High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.
We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.
We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.
We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.
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We acknowledge Kristin Nyman at the Department of Neurosurgery for her technical skills in managing the microdialysis bedside and Professor Thomas Brännström at the Department of Pathology, for verification of IDH mutation status.
The authors declare no competing interests.
Ethics approval and consent to participate
The authors confirm that the study have been conducted within appropriate ethical guidelines and legislation. The local ethics committee in Umeå approved the study, and all patients gave their informed consent to participate in the study (09–199 M). The trial was permitted by the Swedish Medical Product Agency, EudraCT number: 2010-018281-23, registered 4 January 2010, http://www.lakemedelsverket.se.
This study was supported by the Swedish Cancer Society (A.T.B., H.A.), Umeå University Hospital (A.T.B.), the Swedish Research Council (H.A.), the Cancer Research Foundation in Northern Sweden (B.B.), the Research Foundation of Clinical Neuroscience, Umeå University (A.T.B.) and by the regional agreement between Umeå University and Västerbotten County Council on the cooperation in the field of Medicine, Odontology and Health (A.T.B.).
Summarised datasets supporting the conclusions of this article are included within the article and as additional supplementary files.
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Björkblom, B., Jonsson, P., Tabatabaei, P. et al. Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma. Br J Cancer 122, 221–232 (2020). https://doi.org/10.1038/s41416-019-0652-x
British Journal of Cancer (2020)