Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy

Abstract

Purpose Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults. The goal of this study was to test the predictive value of MR parameters in relation to the survival of patients with newly diagnosed GBM who were scanned prior to receiving adjuvant radiation and chemotherapy. Methods The study population comprised 68 patients who had surgical resection and were to be treated with fractionated external beam radiation therapy and chemotherapy. Imaging scans included anatomical MRI, diffusion and perfusion weighted imaging and (1)H MRSI. The MR data were acquired 3-5 weeks after surgery and approximately 1 week before treatment with radiation therapy. The diffusion, perfusion and spectroscopic parameter values were quantified and subjected to proportional hazards analysis that was adjusted for age and scanner field strength. Results The patients with larger lesion burden based upon volumes of anatomic lesions, volume of CNI2 (number of voxels within the T2 lesion having choline to NAA index >2), volume of CBV3 (number of pixels within the T2 lesion having relative cerebral blood volume >3), and volume of nADC1.5 (number of pixels within the T2 lesion having normalized apparent diffusion coefficient <1.5) had a higher risk for poor outcome. High intensities of combined measures of lactate and lipid in the T2 and CNI2 regions were also associated with poor survival. Conclusions Our study indicated that several pre-treatment anatomic, physiological and metabolic MR parameters are predictive of survival. This information may be important for stratifying patients to specific treatment protocols and for planning focal therapy.

Figures

Fig. 1

Example of a FLAIR image (a), a T1 weighted post-contrast image (b), and an apparent diffusion coefficient map (c) from corresponding slices in a 68 year old patient with a newly diagnosed GBM post surgery and prior to radiation therapy

Fig. 2

Example of a post-contrast T weighted image (a) and overlaid perfusion maps showing (b) rCBV and (c) ΔR2* peak height maps for a patient with a 46 year old patient with GBM

Fig. 3

Spectra and images from the same patient as in Fig. 2. The individual spectra from normal brain (a) shows peaks corresponding to NAA, choline and creatine, from the summed spectra in the tumor (b) with an additional peak from lipid, and from the difference spectra in the tumor (c) showing the lactate peak. The T1-weighted post-contrast (d) and FLAIR (e) images display the PRESS selected volume and the corresponding arrays of summed (left) and difference (right) of the lactate-edited spectra. Voxels in the spectral arrays that are highlighted in blue have CNI >2 but no lipid, voxels in red have both CNI >2 and lipid with SNR >6.0 and voxels in green have lactate with SNR >6.0

Fig. 4

Kaplan–Meier survival curves for (a) all patients and (b) for groups of patients with T2ALL lesion volume greater than (gray line) or less than (black line) the median value

Fig. 5

T1 post contrast and FLAIR images from a 49 year old patient with a newly diagnosed GBM whose lesion was classified as a gross total resection at the time of surgery. Four weeks later and immediately prior to treatment with radiation small regions of Gadolinium enhancement can be observed in the medial edge of the lesion and a more extensive area of hyperintensity on FLAIR images. The MRSI data show that this abnormality has highly elevated CNI with the blue shading showing voxels in the axial and coronal planes that have abnormal CNI which ranges from 3.2 to 30.7. Note that the level of choline is so high in tumor relative to normal voxels that the intensity scale has to be reduced by a factor of 4 to be able to visualize them within the same array

Fig. 6

Distribution of rCBV, ADC, CNI and Lac/nNAA values in normal appearing white matter (NAWM—green curves), contrast enhancement lesion (CEL—dark blue curves) and non-enhancing lesion (NEL—light blue curves) regions for the patient who was shown in Fig. 1