Embryonic origin and treatment of disseminated neuroblastoma

Abstract

Neuroblastoma is a common pediatric malignancy of the developing autonomic nervous system. Neuroblastoma tumors arise from neural crest cells of the developing autonomic nervous system. The clinical course is variable, ranging from low risk tumors which can show spontaneous regression to highly aggressive chemoresistant tumors. This thesis describes different clinical subgroups of neuroblastoma to better understand tumor biology and tumor origin. The most important findings are: 1) Neonates with neuroblastoma stage 4S/MS are at high risk of fast progression of mainly liver metastases. 2) Patients can be identified who have stage 4/M ganglioneuroblastoma without response to induction chemotherapy. These patients had very slow progressing primary tumors that became less active over time. 3) Incidence of neuroblastoma increased between 1990 and 2014. This increase was mainly seen in the subgroup of high-risk patients. In this period, overall survival improved, especially for high-risk neuroblastoma patients. This improvement could largely be explained by the introduction of high-dose chemotherapy and immunotherapy. 4) Patients receiving anti-GD2 immunotherapy according to the American COG protocol, after induction treatment according to the German GPOH protocol had a 15% improved overall and event free survival. This improvement corresponds with other studies, indicating that the effect of immunotherapy is independent of prior treatment given. This thesis contributed to the current knowledge on the origin of neuroblastoma during embryonic development, and on the correlation of tumorigenesis and clinical subgroups. Ultimately, better understanding of tumor etiology and malignant processes will enhance tumor specific treatment strategies, minimizing toxicity and maximizing response.