Primary Central Nervous System Lymphoma in a Community Academic Oncology Practice: Aggressive Disease with Suboptimal Outcomes Regardless of the Available Management Options
Authors: Pinnamaneni Ramya , Navaid Musharraf , Liles Darla , Hanson Laura , Juskevicius Ridas 
Published: November 2019

Abstract
Introduction:
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extra-nodal lymphoma which has historically shown to be therapeutically challenging.
Currently, the standard treatment remains to be high dose methotrexate (HD-MTX)-based combination chemotherapy with or without whole-brain radiotherapy. The rarity of this disease has precluded large and randomized controlled trials from taking place.
In this retrospective study performed at our tertiary care academic medical center, we report our experience and characterize the nature of this disease in our patient population in a predominantly rural area of North Carolina.
We demonstrate the reality and challenges of the therapeutic approaches in an attempt to achieve more durable responses and better outcomes with available treatment regimens in our patient population.
Methods:
After approval from our Institutional Review Board, medical records and pathology data base at our institution were reviewed to identify patients diagnosed with PCNSL between the years of 2004 and 2014.
Eleven cases with no radiographic or other evidence of systemic disease who fulfilled the criteria for PCNSL according to the most recent WHO classification were included in the study.
Patients' demographics, clinical presentation, radiographic and pathologic findings and treatment details and outcomes were collected and analyzed.
Results:
The median age at diagnosis was 60. Most patients were Caucasians (90%) with a slight predominance of males (54% males, 45% females).
Clinically, most patients presented with neurologic symtpoms and deficits rather than with 'B' symptoms.
Radiographically, all patients had supratentorial and multifocal involvement mostly with frontotemporal lesions. The lesions were seen crossing the corpus callosum mimicking glioblastoma multiforme in 4 patients.
The pathologic features in all patients were consistent with diffuse large B-cell lymphoma (DLBCL) characterized by a diffuse intraparenchymal growth pattern. At least focal perivascular distribution of tumor cells was present in 3 cases. CD20 expression was present in all cases and 10 of 11 cases were negative for CD10, consistent with non-germinal center (non-GC) phenotype. Most tumors showed a high Ki67 proliferation rate (80-100%).
Six of eleven patients had cytological assessment of the cerebrospinal fluid (CSF) at the time of diagnosis. No patients had lymphoma cells in the CSF indicating lack of leptomeningeal involvement.
A total of 2 patients received induction chemotherapy based on the CALBG 50202 protocol including HD-MTX, Temozolamide and Rituxumab. Of the remaining 9 patients, 4 received HD-MTX alone, 3 received HD-MTX with concomitant intrathecal cytarabine, 1 received HD-MTX plus rituximab and 1 received Pemetrexed alone. A total of 2 patients received radiation therapy (WBRT).
Five patients died of disease with time to death of disease ranging from 1.5 to 8 months. Three patients are alive at months ranging from 8 months to 3.5 years after diagnosis. One patient has been cured of their PCNSL but developed a secondary systemic DLBCL seven years later. The remaining 2 patients were lost to follow up.
We were unable to determine any impact of the individual treatment modalities on the overall survival due to the small number of patients in our study.
Conclusion:
Our patients were predominantly Caucasian with a median age at diagnosis of 60 years. The tumors were exclusively CD20+ DLBCLs with a high Ki67 proliferation rate and a predominantly non-GC phenotype, indicating an aggressive disease pattern. Majority of the patients were unable to complete standard chemotherapy regimens previously described in the literature.
Factors contributing to incomplete therapy included age more than 65 and adverse events from chemotherapy including acute kidney failure and neurotoxicity.
We conclude that although HD-MTX with or without radiation therapy is the current standard treatment, it is not necessarily feasible nor appropriate in all patient populations.
In our population, success was seen in patients who were younger, less than 65 years, in those who received methotrexate doses of 4g/m2 rather than the standard 8g/m2 and those who received Rituximab as part of their regimen.
Larger multicenter retrospective studies may provide better insight into finding more optimal treatment regimens.

Disclosures
No relevant conflicts of interest to declare.