Adjuvant oxaliplatin and fall-related injury in patients with colorectal cancer.

Abstract

78 Background: Adjuvant oxaliplatin improves colorectal cancer (CRC) survival but causes dose-dependent peripheral neuropathy, possibly increasing the risk of fall-related injuries (FRI) such as fractures. In this retrospective cohort study, we examined the impact of adjuvant oxaliplatin cycles on FRIs. Methods: All data were ascertained from linked health administrative and population databases. We included Ontarians aged 18-85 years at CRC diagnosis between January 1 2007 to December 31 2018 who underwent curative resection and received adjuvant oxaliplatin. We excluded those with a prior cancer diagnosis within 5 years, prior CRC diagnosis ever, non-adenocarcinoma histology, prior oxaliplatin, and <2 years of Ontario health insurance prior to CRC diagnosis. Oxaliplatin dose was determined in the 382 days after resection and dichotomized (1-6 vs. 7-12 cycles). The outcome was FRI, defined by ICD10 codes W00-W19 for any injury caused by a fall requiring emergency or inpatient care. Follow-up began at the end of the treatment window and terminated at the first of FRI, death, loss of Ontario health insurance, or March 31 2020. To account for differences between groups, clinical and demographic characteristics at diagnosis (Table) were used to estimate propensity scores for treatment and calculate inverse probability of treatment weights. These weights were applied to a Fine & Gray regression model to determine the subdistribution hazard ratio (sHR) estimating the association between FRI and 1-6 versus 7-12 cycles of oxaliplatin, with death as a competing risk. Standardized differences <0.1 indicated negligible imbalance. An interaction term tested for effect modification by age at diagnosis. Results: 9,324 patients were included in the study; 1,870 received 1-6 cycles and 7,454 received 7-12 cycles of oxaliplatin. Those exposed to 1-6 cycles were older (61.0 vs. 59.1 years), had higher comorbidity scores (13.5 vs 12.3), and more often had rectal cancer (27.5 vs. 22.2%). Negligible imbalance remained after weighting. Median follow-up was 50.2 months. Total follow-up was 44,472 person-years. There were 1,223 FRIs and 1,913 deaths. The sHR for FRIs comparing 7-12 cycles against 1-6 cycles of oxaliplatin was 0.98 (95% CI 0.85-1.14). The interaction p-value for age and oxaliplatin dose was 0.24. Conclusions: In this population-based retrospective cohort study of 9,324 patients with CRC, the risk of FRIs was similar for 7-12 cycles compared with 1-6 cycles of adjuvant oxaliplatin. This finding was consistent across age at diagnosis. Future research should examine the relationship between oxaliplatin dose and falls not resulting in injury. [Table: see text]