OPTIMAL TIME TO SURGERY AFTER NEOADJUVANT THERAPY IN PANCREATIC ADENOCARCINOMA: IS THERE AN IDEAL WINDOW?
Andrew B. Crocker*1,3, Leah Winer1, Eileen A. O’Halloran2, Dany Barrak1, Karthik Devarajan1, Sanjay S. Reddy1
1Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA; 2OSF Saint Anthony Medical Center, Rockford, IL; 3Saint Elizabeth's Medical Center, Brighton, MA
Introduction:
NCCN guidelines for the management of pancreatic ductal adenocarcinoma (PDAC) recommend pancreatic resection 4-8 weeks after completion of neoadjuvant therapy. Increasing data suggests the benefit of neoadjuvant therapy in PDAC, but few studies have focused on the impact of time to surgery in the setting of neoadjuvant care. Therefore, in this analysis we aim to identify the optimal time between completion of neoadjuvant therapy and definitive surgery.
Methods
Patients with PDAC who underwent single modality neoadjuvant therapy (SMNT) or total neoadjuvant therapy (TNT) prior to pancreatectomy at a single NCI designated cancer center between 2010 and 2020 were included. Where TNT was defined as both neoadjuvant chemotherapy followed by chemoradiation therapy, and SMNT was defined as either neoadjuvant chemotherapy or chemoradiation therapy. Patients were evaluated by treatment type and by time to surgery: ≤4 weeks, 5 to 8 weeks, or >8 weeks, after completion of neoadjuvant therapy. Logistic regression models were used to analyze the relationship between time to surgery and outcome variables, while Cox proportional hazards models were used for survival analyses.
Results:
121 patients who received TNT (n = 68) or SMNT (n = 53) prior to pancreatic resection met inclusion criteria. As shown in figure 1, among all patients those who underwent surgery in ≤4 weeks demonstrated significantly worse disease-free survival (DFS) relative those who had surgery in >8 weeks (12.4 vs 19.5 months, p=0.03). Similarly as shown in figure 2, among patients who received TNT those in both the 5-8 week and >8-week windows demonstrated significantly longer DFS than those in the ≤4-week group (11.3 vs 18.7 months p=0.05, and 11.3 vs 19.5 months p=0.01, respectively). For the entire cohort, those who had surgery after 8 weeks also demonstrated significantly lower rates of fibrosis relative to ≤4 weeks (p=0.013) and 5-8 weeks (p=0.043).
Conclusion:
Patients who underwent pancreatic resection ≤4 weeks after completion of neoadjuvant therapy exhibited significantly shorter DFS, and higher rates of fibrosis relative to patients who underwent surgery after longer intervals. These initial findings suggest that longer intervals to surgery after neoadjuvant therapy may offer significant survival benefits, though additional investigations are needed.
Figure 1: Kaplan-Meier plot depicting Disease-Free Survival between time to surgery groups
Figure 2: Kaplan-Meier plot depicting Disease-Free Survival among patients who recieved total neoadjuvant therapy by time to surgery group
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