LYMPH NODE YIELD IS ASSOCIATED WITH IMPROVED OVERALL SURVIVAL AND INCREASED TIME TO RECURRENCE IN NODE-NEGATIVE PANCREATIC DUCTAL ADENOCARCINOMA FOLLOWING NEOADJUVANT THERAPY
Maximiliano Servin-Rojas*, Zhi Ven Fong, Gabriella Lionetto, Louisa Bolm, Cristina R. Ferrone, Carlos Fernandez-Del Castillo, Dario M. Rocha-Castellanos, Keith D. Lillemoe, Motaz Qadan
Massachusetts General Hospital, Boston, MA
Introduction
Lymph node yield (LNY) has recently been associated with overall survival (OS) in node-negative cancers, including pancreatic ductal adenocarcinoma (PDAC). However, reports in PDAC preceded widespread use of neoadjuvant therapy (NAT). We sought to determine if LNY was associated with OS and time to recurrence (TTR) in node-negative patients with PDAC treated with NAT.
Methods
We conducted a retrospective analysis of an institutional neoadjuvant PDAC database and the National Cancer Database (NCDB). Patients with pathological T-stage I-III, node-negative (N0), PDAC who underwent NAT followed by Whipple pancreaticoduodenectomy were included. Twenty-two lymph nodes were identified as the cutoff point with optimal survival (log-rank test) from the NCDB. Survival analyses were carried out using log-rank, Kaplan-Meier, and Multivariable Cox Regression.
Results
In the institutional dataset, we identified 233 node-negative patients who underwent NAT followed by a Whipple procedure. Median age was 66 years (IQR 59-73), 51% were female, 48% were T2, median serum CA 19-9 was 113 U/mL (IQR 25-358), 79% underwent R0 resection, 25% had lymphovascular invasion, 62% had perineural invasion, and 23% received adjuvant treatment. The median LNY was 19 (IQR 14-24) and 34% of patients had a LNY ≥22. Patients with a LNY ≥22 were associated with prolonged median OS (59 months vs. 25 months, p<0.001) and prolonged TTR (32 months vs. 14 months, p=0.019). On multivariable analysis, LNY was an independent predictor of survival (HR 0.97, 95% CI 0.95-0.99, p=0.034) per sampled node.
In the NCDB, we identified 2,029 node-negative patients who underwent NAT followed by a Whipple procedure. Median age was 65 years old (IQR 58-71), 50% were female, 87% White, 61% were treated in an academic center, 54% had government insurance, 57% were T3, 88% had R0 margins, and 36% received adjuvant treatment. The median LNY was 17 (IQR 12-23). Patients with a LNY ≥22 were associated with prolonged median OS (49 months vs. 33 months, p<0.001). On multivariable analysis, LNY was an independent predictor of survival (HR 0.99, 95% CI 0.98-0.99, p<0.001) per sampled node.
Conclusions
These findings suggest that LNY following Whipple pancreaticoduodenectomy is associated with improved outcomes and OS in the setting of node-negative disease following NAT using two independent datasets. Given these reproducible findings combined with additional recent data, responsible mechanisms by which LNY impacts outcomes in node-negative patients warrant further exploration.
Panel A. Overall Survival (OS) in the National Cancer Database (NCDB). Panel B. Overall Survival in the institutional dataset. Panel C. Time to recurrence (TTR) in the institutional dataset.
Multivariable Cox regression model for survival and recurrence using institutional data.
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