Clinical characterization of adult medulloblastoma and the effect of first-line therapies on outcome; The MD Anderson Cancer Center experience.

BACKGROUND: Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on first-line treatments. METHODS: Two hundred adults with MB seen at a single institution from January 1978 to April 2017 were identified and followed for a median of 8.4 y (7.1, 10.3). RESULTS: Patient's median age at diagnosis was 29 y (18, 63). One hundred eleven (55.5%) were standard-risk, 59 (29.5%) were high-risk, and 30 (15.0%) were indeterminate. Most received post-operative radiation (RT) (184 [92.0%]), and 105 (52.5%) received first-line chemotherapy. Median overall survival (OS) was 8.8 y (7.2, 12.2) and median progression-free survival (PFS) was 6.6 y (4.9, 11.2). High-risk patients had inferior OS (Hazard ratio [HR] = 2.5 [1.5, 4.2], P = .0006) and PFS (HR = 2.3 [1.3, 3.9], P = .002) compared to standard-risk patients. Age, sex, and metastatic disease were not associated with survival. After adjusting for risk status, those who received RT plus adjuvant chemotherapy had superior PFS compared to RT plus neoadjuvant chemotherapy [HR = 0.46 (0.22, 0.95), P = .0357]. Within a subgroup for whom detailed clinical data were available, those who received RT plus adjuvant chemotherapy had improved PFS compared to RT only [HR = 0.24 (0.074-0.76), P = .016]. The substitution of cisplatin for carboplatin and the elimination of vincristine did not negatively affect outcomes. CONCLUSION: This is the largest single-institution retrospective study of adult MB to our knowledge and identifies standard-risk status, first-line RT and adjuvant chemotherapy as factors associated with improved outcomes.

Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood.

ABSTRACT: Brain atrophy has been observed in perinatally HIV-infected patients (PHIV) despite initiation on combined antiretroviral treatment (cART), but neuroimaging studies are limited. We aimed to evaluate cortical thickness (CT) and subcortical gray matter (GM) volumes of PHIV youths with stable immunovirological situation and with a normal daily performance.A prospective cross-sectional study was conducted. A total of 25 PHIV patients on cART and 25 HIV-negative (HIV-) controls matched by age, sex, level of education, and socioeconomic status underwent a magnetic resonance imaging scan. CAT12 toolbox was used to extract CT values from T1w images using parcellations from Desikan-Killiany atlas (DK40). To measure regional brain volumes, native segmented images were parceled in regions of interest according to the Neuromorphometrics Atlas. Neuropsychological assessment and psychopathological symptoms were documented.Fifty participants were included (60% females, median age 20 years [interquartile range, IQR 19-23], 64% Whites). No differences regarding neuropsychological tests or psychopathological symptoms were found between groups (all P > .05). All participants presented an average performance in the Fluid Intelligence (FI) test (PHIV mean: -0.12, HIV- mean: 0.24), When comparing CT, PHIV-infected patients showed thinner cortices compared with their peers in fusiform gyrus (P = .000, P = .009), lateral-orbitofrontal gyrus (P = .006, P = .0024), and right parsobitalis gyrus (P = .047). Regarding subcortical GM volumes, PHIV patients showed lower right amygdala (P = .014) and left putamen (P = .016) volumes when compared with HIV- controls. Within the PHIV group, higher CD4 count was associated with higher volumes in right putamen (B = 0.00000038, P = .045). Moreover, increased age at cART initiation and lower nadir CD4 count was associated with larger volumes in left accumbens (B = 0.0000046, P = .033; B = -0.00000008, P = .045, respectively).PHIV patients showed thinner cortices of areas in temporal, orbito-frontal and occipital lobes and lower volumes of subcortical GM volumes when compared with the HIV- control group, suggesting cortical and subcortical brain alterations in otherwise neuroasymptomatic patients. Nevertheless, larger and longitudinal studies are required to determine the impact of HIV on brain structure in PHIV patients and to further identify risk and protective factors that could be implicated.