Intrathecal methotrexate affects cognitive function in children with medulloblastoma

Riva, Daria; Giorgi, C.; Nichelli, Francesca; Bulgheroni, Sara; Massimino, Maura; Cefalo, Graziella; Gandola, Lorenza; Giannotta, Melania; Bagnasco, Irene; Saletti, Veronica; Pantaleoni, Chiara

doi:10.1212/wnl.59.1.48

Cited by 84 publications

(46 citation statements)

References 36 publications

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“…In a study by Riva et al [10], the neurocognitive outcomes of patients with medulloblastoma treated with craniospinal irradiation (CSI), chemotherapy, and possibly intrathecal methotrexate were compared with controls consisting of patients' siblings and cousins. All patients treated for medulloblastoma had a decline in neurocognitive outcomes relative to controls.…”

Section: Methotrexatementioning

confidence: 99%

Neurotoxicity of chemotherapeutic and biologic agents in children with cancer

Braganca

Packer²

2008

Curr Neurol Neurosci Rep

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Section: Methotrexatementioning

confidence: 99%

Neurotoxicity of chemotherapeutic and biologic agents in children with cancer

Braganca

Packer²

2008

Curr Neurol Neurosci Rep

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“…In the pediatric brain tumor population, deficits seen with chemotherapy treatments are less than those seen with radiation. Nonetheless, specific chemotherapies such as methotrexate have previously demonstrated deleterious effects on neurocognition and chemotherapy, as a whole, has been linked to deficits in executive functioning, attention, visualmotor functioning, visual processing and overall IQ in children treated for leukemia [45,46,47]. Interestingly, a study done by Meyers and Hess, found that decreases in cognition preceded tumor progression on imaging in adult patients with brain tumors [48].…”

Section: Neurocognitive Outcomesmentioning

confidence: 99%

Clinical trials in pediatric neuro-oncology: what is missing and how we can improve

2016

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Brain tumors are the most common solid tumor in childhood, yet outcomes vary dramatically. High-grade gliomas have dismal outcomes with poor survival. By contrast, low-grade gliomas, have high survival rates, but children suffer from morbidity of tumor burden and therapy-associated side effects. In this article, we discuss how current trial designs often miss the opportunity to include end points beyond tumor response and thus fail to offer complete assessments of therapeutic approaches. Quality of life, neurocognitive function and neurofunctional deficits need to be considered when assessing overall success of a therapy. Herein, we identify specific end points that should be included in the interpretation of clinical trial results and accordingly, offer a more comprehensive approach to treatment decision-making. • As a whole, treatment for pediatric brain tumors has greatly improved survival; however, patients can suffer from a myriad of treatment-related morbidities.• In particular, pediatric patients with low-grade tumors frequently go on to survive their tumor, but carry substantial burden related to prior treatments.• Quality of life (QoL), decreased neurocognitive ability and neurofunctional impairments are notable concerns for long-term survivors of pediatric brain tumors and these domains should be assessed when determining treatment strategies.• Historically, clinical trials have not adequately assessed QoL, neurocognition and neurofunctioning. These parameters deserve more attention and should be included as primary or secondary end points of clinical trials.• The Pediatric Quality of Life scales have been validated in the pediatric population and can effectively assess QoL in pediatric brain tumor patients.• Validated neurocognitive assessments such as CogState and the NIH Toolbox can play an important role in the evaluation of neurocognition in pediatric brain tumor patients.• Long-term motor, vision and hearing impairments may occur as a result of tumor and treatment in pediatric brain tumor patients and should be included in pediatric brain tumor clinical trial outcomes. BackgroundIn the USA, the number of adult survivors of pediatric brain tumors has been steadily increasing over recent years. The average 5-year survival rate for all-comers of pediatric brain cancers has risen to approximately 73% [1]. However, there is a broad range of survivorship depending on tumor type. Pure germinomas and pilocytic astrocytomas have 5-year survival rates greater than 90%; however, for diffuse intrinsic pontine glioma and other high-grade gliomas, outcomes remain extremely poor [2][3][4][5]. The main clinical trial objective for brain tumors with poor prognoses is to improve survival; however, quality of life (QoL) remains an important aspect for these children -especially if median survival is relatively short. Though, the current article is not focusing on explicit recommendations for highly aggressive tumors, QoL measures should still be addressed in trials for this group given the conceivably higher impor...

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“…In older children, the acute and delayed neurotoxicity of neoadjuvant high-dose methotrexate was considered acceptable, and intrathecal and systemic methotrexate without irradiation did not result in a consistant pattern of deficits [69][70][71]. However, worsening of cognitive deficits, and particularly of executive skills, has been described, especially if methotrexate was applicated after radiotherapy [72] and the neurotoxicity of methotrexate is discussed controversially. In consequence, the application of intra-CSF methotrexate has not been studied for the past 20 years.…”

Section: Methotrexate-associated Late Effectsmentioning

confidence: 99%

Current treatment approaches to early childhood medulloblastoma

Rutkowski¹

2006

Expert Review of Neurotherapeutics

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Treatment of medulloblastoma, the most common malignant brain tumor of childhood, is particularly challenging in very young children, owing to the increased susceptibility of the immature brain to treatment-induced neurocognitive deficits. Three promising strategies have been developed in combination with systemic postoperative chemotherapy, to avoid craniospinal irradiation for young children with nonmetastatic medulloblastoma, these include: high-dose chemotherapy, with and without local radiotherapy; intraventricular chemotherapy; and local radiotherapy. More intensified strategies may be required for metastatic medulloblastoma. Future studies will clarify the prognostic relevance of desmoplasia, postoperative residual tumor and biological markers to improve stratification criteria by risk-adapted treatment recommendations. An international Phase III trial for young children with nonmetastatic medulloblastoma, comparing survival rates and neurocognitive outcomes of different treatment strategies by standardized criteria, is under discussion.

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Intrathecal methotrexate affects cognitive function in children with medulloblastoma

Abstract: The administration of intrathecal methotrexate to children with medulloblastoma worsens the cognitive deficits induced by chemotherapy and radiotherapy. The use of intrathecal methotrexate in the treatment of medulloblastoma and other malignancies should be reassessed.

Cited by 84 publications

References 36 publications

Neurotoxicity of chemotherapeutic and biologic agents in children with cancer

Neurotoxicity of chemotherapeutic and biologic agents in children with cancer

Clinical trials in pediatric neuro-oncology: what is missing and how we can improve

Current treatment approaches to early childhood medulloblastoma

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