Tolerability, Attrition Rates, and Survival Outcomes of Neoadjuvant FOLFIRINOX for Nonmetastatic Pancreatic Adenocarcinoma: Intent-to-Treat Analysis.

BACKGROUND: FOLFIRINOX is increasingly used in the management of pancreatic ductal adenocarcinoma (PDAC). However, neoadjuvant therapy is associated with toxicity, possible disease progression, and biopsy-related and biliary complications that may preclude operative exploration. Data on the true attrition rate outside of clinical trials or resected surgical series are lacking. STUDY DESIGN: Patients with nonmetastatic PDAC who initiated FOLFIRINOX from 2015 to 2020 were identified from our institution's pharmacy records. Multivariable regression and Cox proportional hazard models were used for adjusted analyses of categorical and survival outcomes, respectively. RESULTS: Of 254 patients who initiated first-line neoadjuvant FOLFIRINOX, 199 (78.3%) underwent exploration, and 54 (21.3%) did not complete their chemotherapy cycles due to poor tolerability (46.3%), poor response (31.5%), or disease progression (14.8%), among other causes (7.4%). A total of 109 (42.9%) patients experienced grade 3/4 FOLFIRINOX-related toxicity, of whom 73 (28.7%) and 100 (39.4%) required an emergency department visit or inpatient admission, respectively. Finally, not undergoing surgical exploration was associated with impaired overall survival (hazard ratio 7.0; 95% CI 3.8 to 12.8; p < 0.001). Independent predictors of not undergoing exploration were remote history of chemotherapy receipt (odds ratio [OR] 0.06; p = 0.02), inability to complete FOLFIRINOX cycles (OR 0.2, p = 0.003), increase in ECOG score (OR 0.2, p < 0.001), and being single or divorced (OR 0.3, p = 0.018). CONCLUSIONS: Among 254 patients with nonmetastatic PDAC initiated on FOLFIRINOX, of whom 52% were locally advanced, a total of 199 (78.3%) were explored, 142 (71.4%) underwent successful resection, and 129 (90.8%) were resected with negative margins. Despite 109 (42.9)% of patients experiencing significant toxicity, most patients could be managed through treatment-related complications to complete planned neoadjuvant chemotherapy and undergo planned surgical exploration.

Perioperative Pharmacologic Prophylaxis of Venous Thromboembolism: A Professional Liability Analysis.

BACKGROUND: Fear of medical liability is a major driver for broad administration of perioperative prophylactic anticoagulation, despite the persistently low rates of clinically symptomatic venous thromboembolism events (VTE) postoperatively. This study was undertaken to evaluate the medicolegal landscape of perioperative VTE and its pharmaceutical prophylaxis. METHODS: The Westlaw legal database was retrospectively searched for verdicts in medical professional liability cases in the United States between 2009 and 2020. One search strategy focused on perioperative VTE, and a second on claims of hemorrhagic complications in patients receiving perioperative anticoagulation. RESULTS: The search for VTE revealed 129 cases, and the search for hemorrhagic complications identified 24 cases. Almost half of the VTE cases were brought following orthopedic surgery (49%), and 29% following general surgery. The most common claims were failure to diagnose and treat during hospital stay or after discharge (74%), and failure to prescribe/administer anticoagulation (46%). Verdict for the health care professional (i.e., the defendant) was reached in 75% of cases. The median payout for patient verdicts was 1,213,644 USD (interquartile range 1,014,100; 150,000-7,700,000). Of hemorrhagic complication cases, 42% occurred in patients receiving VTE prophylaxis. In these cases, 82% resulted in a defendant verdict. CONCLUSIONS: Reasons for in-court medical professional liability claims involving perioperative VTE were mainly failure to diagnose VTE and rescue patients from complications postoperatively. The high rate of defendant verdicts supports the notion that decisions on VTE prophylaxis should not be influenced by fear of liability.