Discussion
This study shows preliminary evidence that cognitive decline is a significant factor experienced by women who are treated for advanced ovarian cancer. Most participants self-reported mild declines, and these were detectable by a sensitive Web-based assessment tool. There are many potential mechanisms of cognitive decline during chemotherapy, ranging from oxidative damage to reduced blood oxygenation due to anemia to stress and anxiety. While it is outside of the scope of this small pilot study to examine the causative factors of decline, it does suggest the need for further investigation of the effect and potential mechanisms of cognitive decline in this population. While most of the prior work in cognitive function has been conducted among breast cancer patients, ovarian cancer patients appear to experience cognitive decline as well. There is a need to further understand this issue so that effective preventive or treatment strategies can be developed.
The significant increase in patient-reported neurotoxicity across each study visit may be a concern for computerized assessments that require dexterity. However, the keyboard proficiency tests did not decline over time, suggesting that the neurotoxicity reported by patients in this study was not great enough to affect their ability to use the computer keyboard. Patients appear to report higher levels of difficulty with memory (eg, forgetfulness) following diagnosis than following the initiation of chemotherapy; however, higher-level cognitive processes (eg, logic, organizational abilities, calculations) reported by patients appear to decline following the initiation of chemotherapy. Although larger, adequately powered trials are needed to determine the extent of this decline, this suggests that patients experience increasing challenges that may interfere with their ability to perform necessary tasks at work and in the household. Further work is needed to examine the duration of these effects following chemotherapy. Since the cognitive impact of chemotherapy reported by patients is mild, investigators must ensure the use of appropriate patient-reported tools that are able to detect these differences. While reported decline may occur, this is likely to remain within the mild category of traditional assessment tools. It is of benefit to use patient-reported tools such as the PAF that also permit the analysis of continuous data.
This study is limited by its design as a pilot study and was challenged by several logistical issues. Four patients were unable to complete all the neurocognitive evaluations. This was due to remote study staff, who would visit various clinics in the Tucson and Phoenix metropolitan regions in Arizona (range of travel more than 120 miles). The lack of completion was entirely due to communication and travel complications. When a patient was rescheduled to a different chemotherapy date, it was not always possible for this to be communicated to the Arizona Cancer Center researchers in a timely manner, resulting in missed visits. It is recommended for future studies that require strict timelines for study assessments (such as this cognitive function study) that the assessments be conducted by staff in those practices who can identify changes in infusion dates when they occur. This will reduce the communication barriers and rate of missed visits. This study was also not designed to be a comprehensive assessment of neurocognitive function but was focused on assessing three domains: attention, processing speed, and response time. It is possible that many other domains of cognitive function could be impacted by chemotherapy that were not evaluated in this study. Many patients were also taking antidepressant medications during the study; however, these were generally not new prescriptions and were also being taken at the baseline assessment. Nevertheless, future studies should incorporate assessments of mood, depression, and anxiety to account for the potential effect of these factors on cognitive assessment scores.
Despite these limitations, the study provides preliminary data demonstrating cognitive decline during chemotherapy among ovarian cancer patients treated in the front-line setting of advanced disease. More than 90% of all patients experienced measurable impairments in cognitive function during primary chemotherapy. More than half of all patients demonstrated impairment on two or more cognitive domains. Prior work has shown that even mild cognitive impairments can influence quality of life and the ability to perform routine daily activities (eg, taking medications, returning to work, managing household finances).23 The data emphasize the critical need to further understand the impact of chemotherapy on cognitive function among ovarian cancer patients so that effective preventive and treatment strategies can be developed. Additional research is needed to understand how long these declines may persist following chemotherapy treatment.
