Sequelae in long-term survivors of small cell lung cancer

Central nervous system (CNS) effects of chemotherapy and prophylactic cranial irradiation (PCI) are studied in long-term small cell lung cancer (SCLC) survivors. The exact significance and pathogenesis of the neurotoxicity is still unknown, as studies on this subject lack sufficient patient numbers and are performed in an extremely varied manner.

Fifty-nine survivors (> 2 years from diagnosis) were examined neurologically and neuropsychologically, and underwent a cranial computer tomography (CT) scan or magnetic resonance (MR). Eight patients were excluded from further analysis for various reasons (not SCLC-related CNS disease, n = 6; no chemotherapy nor PCI treatment, n = 2). The remaining 51 patients were divided into three groups; group 1 = chemotherapy alone (n = 21), group 2 = sequential PCI (n = 19), and group 3 = concurrent or sandwiched PCI (n = 11). Groups were neuropsychologically compared in matched controls.

Performance status did not differ significantly between various treatment groups; all patients remained ambulatory and capable of self-care. Mental impairment (n = 20), motor abnormalities (n = 9), and visual complaints (n = 1), were found in five patients in group 1 (24%), eight patients in group 2 (42%), and eight patients in group 3 (73%). Analysis of brain atrophy revealed no significant results; however, white matter abnormalities were found more frequently in group 3. Neuropsychologically no significant group differences existed, although interference sensitivity and difficulties with divided attention tended to occur more frequently in patients treated with PCI. Mean neuropsychometric results of treatment groups were significantly worse than those of matched controls.

Although more intensively treated patients showed more neurologic impairment and patients in group 3 had more white matter abnormalities, there was no statistic evidence for additional neurotoxicity of PCI. Marked neuropsychometric differences between patients and matched controls may indicate that cognitive impairment is partly disease related, probably due to emotional distress and deteriorated physical condition.