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A pilot microdialysis study in brain tumor patients to assess changes in intracerebral cytokine levels after craniotomy and in response to treatment with a targeted anti-cancer agent

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Abstract

Intracerebral microdialysis enables continuous measurement of changes in brain biochemistry. In this study intracerebral microdialysis was used to assess changes in cytokine levels after tumor resection and in response to treatment with temsirolimus. Brain tumor patients undergoing craniotomy participated in this non-therapeutic study. A 100 kDa molecular weight cut-off microdialysis catheter was placed in peritumoral tissue at the time of resection. Cohort 1 underwent craniotomy only. Cohort 2 received a 200 mg dose of intravenous temsirolimus 48 h after surgery. Dialysate samples were collected continuously for 96 h and analyzed for the presence of 30 cytokines. Serial blood samples were collected to measure systemic cytokine levels. Dialysate samples were obtained from six patients in cohort 1 and 4 in cohort 2. Seventeen cytokines could be recovered in dialysate samples from at least 8 of 10 patients. Concentrations of interleukins and chemokines were markedly elevated in peritumoral tissue, and most declined over time, with IL-8, IP-10, MCP-1, MIP1β, IL-6, IL-12p40/p70, MIP1α, IFN-α, G-CSF, IL-2R, and vascular endothelial growth factor significantly (p < 0.05) decreasing over 96 h following surgery. No qualitative changes in intracerebral or serum cytokine concentrations were detected after temsirolimus administration. This is the first intracerebral microdialysis study to evaluate the time course of changes in macromolecule levels in the peritumoral microenvironment after a debulking craniotomy. Initial elevations of peritumoral interleukins and chemokines most likely reflected an inflammatory response to both tumor and surgical trauma. These findings have implications for development of cellular therapies that are administered intracranially at the time of surgery.

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Acknowledgments

We thank Brenda Williams, RN, for her management of the microdialysis catheters and Keely Walker, PhD, for her valuable editing of the manuscript. Sources of funding: National Institutes of Health (K12CA01727 to J.P.); Phase One Foundation; Pfizer, Inc.

Conflict of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Medical Oncology, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Jana Portnow

  2. Department of Neurosurgery, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Behnam Badie & Mike Chen

  3. Department of Biostatistics, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Xueli Liu & Paul Frankel

  4. Clinical Immunobiology Correlative Studies Laboratory, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Shu Mi

  5. Department of Molecular Pharmacology, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Timothy W. Synold

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  1. Jana Portnow
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  2. Behnam Badie
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  3. Xueli Liu
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Correspondence to Jana Portnow.

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Portnow, J., Badie, B., Liu, X. et al. A pilot microdialysis study in brain tumor patients to assess changes in intracerebral cytokine levels after craniotomy and in response to treatment with a targeted anti-cancer agent. J Neurooncol 118, 169–177 (2014). https://doi.org/10.1007/s11060-014-1415-4

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