Antibiotic use influences outcomes in advanced pancreatic adenocarcinoma patients. (11th July 2021)

• Record Type: Journal Article
• Authors: Mohindroo, Chirayu; Hasanov, Merve; Rogers, Jane E.; Dong, Wenli; Prakash, Laura R.; Baydogan, Seyda; Mizrahi, Jonathan D.; Overman, Michael J.; Varadhachary, Gauri R.; Wolff, Robert A.; Javle, Milind M.; Fogelman, David R.; Lotze, Michael T.; Kim, Michael P.; Katz, Matthew H.G.; Pant, Shubham; Tzeng, Ching‐Wei D.; McAllister, Florencia
• Is Part Of: Cancer medicine. Volume 10:Number 15(2021)
• Page Start: 5041
• Page End: 5050
• Publication Date: 2021-07-11
• Subjects: antibiotics -- autophagy -- chemotherapeutic agents -- immunity -- microbiota -- pancreatic adenocarcinoma; 616.994005
• DOI: 10.1002/cam4.3870
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Recent studies defined a potentially important role of the microbiome in modulating pancreatic ductal adenocarcinoma (PDAC) and responses to therapies. We hypothesized that antibiotic usage may predict outcomes in patients with PDAC. We retrospectively analyzed clinical data of patients with resectable or metastatic PDAC seen at MD Anderson Cancer from 2003 to 2017. Demographic, chemotherapy regimen and antibiotic use, duration, type, and reason for indication were recorded. A total of 580 patients with PDAC were studied, 342 resected and 238 metastatic patients, selected retrospectively from our database. Antibiotic use, for longer than 48 hrs, was detected in 209 resected patients (61%) and 195 metastatic ones (62%). On resectable patients, we did not find differences in overall survival (OS) or progression‐free survival (PFS), based on antibiotic intake. However, in the metastatic cohort, antibiotic consumption was associated with a significantly longer OS (13.3 months vs. 9.0 months, HR 0.48, 95% CI 0.34–0.7, p = 0.0001) and PFS (4.4 months vs. 2 months, HR 0.48, 95% CI 0.34–0.68, p = <0.0001). In multivariate analysis, the impact of ATB remained significant for PFS (HR 0.59, p = 0.005) and borderline statistically significant for OS (HR 0.69, p = 0.06). When we analyzed by chemotherapy regimen, we found that patients who received gemcitabine‐based chemotherapy as first‐line therapy (n = 118) had significantly prolonged OS (HR 0.4, p 0.0013) and PFS (HR 0.55, p 0.02) if they received antibiotics, while those receiving 5FU‐based chemotherapy (n = 98) had only prolonged PFS (HR 0.54, p = 0.03). Antibiotics‐associated modulation of the microbiome is associated with better outcomes in patients with metastatic PDAC. Abstract : We have analyzed the effect of antibiotics' intake on two cohorts of patients with pancreatic adenocarcinoma, resectable, and metastatic. We have found that on the metastatic cohort, antibiotics use was significantly associated with better outcomes, particularly, on patients that received gemcitabine based‐chemotherapy as the first line.