Efficacy of the Nordic and the MSKCC chemotherapy protocols on the overall and progression-free survival in intracranial PCNSL.

BACKGROUND: To compare the Nordic and the Memorial Sloan-Kettering Cancer Center (MSKCC) chemotherapy protocols for Overall Survival (OS) and Progression-Free Survival (PFS) for intracranial primary CNS lymphoma (PCNSL). METHODS: A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003-2014). RESULTS: Overall, 79 patients with PCNSL were identified, of whom 57 received chemotherapy. MSKCC with Rituximab (RTX) was used in 18 patients (32%) who had median OS of 46.3 months [9.8-131.9] and median PFS of 34.6 months [6.4-131.9]. The Nordic protocol was used in 14 patients (25%) who had median OS of 30.9 months [2.7-106.3] and PFS of 14.3 months [0.0-106.3]. The MSKCC was used without RTX in 25 patients (44%) who had OS of 15.2 months [0.7-136.5] and PFS of 12.0 months [0.0-117.0]. MSKCC with RTX had a significantly longer median OS (p < 0.05) compared to the other regimens in univariate analysis. In multivariate analysis, the only prognostic factor for OS and PFS of significance was deep brain involvement (p < 0.005). CONCLUSIONS: In univariate analysis, the MSKCC with RTX achieved significantly longer median OS compared to the Nordic protocol. However, in multivariate analysis, the only prognostic factor for survival of statistical significance was deep brain involvement.

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.

The role of surgery in intracranial PCNSL.

This aimed to evaluate the effect of surgery for overall survival (OS) and progression-free survival (PFS) in intracranial primary CNS lymphoma (PCNSL) of all patients diagnosed at a single center. A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003-2014). Seventy-nine patients with intracranial PCNSL were identified. Deep brain involvement was shown in 63 patients. Thirty-two patients underwent craniotomy with resection, while all other patients had a biopsy. Fifty-seven patients were given chemotherapy: 18 were treated with the MSKCC (Memorial Sloan-Kettering Cancer Center) with rituximab, 21 with the MSKCC without rituximab, and 14 within a Nordic prospective phase II protocol. Forty-four patients achieved complete response (CR) and had OS of 46.3 months. Patients who underwent resection had a median OS of 28.6 versus 11.7 months for those who had a biopsy performed. Resection showed an insignificant prolongation of OS. Multivariate analysis confirmed statistical significance of deep brain involvement only (p < 0.005). Neither chemotherapy regimen, Karnofsky Performance Status (KPS), type of surgery, nor patient age was significant factors for OS or PFS. Resective surgery played no role in significantly improving either OS or PFS and therefore it is not recommended as treatment for PCNSL.

Evaluation of Memorial Sloan-Kettering Cancer Center and International Extranodal Lymphoma Study Group prognostic scoring systems to predict Overall Survival in intracranial Primary CNS lymphoma.

Objectives: To evaluate the validity of Memorial Sloan-Kettering Cancer Center (MSKCC) and International Extranodal Lymphoma Study Group (IELSG) prognostic scoring systems for Overall Survival (OS) in intracranial Primary CNS lymphoma (PCNSL) of all patients diagnosed at a single center. Material and Methods: Pretreatment clinical factors including tumor characteristics and histology, treatment, and survival of PCNSL patients with diagnostic biopsies over a 12-year period (2003-2014) were retrieved from a prospective database at Oslo University Hospital. Results: Seventy-nine patients with intracranial PCNSL were identified. The female:male ratio was 1:1.63 and the median age was 65.3 years [range 18.9-80.7]. Involvement of deep brain structures was shown in 63 patients. Six patients were MSKCC risk group 1, 35 patients were in risk group 2, and 38 patients were in risk group 3. International Extranodal Lymphoma Study Group scores were <2 in 17 patients (22%). After a median follow-up of 70.5 months, 55 patients were dead. Median OS was 16.4 months [range 0.2-157.7]. Age, sLDH by recursive partitioning analysis (RPA), Eastern Cooperative Oncology Group score (ECOG), lesion size, involvement of deep brain structures, IELSG score, and MSKCC score were significant factors for OS in univariate analysis. Multivariate analysis confirmed the significance of age (p < .05), sLDH by RPA (p < .005), ECOG (p < .05), and deep brain structure involvement (p < .05) for OS. The six-tiered IELSG scores had to be dichotomized according to RPA analysis into <2 and ≥2 in order to have prognostic value. In contrast, when using the three-tiered MSKCC, three distinct risk groups were identified. Conclusions: Our study failed to verify the IELSG, but validated the use of MSKCC for prognostication of OS in intracranial PCNSL.