3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

Abstract

Purpose To evaluate the utility of 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 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. 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 radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd 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 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was 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.

Association of early changes in1H MRSI parameters with survival for patients with newly diagnosed glioblastoma receiving a multimodality treatment regimen

“…8,9 The results of the quantitative analysis suggest that metabolic parameters at baseline, one month, and 2 months into treatment were able to capture alterations in tumor burden associated with these effects. The findings are consistent with prior studies using MRSI data to predict response to therapy, [20][21][22] suggesting that it may be helpful for providing an early assessment of the utility of other combination therapies. Previous studies have evaluated the relationship of anatomic imaging parameters to outcome for patients with newly diagnosed GBM receiving standard-of-care treatment with RT and temozolomide.…”

Choline metabolism-based molecular diagnosis of cancer: an update

“…Both 1 H MRS [5] and [ 11 C]-choline-PET [6] imaging are finding important roles in monitoring response to radiation treatment in patients with glioblastoma multiforme [5] and in detecting recurrence in patients with prostate cancer [6]. Increasingly, radiation oncologists are incorporating these imaging modalities in restaging and assessment of response in these patients [5,6].…”

“…Increasingly, radiation oncologists are incorporating these imaging modalities in restaging and assessment of response in these patients [5,6]. A recent study demonstrated that [ 11 C]-choline-PET/CT positive lung tumors also contained high expression levels of choline acetyltransferase and Chk-α [112].…”

“…In 2000, there were 111 annual publications in this field that doubled to 220 by 2010 and have increased to 256 in 2013. PET choline imaging [3,4] has eclipsed 1 H magnetic resonance spectroscopy (MRS) in human oncological applications, including the detection of response to treatment [5,6], although 1 H MRS is still the technique of choice in preclinical studies. The past 5 years have witnessed significant insights into the molecular causes underlying abnormal choline metabolism in cancer, novel directions in targeting choline metabolism for therapy and a clearer understanding of the role of choline metabolism in oncological transformation and oncological pathways.…”

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

“…Moreover, the early change of the Cho-to-NAA index during RT has been shown to predict early progression within an observational study of GBM where the voxel-based analysis of 3D MRSI data retrospectively revealed a significant increase in median Cho/NAA in the group of patients with early recurrent tumour. 79 Alongside with the metabolites mentioned above, there is another promising MRSI approach examining lactate (Lac) accumulation as a surrogate for hypoxic and subsequently radioresistant areas that has also shown the potential to predict local recurrence. Therefore, lactate imaging might also serve as a biological targeting or dose-painting technique.…”