Abstract
Background: Neuroblastoma (NB) is remarkable for its wide spectrum of clinical behavior and biological characteristics in relation to outcome. The use of aggressive therapy, including autologous hematopoietic stem cell transplantation (HSCT) and the addition of isoretionin (cis-Retinoic Acid/cis-RA), has increased survival rates of patients with advanced disease. Methods: Pediatric 271 newly diagnosed high risk NB patients were prospectively enrolled into the study. Patients received neoadjuvant chemotherapy of alternating cycles: [cyclophosphamide, doxorubicin, vincristine (CAdO)] and [etoposide, carboplatin]. Intensification courses of “ICE” (ifosfamide, carboplatin, and etoposide) regimen were administered to patients with bone marrow (BM) residual infiltration. Whenever safely feasible, complete surgical resection or debulking of the primary tumor was attempted for patients achieving partial response. Eligible patients underwent HSCT, while radiation therapy to the primary and metastatic sites, as well as maintenance with cis-RA was given for 6 months. Results: The median age of our patients was 2.8 years with male to female ratio of 1.65:1. At 4 years, the overall and event free survivals were 33.7% and 23.3% for the entire group under study, with significantly higher rates (42.7% and 35.6%, respectively) for HSCT patients (n = 94; p 0.001). The outcome was also significantly correlated with response to induction therapy, pathological subtype, as well as other variables. Conclusion: Myeloablative therapy followed by stem cell rescue is regarded as the most important goal of high risk NB treatment to improve survival till present. Each of consolidation HSCT, post induction disease status, as well as international neuroblastoma pathology classification (INPC) subtype was an independent predictive variable of survival. A collaborative effort with an emphasis on biologic characteristics of aggressive disease and tailored therapy needs to be strengthened to further our understanding of this disease.
Highlights
Neuroblastoma (NB) accounts for more than 8% of malignancies in patients younger than 15 years of age, and is responsible for 15% of all pediatric oncology deaths [1]
While adding isoretionin to consolidation therapy independently resulted in a significantly improved Overall Survival (OS); analysis of consecutive trials from a single center demonstrated that combining cis-RA with monoclonal antibody (MoAb 3F8), and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) has improved survival significantly in HR-NB [5,6]
The international criteria were used for risk stratification (International Neuroblastoma Staging System/INSS), and assessment of disease response defined as; complete response (CR), very good partial response (VGPR), partial response (PR), no response (NR), progressive disease (PD) or mixed response (MR); according to the International Neuroblastoma Response Criteria (INRC) [9]
Summary
Neuroblastoma (NB) accounts for more than 8% of malignancies in patients younger than 15 years of age, and is responsible for 15% of all pediatric oncology deaths [1]. Myeloablative therapy and autologous hematopoietic stem cell rescue can significantly result in a better 5-year Overall Survival (OS) and Event Free Survival (EFS) than nonmyeloablative chemotherapy. Neuroblastoma (NB) is remarkable for its wide spectrum of clinical behavior and biological characteristics in relation to outcome. The use of aggressive therapy, including autologous hematopoietic stem cell transplantation (HSCT) and the addition of isoretionin (cis-Retinoic Acid/cis-RA), has increased survival rates of patients with advanced disease. At 4 years, the overall and event free survivals were 33.7% and 23.3% for the entire group under study, with significantly higher rates (42.7% and 35.6%, respectively) for HSCT patients (n = 94; p < 0.001). Conclusion: Myeloablative therapy followed by stem cell rescue is regarded as the most important goal of high risk NB treatment to improve survival till present. A collaborative effort with an emphasis on biologic characteristics of aggressive disease and tailored therapy needs to be strengthened to further our understanding of this disease
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