Doolittle, Nancy D.

Abstract Background: Isolated brain parenchyma relapse as initial site of relapse is a rare complication of NHL and carries a poor prognosis. Few large series focus on treatment characteristics and outcomes of isolated brain parenchyma relapse of NHL. Methods: The IPCG conducted a retrospective review of patient and treatment characteristics and outcomes of this complication. Following initial diagnosis and treatment of NHL (1980–2004), cases with brain parenchyma relapse as initial relapse site, with no evidence of lymphoma elsewhere in the body at the time of brain relapse, were eligible. Cases with brain, spine or leptomeningeal involvement at NHL diagnosis were not eligible. Results: 113 cases were assembled from 13 investigators in 8 countries. Preliminary data summaries are: 94 (83%) cases had diffuse large B-cell NHL, 5 (4%) follicular lymphoma, 3 (3%) Burkitt’s lymphoma, other NHL subtypes (11) . Median age at NHL diagnosis was 61yrs (16–85 yrs). 55% were male. Median ECOG at NHL diagnosis was 1. Median time from NHL diagnosis to isolated brain relapse was 1.8 yrs (3 months–15.9 yrs). 76 (67%) relapsed in brain less than 3 yrs after NHL diagnosis. Symptoms at brain relapse included mental status changes in 37%, gait/balance disturbance (27%), motor/sensory symptoms (23%). Median ECOG at brain relapse was 2. Parenchyma relapse was documented by brain imaging plus biopsy in 54 (48%), or imaging without biopsy in 58 (52%); not reported (1). 53 (48%) cases had one brain lesion; 56 (50%) had two or more lesions; not reported (4). Site of relapse was cerebral hemispheres in 53 (48%) cases, deep brain structures (brain stem/cerebellum) in 30 (27%), cerebral hemispheres and deep brain structures in 23 (21%); not reported (7). At brain relapse, CSF was positive in 11 (10%) cases, negative in 56 (50%); not reported (46[40%]). Treatment for brain relapse was chemotherapy alone in 52 (46%) cases, WBRT alone in 34 (30%), chemotherapy followed by RT in 26 (23%), and brain surgery alone (1). 78 (69%) cases are deceased. Median survival from brain parenchyma relapse to death was 1.6 yrs (95% CI: 11 months–2.6 yrs). Effect of treatment type at brain relapse on survival, will be reported. Brain lymphoma was the cause of death in 49 (63%) cases; CNS toxicity was the cause in 6 (8%) cases. Conclusion: Though a rare relapse site, prospective studies are needed to improve understanding and outcomes of isolated brain parenchyma relapse of NHL.

Abstract Purpose: To describe the demographic and clinical features and outcomes for children and adolescents with primary CNS lymphoma (PCNSL). Experimental Design: A retrospective series of children and adolescents with PCNSL was assembled from 10 cancer centers in 3 countries. Results: Twenty-nine patients with a median age of 14 years were identified. Sixteen (55%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or greater. Frontline therapy consisted of chemotherapy only in 20 patients (69%), while 9 (31%) had chemotherapy plus cranial radiotherapy. Most patients received methotrexate (MTX)-based regimens. Overall response rate was 86% (complete remission 69%, partial remission 17%). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 61% and 86%, respectively; the 3-year OS was 82%. Univariate analyses were conducted for age (≤14 vs. >14 years), PS (0 or 1 vs. >1), deep brain lesions, MTX dose, primary treatment with chemotherapy alone, intrathecal chemotherapy, and high-dose therapy. Primary treatment with chemotherapy alone was associated with better overall response rates with an odds ratio (OR) of 0.125 (P = 0.02). There was a marginally significant relationship between higher doses of MTX and response (OR = 1.5, P = 0.06). ECOG-PS of 0 to 1 was the only factor associated with better outcome with hazard ratios of 0.136 (P = 0.017) and 0.073 (P = 0.033) for PFS and OS, respectively. Conclusion: This is the largest series collected of pediatric PCNSL. The outcome of children and adolescents seems to be better than in adults. PS of 0 to 1 is associated with better survival. Clin Cancer Res; 17(2); 346–52. ©2011 AACR.

Abstract Isolated central nervous system (CNS) relapse involving the brain parenchyma is a rare complication of systemic non-Hodgkin lymphoma. We retrospectively analyzed patient characteristics, management, and outcomes of this complication. After complete response to initial non-Hodgkin lymphoma treatment, patients with isolated CNS relapse with the brain parenchyma as initial relapse site were eligible. Patients with isolated CNS relapse involving only the cerebrospinal fluid were not eligible. Information on 113 patients was assembled from 13 investigators; 94 (83%) had diffuse large B-cell lymphoma. Median time to brain relapse was 1.8 years (range, 0.25-15.9 years). Brain relapse was identified by neuroimaging in all patients; in 54 (48%), diagnostic brain tumor specimen was obtained. Median overall survival from date of brain relapse was 1.6 years (95% confidence interval, 0.9-2.6 years); 26 (23%) have survived 3 years or more. Median time to progression was 1.0 year (95% confidence interval, 0.7-1.7 years). Age less than 60 years (P = .006) at relapse and methotrexate use (P = .008) as front-line treatment for brain relapse were significantly associated with longer survival in a multivariate model. Our results suggest systemic methotrexate is the optimal treatment for isolated CNS relapse involving the brain parenchyma. Long-term survival is possible in some patients.