Impact of Recombinant Granulocyte Colony-Stimulating Factor During Neoadjuvant Therapy on Outcomes of Resected Pancreatic Cancer

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. The granulocyte colony-stimulating factor (G-CSF)-neutrophil axis promotes oncogenesis and progression of PDAC. Despite frequent use of recombinant G-CSF in the management and prevention of chemotherapy-induced neutropenia, its impact on oncologic outcomes of patients with resected PDAC is unclear.

Patients and methods: This cohort study assessing the impact of G-CSF administration was conducted on 351 patients with PDAC treated with neoadjuvant therapy (NAT) and pancreatic resection at a high-volume tertiary care academic center from 2014 to 2019. Participants were identified from a prospectively maintained database and had a median follow-up of 45.8 months.

Results: Patients receiving G-CSF (n=138; 39.3%) were younger (64.0 vs 66.7 years; P=.008), had lower body mass index (26.5 vs 27.9; P=.021), and were more likely to receive 5-FU-based chemotherapy (42.0% vs 28.2%; P<.0001). No differences were observed in baseline or clinical tumor staging. Patients receiving G-CSF were more likely to have an elevated (>5.53) post-NAT neutrophil-to-lymphocyte ratio (45.0% vs 29.6%; P=.004). G-CSF recipients also demonstrated higher circulating levels of neutrophil extracellular traps (+709 vs -619 pg/mL; P=.006). On multivariate analysis, G-CSF treatment was associated with perineural invasion (hazard ratio [HR], 2.65; 95% CI, 1.16-6.03; P=.021) and margin-positive resection (HR, 1.67; 95% CI, 1.01-2.77; P=.046). Patients receiving G-CSF had decreased overall survival (OS) compared with nonrecipients (median OS, 29.2 vs 38.7 months; P=.001). G-CSF administration was a negative independent predictor of OS (HR, 2.02; 95% CI, 1.45-2.79; P<.0001). In the inverse probability weighted analysis of 301 matched patients, neoadjuvant G-CSF administration was associated with reduced OS.

Conclusions: In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration may be associated with worse oncologic outcomes and should be further evaluated.

Keywords: G-CSF; NLR; Neoadjuvant therapy; Pancreatic Cancer.