Is deep brain involvement in intracranial primary central nervous system lymphoma of importance for penetration of chemotherapeutic agents?

PURPOSE

The purposes of this study are to study the impact of deep brain involvement on overall survival (OS) and progression-free survival (PFS) in intracranial primary CNS lymphoma (PCNSL), and to explore possible mechanisms for this impact using advanced MRI techniques.

METHODS

Seventy-nine patients with histologically verified PCNSL were identified from a prospective clinical database of patients treated at Oslo University Hospital between 2003 and 2014. Patients were treated per standard chemotherapeutic regimens (N = 57) or no chemotherapy (N = 22). Anatomical MRIs were available in all patients to assess tumor load and location based on contrast agent enhancement visible on T1-weighted images. Diffusion MRIs were available in 33 (42%) patients and perfusion MRI in 13 (16%) patients that received active treatment.

RESULTS

Across all patients, OS and PFS were 16.4 and 9.8 months, respectively. In multivariate analysis, MRI-based deep brain involvement (80%) was the only negative significant factor of OS (OR = 14.2; P < 0.005). While a reduced Karnofsky performance status was associated with deep brain involvement (P < 0.05), neither chemotherapy regimen, neurologic status, nor patient age were independent significant factors for OS or PFS in this setting. Compared to other tumors and healthy tissue levels, MRI perfusion showed more pathologic hemodynamic flow signatures in tumors with deep brain involvement.

CONCLUSION

In intracranial PCNSL, the only significant prognostic factor for OS and PFS in multivariate analysis was age and deep brain involvement. While contingent on a small study sample, we hypothesize this may in part be explained by regional differences in vascular supply and delivery from a dysfunctional perfusion signature.