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Cancers (Basel). 2019 Mar 26;11(3). pii: E432. doi: 10.3390/cancers11030432.

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

Author information

1
CRCM, Department of Medical Oncology, Institut Paoli-Calmettes, INSERM, CNRS, Aix-Marseille University, 13009 Marseille, France. denonnevillea@ipc.unicancer.fr.
2
SMARTc Unit, CRCM Inserm U1068, Aix-Marseille Université, 13005 Marseille, France. dominique.barbolosi@univ-amu.fr.
3
Department of Medical Oncology, Hôpital de la Timone, APHM, INSERM U910, Aix-Marseille University, 13005 Marseille, France. maeva.andriantsoa@gmail.com.
4
SMARTc Unit, CRCM Inserm U1068, Aix-Marseille Université, 13005 Marseille, France. elcheikhraouf@gmail.com.
5
Department of Medical Oncology, Hôpital de la Timone, APHM, INSERM U910, Aix-Marseille University, 13005 Marseille, France. Florence.DUFFAUD@ap-hm.fr.
6
CRCM, Department of Medical Oncology, Institut Paoli-Calmettes, INSERM, CNRS, Aix-Marseille University, 13009 Marseille, France. bertuccif@ipc.unicancer.fr.
7
Department of Medical Oncology, Hôpital de la Timone, APHM, INSERM U910, Aix-Marseille University, 13005 Marseille, France. Sebastien.SALAS@ap-hm.fr.

Abstract

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.

KEYWORDS:

mathematical modelling; neutrophil; predictive marker; soft tissue sarcomas; trabectedin

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