Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study

Abstract

Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally, radiological abnormalities expressed as white matter hyperintensities (WMH) and cerebral atrophy (CA) can develop. In this study, these functional and morphological parameters are evaluated, and their relation is investigated. After surgery, HGG patients underwent chemo-irradiation for six weeks, followed by six cycles of temozolomide. Assessments were performed before chemo-irradiation, post-concomitantly, after the third and sixth adjuvant cycle, and 3 and 7 months after treatment. Degree of WMH and CA was scored on MRI. Patients' neuropsychological performance was compared to healthy matched controls, yielding six cognitive domain z-scores. Development or progression of pre-existing WMH and CA during follow-up was observed in 36 and 45 % of the patients (n = 39) respectively. Cognitive functioning remained stable or improved in 70 % of the patients and deteriorated in 30 % of the patients (n = 33). Of the cognitive decliners, 80 % had tumor progression within 4 months thereafter. No clear association between cognitive functioning and WMH or CA was found. Central neurotoxic effects of combined modality treatment in HGG patients expressed by radiological abnormalities are encountered in approximately 40 % of patients. However, functional impact as indexed by cognitive functioning was found to be limited. Furthermore, development or progression of pre-existing WMH and CA does not consistently result in functional impairment as measured by cognitive tests.

MiR-302c-3p suppresses invasion and proliferation of glioma cells via down-regulating metadherin (MTDH) expression

“…20 proved for the first time that the expression of miR-302c-3p in glioma tissues was significantly lower than those in normal brain tissues. Furthermore, the decreased expression of mi-302c-3p in glioma was positively associated with high WHO grade.…”

Melatonergic system‐based two‐gene index is prognostic in human gliomas

“…Overall, our data indicate that glioma‐synthesized melatonin has a role in tumor progression and thus lays some groundwork for further investigations of the autocrine anticancer effects of this indolamine. Challenges in the treatment of gliomas include the difficulty of drug delivery across the blood–brain barrier and their neurotoxicity associated side effects . In this sense, melatonin is soluble in both water and lipid and therefore readily crosses the blood–brain barrier .…”

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

“…In addition, metabolic disorders and tumour regeneration may have a negative impact on cognitive function (Williams et al, 2015;Quant et al, 2009). The cognitive impairment caused by the side effects of radiotherapy and chemotherapeutic drugs is prone to the whole cerebral hemisphere (Froklage et al, 2014;Hilverda et al, 2010). Thus, it is important to create some new therapies and develop some new drugs to repair patients' cognitive impairment.…”