Validation of Neutrophil Count as An Algorithm-Based Predictive Factor of Progression-Free Survival in Patients with Metastatic Soft Tissue Sarcomas Treated with Trabectedin.

Introduction: Based on a mathematical model of trabectedin-induced neutropenia, we assessed the predictive value of absolute neutrophil count (ANC) on progression-free survival (PFS) in an independent validation cohort of patients treated with trabectedin. Methods: We collected data from 87 patients in two expert centers who received at least two cycles of trabectedin for soft tissue sarcomas (STS) treatment. Correlations between ANC, patients' characteristics, and survival were assessed, and a multivariate model including tumor grade, performance status, ANC, and hemoglobin level was developed. Results: Therapeutic ANC ≥ 7.5 G/L level was associated with shorter PFS: 3.22 months (95% confidence interval (CI), 1.57⁻4.87) in patients with ANC ≥ 7.5 G/L vs. 5.78 months (95% CI, 3.95⁻7.61) in patients with ANC < 7.5 G/L (p = 0.009). Age, primary localization, lung metastases, dose reduction, hemoglobin, and albumin rates were also associated with PFS. In multivariate analysis, ANC ≥ 7.5 G/L was independently associated with poor PFS and overall survival. Conclusion: We validated increased pre-therapeutic ANC as a predictive factor of short PFS in patients starting trabectedin for STS. ANC appears to have an impact on survival rates and may be used as a decision-making tool for personalizing second-line strategies in patients with metastatic STS.

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

BACKGROUND: In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. RESULTS: Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). CONCLUSIONS: Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.