Background: 177Lu-DOTATATE is increasingly used in patients with advanced neuroendocrine tumour (NET). However, few circulating biomarkers are available to predict progression-free survival (PFS) of patients received 177Lu-DOTATATE.
Materials and methods: Clinicopathological data and data of baseline circulating biomarkers including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), erythrocyte sedimentation rate (ESR), creatinine, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, c-reactive protein (CRP), estimated glomerular filtration rate (eGFR) and chromogranin A (CgA) of patients with advanced NET received 177Lu-DOTATATE were retrospectively collected. Continuous variables were normalized by divided them by their upper normal limits (UNL) and classification and regression trees (CART) was used to determine optimal cutoff value. Univariate and multivariate cox regression analysis were used to identify independent biomarkers to predict PFS. Decision curve analysis (DCA) was applied to determine the clinical net benefit of using different biomarkers to guide treatment decision.
Results: 195 patients were included. Using CART method, the optimal cutoff value of NLR, normalized ESR, normalized ALP, normalized CRP and normalized CgA to identify patients with shorter PFS were 3, 0.5, 1, 3 and 50 respectively. Multivariate cox analysis indicated that besides primary site of pancreas, only normalized ESR≥0.5, normal baseline creatinine and CgA≥50 were independently associated with shorter PFS. After combining these three risk biomarkers, patients could be divided into three groups with progressively shorter PFS: patients with ≤1 risk biomarker (median PFS, 37 months), patients with two risk biomarkers (median PFS, 23 months) and patients with three risk biomarkers (median PFS, 11 months). Subgroup analysis found that risks of progression of these three groups were still significantly different in different subgroup of patients. DCA showed an increased net benefit by using these risk biomarkers to guide treatment decision.
Conclusion: Normalized ESR≥0.5, normal baseline creatinine and CgA≥50 are independently associated with shorter PFS of patients with advanced NET received 177Lu-DOTATATE and can be used to guide treatment decision.