years.

Cognitive testing after the chemotherapy showed significant improvements in executive function and verbal memory, at P<0.01 and P<0.05, respectively, that were stable over the follow up.

Long-term survivors had only minimal changes in white matter on the Fazekas scale, which provides an overall impression of white matter lesions, the researchers found. Some 36% had no change in Fazekas scores and 64% developed scores of 1 or 2, but no patient had a higher score.

Differences in apparent diffusion coefficient on MRI did not predict response to chemotherapy, PFS, or overall survival, they found.

The approach is both safe and effective, they concluded, with survival outcomes comparable to full-dose whole-brain radiation, good cognitive results, and no significant changes in white matter over time.

A randomized trial is under way to study the chemotherapy regimen with or without reduced-dose radiation, Curry and colleagues noted.

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