Association of early cognitive decline with compromised delivery of adjuvant chemotherapy.

11010 Background: Cancer-related cognitive impairment (CRCI, “chemobrain”) is a common condition among patients (pts) receiving adjuvant chemotherapy (CT) and has been shown to negatively affect quality of life (QoL). However, the clinical relevance of early CRCI beyond symptom burden remains poorly characterized. We evaluated whether early CRCI is associated with compromised delivery of adjuvant CT, including reduced relative dose intensity (RDI). Methods: This prospective study was conducted at the University Hospital of Larissa and represents an expanded analysis of a previously reported population with treatment delivery endpoints. Pts with early stage (ES) breast (BC) or colorectal (CRC) cancer scheduled to receive adjuvant CT containing taxanes or oxaliplatin, respectively, were eligible for this study (C1). Two control groups were included: ES cancer pts that were not eligible for adjuvant CT (C2) and age-matched healthy controls (C3). Eligibility criteria included age > 45 years and fluency in Greek; pts with pre-existing dementia or anxiety disorders were excluded. C1 pts were assessed at baseline and every 3 months (mo) up to 12 mo after CT initiation, while C2 and C3 were assessed at 3-mo intervals. CRCI was evaluated using the Greek Version of Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Early CRCI was defined as a ≥10-point decline in total FACT-Cog score at 3 mo after CT initiation, in the absence of severe anemia (CTCAE grade ≥3). Treatment delivery outcomes included RDI (reduced RDI: < 85%), treatment delays, CT discontinuation, unplanned healthcare use and CT-related neurotoxicity (ntx). Results: Overall, 164 pts were included in C1 (111 BC, 63 CRC), 61 in C2 (38 BC, 23 CRC) and 25 in C3. Early CRCI was observed in a substantial proportion of pts receiving adjuvant CT (99/164, 60%). Pts with early CRCI were significantly more likely to receive reduced CT dose intensity compared to those without CRCI (OR 3.27, 95% CI 1.34-7.98). Early CRCI was also associated with an increased risk of clinically relevant concurrent treatment-related ntx (CTCAE grade > 1; OR 4.05, 95% CI 1.81-9.08). CT discontinuation occurred more frequently among pts with early CRCI than among those without CRCI (12% vs 3%). In addition, these pts more frequently experienced treatment delays and unplanned healthcare use. These associations were independent of baseline ECOG PS. Early CRCI persisted beyond 3 mo in a substantial proportion of affected pts during follow up, while cognitive scores remained stable among controls. Conclusions: In this expanded cohort, early CRCI was associated with reduced RDI and higher rates of treatment discontinuation. Beyond its impact on QoL, early CRCI identifies a vulnerable subgroup of pts at risk for compromised treatment delivery and may represent a clinically actionable target for risk-adapted supportive strategies aimed at preserving curative-intent treatment intensity.