title: Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab.
abstract: Interpretation of changes in the T1- and T2-weighted MR images from patients with newly diagnosed glioblastoma (GBM) treated with standard of care in conjunction with anti-angiogenic agents is complicated by pseudoprogression and pseudoresponse. The hypothesis being tested in this study was that 3D H-1 magnetic resonance spectroscopic imaging (MRSI) provides estimates of levels of choline, creatine, N-acetylaspartate (NAA), lactate and lipid that change in response to treatment and that metrics describing these characteristics are associated with survival. Thirty-one patients with newly diagnosed GBM and being treated with radiation therapy (RT), temozolomide, erlotinib and bevacizumab were recruited to receive serial MR scans that included 3-D lactate edited MRSI at baseline, mid-RT, post-RT and at specific follow-up time points. The data were processed to provide estimates of metrics representing changes in metabolite levels relative to normal appearing brain. Cox proportional hazards analysis was applied to examine the relationship of these parameters with progression free survival (PFS) and overall survival (OS). There were significant reductions in parameters that describe relative levels of choline to NAA and creatine, indicating that the treatment caused a decrease in tumor cellularity. Changes in the levels of lactate and lipid relative to the NAA from contralateral brain were consistent with vascular normalization. Metabolic parameters from the first serial follow-up scan were associated with PFS and OS, when accounting for age and extent of resection. Integrating metabolic parameters into the assessment of patients with newly diagnosed GBM receiving therapies that include anti-angiogenic agents may be helpful for tracking changes in tumor burden, resolving ambiguities in anatomic images caused by non-specific treatment effects and for predicting outcome.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. sarah.nelson@ucsf.edu.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA. sarah.nelson@ucsf.edu.|Department of Neurology, University of California, San Francisco, CA, USA. sarah.nelson@ucsf.edu.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA. sarah.nelson@ucsf.edu.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Lupo
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Marram
authors.initials: M
authors.lastname: Olson
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Crane
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Molinaro
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.|Department of Neurology, University of California, San Francisco, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clarke
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Butowski
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
authors.forename: Susan M
authors.identifier: 0000-0001-8015-5157
authors.initials: SM
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D061766:Proton Therapy / Q000379:methods; D018709:Statistics, Nonparametric; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab; D001224:Aspartic Acid; D003606:Dacarbazine; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline; D000077204:Temozolomide
keywords: Anti-angiogenic therapy; MRSI; Metabolic imaging; Newly diagnosed glioblastoma; Survival