Andrea Cappellano

Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study.

The treatment of central nervous system (CNS) germ cell tumors (GCT) remains controversial. The purpose of this study was to demonstrate efficacy of a chemotherapy only strategy, with less morbidity, when compared to regimens with irradiation.

Pediatric central nervous system tumors: a single-center experience from 1989 to 2009.

The objective of this study was to determine the epidemiology of primary tumors of the central nervous system (CNS) in pediatric patients from a Brazilian oncology institute. We retrospectively analyzed 741 charts (415 males and 326 females) of patients under 21 years of age who were diagnosed with a CNS tumor. The analysis included patients from 1989 to 2009 and was performed using the World Health Organization criteria. We evaluated the distribution of age, sex, topography, clinical symptoms, symptom intervals, and classification of the tumors. Patients with clinical/radiologic diagnoses were included. Seven hundred forty-one patients with tumors in the CNS were reviewed, and 83% of the patients presented a histologic diagnosis. Males (56%) were more prevalent than females. In children under the age of 1 year, the supratentorial compartment was the predominant region involved (62.0%). Astrocytoma was the most frequent tumor type (37.0%), followed by medulloblastoma (13.6%), craniopharyngioma (10.5%), and ependymoma (6.8%). Headaches were the most common symptom, and the symptom intervals varied from 1 to 5010 days. Approximately 4% of the patients had associated genetic syndromes. Although it was not a population study and selection bias may have occurred, this study supplies important epidemiologic data from an emerging country in which population studies are rare.

PRAME gene expression profile in medulloblastoma

Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

Diffuse intrinsic brainstem tumor in an infant: a case of therapeutic efficacy with vinorelbine.

Brainstem gliomas constitute 10% to 20% of all pediatric tumors of the central nervous system, and diffusely infiltrative brainstem gliomas are the most common brainstem tumors associated with a poor prognosis. A small subset of these tumors is benign, showing low-grade features on histology. The role of chemotherapy in the management of these tumors is ill defined, especially in the neonates. There are anecdotal reports of spontaneous remission, but the natural history of these tumors does not support a wait-and-see approach. Thus, we report a successful experience of chemotherapy in a 4-month-old girl with a diffuse brainstem fibrillary astrocytoma, treated with vinorelbine (30 mg/m2/d on days 0, 8, and 22), a vinca alkaloid that has shown activity against glioma. Our experience suggests that vinorelbine may be effective in pediatric low-grade gliomas as this patient showed significant clinical improvement over a short period of time.

Relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated without irradiation: Findings from the Third International Central Nervous System (CNS) Germ Cell Tumor (GCT) Study

To evaluate patterns of relapse and outcome in patients newly diagnosed with CNS Mixed Malignant GCT (MMGCT) treated initially with chemotherapy alone.

Medulloblastoma and Drop Metastasis: MRI Evaluation and Optimized Protocol

Cerebrospinal fluid (CSF) seeding, with spinal intradural drop metastasis, is a form of spread encountered more frequently in pediatric patients than in adults, and it is frequently observed in medulloblastoma. Up to one-third of patients with medulloblastoma will eventually disperse through the CSF, in many instances in the spinal canal. Magnetic resonance imaging (MRI) is an accurate modality that can identify the localization and extent of lesions. The purpose of this paper is to review the evaluation of the spinal canal for drop metastasis related to disseminate medulloblastoma and details an optimized protocol for MRI of the spinal canal.

Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology

Background Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. Results We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. Conclusions We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. Methods In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients (n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model.

Childhood Craniopharyngioma: A 22-Year Challenging Follow-Up in a Single Center

Craniopharyngioma is a sellar/suprasellar benign tumor whose aggressiveness may imply in endocrine disturbances (hypothalamic obesity and hormone deficiencies). Fifty-seven patients were evaluated according to clinical characteristics, hypothalamic involvement, type of treatment, anthropometric variables, adiposity indexes (body mass index Z score category at diagnosis and post-treatment, total body fat, visceral adipose tissue, and metabolic syndrome components) and analyzed through multiple regression and logistic models. Patients were stratified according to growth hormone deficiency and recombinant human growth hormone use. Mean ages at diagnosis and at study evaluation were 9.6 and 16.6 years old, respectively. A set of 43/57 (75.4%) patients presented with important hypothalamic involvement, 24/57 (42.1%) received surgical treatment and cranial radiotherapy, and 8/57 (14%) interferon-α exclusively. Fifty-five patients (96.5%) were considered growth hormone deficient, and 26/57 (45.6%) grew despite no recombinant human growth hormone replacement therapy. At diagnosis, 12/57 (21%) patients were obese, and 33/57 (57.9%) at study evaluation, and after 3.2 years (median) post first therapy. There was no influence of height Z score on body mass index Z score. Body mass index Z score at diagnosis positively influenced body mass index Z score, total body fat, waist circumference and the presence of the metabolic syndrome post-treatment. Replacement of recombinant human growth hormone decreased total body fat and visceral adipose tissue. Craniopharyngioma patients worsened body mass index Z score category 3.2 years (median) after first treatment. Body mass index Z score increased due to real weight gain, without height decrease. Replacement of recombinant human growth hormone had beneficial effect on adiposity.