Liver‐Related Late Effects in Long‐Term Survivors of High‐Risk Neuroblastoma: Insights From a Comprehensive Prospective Follow‐Up Study

Background: Therapeutic advances in pediatric oncology have significantly improved overall survival, with a higher incidence of long-term adverse effects and sequelae. Among pediatric cancer survivors, the highest incidence of hepatic lesions has been observed in those previously treated for high-risk neuroblastoma (HRNB). While hepatic nodules in these patients historically raised concern for tumor locations, recent attention has shifted toward non-tumoral, late-onset hepatic sequelae. Methods: In this study, we retrospectively reviewed long-term liver outcomes from an institutional perspective follow-up protocol, including long-term HRNB survivors (>5 years from diagnosis) treated between 1996 and 2018 at a tertiary pediatric center. Results: A total of 47 patients were included, with a median follow-up of 11.1 years. Liver parenchyma was normal in 11 (23%) patients throughout the whole follow-up period. Diffuse parenchymal inhomogeneity was observed in 36 patients out of 47 (76%). Out of 36 patients, 16 showed a stable, diffuse, non-nodular alteration of the liver during the whole follow-up period, while in seven patients, the liver involvement completely regressed after a median of 2.8 years. Moreover, 13 out of 36 patients (36%) with diffuse parenchymal inhomogeneity developed nodular lesions after a median of 7.7 years from diagnosis and 1.7 years from the onset of parenchymal alterations. Alpha-fetoprotein levels were normal in all patients. Conclusions: A structured, integrated, multidisciplinary follow-up program revealed an unexpectedly high prevalence of hepatic abnormalities on imaging. Further studies are needed to define the long-term risk of developing liver complications, both in terms of malignancy and functional impairment.