Post-radiation neutrophil-to-lymphocyte ratio is a prognostic marker in patients with localized pancreatic adenocarcinoma treated with anti-PD-1 antibody and stereotactic body radiation therapy

Abstract

Purpose: To investigate the role of pre- and post-stereotactic body radiation therapy (SBRT) neutrophil-to-lymphocyte ratio (NLR) in patients with localized pancreatic cancer treated with anti-PD-1 (programmed cell death protein-1) antibody and SBRT.

Materials and methods: This was a retrospective review of 68 patients with borderline resectable or locally advanced pancreatic cancer treated with anti-PD-1 antibody and SBRT after multi-agent chemotherapy. Immunotherapy was administered with 5-fraction SBRT in the neoadjuvant, concurrent, or adjuvant/maintenance setting. Clinical outcomes included overall survival (OS), local progression-free survival, distant metastasis-free survival, and progression-free survival. Median pre- and post-SBRT peripheral blood markers were compared with the Mann-Whitney U test. Univariate and multivariable analyses (UVA and MVA) were performed to identify variables associated with clinical outcomes. Linear regression was performed to determine correlations between variables and peripheral blood markers.

Results: A total of 68 patients were included in the study. The percent change between median pre- and post-SBRT absolute lymphocyte count (ALC), absolute neutrophil count, and NLR were -36.0% (p < 0.001), -5.6% (p = 0.190), and +35.7% (p = 0.003), respectively. Median OS after SBRT was 22.4 months. On UVA, pre-SBRT CA19-9 (hazard ratio [HR] = 1.001; 95% confidence interval [CI], 1.000-1.001; p = 0.031), post-SBRT ALC (HR = 0.33; 95% CI, 0.11-0.91; p = 0.031), and post-SBRT NLR (HR = 1.13; 95% CI, 1.04-1.22; p = 0.009) were associated with OS. On MVA, induction chemotherapy duration (HR = 0.75; 95% CI, 0.57-0.99; p = 0.048) and post-SBRT NLR (HR = 1.14; 95% CI, 1.04-1.23; p = 0.002) predicted for OS. Patients with post-SBRT NLR ≥3.2 had a median OS of 15.6 months versus 27.6 months in patients with post-SBRT NLR <3.2 (p = 0.009). On MVA linear regression, log10CTV had a negative correlation with post-SBRT ALC (regression coefficient = -0.314; 95% CI, -0.626 to -0.003; p = 0.048).

Conclusion: Elevated NLR after SBRT is primarily due to depletion of lymphocytes and associated with worse survival outcomes in localized pancreatic cancer treated with anti-PD-1 antibody. Larger CTVs were associated with decreased post-SBRT ALC.

Keywords: Immune checkpoint inhibitor; Immunotherapy; Lymphocyte; Neutrophil; PD-1 inhibitor; Pancreatic cancer; Stereotactic body radiotherapy.

Fig. 1.

Receiver operating characteristic (ROC) curve showing (A) optimal post-SBRT NLR value predicting overall survival and (B) Kaplan-Meier curve showing overall survival stratified by post-SBRT NLR of 3.2. Intersection of yellow line and ROC curve in Fig. 1A corresponds to the optimal NLR cut-off value of 3.2. SBRT, stereotactic body radiation therapy; NLR, neutrophil to lymphocyte ratio.

Fig. 2.

Correlations among (A) post-SBRT ALC, (B) pre-SBRT ALC, and (C) post-SBRT ANC with log10(CTV). Spearman correlation coefficients (r) and p-values are displayed. SBRT, stereotactic body radiation therapy; ALC, absolute lymphocyte count; ANC, absolute neutrophil count; CTV, clinical target volume.