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IRON-DEFICIENCY ANEMIA DECREASES SURVIVAL IN POST-PANCREATICODUODENECTOMY PANCREATIC DUCTAL ADENOCARCINOMA PATIENTS
Joseph Gorman
*2, Zachary Kaplan
2, Matthew Kraft
2, Elijah Hoffman
2, Harish Lavu
1,2, Wilbur Bowne
1,2, Charles Yeo
1,2, Avinoam Nevler
1,21Department of Surgery, Thomas Jefferson University, Philadelphia, PA; 2Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA
Introduction: Resection of the duodenum and proximal jejunum can pose a risk for iron malabsorption and subsequent iron-deficiency (ID) anemia. Anemia has been associated with poorer outcomes in various cancer patient cohorts. This study aims to evaluate the prevalence of iron-deficiency and its effect on survival in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy (PD).
Methods:In this staged investigation, an initial multi-institutional research network (MRN) analysis using TriNetX was performed to analyze the incidence of ID post-PD in pancreatic cancer patients compared to non-resected, healthy controls. Next, we assessed the impact of ID on survival in pancreatic cancer patients post-PD. Both analyses were performed using propensity-score matching (PSM). The final step included a validative retrospective single-institution analysis of data from patients with PDAC who underwent PD between 2016 and 2022 which evaluated survival assessing CBCs, iron-indices, and anemia subtype using Cox proportional hazards regression analyses and a K-means clustering algorithm with survival modeling.
Results:The initial MRN analysis compared 19,222 PSM patients and demonstrated higher rates of ID in post-PD pancreatic cancer patients at 3-6, 6-12, and 24-36 month intervals. The MRN survival analysis of post-PD pancreatic cancer patients yielded 2,150 patient pairs (ID and non-ID) and showed that ID was associated with shorter overall survival (HR=1.14, 95%CI [1.03-1.25], P<0.01, Figure 1A) and increased metastatic progression (OR=1.51, 95%CI [1.34-1.69], P<0.0001, Figure 1B). Finally, the single-institution analysis indicated increased mortality risk associated with low TIBC (HR=0.990/unit, 95%CI [0.982,0.999], P=0.02) and low ferritin (HR=0.974/unit, 95%CI [0.996,0.999], P=0.006). K-means clustering based on hemoglobin levels and iron-indices identified three distinct patient groups, and found that patients with lower transferrin saturation and ferritin were at increased risk of mortality (Group 1: HR=4.358, 95%CI [1.069,17.691], P=0.04 and Group 3: HR=5.196, 95%CI [1.075,25.112], P=0.04), with regression modeling estimating decreased median survival in these groups (Figure 2). Clinical classification of patients into ID anemia, anemia of chronic disease (CD), mixed ID/CD anemia, and other anemia types also revealed that patients with mixed ID/CD anemia had increased mortality risk compared to patients with only CD anemia (HR=3.067, 95%CI [1.023,9.174], P=0.045).
Conclusions:Iron-deficiency after PD is prevalent and associated with poorer survival in PDAC patients. Mortality risk may be particularly high in patients with low ferritin and low transferrin saturation. Continued surveillance for iron-deficiency is advised in all patients post-PD, and prompt treatment is advised in patients diagnosed with ID anemia.
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