Therapy-related second malignant neoplasms on top of neuroblastoma: frequency, types and risk factors

The aim of the study was to evaluate the long-term effect of multi-modal, risk-based treatment protocols on the development of treatment-related secondary malignant neoplasm (SMN) in patients during or after treatment of Neuroblastoma.

This retrospective study included all patients with neuroblastoma treated at Children's Cancer Hospital-Egypt from July 2007 to December 2022.

24 out of 2290 patients (1%) received risk-tailored multimodal treatment protocols suffered from either hematological (21/24) or solid (3/24) treatment-related SMN during or after treatment of their primary neuroblastoma disease. Age at neuroblastoma diagnosis ranged from 6 mo to 9.5 y (median age: 2 y) with male to female ratio of 1.2:1. Time to development of hematological treatment-related SMN was 14 mo to 8.3 y (mean: 3.7 y) versus 5.5-9.2 y (mean: 7.6 y) for solid treatment-related SMN. High cummulative doses of ifosfamide, cyclophosphamide, and etoposide were most frequently encountered among study patients.

Patients with neuroblastoma are at more risk of developing hematological than solid treatment-related SMN after relatively longer duration for latter compared to former tumor subtypes. High-risk treatment regimens and higher cumulative doses of alkylating agents and Topoisomerase-II inhibitors are likely associated with increased risk of treatment-related SMN.