Screening tools for interferon-related cognitive decline in melanoma patients.

Abstract

8539 Background: Interferon α-2b (IFN) is the only approved adjuvant therapy for high-risk melanoma. IFN-related cognitive deficiencies and mood alterations have been reported. Antidepressants are able to remedy mood, but therapies targeting the cognitive effects of IFN are lacking. Development of therapies requires validation of quantitative measures of cognitive dysfunction in this population. Methods: Melanoma patients who received 1 month high-dose IFN (n = 9), were compared to IFN eligible patients (> stage IIA) who declined therapy (n = 10). Five cognitive function tests were administered: mini-mental status exam, Hopkins Verbal Learning Test-Revised (HVLT), controlled oral word association test (COWAT), Ruff 2 and 7 and Trail Making Tests A and B. The Profile of Mood States-Short Form (POMS) was used to assess mood changes. Test scores were compared as the change from baseline to after IFN or 1-3 months of observation. Welch's t test was used to determine significance. Results: Significant differences were seen in the COWAT, HVLT and POMS. COWAT results showed a significant decrease in word generation (p = 0.013) in IFN patients. HVLT results showed a significant decrease in immediate recall (p = 0.017), but no change in delayed recall or recognition. Significant self-reported mood changes included increased fatigue (p = 0.034), decreased vigor (p = 0.046) and increased confusion (p = 0.034). 8 of 9 IFN patients scored 1 standard deviation (SD) below the observation patient mean on at least one cognitive function test. 5 patients scored 1 SD below on either the HVLT or COWAT. 3 patients scored 1 SD below on the HVLT while 4 scored 1 SD below on the COWAT. Conclusions: In this pilot study, COWAT and HVLT results demonstrate neurocognitive differences between IFN-treated and untreated melanoma patients. It may be possible to use these tests to screen for cognitive dysfunction in IFN patients. Based on these preliminary results, the combination of COWAT and the HVLT immediate recall item is most sensitive. COWAT alone may be more practical than the combination, as it is freely available, easy to administer, and has a sensitivity of 80% vs. the combination. These results must be validated in a larger population and correlated with functional impairment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Schering-Plough Merck, Schering-Plough