title: 3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.
abstract: OBJECTIVE
  To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme.
  
  
  METHODS
  Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression.
  
  
  RESULTS
  After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred.
  
  
  CONCLUSIONS
  Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Manickam
authors.initials: M
authors.lastname: Muruganandham
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Clerkin
authors.affiliation: Department of Biostatistics, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Carryn M
authors.initials: CM
authors.lastname: Anderson
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Ann
authors.initials: A
authors.lastname: Morris
authors.affiliation: Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Aristides A
authors.initials: AA
authors.lastname: Capizzano
authors.affiliation: Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magnotta
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: McGuire
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
authors.forename: John E
authors.initials: JE
authors.lastname: Bayouth
authors.affiliation: Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa. Electronic address: john-buatti@uiowa.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Buatti
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000379:methods; D002794:Choline / Q000378:metabolism; D003287:Contrast Media; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005682:Gadolinium; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D003287:Contrast Media; D001224:Aspartic Acid; D003606:Dacarbazine; C000179:N-acetylaspartate; D005682:Gadolinium; D002794:Choline; D000077204:Temozolomide