The implications of treatment delays in adjuvant therapy for cholangiocarcinoma patients.

Abstract

291 Background: To understand the factors associated with timing of adjuvant therapy in the management of intrahepatic and extrahepatic cholangiocarcinoma and the impact of delays on overall survival (OS). Methods: Data from the NCDB for patients with pathologically proven non-metastatic adenocarcinoma of the bile ducts from 2004 to 2014 were pooled and screened. Patients were included only if they underwent surgery and adjuvant chemotherapy (CMT) and/or radiotherapy (RT). Patients who underwent neoadjuvant therapy or received CMT or RT with palliative intent were excluded. Pearson’s chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity-score matching with inverse probability of treatment weighting, OS was compared between patients who had initiation of adjuvant therapy past various time points using Kaplan Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling. Results: In total, 7,422 patients in our analysis underwent adjuvant treatment. This represented 43% of the study cohort of 17,123 patients. Of the patients who underwent adjuvant treatment, 3,956 (53%) initiated adjuvant therapy by two months, 6,234 (84%) by 3 months and 6,987 (94%) by four months. High-grade disease, macroscopically positive margins, tumors larger than five centimeters, and unknown LVSI status, were associated with earlier initiation of adjuvant treatment at two months or earlier. Patients who received early adjuvant therapy were also more likely to be treated with a combination of CMT and RT. Factors associated with delay of adjuvant therapy beyond three months post-surgery included Charlson scores of one or greater and Hispanic race. After propensity score weighting, there was no survival difference between groups when comparing initiation of adjuvant therapy before or after two, three or four month time points Conclusions: We identified a number of patient characteristics related to the timing of initiating adjuvant therapy in patients with biliary cancers. There were no significant difference in OS associated with delaying adjuvant therapy beyond two, three or four month time-points. Our findings are relevant in the era of COVID-19 when minimizing patient exposure to health-care settings during a pandemic may need to be considered when deciding on the timing of adjuvant therapy. If a delay is necessary, our results suggest that there is no survival detriment to initiating adjuvant therapy beyond three or four months after surgery for biliary cancers.