Diffusion-Weighted MR Imaging Derived Apparent Diffusion Coefficient Is Predictive of Clinical Outcome in Primary Central Nervous System Lymphoma

R.F Barajas,S Cha,J.L Rubenstein,J.S Chang,J Hwang

doi:10.3174/ajnr.a1750

Abstract

There is evidence that increased tumor cellular density within diagnostic specimens of primary central nervous system lymphoma (PCNSL) may have significant prognostic implications. Because cellular density may influence measurements of apparent diffusion coefficient (ADC) by using diffusion-weighted MR imaging (DWI), we hypothesized that ADC measured from contrast-enhancing regions might correlate with clinical outcome in patients with PCNSL. PCNSL tumors from 18 immunocompetent patients, treated uniformly with methotrexate-based chemotherapy, were studied with pretherapeutic DWI. Enhancing lesions were diagnosed by pathologic analysis as high-grade B-cell lymphomas. Regions of interest were placed around all enhancing lesions allowing calculation of mean, 25th percentile (ADC(25%)), and minimum ADC values. Histopathologic tumor cellularity was quantitatively measured in all patients. High and low ADC groups were stratified by the median ADC value of the cohort. The Welch t test assessed differences between groups. The Pearson correlation examined relationships between ADC measurements and tumor cellular density. Single and multivariable survival analysis was performed. We detected significant intra- and intertumor heterogeneity in ADC measurements. An inverse correlation between cellular density and ADC measurements was observed (P < .05). ADC(25%) measurements less than the median value of 692 (low ADC group) were associated with significantly shorter progression-free and overall survival. Patients with improved clinical outcome were noted to exhibit a significant decrease in ADC measurements following high-dose methotrexate chemotherapy. Our study provides evidence that ADC measurements within contrast-enhancing regions of PCNSL tumors may provide noninvasive insight into clinical outcome.

Highlights

AND PURPOSE: There is evidence that increased tumor cellular density within diagnostic specimens of primary central nervous system lymphoma (PCNSL) may have significant prognostic implications
Our study provides evidence that apparent diffusion coefficient (ADC) measurements within contrast-enhancing regions of PCNSL tumors may provide noninvasive insight into clinical outcome
Primary central nervous system lymphoma (PCNSL) is a potentially curable brain tumor, the incidence of which is increasing among immunocompetent patients.[1,2,3]

Summary

Methods

PCNSL tumors from 18 immunocompetent patients, treated uniformly with methotrexate-based chemotherapy, were studied with pretherapeutic DWI. Methotrexate is the only treatment-related variable that has been reproducibly positively associated with favorable outcome in PCNSL.[17] Of 70 patients who met the inclusion criteria for this investigation, only 18 were studied on the basis of having received pretherapeutic contrast-enhanced MR imaging of the brain with DWI. In patients who achieved a complete response (CR), defined as resolution of contrast-enhancing lesions on follow-up MR imaging and, if indicated, by CSF cytologic analysis (if CSF cytology was positive for malignant cells at the time of diagnostic staging), to induction chemotherapy, 2–3 additional cycles of methotrexate (3– 8 g/m2) were administered every 14 –21 days as consolidation therapy. All patients with PCNSL included in this study underwent restaging with follow-up contrast-enhanced MR imaging within 5 cycles of methotrexate chemotherapy.[5]

Results

Discussion

Conclusion