Survival analysis in patients with newly diagnosed glioblastoma using pre- and postradiotherapy MR spectroscopic imaging

Abstract

Background: The objective of this study was to examine the predictive value of parameters of 3D (1)H magnetic resonance spectroscopic imaging (MRSI) prior to treatment with radiation/chemotherapy (baseline) and at a postradiation 2-month follow-up (F2mo) in relationship to 6-month progression-free survival (PFS6) and overall survival (OS).

Methods: Sixty-four patients with newly diagnosed glioblastoma multiforme (GBM) being treated with radiation and concurrent chemotherapy were involved in this study. Evaluated were metabolite indices and metabolite ratios. Logistic linear regression and Cox proportional hazards models were utilized to evaluate PFS6 and OS, respectively. These analyses were adjusted by age and MR scanner field strength (1.5 T or 3 T). Stepwise regression was performed to determine a subset of the most relevant variables.

Results: Associated with shorter PFS6 were a decrease in the ratio of N-acetyl aspartate to choline-containing compounds (NAA/Cho) in the region with a Cho-to-NAA index (CNI) >3 at baseline and an increase of the CNI within elevated CNI regions (>2) at F2mo. Patients with higher normalized lipid and lactate at either time point had significantly worse OS. Patients who had larger volumes with abnormal CNI at F2mo had worse PFS6 and OS.

Conclusions: Our study found more 3D MRSI parameters that predicted PFS6 and OS for patients with GBM than did anatomic, diffusion, or perfusion imaging, which were previously evaluated in the same population of patients.

Fig. 1

(A) Images and spectra at baseline, (B) 2-month follow-up after baseline (F2mo), and (C) progression (PG) from a patient with newly diagnosed GBM. The postcontrast and FLAIR images display the PRESS selected volume and the corresponding arrays of spectra. The corresponding Cho-to-NAA index (CNI) values are shown in the spectral array. Voxels with CNI > 3.0 are highlighted in light red, voxels in light green had CNI between 2 and 3, and voxels in the T2 lesion within the PRESS volume (T2L) are outlined in blue. The patient had PFS of 4 mo and OS of 8 mo. CNI values varied in the T2L at PG (C).

Fig. 2

3D (non-Lac-edited) MRSI acquired from a patient with PFS of 2 mo and OS of 7 mo at F2mo. The individual spectra show peaks corresponding to Cho, Cr, NAA, Lac, and Lip in the lesions. Voxels with a Cho-to-NAA index (CNI) > 3.0 are highlighted in dark grey, voxels in light grey had CNI between 2 and 3, and voxels in the T2 lesion within the PRESS volume (T2L) were outlined in black thick line. Numbers in the spectral array represent values of excess Cho (exCho), the differences in Cho compared with those in NAWM adjusted by the changes in NAA. Spectrum from the top left corner with a relatively high NAA peak had exCho of 0.07, whereas that in the opposite corner with a low NAA was 0.72. Elevated exCho values are seen in the regions of the T2L with increased CNI.

Fig. 3

Box plots of the numbers of voxels in the T2 lesion within the PRESS volume (T2L), regions that had CNI value >2 (CNI2), regions that had CNI value >3 (CNI3), intersection of the T2L and CNI2 (CNI2T), CNI2-T2L and T2L-CNI2T at baseline, F2mo, and progression (PG). Number of patients are 64, 41, and 36, respectively, at these 3 time points. CNI2-T2L and T2L-CNI2T represent the difference in number of voxels between CNI2 and T2L and between T2L and CNI2T, respectively. Metabolic lesions were larger than the T2L, and the percent of the metabolic lesions within the T2L varied at PG.

Fig. 4

Box plots of median NAA/Cho in the regions that had CNI value >3 (CNI3) at baseline, median NAA/Cho in the T2 lesion within the PRESS volume (T2L), maximum Cho-to-NAA index (CNI) in the regions that had CNI value >2 (CNI2), median CNI in the CNI3 and intersection of the T2L and CNI2 (CNI2T) at F2mo in the groups of early progressor (EP) and late progressor (LP). N represents the number of patients. Smaller CNI values and higher NAA/Cho are seen in patients who progressed later.

Fig. 5

3D (Lac-edited) MRSI acquired from a patient with PFS of 2 mo and OS of 11 mo at F2mo. Spectral array corresponded to (A) summed and (B) difference of the Lac-edited spectra. Voxels having Lac or Lip with signal-to-noise ratio ≥ 5.0 are labeled, and voxels within the T2 lesion within the PRESS volume (T2L) are outlined in black thick line.

Fig. 6

Box plots of median Cho/NAA in the regions that had CNI value >2 (CNI2), median exCho in the regions that had CNI value >3 (CNI3), maximum nCr in the T2 lesion within the PRESS volume (T2L) or maximum excess creatine (exCr) in the intersection of T2L and CNI2 (CNI2T) at F2mo in 3 groups of patients, who died within a year, between 1 and 2 years, and lived longer than 2 years. N represents the number of patients. Patients who had elevated metabolic values had relatively shorter OS.

Fig. 7

Postcontrast T1-weighted FLAIR images and 3D (non-Lac-edited) MRSI from 2 patients (A, B) with GBM at F2mo. Voxels with Cho-to-NAA index (CNI) >3.0 are highlighted in dark grey, voxels in light grey had CNI between 2 and 3, and voxels in the T2 lesion within the PRESS volume (T2L) were outlined in black thick line. Numbers in the spectral array represent values of normalized creatine (nCr). Patient A had a short OS of 11 mo and patient B died at 61 mo.