9506 Background: Although existing evidence suggests that cytokines play an intermediary role in the development of post-chemotherapy cognitive changes, specific cytokines associated with this neurotoxic sequela of chemotherapy are still unknown. This study was designed to identify pro-inflammatory biomarkers that are associated with memory and attention impairment in Asian patients receiving chemotherapy. Methods: This is a prospective, cohort study conducted at the National Cancer Centre Singapore. Early-stage Asian breast cancer patients (Stage I to III), who received anthracycline and/or taxane-based chemotherapy were recruited. Computerized neuropsychological assessments (Headminder) were administered to evaluate patients’ memory and attention performances and a panel of pro-inflammatory plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α) was evaluated using multiplex immunoassay at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Memory and attention impairment were defined as a >2.5 reduction of the Zscore from baseline, as calculated by the reliable change index for repeated cognitive measurements. Results: Thirty-six patients were included (mean age 49.7±9.0 years; 80.6% Chinese). Comparing to T1, 50.0% and 36.1% of the patients suffered memory and attention impairment at T3, respectively. Comparing patients with intact memory to those who suffered impairment from T2 to T3, they had higher levels of circulating IL-1β [median (IQR): 0.44 (0.1-0.5) vs 0.56 (0.4-0.7) pg/ml, p=0.069], IL-4 [0.41 (0.0-0.8) vs 0.85 (0.2-1.5) pg/ml, p=0.067) and TNF-α [1.78 (1.3-2.2) vs 3.01 (1.3-3.5) pg/ml, p=0.069]. At T3, reduction of attention scores were associated with higher levels of IL-1β (rs= -0.37, p=0.023) and IL-6 (rs= -0.33, p=0.045). No significant associations were identified with IL-2, IL-8, IL-10, GM-CSF and IFN-γ. Conclusions: These findings suggest that an increase in the post-chemotherapy levels of TNF-α, IL-1β, IL-4 and IL-6 may have an association with the manifestations of memory and attention impairment in Asian breast cancer patients.
e20566 Background: It is suggested that vascular endothelial growth factor (VEGF) induces neurogenesis in the brain and provides neuroprotectiveeffects. This study was designed to examine the relation between plasma VEGF level and cognitive functioning in breast cancer patients who have received chemotherapy. Methods: Early-stage breast cancer patients (stage I to III) who received anthracycline- and/or taxane-based chemotherapy were prospectively recruited at a single center. Perceived cognitive functioning (FACT-Cog) and computerized neuropsychological assessment (Headminder) were used to evaluate patients’ cognitive function at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Headminder evaluated four cognitive domains: Attention, Memory, Processing, and Response speed. Impairment in each domain were defined as a >2.5 reduction of the Z score from baseline, as calculated by the reliable change index for repeated cognitive measurements. Plasma VEGF levels were analyzed at each time point using the multiplex immunoassay. Spearman Correlation (rs) was utilized to correlate the change in plasma VEGF and neurocognitive functioning. Results: Thirty-six patients were recruited (median age: 51.5; Chinese: 80.6%; post-menopausal: 58.3%). Median plasma VEGF levels were T1: 19.2 pg/ml; T2: 26.5 pg/ml; T3: 21.9 pg/ml. Weak correlations were observed between the change in VEGF level and the change in FACT-Cog and Headminder scores for individual cognitive domain (Table). Conclusions: Results suggest a weak correlation between plasma VEGF level and cognitive functioning in the domains of attention, concentration, functional interferences, mental acuity and response speed. Larger sample size and longer follow up are required to further explore the findings. [Table: see text]
6589 Background: Establishing the Minimal Clinically Important Difference (MCID) is essential for interpreting the clinical relevance of patient reported outcomes. This is the first study to date to determine the MCID of FACT-Cog, a 37-item validated subjective neuropsychological instrument designed to evaluate cancer patients’ perceived cognitive deterioration on their quality of life. Methods: This prospective, observational study involved 220 breast cancer patients who have completed FACT-Cog and EORTC-QLQ-C30 at two time points: baseline and at least 3 months following chemotherapy. The MCID was computed using 3 approaches: 1) an anchor-based approach utilized the validated EORTC-QLQ-C30-Cognitive Functioning scale (CF) as the anchor for patients who showed a minimal deterioration on the CF (defined as a one-step deterioration on the CF scale); 2) a Receiver Operating Characteristic (ROC) curve was used to identify an optimal MCID cut-off point for deterioration; 3) a distribution-based approach utilized the 0.33 SD, 0.5 SD and one standard error of measurement (SEM) of the total FACT-Cog score (148 points) to estimate the MCID. Results: There was moderate correlation between the mean change scores of FACT-Cog and CF (rp= 0.43, p<0.001). The CF-anchored MCID was 9.6 points (95% CI 4.4 - 14.8). MCID derived from the ROC method was 7.5 points (AUC: 0.75; sensitivity: 75.6%; specificity: 68.8%). Using the distribution-based approach, MCID corresponding to effect sizes of 0.33SD to 0.5SD of the total FACT-Cog score ranged from 6.9 – 10.3 points and one-SEM criterion resulted in a MCID estimate of 10.6 points. Combining results from all approaches, the MCID identified for FACT-Cog ranged from 6.9 – 10.6 points (4.7% to 7.2% of total score). Conclusions: A 6.9 to 10.6 points reduction of the FACT-Cog score corresponds to the smallest clinically-relevant perceived cognitive deterioration. These estimates are important as they can facilitate the interpretation of patient-reported cognitive changes and sample size estimation in future studies.
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