Brain damage from anticancer treatments in adults

Treatment-induced brain toxicity remains a major cause of morbidity in adult patients with cancer. Contrasting with the 40-year-old unresolved controversy about the primary damaging event (vascular versus parenchymal) in the physiopathology, numerous prospective clinical trials have recently addressed the question of brain toxicity. Despite remarkable efforts in methodological design, they often only partially answer the questions of which treatment modalities are responsible, which brain functions are mainly impaired, how long the impairment duration is and which characteristics make patients vulnerable.

Real advances in the design of safer radiation procedures have been counterbalanced by a wider use of combined radiotherapy-chemotherapy regimens, the development of radiosurgery and the increasing number of long-term survivors. Although classic radionecrosis or chemonecrosis has become less common, more subtle changes such as progressive cognitive dysfunction are increasingly reported after radiotherapy (radiation-induced leukoencephalopathy) or chemotherapy, administered alone or in combination as reviewed here. The methodological aspects of published studies are questioned and suggestions are provided that may improve the design of future trials.

The abovementioned issue is of clinical importance given the number of patients treated for brain tumors, including patients with brain metastases, and the number of patients who are at high risk for brain metastasis who could benefit from prophylactic cranial irradiation. Moreover, drugs used in nonbrain tumors are now recognized to impair brain normal functioning.