Cerebral Toxicity in Patients Treated for Small Cell Carcinoma of the Lung

Objective: To present the clinical characteristics of patients enrolled in a trial of treatment of small cell carcinoma (SCC) of the lung and to describe the central nervous system toxicity associated with the chemotherapy and prophylactic cranial irradiation (PCI).

Material And Methods: We performed a retrospective analysis of 60 patients with SCC who received chemotherapy and thoracic radiation therapy. PCI was administered to patients who had limited disease or who had extensive disease that was subsequently down-staged to only residual chest disease after initial treatment. The total PCI dose was 3,200 cGy administered in 16 fractions of 200 cGy, given concurrently with systemic chemotherapy. Diagnostic criteria for leukoencephalopathy were based on previously published guidelines.

Results: Of the 60 eligible and enrolled patients, 35 received PCI and 25 did not. Leukoencephalopathy developed in 5 of the 35 patients (14%) who received PCI. The median age of the patients in whom leukoencephalopathy developed was 64 years (range, 57 to 69), and the median follow-up time was 59 months. The most common signs and symptoms of leukoencephalopathy were intellectual changes, memory alterations, and motor abnormalities. The mean time to onset of symptoms after termination of irradiation was 357 days (range, 30 to 524). Of all 60 patients, 6 were still alive 4 years after enrollment, and 3 of them (50%) already had leukoencephalopathy.

Conclusion: Small dosage fractions of PCI may still result in leukoencephalopathy. The routine use of PCI in the management of SCC should be reassessed because of increasing evidence of the toxicity associated with it.