Neurooncology

Resumen La tomografía por emisión de positrones con metionina carbono 11 (11 C-metionina PET/TC) se utiliza en la evaluación de los tumores primarios del sistema nervioso central. Describimos nuestra expe-riencia sobre los primeros 4 pacientes con tumores de la serie glial estudiados con 11 C-metionina PET/TC. Este es un estudio descriptivo, observacional y prospectivo. Se presentan 4 pacientes entre 38-50 años de edad con diagnóstico de gliomas (clasificación de la OMS). A todos se les realizó RM y 11 C-metionina PET/TC para evaluar actividad tumoral y diferenciar progresión tumoral de pseudoprogresión. Caso 1, gliomatosis cerebri grado II posradioterapia. Caso 2, glioblastoma grado IV postratamiento RT + temozolomida. Caso 3, oligodendroglioma grado II posradioterapia en 1993. Caso 4, oligoastrocitoma anaplásico grado III postratamiento RT + temozolo-mida. El patrón de captación de la 11 C-metionina comparativamente con la RM, demostró progresión tumoral en los casos 1, 3 y 4; en el caso 2 mostró captación aunque el diagnóstico final fue pseudoprogresión. A diferencia del PET con 18 fluordeoxiglucosa, la captación de 11 C-metionina en el tejido cerebral normal y en la pseudopro-gresión es baja, y los gliomas se visualizan como áreas metabólicamente activas. En los casos presentados, el 11 C-metionina PET/TC proveyó información valiosa sobre el comportamiento y extensión de la lesión, aunque en uno de los casos presentados no diferenció progresión tumoral de pseudoprogresión. El 11 C-metionina PET/ TC sería una herramienta útil en el estudio y seguimiento de los pacientes con gliomas. Abstract Utility of 11 C-methionine PET/CT in neuro-oncology. Positron emission tomography (PET) with 11 C-methionine (11 C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11 C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11 C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11 C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18 fluordeoxiglucose PET/TC, 11 C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11 C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11 C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

We evaluated the potential effects of ATO in different pediatric SHH-MB cell lines (ONS-76: TP53-wild type; DAOY and UW402: TP53-mutated). MB cell lines molecular subgroup was confirmed and TP53 mutations were validated. Cell viability, clonogenicity and apoptosis were evaluated after ATO treatment at different concentrations (1-16 µM) alone or combined with irradiation doses (0.5, 1, 2 and 4 Gy). Rad51 and Ku86 proteins were evaluated by WB. ATO treatment reduced cell viability for all SHH-MB cell lines. Significant decrease of clonogenic capacity and higher apoptosis rates were also observed after ATO exposure, being cell death more pronounced (>70%) for the SHH-MB TP53-mutated. Combined treatment of ATO with irradiation also reduced colonies formation in UW402 tumor cells, which was independent of DNA damage repair proteins Rad51 and Ku86. In silico analyses suggested that a set of genes from cell cycle and p53 pathways are differentially expressed in SHH tumor subtypes, suggesting that cell lines may respond to therapies according to the gene expression profiles. Herein, we showed ATO cytotoxicity in pediatric SHH cell lines, with marked radiosensitizing effect for the MB-SHH TP53-mutated cells. These results highlight the potential of ATO, alone or in combination with radiotherapy, supporting further clinical investigations. Medulloblastoma (MB) is the most common malignant brain tumor in children, corresponding to approximately 20% of all brain tumors in patients less than 15 years of age. MB is responsible for significant morbidity and mortality rates 1. Recently, twelve distinct subgroups allocated to four main molecular classes (SHH, WNT, Group 3 and Group 4) have been recognized for MB: WNT-alpha and beta; SHH-alpha, beta, gamma and delta; Group 3-alpha, beta and gamma; and Group 4-alpha, beta, and gamma 2. Considering the clinical significance of the MB molecular classification, new therapies that contemplate the genetic aspects of the disease are required 3. The majority of SHH-MB cases presents somatic mutation in one or more genes of the Sonic Hedgehog (SHH) pathway (i.e., PTCH1, SUFU, or SMO), contributing to its constitutive activation. SHH signaling is essential for embryonic development, as well as it can lead to a tumor arising when aberrantly activated 4. The SHH-MB subgroup prognosis in children is mostly favorable, but the clinical outcome varies within this subgroup. SHH-MB alpha cases are rarely observed in infants and carry the poorest prognosis, which is associated with MYCN and GLI (glioma-associated oncogene homolog) amplification, and higher TP53 mutational burden. In contrast, SHH-MB beta and gamma subtypes affect mainly infants, being one-third of the SHH-MB beta cases meta-static at presentation with frequent focal PTEN deletions. The SHH-MB gamma is strongly related to MB with extensive nodularity (MBEN) histology, in general, presents wild type TP53, and excellent prognosis 2. Lastly,

Introduction: High-grade gliomas (HGG), including Glioblastoma multiforme (GBM), account for the majority of primary brain tumors. Nevertheless, prognostic and diagnostic biomarkers are quite limited for HGG. The objective of this study was to investigate the prognostic value of sRANKL and sTREM2 levels in HGG patients. Methods: Twelve consecutive patients with HGG, 14 patients with nonglial tumors (non-GT) and 20 age and gender-matched healthy controls were recruited. Overall survival duration of the patients was recorded. Pre-operative serum levels of sRANKL and sTREM2 were measured by ELISA. Tumors of HGG patients were analyzed by immunohistochemical staining for p53 and Ki67 and percentage scores were calculated. Results: Patients with HGG and non-GT showed lower serum sRANKL and sTREM2 levels than healthy individuals. Levels of sRANKL were inversely correlated with the overall survival of patients (p=0.002, R=-0.787), while sTREM2 levels were inversely correlated with p53 score (p=0.018, R=-0.666) but not survival. Conclusion: Brain tumor patients show suppressed levels of glial activity biomarkers in the peripheral circulation. Serum sRANKL levels may serve as a potential prognostic biomarker for HGG.

ABSTRACT
Objectives: The objective of our study is to evaluate the impact of neurosurgical operative treatment on the performance status assessed by the Karnofsky Performance Scale (KPS) in patients with HGG for the first, for the second intervention and for the different age groups. Methods: A group of 425 patients operated consecutively for high-grade gliomas were included in this study. The performance status was evaluated preoperatively and 15 days postoperatively with the KPS. Analyses for the different histological grade, tumor locations and age groups divided by decades have been made.
Results: The initial, preoperative KPS score for patients with grade III tumor was 77.65 and for grade IV – 71.35. Following the first operation mean KPS has a statistically significant increase and reaches 82.24 and 78.41, respectively. The improvement of the performance status after the first operation was significant for all relevant age groups, including the sixth, seventh and eighth decades. Although the obtained mean KPS scores after the second operation did not show improvement there was also no clear evidence for worsening in this group of patients (n = 100) and the negative results obtained were not statistically significant.
Conclusion: According to our study, the first operation has a beneficial effect on the perfor- mance status in patients with HGG. The results for the second operation are more ambiguous, but there is no clear evidence for worsening of the KPS score after the second intervention. These results were relevant for all age groups, so we may expect amelioration in the perfor- mance status even in older patients.