Natriuretic factors and inflammation biomarkers as predictors of survival in [177Lu]Lu-DOTA-TATE therapy of neuroendocrine tumors

Abstract

Objective

To analyze the prognostic value of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and other biomarkers of inflammation in patients with neuroendocrine tumors (NETs) treated with [¹⁷⁷Lu]Lu-DOTA-TATE (Lutathera®). The prognostic value of histological characteristics of the tumor was also analyzed.

Patients and methods

Prospective study of a cohort of patients with advanced and metastatic NETs treated with [¹⁷⁷Lu]Lu-DOTA-TATE. Before the administration of doses, NT-proBNP, hemoglobin, hematocrit, C-reactive protein, leukocytes, lymphocytes, neutrophils, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been determined. Overall survival (OS) and progression free survival (PFS) were calculated, using the Kaplan-Meier method, and curves were compared with a log-rank test. To determine the predictor variables of OS, a Cox regression model was fitted.

Results

48 NET patients treated with [177Lu]Lu-DOTA-TATE. Median OS was 96 months and PFS was 29 months. Factors associated with lower OS were: NTproBNP values>300 pg/mL (HR: 10,5; p = 0,005) in the subgroup of patients with grades 2–3, in addition to inflammatory indices NLR > 2 (HR: 3,87; p = 0,049) and PLR > 300 (HR: 11,88; p = 0,01) and higher tumor grade (HR: 6,45; p = 0,011). PLR > 300 (HR: 5,506; p = 0,003) was also associated with lower PFS. In contrast, higher levels of lymphocytes (HR: 0,21; p = 0,002), hemoglobin (HR: 0,65; p = 0,041) and hematocrit (HR: 0,862; p = 0,031) were associated with higher OS, without significant changes in PFS.

Conclusion

In patients with NETs treated with [¹⁷⁷Lu]Lu-DOTA-TATE, the determination of natriuretic factors (NT-ProBNP) and other inflammatory biomarkers may be useful as predictors of survival and prognostic factors.