3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

PURPOSE 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 AND MATERIALS 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. CONCLUSION 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.

[1]  D. Cox,et al.  Analysis of Survival Data. , 1985 .

[2]  K. Camphausen,et al.  Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience , 2013, PloS one.

[3]  Mark E Mullins,et al.  Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis. , 2005, AJNR. American journal of neuroradiology.

[4]  Wolzt,et al.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. , 2003, The Journal of the American College of Dentists.

[5]  R. Hatlevoll,et al.  Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: A prospective multicenter trial of the scandinavian glioblastoma study group , 1981, Cancer.

[6]  E. Shaw,et al.  Radiation oncology in brain tumors: current approaches and clinical trials in progress. , 2010, Neuroimaging clinics of North America.

[7]  Isabelle Berry,et al.  Proton magnetic resonance spectroscopic imaging in newly diagnosed glioblastoma: predictive value for the site of postradiotherapy relapse in a prospective longitudinal study. , 2008, International journal of radiation oncology, biology, physics.

[8]  W. Curran,et al.  Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06. , 1998, International journal of radiation oncology, biology, physics.

[9]  T. Cascino,et al.  Response criteria for phase II studies of supratentorial malignant glioma. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Andrew D Norden,et al.  Response Assessment Challenges in Clinical Trials of Gliomas , 2010, Current oncology reports.

[11]  D. Vigneron,et al.  An automated technique for the quantitative assessment of 3D‐MRSI data from patients with glioma , 2001, Journal of magnetic resonance imaging : JMRI.

[12]  Geon-Ho Jahng,et al.  Pseudoprogression in patients with glioblastoma: added value of arterial spin labeling to dynamic susceptibility contrast perfusion MR imaging , 2013, Acta radiologica.

[13]  Jian Z. Wang,et al.  Ultra‐early predictive assay for treatment failure using functional magnetic resonance imaging and clinical prognostic parameters in cervical cancer , 2010, Cancer.

[14]  P. Sundgren,et al.  Developing a clinical decision model: MR spectroscopy to differentiate between recurrent tumor and radiation change in patients with new contrast-enhancing lesions. , 2009, AJR. American journal of roentgenology.

[15]  Christiane,et al.  WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI: Ethical Principles for Medical Research Involving Human Subjects , 2001, Journal of postgraduate medicine.

[16]  Sarah J Nelson,et al.  Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI , 2011, NMR in biomedicine.

[17]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[18]  D. Nass,et al.  Delayed Contrast Extravasation MRI for Depicting Tumor and Non-Tumoral Tissues in Primary and Metastatic Brain Tumors , 2012, PloS one.

[19]  A. Brandes,et al.  Glioblastoma in adults. , 2008, Critical reviews in oncology/hematology.

[20]  T. Mikkelsen,et al.  Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[22]  D. Nelson,et al.  Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. , 1993, International journal of radiation oncology, biology, physics.

[23]  Christos Trantakis,et al.  Intraoperative MRI to guide the resection of primary supratentorial glioblastoma multiforme—a quantitative radiological analysis , 2005, Neuroradiology.

[24]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[25]  Dieta Brandsma,et al.  Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. , 2008, The Lancet. Oncology.

[26]  Manish K. Aghi,et al.  New advances that enable identification of glioblastoma recurrence , 2009, Nature Reviews Clinical Oncology.

[27]  D. Born,et al.  Pseudoprogression: Relevance With Respect to Treatment of High-Grade Gliomas , 2011, Current treatment options in oncology.

[28]  Namkug Kim,et al.  Percent change of perfusion skewness and kurtosis: a potential imaging biomarker for early treatment response in patients with newly diagnosed glioblastomas. , 2012, Radiology.

[29]  Ilwoo Park,et al.  Patterns of recurrence analysis in newly diagnosed glioblastoma multiforme after three-dimensional conformal radiation therapy with respect to pre-radiation therapy magnetic resonance spectroscopic findings. , 2007, International journal of radiation oncology, biology, physics.

[30]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.