Reply to Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer

Abstract

We appreciate Dr. Hermelink's interest in our article1 and her passionate pursuit of the “truth” regarding chemotherapy-associated cognitive dysfunction, although she suggests that truth is unlikely to be found because “most published research claims are false.” We concede that our study did not provide all the answers on this issue. Nevertheless, we are confident that we were dispassionate in our analysis and interpretation and attempted to “safeguard against false findings.” Dr. Hermelink asserts that we did not acknowledge “any limitations.” However, in the Discussion section, we indeed acknowledged small sample size, the marginal significance level of some analyses, and the use of a single control sample as limitations, and encouraged additional investigations to replicate these findings in larger samples. Although the practice effect-adjusted analysis we used is imperfect, Dr. Hermelink's example reflects a misunderstanding of its application in our study: 1) the practice effect adjustment is applied to each subsequent time point (eg, baseline to acute, acute to late) and not serially subtracted from baseline; 2) all decliners exhibited worsened performance over time; and 3) the practice effect-adjusted Reliable Change Index (RCI) has been reported to be preferable to an unadjusted approach.2 However, we re-ran the “late interval” analyses reported in the article using the RCI unadjusted for practice effect, which resulted in 54% versus 61% of patients demonstrating late cognitive decline. This supports our assertion that the declines were not an artifact of using the practice effect-adjusted RCI. The time course of chemotherapy-associated cognitive dysfunction is largely unknown. However, previous research3,4 has suggested that increased exposure to more chemotherapy is a risk factor. Thus, we allowed identification of cognitive decline at either of the acute interval time points. We used the acute interval time point with evidence of decline as the start point to determine whether there was further decline at the late follow-up time point. This biased against identifying further decline and increased the chances of observing improvement at the late interval. The correspondence between our results and those reported in the animal literature we cited provide external support for our findings and a theoretical framework with which to explain them. Despite Dr. Hermelink's indictment of our study, we believe we have identified a potential adverse effect associated with chemotherapy that may be experienced by a subset of cancer patients that deserves further attention and replication to help understand these important survivorship needs. Jeffrey S. Wefel PhD*, Christina A. Meyers PhD*, * Section of Neuropsychology, Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.