510 research outputs found
Primary CNS Lymphomas: Challenges in Diagnosis and Monitoring
Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm that can involve brain, eye, leptomeninges, and rarely spinal cord. PCNSL lesions most typically enhance homogeneously on T1-weighted magnetic resonance imaging (MRI) and appear T2-hypointense, but high variability in MRI features is commonly encountered. Neurological symptoms and MRI findings may mimic high grade gliomas (HGGs), tumefactive demyelinating lesions (TDLs), or infectious and granulomatous diseases. Advanced MRI techniques (MR diffusion, spectroscopy, and perfusion) and metabolic imaging, such as Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) or amino acid PET (usually employing methionine), may be useful in distinguishing these different entities and monitoring the disease course. Moreover, emerging data suggest a role for cerebrospinal fluid (CSF) markers in predicting prognosis and response to treatments. In this review, we will address the challenges in PCNSL diagnosis, assessment of response to treatments, and evaluation of potential neurotoxicity related to chemotherapy and radiotherapy
Lower grade gliomas: relationships between metabolic and structural imaging with grading and molecular factors
Background: Positron emission tomography (PET) is a valuable tool for the characterization of brain tumors in vivo. However, few studies have investigated the correlation between carbon-11-methionine (11C-METH) PET metrics and the clinical, radiological, histological, and molecular features of patients affected by lower grade gliomas (LGGs). The present observational study evaluated the relationships between 11C-METH PET metrics and structural magnetic resonance imaging (MRI) findings with the histomolecular biomarkers in patients with LGGs who were candidates for surgery. Methods: We enrolled 96 patients with pathologically proven LGG (51 men, 45 women; age 44.1 \ub1 13.7 years; 45 with grade II, 51 with grade III), who had been referred from March 2012 to January 2015 for tumor resection and had undergone preoperative 11C-METH PET. The semiquantitative metrics for 11C-METH PET included maximum standardized uptake value (SUVmax), SUV ratio to normal brain, and metabolic tumor burden (MTB). The PET semiquantitative metrics were analyzed and compared with the MRI features, histological diagnosis, isocitrate dehydrogenase-1/2 status, and 1p/19q codeletion. Results: Histological grade was associated with SUVmax (P = 0.002), SUV ratio (P = 0.011), and MTB (P = 0.001), with grade III lesions showing higher values. Among the nonenhancing lesions on MRI, SUVmax (P = 0.001), SUV ratio (P = 0.003) and MTB (P < 0.001) were significantly different statistically for grade II versus grade III. The MRI lesion volume correlated poorly with MTB (r 2 = 0.13). The SUVmax and SUV ratio were greater (P < 0.05) in isocitrate dehydrogenase-1/2 wild-type lesions, and the SUV ratio was associated with the presence of the 1p19q codeletion. Conclusions: The 11C-METH PET metrics correlated significantly with histological grade and the molecular profile. Semiquantitative PET metrics can improve the preoperative evaluation of LGGs and thus support clinical decision-making
MGMT promoter methylation in plasma of glioma patients receiving temozolomide.
Promoter methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene plays a role in cellular response to alkylating agents. In the present study aimed to: (i) evaluate the concordance between MGMT promoter methylation status in tumor tissue and plasma; (ii) monitor MGMT promoter methylation status in plasma taken before and during temozolomide treatment; (iii) explore the value of MGMT promoter methylation status in plasma as a prognostic/predictive biomarker in glioma patients. We enrolled 58 patients with histologically confirmed glioma at different grades of malignancy. All patients underwent surgical resection and temozolomide treatment. Paraffin-embedded tumor tissue was available for 48 patients. Blood samples were collected from all patients before temozolomide treatment (baseline) and at each MRI examination for a 12-month period. MGMT promoter methylation status was assessed in both sample types by real time PCR with a specific probe. The frequency of MGMT promoter methylation was 60.4 % in tumor tissue and 41.38 % in plasma. MGMT promoter methylation status was concordant in the two sample types (Kappa = 0.75, 95 % confidence interval (CI) 0.57-0.93; p value <0.001). Overall and progression-free survival were longer in patients with methylated MGMT promoter. Mortality was higher in patients with unmethylated MGMT promoter, whether in tumor tissue [hazard ratio (HR) 2.21; 95 % CI 0.99-4.95] or plasma (HR 2.19; 95 % CI 1.02-4.68). Progression-free survival was shorter in patients with unmethylated MGMT promoter, whether in tissue (HR 2.30; 95 % CI 1.19-4.45) or plasma (HR 1.77; 95 % CI 0.95-3.30). The cumulative incidence of unmethylated MGMT promoter in plasma at baseline was 58 %, and reached virtually 100 % at 12 months. In conclusion MGMT promoter methylation status in tumor tissue and plasma was highly concordant, and both were associated with longer survival, supporting the role of the detection of methylated MGMT promoter in predicting treatment response. However we suggest caution in using plasma as a surrogate of tumor tissue due to possible false-negative results
- …