Short and Long-Term Toxicity in Pediatric Cancer Treatment: Central Nervous System Damage

Abstract

Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS solid malign tumors. The effects on the CNS are disabling and often permanent with limited treatments, thus it is important that clinicians recognize the effects of cancer therapy on the CNS. Knowledge of these conditions can help the practitioner be more vigilant for signs and symptoms of potential neurological complications during the management of pediatric cancers. As early detection and more effective anticancer therapies extend the survival of cancer patients, treatment-related CNS toxicity becomes increasingly vital. This review highlights major neurotoxicities due to pediatric cancer treatments and new therapeutic strategies; CNS primary tumors, the most frequent solid tumors in childhood, are excluded because of their intrinsic neurological morbidity.

Keywords: chemotherapy; neurotoxicity; pediatrics cancer.

Figure 1

Acute myelitis due to chemotherapy (Nelarabina) in an ALL—T patient. Sagittal MRI shows the abnormal medullar signal of the spine (arrows, A) without contrast enhancement after gadolinium administration (arrows, B). (C,D) show an abnormal hyperintensity of the distal part of the medullar signal (arrows, C) associated with a peripherical aspecific gadolinium enhancement (arrows, D). A metastatic nodule was also seen (arrowhead, C).

Figure 2

Acute Methotrexate-Induced Neurotoxicity during childhood acute lymphoblastic leukemia (ALL) therapy. MRI shows the characteristic pattern of acute MTX toxicity. Bilateral and symmetric white matter lesion areas of the corona radiata are defined by a high signal on T2 w (arrows, A) and no contrast enhancement after gadolinium administration (B) associated with restricted diffusion on DWI (C) and ADC map (D).

Figure 3

Methotrexate -Induced Neurotoxicity during childhood acute lymphoblastic leukemia (ALL) therapy. Axial T2 w (A) shows an asymmetric area of hyperintense signal in the left corona radiata/centrum semiovale (arrow) with restricted diffusion on DWI (C) and ADC map (D), and no enhancement after gadolinium administration (B).

Figure 4

Patient affected by Hodgkin lymphoma during treatment. T1 w MRI after gadolinium administration demonstrates the presence of a complete venous thrombosis of the right jugular vein (arrow, A,B) and a non-complete thrombus into the superior sagittal sinus on the T1 sagittal view (arrow, C) and coronal view (arrow, D).