期刊
JOURNAL OF NEURO-ONCOLOGY
卷 90, 期 1, 页码 63-76出版社
SPRINGER
DOI: 10.1007/s11060-008-9632-3
关键词
brain neoplasm; chemotherapy; glioma; magnetic resonance imaging; magnetic resonance spectroscopy; tamoxifen
资金
- Montreal Neurological Institute
- Jeanne Timmins Costello Foundation
- Killam Foundation
- Barrow Neurological Institute
- Barrow Neurological Foundation
- Newsome Chair of Neurosurgery Research
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 (H-1-MRSI) to identify intratumoral metabolic changes preceding clinical and radiological failure. Methods We performed serial H-1-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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