Abstract
:
Neuroblastoma (NBL) is a highly malignant embryonal tumor that originates from the
primordial neural crest cells. NBL is the most common tumor in infants and the most common extracranial
solid tumor in children. The tumor is more commonly diagnosed in children of 1-4 years
of age. NBL is characterized by enigmatic clinical behavior that ranges from spontaneous regression
to an aggressive clinical course leading to frequent relapses and death. Based on the likelihood
of progression and relapse, the International Neuroblastoma Risk Group classification system categorized
NBL into very low risk, low risk, intermediate risk, and high risk (HR) groups. HR NBL is
defined based on the patient's age (> 18 months), disease metastasis, tumor histology, and MYCN
gene amplification. HR NBL is diagnosed in nearly 40% of patients, mainly those > 18 months of
age, and is associated with aggressive clinical behavior. Treatment strategies involve the use of intensive
chemotherapy (CTR), surgical resection, high dose CTR with hematopoietic stem cell support,
radiotherapy, biotherapy, and immunotherapy with Anti-ganglioside 2 monoclonal antibodies.
Although HR NBL is now better characterized and aggressive multimodal therapy is applied, the
outcomes of treatment are still poor, with overall survival and event-free survival of approximately
40% and 30% at 3-years, respectively. The short and long-term side effects of therapy are tremendous.
HR NBL carries a high mortality rate accounting for nearly 15% of pediatric cancer deaths.
However, most mortalities are attributed to the high frequency of disease relapse (50%) and disease
reactiveness to therapy (20%). Newer treatment strategies are therefore urgently needed. Recent
discoveries in the field of biology and molecular genetics of NBL have led to the identification
of several targets that can improve the treatment results. In this review, we discuss the different
aspects of the epidemiology, biology, clinical presentations, diagnosis, and treatment of HR
NBL, in addition to the recent developments in the management of the disease.