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Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma

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Abstract

Objective Early prediction of imminent failure during chemotherapy for malignant glioma has the potential to guide proactive alterations in treatment before frank tumor progression. We prospectively followed patients with recurrent malignant glioma receiving tamoxifen chemotherapy using proton magnetic resonance spectroscopic imaging (1H-MRSI) to identify intratumoral metabolic changes preceding clinical and radiological failure. Methods We performed serial 1H-MRSI examinations to assess intratumoral metabolite intensities in 16 patients receiving high-dose oral tamoxifen monotherapy for recurrent malignant glioma (WHO grade III or IV) as part of a phase II clinical trial. Patients were followed until treatment failure, death, or trial termination. Results Patients were officially classified as responders (7 patients) or non-responders (9 patients) 8 weeks into treatment. At 8 weeks, responders and non-responders had different intratumoral intensities across all measured metabolites except choline. Beyond 8 weeks, metabolite intensities remained stable in all responders, but changed again with approaching disease progression. Choline, lipid, choline/NAA, and lactate/NAA were significantly elevated (P < 0.02), while creatine (P < 0.04) was significantly reduced, compared to stabilized levels on average 4 weeks prior to failure. Lactate was significantly elevated (P = 0.036) fully 8 weeks prior to failure. In one patient who was still responding to tamoxifen at the conclusion of the trial, metabolite intensities never deviated from 8-week levels for the duration of follow-up. Conclusions Characteristic global intratumoral metabolic changes, detectable on serial 1H-MRSI studies, occur in response to chemotherapy for malignant glioma and may predict imminent treatment failure before actual clinical and radiological disease progression.

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Acknowledgements

This study was supported by funds from the Montreal Neurological Institute, including the Jeanne Timmins Costello Foundation, the Killam Foundation, and funds from the Barrow Neurological Institute, including the Barrow Neurological Foundation, and the Newsome Chair of Neurosurgery Research.

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Authors and Affiliations

  1. Neurosurgery Research Laboratory, Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Road, Phoenix, AZ, 85013, USA

    Tejas Sankar, Rachid Assina & Mark C. Preul

  2. MR Spectroscopy Unit, Montreal Neurological Institute, McGill University, Montreal, QC, Canada

    Zografos Caramanos, Douglas L. Arnold & Mark C. Preul

  3. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

    Jean-Guy Villemure, Richard Leblanc & Douglas L. Arnold

  4. Division de neurochirurgie, Departement de chirurgie, Universite de Montreal, Montreal, QC, Canada

    Jean-Guy Villemure

  5. Department of Oncology, McGill University, Montreal, QC, Canada

    Adrian Langleben

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  1. Tejas Sankar
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Correspondence to Mark C. Preul.

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Sankar, T., Caramanos, Z., Assina, R. et al. Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma. J Neurooncol 90, 63–76 (2008). https://doi.org/10.1007/s11060-008-9632-3

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