Late-onset vascular complications of radiotherapy for primary brain tumors: a case-control and cross-sectional analysis.

PURPOSE: Radiotherapy (RT) is a recognized risk factor for cerebrovascular (CV) disease in children and in adults with head and neck cancer. We aimed to investigate whether cerebral RT increases the risk of CV disease in adults with primary brain tumors (PBT). METHODS: We retrospectively identified adults with a supratentorial PBT diagnosed between 1975 and 2006 and with at least 10 years follow-up after treatment. We analyzed demographic, clinical, and radiological features with special attention to CV events. We also described CV events, vascular risk factors, and intracranial artery modifications in a cross-sectional study of irradiated patients alive at the time of the study. RESULTS: A total of 116 patients, treated with RT (exposed group), and 85 non-irradiated patients (unexposed group) were enrolled. Stroke was more frequent in irradiated PBT patients than in the unexposed group (42/116 (36%) vs 7/85 (8%); p < 0.001), with higher prevalence of both ischemic (27/116 (23%) vs 6/85 (7%); p = 0.004) and hemorrhagic (12/116 (10%) vs 1/85 (1%); p = 0.02) stroke. In the irradiated group, patients with tumors near the Willis Polygon were more likely to experience stroke (p < 0.016). Fourty-four alive irradiated patients were included in the cross-sectional study. In this subgroup, intracranial arterial stenosis was more prevalent (11/45, 24%) compared to general population (9%). CONCLUSIONS: Stroke prevalence is increased in long-surviving PBT patients treated with cranial RT. IMPLICATIONS FOR CANCER SURVIVORS: CV events are frequent in long survivors of PBT treated with cerebral RT. We propose a check list to guide management of late CV complications in adults treated with RT for PBT.

Pretreatment Hemoglobin as an Independent Prognostic Factor in Primary Central Nervous System Lymphomas.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma. Despite established clinical prognostic scoring such as that of the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Extranodal Lymphoma Study Group, outcome prediction needs to be improved. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in PCNSL. We sought to assess the association between hematological parameters and overall survival (OS) in patients with PCNSL. METHODS: Pretreatment blood tests were analyzed in patients with newly diagnosed PCNSL (n = 182), and we divided the analysis into two cohorts (A and B, both n = 91). OS was evaluated using the Cox proportional hazards models and log-rank test. Furthermore, the accuracy of the different multivariate models was assessed by Harrell's concordance index (C-index). RESULTS: Using prechemotherapy blood tests, anemia was found in 38 patients (41.8%) in cohort A and 34 patients (37.4%) in cohort B. In univariate analysis, anemia (<12 g/dL in women and <13 g/dL in men) was significantly associated with OS. None of the other blood tests parameters (neutrophils, lymphocyte, or platelets counts) or their ratios (neutrophil-to-lymphocyte ratio and neutrophil-to-platelets ratio) were associated with OS. In multivariate analysis, after adjusting by MSKCC score, anemia remained an independent prognostic factor. Interestingly, the prediction accuracy of OS using Harrell's C-index was similar using anemia or MSKCC (mean C-index, 0.6) and was increased to 0.67 when combining anemia and MSKCC. CONCLUSION: The presence of anemia was associated with poor prognosis in both cohorts of PCNSL. Validation of these results and biologic role of hemoglobin levels in PCNSL requires further investigation. IMPLICATIONS FOR PRACTICE: The prediction of the outcome of primary central nervous system lymphoma (PCNSL) using the most frequently used scores (i.e., Memorial Sloan Kettering Cancer Center [MSKCC] or International Extranodal Lymphoma Study Group) needs to be improved. We analyzed a large cohort of PCNSL to dissect the potential prognostic value of blood tests in this rare entity. We found anemia as an independent predictor for overall survival in PCNSL. Interestingly, the accuracy to predict PCNSL outcome was improved using hemoglobin level. This improvement was additional to the currently used clinical score (i.e., MSKCC). Finally, none of the other blood tests parameters or their ratios had a prognostic impact in this study.

Brain volumetric analysis and cortical thickness in adults with saccadic intrusions (ocular flutter or opsoclonus-myoclonus syndrome).

OBJECTIVES: Ocular flutter (OF) and opsoclonus are considered a continuum with a similar pathogenesis. Due to the rarity of this disease in the adult population, little is known about the brain morphological changes in the chronic phase of the disease. PATIENTS AND METHODS: Six magnetic resonance imaging from adults with previous history of OF/Opsoclonus and 12 healthy patients (paired by age and sex) were analyzed in order to identify the long term cortical thickness pattern in this rare disease by using Freesurfer. RESULTS: Patients with OF/Opsoclonus showed reduced cerebellum cortical volume with a subsequent diminution in total cerebellar volume. White mater cerebellum volume was not modified. In addition, we have also identified a significant supratentorial gray matter volume decrease in OF/Opsoclonus patients, involving both the cortical and the subcortical gray matter. CONCLUSIONS: OF/Opsoclonus in adults may be associated with cortical and subcortical gray matter atrophy, as well as decreased cerebellar cortical volume. Further larger prospective studies are necessary to confirm these results.

Infections of the Central Nervous System after Unrelated Donor Umbilical Cord Blood Transplantation or Human Leukocyte Antigen-Matched Sibling Transplantation.

We analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (CNS) infections in consecutive patients with receiving umbilical cord blood transplantation (UCBT) (n = 343) or HLA-matched sibling donor stem cell transplantation (MST) (n = 366). Thirty-four CNS infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). The cumulative incidence (CI) risk of developing a CNS infection was .6% at day +30, 2.3% at day +90, and 4.9% at 5 years. The 5-year CI of CNS infection was 8.2% after UCBT and 1.7% after MST (P < .001). The causative micro-organisms of CNS infections were fungi (35%), virus (32%), Toxoplasma spp. (12%), and bacteria (12%). Fungal infections occurred in 11 patients after UCBT and 1 after MST and were due to Aspergillus spp. (n = 8), Cryptococcus neoformans (n = 2), Scedosporium prolificans (n = 1), and Mucor (n = 1). Except for 1 patient, all died from CNS fungal infection. Viral infections occurred in 9 patients after UCBT and 1 after MST and were due to human herpes virus 6 (n = 7), cytomegalovirus (n = 2), and varicella zoster virus (n = 1). CNS toxoplasmosis was diagnosed in 3 patients after UCBT and 1 after MST. Other pathogens were Staphylococcus spp, Nocardia spp, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Twenty of the 34 patients (59%) died from the CNS infection. In multivariable analysis, UCBT and disease stage beyond first complete remission were independently associated with the risk of developing CNS infections. The 5-year overall survival was 19% in patients who developed a CNS and 39% for those who did not (P = .006). In conclusion, our study showed that CNS infections are a significant clinical problem after stem cell transplantation associated with poor survival. They were more frequent after UCBT compared to MST.