Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

Kalm, Marie; Abel, Edvard; Wasling, Pontus; Nyman, Jan; Hietala, Max Albert; Bremell, Daniel; Hagberg, Lars; Elam, Mikael; Blennow, Kaj; Björk‐Eriksson, Thomas; Zetterberg, Henrik

doi:10.1016/j.ijrobp.2014.03.019

Cited by 17 publications

(21 citation statements)

References 34 publications

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“…The latter can be irreversible and cause neurocognitive deficits, leuko-encephalopathy, cerebral atrophy or even radiation induced necrosis (Dietrich et al, 2008; Le Pechoux et al, 2011). Markers for neuronal injury can be detected in the cerebrospinal fluid of patients after PCI, despite the moderate radiation doses used (Kalm et al, 2014). Similarly, RTKs such as lapatinib can induce significant toxicities, including cutaneous, gastrointestinal and hematologic side effects, as well as fatigue (Crown et al, 2013).…”

Section: Can Breast Cancer Brain Metastases Be Prevented?mentioning

confidence: 99%

Emerging Strategies for Treating Brain Metastases from Breast Cancer

et al. 2015

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Summary Brain metastasis is an end stage in breast cancer progression. Traditional treatment options have minimal efficacy, and overall survival is on the order of months. The incidence of brain metastatic disease is increasing with the improved management of systemic disease and prolongation of survival. Unfortunately, the targeted therapies that control systemic disease have diminished efficacy against brain lesions. There are reasons to be optimistic, however, as emerging therapies have shown promise in preclinical and early clinical settings. This review discusses recent advances in breast cancer brain metastasis therapy and potential approaches for successful treatment.

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Section: Can Breast Cancer Brain Metastases Be Prevented?mentioning

confidence: 99%

Emerging Strategies for Treating Brain Metastases from Breast Cancer

et al. 2015

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“…Our group has previously investigated markers of neuronal degradation in CSF following PCI. In that study, both NFL and tau were highly elevated 3 months following PCI . Both NFL and tau are well‐established CSF markers for axonal injury.…”

Section: Discussionmentioning

confidence: 78%

“…Those findings in combination with the decreased levels of brevican and sAPPα suggest that the ECM and plasticity are negatively affected by irradiation. It should be noted, however, that sAPPα correlates strongly with sAPPβ ; most of the correlations for sAPPα were also seen for sAPPβ, although less strongly. As mentioned in the introduction, these peptides belong to different pathways, but the decline indicates that there could be an accumulation of full‐length APP in the brain tissue, hence less peptides in the CSF.…”

Section: Discussionmentioning

confidence: 83%

“…Visual comparison of ECM biomarkers with the longitudinal changes in biomarker levels from the previous study revealed a similarity between longitudinal changes in brevican and soluble amyloid precursor protein α (sAPPα) levels, as well as between GAP‐43 and NFL. To assess this, data on sAPPα and NFL levels, as published previously , were included in the repeated‐measures correlation analysis.…”

Section: Resultsmentioning

confidence: 99%

“…precursor protein a (sAPPa) levels, as well as between GAP-43 and NFL. To assess this, data on sAPPa and NFL levels, as published previously [8], were included in the repeated-measures correlation analysis.…”

Section: Plasticity and Inflammatory Markersmentioning

confidence: 99%

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Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy

et al. 2018

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CSF biomarkers of neurotoxicity in childhood cancer survivors after cranial radiotherapy or surgery

Fernström,

Jarfelt,

Blomstrand

et al. 2024

Ann Clin Transl Neurol

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ObjectiveTreatment of pediatric brain tumors is associated with potential long‐term cognitive sequelae. Patients treated with craniospinal irradiation for posterior fossa tumors are at high risk. New biomarkers that could help to differentiate treatment effects from other causes of cognitive dysfunction would be valuable in tailoring optimal survivorship care. Biomarkers that reflect biological mechanisms behind treatment‐associated cognitive decline would also be important in the evaluation of future treatment regimens for pediatric brain or skull base tumors.MethodsIn this biomarker‐finding study, 10 adult survivors of pediatric medulloblastoma, skull base tumors, and posterior fossa low‐grade glioma underwent study specific lumbar puncture at a minimum of 17 years following treatment. We analyzed cerebrospinal fluid biomarkers reflecting neuron and astrocyte integrity, amyloid metabolism, inflammation, extracellular matrix, synaptic integrity, and blood–brain barrier function. The values were compared with biomarker levels in healthy controls of comparable age.ResultsBiomarkers reflecting neuronal injury (neurofilament light chain protein), astrocyte injury or activation (glial fibrillary acidic protein) as well as inflammation (YKL‐40) were significantly elevated in cancer survivors compared to controls. Biomarkers reflecting amyloid metabolism showed a pattern of decrease in patients treated for medulloblastoma.InterpretationThe results suggest a potential chronic low‐grade neurodegeneration and astrocyte activation in patients treated for pediatric brain or skull base tumors. Protein biomarkers of CNS disease could potentially be used to increase our understanding of the contribution from different tumor treatments with regard to long‐term symptoms in cancer patients.

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Neurochemical Evidence of Potential Neurotoxicity After Prophylactic Cranial Irradiation

Cited by 17 publications

References 34 publications

Emerging Strategies for Treating Brain Metastases from Breast Cancer

Emerging Strategies for Treating Brain Metastases from Breast Cancer

Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy

CSF biomarkers of neurotoxicity in childhood cancer survivors after cranial radiotherapy or surgery

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