Combined Treatment Strategy and Outcome of High Risk Neuroblastoma: Experience of the Children’s Cancer Hospital-Egypt

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.

The Impact of Pretransplant Disease Characteristics on the Outcome of Autologous Stem Cell Transplantation for Neuroblastoma with High-Risk Features: A Retrospective Model from a Limited Resources Country

“…When comparing the current results with another study previously done in our hospital, Mousa et al reported 4-year OS and EFS for transplanted high-risk neuroblastoma of 42.7% and 35.6%, respectively [23]. The explanation for this may be related to the more intensified induction in COG A3973 protocol used by our center starting from 2012 compared to the less intensified SFOB protocol used before 2012, which highlights the importance of induction response on the transplant outcome.…”

Management of neuroblastoma in limited-resource settings

“…Data from Asia (China, India, Pakistan, Thailand and Vietnam)[ 13 , 17 - 22 ], the Middle East and North Africa (Egypt, Iran, Iraq and Morocco)[ 23 - 28 ] and the Americas (Argentina, Brazil, Chile, Cuba, Mexico and Uruguay)[ 12 , 16 , 29 - 35 ] were accessible, but reports from sub-Saharan Africa and the Pacific Ocean were limited to single reports from the French-African Paediatric Oncology Group (GFAOP) and reunion[ 15 , 36 ]. The differences between HICs and LMICs could be evaluated from these reports, but complete management and outcome data for interregional variations among LMIC regions were less robust.…”

Neuroblastoma: The basis for cure in limited‐resource settings

“…5 While diagnosis and treatment in LMICs are not as obvious as in HIC, the outcomes in Egypt and Argentina have reached 50% overall survival (OS). 8,9 Three African middle-income countries (MICs) Egypt, Nigeria, and South Africa differ in their approaches to the management of NB. Egypt has reported transplanting up to 35% of high-risk (HR) NB patients versus only 3.7% in South Africa, with no literature available from Nigeria.…”

“…Egypt has reported transplanting up to 35% of high-risk (HR) NB patients versus only 3.7% in South Africa, with no literature available from Nigeria. 8,10 We will further explore the varied reasons for the development of paediatric oncology services in LMICs and the perceptions of oncologists who treat NB in various economic regions of the world. We aim to (1) evaluate the current research activities on NB in LMICs, and…”

“…In children younger than 12 months, a localized lesion may need observation only or a surgical resection may be curative whilst advanced disease needs multimodal oncological management including autologous stem cell transplants and immunotherapy 5 . While diagnosis and treatment in LMICs are not as obvious as in HIC, the outcomes in Egypt and Argentina have reached 50% overall survival (OS) 8,9 . Three African middle‐income countries (MICs) Egypt, Nigeria, and South Africa differ in their approaches to the management of NB.…”