It is likely that the true incidence of treatment-related side effects of cranial irradiation in adults who survive more than 6 months without brain tumor growth or recurrence has been significantly underestimated. Research designs that include formal neuropsychologic assessment in conjunction with other neurodiagnostic tests can provide more comprehensive evaluation of long-term neurobehavioral outcomes.
Combination chemotherapy with or without radiotherapy has had only modest efficacy in the treatment of primary CNS lymphoma. Median survival of these patients, treated primarily with radiotherapy, is 13 months; 5-year survival is less than 5%. Thirty consecutive non-acquired immune deficiency syndrome patients with primary CNS lymphoma were treated with barrier-dependent chemotherapy using intraarterial mannitol to open the blood-brain barrier (BBB). Follow-up included extensive neuropsychologic testing of all patients. Thirteen patients received cranial radiation 1 to 9 months before referral (group 1). Seventeen patients received initial BBB disruption chemotherapy with subsequent radiation only for tumor progression or recurrence (group 2). The difference in median survivals from diagnosis--17.8 months for group 1 and 44.5 months for group 2--was statistically significant (P = .039). Group 1 survival is comparable with the 20-month median survival of a historical series of patients (n = 208) treated with radiotherapy with or without chemotherapy. Group 2 patient survival represents an advance in the survival of CNS lymphoma and was associated with preservation of cognitive function in six of seven nonirradiated complete responders observed for 1 to 7 years. Patient toxicity was manageable in this intensive therapeutic regimen. In this series, a plateau in survival curves suggests that a major portion of these patients may be cured without the neuropsychologic sequelae associated with cranial radiation.
BBBD-enhanced chemotherapy delivery, without subsequent radiotherapy, resulted in favorable survival and cognitive outcomes for patients with primary central nervous system lymphomas who had not previously undergone irradiation. A cooperative multicenter study of intravenous chemotherapy without radiotherapy versus BBBD-enhanced chemotherapy would address the feasibility and necessity of performing a Phase III study for these rare central nervous system malignancies.
BBBD-enhanced chemotherapy delivery, without subsequent radiotherapy, resulted in favorable survival and cognitive outcomes for patients with primary central nervous system lymphomas who had not previously undergone irradiation. A cooperative multicenter study of intravenous chemotherapy without radiotherapy versus BBBD-enhanced chemotherapy would address the feasibility and necessity of performing a Phase III study for these rare central nervous system malignancies.
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