Gunchick, Valerie

AbstractBiliary tract cancer (BTC) is a rare and aggressive malignancy with increasing incidence. Most BTC cases are diagnosed with metastatic disease which carries a 5‐year survival rate of <5%. Physical activity, diet, and obesity might be associated with BTC risk, but studies have been limited particularly in African descendants. We addressed this knowledge gap by evaluating associations of BTC risk with obesity, physical activity, and dietary intakes in 723,326 adult participants in four cohort studies conducted in China, the United Kingdom, and the United States. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) in each cohort; results were combined using meta‐analysis. All cohorts had ≥11 median follow‐up years with 839 incident BTC cases combined. BTC risk was positively associated with body mass index (BMI) and waist‐to‐hip ratio (WHR) whereas physical activity, fruit intake, and fish intake were inversely associated. HR and (95% CI) comparing BMI >35.0 to 18.5–24.9: 1.71 (1.26, 2.31), p‐trend <.0001; comparing BMI‐adjusted WHR top to bottom quartile: 1.20 (0.94, 1.53), p‐trend = .05; comparing ≥15–0 metabolic equivalent task‐hours/week 0.76 (0.61, 0.94), p‐trend = .009; comparing highest to lowest intake tertile for fruit and fish 0.79 (0.66, 0.95), p‐trend = .01; 0.82 (0.68, 0.98), p‐trend = .04, respectively. Associations were, in general, similar across ancestry groups. Our study provides strong evidence for important roles of obesity, diet, and physical activity in BTC etiology and stresses the need for lifestyle modification to combat the rising incidence of this fatal malignancy.

451 Background: Gemcitabine plus platinum (GP) is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report progression-free survival (PFS) for second-line treatment to be < 3 months. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients (pts) with BTC who have progressed on GP, though there is a paucity of data regarding its efficacy in this population. Methods: We retrospectively evaluated pts with advanced BTC who were treated with FOLFIRI at MD Anderson, University of Michigan and Mayo Clinic in Jacksonville. Data were obtained on pt demographics, type of BTC, PFS, and overall survival (OS). Results: Ninety-eight pts were included of which 74 (76%) had metastatic disease at the time of treatment with FOLFIRI. The median age was 59 (range, 22 to 86) years. The number of pts with extrahepatic cholangiocarcinoma (CCA)/gall bladder (GB)/intrahepatic CCA were 10, 17, and 71. FOLFIRI was used as 1st, 2nd, 3rd or 4th – Nth lines in 8, 50, 36, and 4 pts, respectively. Of the 65 pts whose best responses were documented, 23 (35%) had stable disease and 7 (11%) had a partial response per RECIST v1.1. Median duration on FOLFIRI was 2.2 months. The median PFS and OS were 2.4 (95% CI 1.7 to 3.1) and 6.6 (95% CI 4.7 to 8.4) months, respectively. Median PFS for pts treated with FOLFIRI in 1st, 2nd, 3rd or 4th – Nth lines were 3.1, 2.5, 2.3 and 1.5 months, respectively. Eighteen pts received concurrent bevacizumab (13) or EGFR-targeted therapy (5) with FOLFIRI, and both of groups exhibited a median PFS of 2.7 months. Eastern Cooperative Oncology Group performance status (PS) of 0-1 was associated with improved OS (P = 0.006) compared to PS of 2-3. Conclusions: In this multi-institution retrospective review of 98 pts with BTC treated with FOLFIRI, efficacy of this regimen appears to be modest. While PFS and OS outcomes were similar to what has been previously reported, the 46% disease control rate in this group of predominantly pretreated pts is encouraging. Given the lack of other standard therapies, FOLFIRI may still have a role in this pt population, but these results emphasize the need for more effective treatment options for pts with advanced, pretreated BTC.