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Results of Whole-Brain Radiation As Salvage of Methotrexate Failure for Immunocompetent Patients With Primary CNS Lymphoma

From the Departments of Radiation Oncology, Neurology, Medicine, and Biostatistics, Harvard Medical School, Massachusetts General Hospital, Boston, MA.

Address reprint requests to Jay S. Loeffler, MD, Massachusetts General Hospital, Department of Radiation Oncology, 100 Blossom St, Cox 301, Boston, MA 02114; e-mail: jloeffler{at}partners.org

PURPOSE: This study evaluates the efficacy and toxicity of whole-brain radiation therapy (WBRT) as salvage therapy for immunocompetent patients who failed initial high-dose methotrexate for primary CNS lymphoma (PCNSL).

PATIENTS AND METHODS: The study cohort included 27 consecutive patients who failed initial high-dose methotrexate and then received salvage WBRT (median dose, 36 Gy). Actuarial survival was measured from the initiation of radiotherapy.

RESULTS: Ten patients (37%) achieved a complete radiographic response (CR), and 10 patients (37%) a partial response to WBRT, for a 74% overall radiographic response rate. At the time of maximal response, Karnofsky performance status improved in 12 (44%) of 27 patients and at least stabilized in 67%. Median estimated survival from initiation of WBRT was 10.9 months (range, 0.3 to 63.7 months). The univariate predictor of longer survival was age less than 60 years at the time of WBRT (P = .028). Among patients who survived 4 months, achievement of a CR to WBRT by 4 months (P = .002) predicted longer survival. Late treatment-associated neurotoxicity was diagnosed in four patients (15%) and was significantly associated with total radiation doses greater than 36 Gy (P = .04). No patient treated with daily fractions less than 1.8 Gy developed late neurotoxicity.

CONCLUSION: For patients with PCNSL who experience treatment failure with methotrexate, WBRT provides high response rates (74%) and a median survival of 10.9 months. Age less than 60 years and response to WBRT predict post-WBRT survival. Modest rates of late neurotoxicity (15%) were seen and were associated with a total dose greater than 36 Gy.

Supported by the Clinical Research Fellowship Program at Harvard Medical School offered by the Doris Duke Charitable Foundation, the Harvard PASTEUR Program, and the Harvard Office of Enrichment Programs.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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