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

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

Authors :
Adrian Langleben
Mark C. Preul
Rachid Assina
Jean-Guy Villemure
Douglas L. Arnold
Zografos Caramanos
Richard Leblanc
Tejas Sankar
Source :
Journal of Neuro-Oncology. 90:63-76
Publication Year :
2008
Publisher :
Springer Science and Business Media LLC, 2008.

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.

Details

ISSN :
15737373 and 0167594X
Volume :
90
Database :
OpenAIRE
Journal :
Journal of Neuro-Oncology
Accession number :
edsair.doi.dedup.....677325b6b0a1fde0eda479150fd6f589
Full Text :
https://doi.org/10.1007/s11060-008-9632-3