ABSTRACT
INTRODUCTION: To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. METHODS: Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. RESULTS: Median age was 64 years (range: 19-84; 33% ≥ 70 years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24-81). Diagnostic delay > 47 days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age ≥ 65 years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. CONCLUSIONS: Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70 years.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/mortality , Chemoradiotherapy/mortality , Cranial Irradiation/mortality , Delayed Diagnosis/statistics & numerical data , Immunocompetence , Lymphoma, Non-Hodgkin/mortality , Adult , Aged , Aged, 80 and over , Carmustine/administration & dosage , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/immunology , Central Nervous System Neoplasms/therapy , Cytarabine/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/therapy , Male , Methotrexate/administration & dosage , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young AdultSubject(s)
Anticonvulsants/administration & dosage , Drug Therapy, Combination , Epilepsy/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (ICH). Familial forms of CAA are because of mutations in the gene encoding the beta-amyloid precursor protein (APP) and duplications of this gene can cause early-onset Alzheimer's disease associated with CAA. However, the contribution of APP genetic variants in the development of sporadic CAA remains unknown. METHODS: The presence of genetic variants in the APP was examined in 78 patients with CAA-related ICH by sequencing exons 16 and 17 coding the ß-amyloid protein and analyzing the presence of possible duplications of APP by microsatellite analysis and quantitative PCR. RESULTS: We did not identify any pathogenic mutation or chromosomal duplication of APP. CONCLUSIONS: Our results suggest that APP genetic variants, point mutations and locus duplication, are not a common cause of CAA-related ICH in the Spanish population.