An Intensive Induction Protocol for High Risk Neuroblastoma in Morocco
Authors: Salman Zeena , El Kababri Maria , Hessissen Laila , Khattab Mohammed , Matthay Katherine 
Published: July 2016

Abstract 72 Background: Neuroblastoma is the most common extracranial solid tumor of childhood, accounting for 10% of childhood cancers in high-income countries (HIC), with an unknown incidence in most low- and middle-income countries (LMIC). A multidisciplinary approach to the treatment of high-risk (HR) neuroblastoma consisting of a combination of chemotherapy, surgery, radiation and immunotherapy, has lead to improvements in survival in HICs, approaching 40-50%. Morocco, a LMIC, has historically had a survival rate for HR neuroblastoma of 10-15% at three years, with almost no survival at five years from diagnosis, due to a combination of limited availability of accurate diagnosis, staging, and risk stratification, as well as lack of some of the necessary treatment modalities and high abandonment rates. The International Society for Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) committee developed adapted risk stratification and treatment guidelines using locally available chemotherapeutic agents in doses that limit toxicity. This approach was implemented at the four cancer treatment centers in Morocco beginning in January of 2012. This study aims to describe HR neuroblastoma patients presenting in Rabat, Morocco, in the last four years; test feasibility of an intensive induction regimen for HR neuroblastoma; and assess response to a novel intensive induction chemotherapy regimen adapted for a LMIC setting. Methods: This treatment protocol was first implemented in January of 2012 with approval of the local ethics board. Chart review was performed on patients with high risk neuroblastoma enrolled on the protocol at Pediatric Hematology and Oncology Center of Rabat between January of 2012 and September of 2015. Data regarding demographics, toxicity, and outcomes was collected and descriptive statistics were performed. Results: 40 patients were diagnosed with high risk neuroblastoma between January of 2012 and September of 2015 in Rabat. There were 14 females (35%) and 26 males (65%) with a median age of 40 months (age range 13m to 11y5m). With regards to diagnostic testing, 100% of patients underwent CT scan, while 47.5% (19/40) of patients underwent MIBG and 47.5% underwent bone scintigraphy. Only 9 patients (22.5%) had MYCN status determined, however MYCN testing increased over time during this protocol, as 53.8% (7/13) of patients diagnosed with HR neuroblastoma in the past year had MYCN testing performed. 82.5% of patients (33/40) completed all five cycles of induction chemotherapy, with 9/40 (22.5%) experiencing delays of 1 or 2 cycles (delay defined as >5 weeks) due to toxicity. Of the 33 patients who completed induction, 60.6% (20 patients) experienced a PR or VGPR, continuing on to local control with surgery or consolidation therapy. Only one patient was lost to follow up due to abandonment. Conclusion: Adapted risk stratification and treatment guidelines for LMICs allow for more accurate diagnosis and systematic treatment. Standardizing a protocol for high risk patients has led to more consistent MYCN evaluation, performed by immunohistochemistry, as well as the introduction of MIBG to the Rabat Children's Hospital. While this is a multi-center study (a known study obstacle in LMICs), this protocol has led to a decrease in the barriers to accurate diagnosis and optimal treatment. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.