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

Tejas Sankar, Zografos Caramanos, Rachid Assina, Jean Guy Villemure, Richard Leblanc, Adrian Langleben, Douglas L. Arnold, Mark C. Preul

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)63-76
Number of pages14
JournalJournal of neuro-oncology
Volume90
Issue number1
DOIs
StatePublished - Jul 4 2008
Externally publishedYes

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Tamoxifen
Glioma
Protons
Choline
Treatment Failure
Drug Therapy
Disease Progression
Lactic Acid
Phase II Clinical Trials
Creatine
Magnetic Resonance Imaging
Lipids
Therapeutics
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Sankar, Tejas ; Caramanos, Zografos ; Assina, Rachid ; Villemure, Jean Guy ; Leblanc, Richard ; Langleben, Adrian ; Arnold, Douglas L. ; Preul, Mark C. / Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma. In: Journal of neuro-oncology. 2008 ; Vol. 90, No. 1. pp. 63-76.
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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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Sankar, T, Caramanos, Z, Assina, R, Villemure, JG, Leblanc, R, Langleben, A, Arnold, DL & Preul, MC 2008, 'Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma', Journal of neuro-oncology, vol. 90, no. 1, pp. 63-76. https://doi.org/10.1007/s11060-008-9632-3

Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma. / Sankar, Tejas; Caramanos, Zografos; Assina, Rachid; Villemure, Jean Guy; Leblanc, Richard; Langleben, Adrian; Arnold, Douglas L.; Preul, Mark C.

In: Journal of neuro-oncology, Vol. 90, No. 1, 04.07.2008, p. 63-76.

Research output: Contribution to journalArticle

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T1 - Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma

AU - Sankar, Tejas

AU - Caramanos, Zografos

AU - Assina, Rachid

AU - Villemure, Jean Guy

AU - Leblanc, Richard

AU - Langleben, Adrian

AU - Arnold, Douglas L.

AU - Preul, Mark C.

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N2 - 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.

AB - 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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