Neurotoxicidad cognitiva inducida por la radioterapia cerebral en adultos / Radiation-induced cognitive toxicity in adults

La toxicidad cognitiva inducida por la radioterapia craneal es una de las limitaciones mas importantes del tratamiento radioterapico y con mas impacto sobre la calidad de vida de los largos supervivientes de tumores cerebrales. Esta revision incluye una actualizacion del diagnostico clinico y radiologico de la toxicidad radioinducida con la incorporación de baterias neuropsicologicas y tecnicas avanzadas en neuroimagen. Ambas herramientas han permitido en los últimos anos no solo una mejor definicion de la disfuncion cognitiva, sino tambien la identificacion de los cambios anatomicos y funcionales asociados. La fisiopatologia subyacente implica diferentes estirpes celulares y vias de senalizacion molecular, y el mecanismo es multifactorial. Aunque no existe actualmente una estrategia terapeutica que haya demostrado una clara eficacia, varios estudios, incluyendo los que proponen respetar el hipocampo o el uso de la memantina, han resultado prometedores. Profundizar en el estudio de la toxicidad cognitiva inducida por la radioterapia permitira definir mejor los pacientes que se benefician de la radioterapia, asi como estudiar nuevas dianas terapeuticas para mejorar la calidad de vida de los pacientes con dano cerebral radioinducido

Cognitive toxicity induced by cranial radiation is one of the most important limitations of radiation therapy and has a significant impact on brain tumor survivors’ quality of life. This review comprehends an up to date of recent studies including complete neuropsychological battery and/or advanced neuroimaging techniques. These studies identified critical anatomical and/or functional brain areas related to radiation-induced brain injury, thus improving clinical and radiological diagnosis. Pathophysiological mechanisms underlying cognitive toxicity are complex and involve different cell lines and molecules. Although there is no currently therapeutic strategy that has a demonstrated efficacy, several studies including sparing of hippocampus or the use of memantine are quite promising. A better knowledge of the characteristics of cognitive toxicity induced by cranial radiation, will help us to identify patients who will benefit from treatment and also to examine new therapeutic targets in order to improve patients’ quality of life

Cisplatin-induced neurotoxicity in vivo can be alleviated by riboflavin under photoillumination.

Cisplatin (CP)-induced neurotoxicity is one of the major clinical problems in CP-based chemoradiotherapy, leading to its discontinuation depending upon their severity. In the present investigation, the photosensitizing property of riboflavin (RF) has been used to ameliorate the CP-induced neurotoxicity. According to dosing plan, the healthy mice were given RF, CP, and their combinations under photoillumination with their controls without any light exposure. After the treatment, antioxidant enzymes, cellular reductants, glutathione-S-transferase, brain markers, and oxidation products were assessed besides histopathology in their brain samples. These parameters revealed that RF ameliorates CP-induced neurotoxicity in a dose-dependent manner under photoillumination. Hence, inclusion of RF in CP-based chemoradiotherapy can be an effective strategy to counter CP-induced neurotoxicity.

Salvage therapy and late neurotoxicity in patients with recurrent primary CNS lymphoma treated with a modified ProMACE-MOPP hybrid regimen.

We report the efficacy of salvage therapy with a modified ProMACE-MOPP combined with radiation in patients with primary central nervous system lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristin, and methotrexate (MTX: 500 mg/m(2)) administered in 21-day cycles. Patients received 20 Gy of whole-brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every four months for two years. Nine patients with CNS relapse were retreated with additional cycles of the ProMACE-MOPP hybrid regimen with a 90% objective response rate. Median complete response (CR) duration was 13.2 months and median survival time (MST) for the nine patients treated after initial relapse was 30 months. One of 17 patients (5.8%) who had less than 20 Gy of whole brain irradiation developed dementia. In contrast, six of seven (85.7%) patients who had more than 30 Gy of whole brain radiotherapy became demented. Maintaining a moderate dose of MTX, while adding chemotherapeutic agents and 20 Gy of whole brain radiation therapy, improved disease control and overall survival and lowered the incidence of delayed neurologic toxicity in patients with PCNSL. Additional treatment with a ProMACE-MOPP hybrid regimen is still effective for relapsed disease.