Hypovascular Cellular Tumor in Primary Central Nervous System Lymphoma is Associated with Treatment Resistance: Tumor Habitat Analysis Using Physiologic MRI

Abstract

Abstract Background and purpose: The microenvironment of lymphomas is known to be highly variable and closely associated with treatment resistance and survival. We tried to develop a physiologic MR imaging-based spatial habitat analysis to identify regions associated with treatment resistance to facilitate the prediction of tumor response after initial chemotherapy in patients with primary central nervous system lymphoma.

Materials and methods: Eighty-one patients with pathologically confirmed primary central nervous system lymphoma were enrolled. Pretreatment physiologic MR imaging was performed, and K-means clustering was used to separate voxels into 3 spatial habitats according to ADC and CBV values. Associations of spatial habitats and clinical and conventional imaging predictors with time to progression were analyzed using Cox proportional hazards modeling. The performance of statistically significant predictors for time to progression was assessed using the concordance probability index.

Results: The 3 spatial habitats of hypervascular cellular tumor, hypovascular cellular tumor, and hypovascular hypocellular tumor were identified. A large hypovascular cellular habitat was most significantly associated with short time to progression (hazard ratio, 2.83; P = . 017). The presence of an atypical finding (hazard ratio, 4.41; P = . 016), high performance score (hazard ratio, 5.82; P = . 04), and high serum lactate dehydrogenase level (hazard ratio, 1.01; P = .013) was significantly associated with time to progression. A predictive model constructed using the habitat score and other imaging parameters showed a concordance probability index for prediction of time to progression of 0.70 (95% CI, 0.54-0.87).

Conclusions: A hypovascular cellular tumor habitat is associated with treatment resistance in primary central nervous system lymphoma, and its assessment may refine prechemotherapy imaging-based response prediction for patients with primary central nervous system lymphoma.