High Pretreatment Plasma D-dimer Levels Predict Unfavorable Outcomes in Patients with Neuroblastoma

Abstract

Background: Neuroblastoma (NB) is the most common malignant solid tumor in children. This study aimed to investigate investigate the prognostic value of pretreatment plasma D-dimer levels, and its relationship with clinical features in patients with NB. Methods: A total of 136 patients were included in this retrospective study. Information of diagnosis, laboratory examination, imaging examination and treatment in medical records was collected. The correlation between plasma D-dimer levels and other clinical characteristics and outcomes was analyzed statistically. Results: Pretreatment plasma D-dimer levels were significantly associated with unfavorable clinical characteristics including INSS III and IV stage, high-risk disease, metastatic disease, MYCN-amplification, poor histologic type, large tumor size, and elevated levels of lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and serum ferritin (SF). Compared to levels before treatment, levels of plasma D-dimer significantly decreased after 2 and 4 cycles of chemotherapy. The patients who had higher D-dimer levels had worse overall survival (3-year OS rate, high vs. middle vs. low D-dimer group, 25.8% ± 7.8% vs. 57.1% ± 10.8% vs. 86.8% ± 4.4%, P< .001) and progression-free survival (3-year PFS rate, high vs. middle vs. low D-dimer group, 17.2% ± 7.2% vs. 43.7% ± 11.6% vs. 70.9% ± 5.9%, P< .001). According to multivariate analysis, high D-dimer level was confirmed to be an independent prognostic factor for OS (high vs. low, HR, 4.715; 95% CI, 1.143-19.452; P= .032). Conclusions: High pretreatment plasma D-dimer levels were remarkably associated with advanced disease and could serve as a novel biomarker predicting the outcomes of NB patients. Funding Statement: This work was sponsored by Personnel training program for distinguished medical young scholar (2017 Kai Li), New hundred people plan of Shanghai health and Family Planning Commission (2017 BR052 Kai Li). Declaration of Interests: All the authors had nothing to disclose. Ethics Approval Statement: This retrospective study was approved by the Ethics Committee of Children’s Hospital of Fudan University. The written informed consents were received from the patients' parents before treatment.