BRAIN TUMORS

By Dr. Veronica Villani

Despite standard multimodality treatment including surgical ablation followed by radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide, the prognosis of malignant gliomas remains unsatisfactory. Median survival in Glioblastoma Multiforme (GBM) patients is of 14.6 months and the average 5-years survival rate is less than 9.8%, with very few cases of long-term survivor, thus justifying the research on novel more effective therapies. The understanding of the molecular mechanisms of Glioma tumors has significantly evolved over the last decade and translational programs based on a large clinicobiological database are required to improve our understanding of GB biology, potentially facilitating the development of personalized and specifically targeted therapies and research applications. Successful biomaterial collection is a key requirement for the application of contemporary methodologies for the validation of candidate prognostic factors, discovery of new biomarkers and clinical implementation of precision medicine (eg, target therapies and immunotherapies).

Recent progress has been made possible by using advanced molecular analysis of brain tissue specimens systematically collected and stored in tissue repositories, including bioinformatics analysis of molecular data and integration with clinical information.

In the last years , the Regina Elena Cancer Institute promoted the Glioma Translatonal Group through multidisciplimnary collaboration between clinicians and researchers.

The primary aim of this collaborative group was to create a joint repository of tumor tissue, blood and CSF samples developing and mantaining a neuroncological biobank.

Collection and storage of biospecimens are offered to all patients undergoing surgery or submitted to neuroncological treatments including those obtained not only at disease onset but also at recurrence. In general, brain tumor patients are followed longitudinally from diagnosis throughout their disease course. An imaging repository is annexed to the clinical data and specimens that include MRI studies following a standardized protocol with pre- and postcontrast T1, T2, diffusion and non-morphological sequences.

With tissue specimens and pertinent clinical information the database has a role in both clinical and research development: at an individual level a personalized approach to precision medicine allows direct patient treatment

At present, several translational studies are ongoing:

  • Radiomic imaging studies are under development to align patterns in MR images with molecular and clinical features (Glioma Project);
  • In the framework of glioma’s group, Next generation sequencing in glioma patients for identification of potential target therapy:NGS panels assessment such as Ion-AmpliSeq (Thermo Fisher Scientific) to identify either the presence of point variants and fusion genes or variations in the number of gene copies with a panel of 50 genes that are recognized to have a key role in tumour development, with the aim to identify potential therapeutic target . Also for In order to dissect the microenvironment heterogeneity of our samples, we started applying whole transcriptome sequencing (RNA-seq) on a subset casuistry of the Glioma Project.
  • To investigate if circulating miRNAs could mirror the mutational status of IDH1 we explored, through genome-wide methodologies, the miRNA expression profile in serum samples of a discovery cohort of IDH1 mutant and IDH1wt glioma patients. We found, on the basis of prognostic value and IDH1 status, a serum signature of 10 miRNAs with a promising diagnostic and prognostic value as non-invasive tool to stratify gliomas according to IDH1 status and useful to complement the molecular analyses routinely carried out on formalin-fixed paraffin-embedded tissue biopsies.

Translational approach and the development of dedicated biobank are critical to promote translational researches in neuroncology