Predictive and prognostic impact of blood-based inflammatory biomarkers in patients with gastroenteropancreatic neuroendocrine tumors commencing peptide receptor radionuclide therapy

Ziel/Aim Tumor microenvironment inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response in chemotherapy. Consistently, both tumor immune infiltration and inflammatory biomarkers have demonstrated prognostic significance in various types of cancer.

Methodik/Methods We retrospectively analyzed 33 patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). Pretreatment blood-based inflammatory biomarkers, e.g. C-reactive protein levels (CRP), white blood cell count (WBC), were documented and inflammation indexes, e.g. neutrophil-lymphocyte ratio (NLR), were calculated. Tumor burden was determined using Ga-68-DOTA-TATE PET/CT before enrollment and every 2 cycles thereafter. Therapy response was assessed using RECIST 1.1, including its volumetric modification.

Ergebnisse/Results 16 patients demonstrated progressive disease. Absolute neutrophil count (ANC) (P < 0.0001, median 6.9x10⁹/L vs 4.1x10⁹/L), CRP (P = 0.01, median 42 mg/L vs 1.6 mg/L) and the high-sensitivity inflammation-based prognostic index (P = 0.015) were higher in non-responders. Change in whole-body tumor burden after two cycles was associated with WBC (r = 18.81, P = 0.003), ANC (r = 17.175, P = 0.019) and NLR (r = 15.88, P = 0.001) in univariate analysis. CRP (r = 1.02, P = 0.039) and NLR (r = 13.39, P = 0.002) remained significant in multivariate analysis. ROC analysis identified CRP < 2.5 mg/L as optimal cut-off to differentiate between responders and non-responders (AUC = 0.84, P = 0.001). Median PFS was 508 days in patients with CRP < 2.5 mg/L, whereas median PFS was not yet reached in patients CRP ≤ 2.5 mg/L (P = 0.01).

Schlussfolgerungen/Conclusions Tumor-driven systemic inflammatory networks are associated with treatment response and prognosis in patients with GEP-NETs receiving PRRT, and modulation of tumor inflammation may emerge as therapeutic co-target to improve outcomes.