Serial analysis of imaging parameters in patients with newly diagnosed glioblastoma multiforme

Abstract

The objective of this study was to test the predictive value of serial MRI data in relation to clinical outcome for patients with glioblastoma multiforme (GBM). Sixty-four patients with newly diagnosed GBM underwent conventional MRI and diffusion-weighted and perfusion-weighted imaging postsurgery and prior to radiation/chemotherapy (pre-RT), immediately after RT (post-RT), and every 1-2 months thereafter until tumor progression, up to a maximum of 1 year. Tumor volumes and perfusion and diffusion parameters were calculated and subject to time-independent and time-dependent Cox proportional hazards models that were adjusted for age and MR scanner field strength. Larger volumes of the T2 hyperintensity lesion (T2ALL) and nonenhancing lesion (NEL) at pre-RT, as well as increased anatomic volumes at post-RT, were associated with worse overall survival (OS). Higher normalized cerebral blood volumes (nCBVs), normalized peak height (nPH) and normalized recirculation factors (nRF) at pre-RT, and nCBV at post-RT, in the T2ALL and NEL, were associated with shorter progression-free survival (PFS). From pre- to post-RT, there was a reduction in nCBV and nPH and an increase in apparent diffusion coefficient (ADC). Patients with lower nRF values at pre-RT, or a larger increase in nRF from pre-RT to post-RT, had significantly longer PFS. Time-dependent analysis showed that patterns of changes in ADC and anatomic volumes were associated with OS, while changes in nCBV, nPH, and the contrast-enhancing volume were associated with PFS. Our studies suggest that quantitative MRI variables derived from anatomic and physiological MRI provide useful information for predicting outcome in patients with GBM.

Fig. 1.

Axial T1-weighted postcontrast, FLAIR, and ADC maps from a patient with GBM. Lines represent CEL, T2ALL, and NEL contours, respectively.

Fig. 2.

Event chart for the 64 patients who were followed in the study. Each line represents a single patient. Patients are sorted by PFS.

Fig. 3.

Kaplan–Meier survival curves for OS and PFS. The median OS (A) was 588 days, and median PFS (B) was 186 days. Survival curves (C) and (D) are for populations split based upon whether the patient progressed or was stable by 6 months and 12 months. Patients who progressed within 6 months or 12 months had shorter survival; but there was no significant difference between patients who progressed by 6 months and patients who progressed between 6 and 12 months (E). Patients who progressed within a year benefited from the combination of reoperation and chemotherapy (P-C + S) (F).

Fig. 4.

Postcontrast T1-weighted, T2-weighted, ADC, nCBV, and nPH images from 2 patients with GBM and the corresponding ΔR2* curves showing the magnitude of PH and Rec parameters in the T2ALL and NAWM regions at pre-RT. All the nCBV and nPH maps were plotted with the range between 0 and 5. Patient A had a short PFS of 128 days, and Patient B was stable at 378 days.

Fig. 5.

[Left] The mean and standard deviation of the mean for volumes of abnormalities in each individual group over time. Higher volumes at any given time point are seen in patients who had shorter survival. The median volumes of the T2ALL in the patients who died within a year were 21.6 (n = 19), 53.6 (n = 16), 48.2 (n = 8), 104.3 (n = 7), and 113.6 cc (n = 1) at 0, 2, 4, 6, and 8 months, respectively, while they were 12.4 (n = 13), 9.6 (n = 12), 10.3 (n = 10), 10.1 (n = 7), 11.7 (n = 4), 30.6 (n = 5), and 11.8 cc (n = 5) at 0, 2, 4, 6, 8, 10, and 12 months in the population who lived longer than 2 years. [Middle] Changes in volume for patients with progression by 6 months (red), between 6 and 12 months (blue), and after 12 months (green). Note that some patients who progressed show an initial reduction in lesion volume. [Right] Time course of median nADC in 3 groups of GBM patients. Values refer to mean and standard deviation of the mean. Smaller nADC values in CEL and higher in T2ALL and NEL are seen in patients who died within a year.