Hyperbaric oxygen therapy as a complementary treatment in neuroblastoma - a narrative review

Abstract

Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia. The clinical presentation can vary from an asymptomatic mass to symptoms resulting from local invasion and/or spread of distant disease spread. The natural history of neuroblastoma is highly variable, ranging from relatively indolent biological behavior to a high-risk clinical phenotype with a dismal prognosis. Age, stage, and biological features are important prognostic risk stratification and treatment assignment prognostic factors. The multimodal therapy approach includes myeloablative chemotherapy, radiotherapy, immunotherapy, and aggressive surgical resection. Hyperbaric oxygen therapy (HBOT) has been proposed as a complementary measure to overcome tumor hypoxia, which is considered one of the hallmarks of this cancer treatment resistance. This article aims to review the relevant literature on the neuroblastoma pathophysiology, clinical presentation, and different biological and genetic profiles, and to discuss its management, focusing on HBOT.

Keywords: hyperbaric oxygen therapy; hyperbaric oxygenation; iodine radioisotopes; iodine-131; neuroblastoma; radiopharmaceuticals; therapy; treatment.

Figure 1

Effects of ¹³¹I-MIBG combined with HBOT on neuroblastoma cells. The ¹³¹I-MIBG has an antiproliferative effect by inhibiting complex I of the mitochondrial respiratory chain, leading to increased production of superoxide radicals. In neuroblastoma cells, the activity of H₂O₂ detoxifying enzymes is reduced, meaning that superoxide radicals are not converted into hydrogen peroxide and, consequently, into water and O₂. In the presence of superoxide radicals, hydrogen peroxide is converted to hydroxyl radicals in the iron-catalyzed Haber-Weiss reaction, leading to proteins, lipids, and DNA peroxidation. The ¹³¹I emits ionizing radiation through the decay of the ¹³¹I radionuclide, directly and indirectly affecting DNA damage. The indirect effect occurs through the formation of ROS by radiolysis of the water molecule, dependent on O₂. In turn, HBOT potentiates the effect of ¹³¹I by increasing tumor O₂ levels. Cyt C, Cytochrome complex; Gpx, Glutathione peroxidase; HBOT, Hyperbaric oxygen therapy; HO₂ ^· , Perhydroxyl radicals; H₂O, Water molecule; H₂O₂, Hydrogen peroxide; ¹³¹I-MIBG, Meta-iodobenzylguanidine; OH ^·, Hydroxyl radical; O₂, Oxygen; O₂ ^{· -}, Superoxide radical; ROS, Reactive oxygen species; SOD, Superoxide dismutase.