ASCO 2026 | CRCI and compromised adjuvant chemotherapy delivery in cancer

This year at ASCO, I presented our prospective analysis results on the association between early cancer-related cognitive impairment or CRCI and compromised delivery of adjuvant chemotherapy. So what we know about CRCI? CRCI affects up to 75% of patients receiving adjuvant chemotherapy and has a negative impact on quality of life. But beyond its clinical implications, beyond its established role on quality of life, its clinical implications are not well characterized. So important questions remain unanswered. Can it affect a patient’s ability to receive unplanned chemotherapy? And our hypothesis was straightforward. Early CRCI is not just a symptom, a quality of life issue. It’s rather an indicator of impaired treatment tolerance. So our study was conducted at the University Hospital of Larissa and it was a prospective study. The study group included patients with early-stage breast and colorectal cancer receiving adjuvant taxane and oxaliplatin-based chemotherapy. We also included two control groups, one with patients not receiving chemotherapy and another one with age-matched healthy individuals. Patients with pre-existing dementia or anxiety disorders or anemia were excluded from the study. Cognitive function was assessed using the Greek validated version of a FACT-COG questionnaire at baseline and every three months for up to 12 months and early CRCI was defined as a 10-point or greater decline at the three-month time points. So moving on to the results, early CRCI was remarkably common: 60 percent of patients receiving adjuvant chemotherapy developed early CRCI. In sharp contrast, cognitive scores remained stable in both control groups, suggesting that chemotherapy exposure might be the driver of CRCI in this setting. Patients with early CRCI had more than threefold higher odds of receiving reduced dose intensity. Importantly, these were patients receiving curative-intent treatment. Therefore, the observed reduction in dose intensity might have important clinical implications in long-term oncologic outcomes. CRCI was also strongly associated with neurotoxicity. Patients with early CRCI had more than fourfold higher odds of developing a clinically significant grade two or greater neurotoxicity, raising the possibility of a third underlying neurobiological susceptibility underlying both cognitive impairment and chemotherapy-induced neurotoxicity. Treatment continuity was also affected. Chemotherapy discontinuation occurred in 12% of patients with early CRCI versus 3% of those without. Treatment delays were more than threefold more frequent in the early CRCI group. Moreover, ER visits and hospitalization rates were higher among patients with early CRCI. And all these findings were consistent. So, across all treatment delivery points, early CRCI was associated with substantially worse outcomes. Importantly and notably, CRCI was not transient. It persisted for beyond three months in a substantial proportion of affected patients, while cognitive scores remained stable in both control groups. So, in conclusion, early CRCI is common among patients, affecting 6 out of 10 patients receiving adjuvant taxane or oxaliplatin-based chemotherapy. It is strongly associated with reduced dose intensity, with higher rates of clinically significant neurotoxicity, with chemotherapy treatment discontinuation, with treatment delays, and with more frequent unplanned healthcare utilization. So we propose that early CRCI may identify a vulnerable subgroup of patients at risk for compromised delivery of adjuvant chemotherapy. Beyond its established role on quality of life, CRCI may represent an actionable indicator of poor treatment tolerance that could be targeted with, let’s say, risk-adapted supportive strategies aiming at improving treatment tolerance and preserving dose intensity in the adjuvant setting.

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