Glioma C6 perivascular changes of invasion structural parameters variation (research study).

A comparative study of the structural characteristics of microvessels with a perivascular arrangement of tumor cells and microvessels with normal structure located in the peritumoral zones of an intracranially implanted glioblastoma ("glioma C6") was conducted. The study was performed on rats. Morphometric method was used to determine the area, internal diameter and length of microvessels for 21 days after the introduction of tumor cells into the brain of rats. Changes in the structure of microvessels with glioblastoma cells were registered throughout the entire observation period. The active role of perivascularly located tumor cells in the transformation of the structure and properties of microvessels involved in the process of glioblastoma invasion into brain tissue is considered. Key words: glioblastoma, microvessels, morphometry, peritumoral zones.

Magnetic resonance and its diagnostic accuracy of glioblastoma: narrative review

Introduction: Glioblastoma (GBM) is the most common and lethal Central Nervous System (CNS) malignant cancer, and the exclusion of differential diagnoses - eg primary central nervous system lymphoma (PCNSL) - often occurs via various Magnetic Resonance Imaging (MRI) methodologies. Objective: To describe which best image sequences are critical for greater accuracy in the diagnosis of GBM and for their distinction from other CNS tumors. Methods: This is a literature narrative review, initiated by research in Pubmed database, using associated Key words: “Glioblastoma” and “Magnetic Resonance”; and filters: systematic reviews + last 5 years publications. Productions that didn’t meet the objective were discarded. Results: MRI has accuracy for diagnosing GBM using the combination T2 + FLAIR + T1 with pre and post-gadolinic contrast. Diffusion and perfusion-weighted MRI association show an improvement in specificity. Computed tomography is used when MRI is unviable, identifying calcifications or hemorrhages and determining the lesion location and surgical potential. Also, spectroscopic MRI, diffusion tensor imaging and PET 18F-FDG, and 11C-MET were reported as important additional diagnostic criteria. Diffusion MRI (DWI) is a non-invasive, convenient, economical, and quick procedure when compared to GBM biopsy. Therefore, adding reliable evidence for moderate differentiation between GBM and PCNSL through DWI. Conclusion: Reliable methods are needed for GBM accurate diagnosis and its differential diagnoses, using at least T2 + FLAIR + T1, and physiological exams to enhance specificity.

TMOD-08. SERUM ESTABLISHED CANCER STEM CELL CULTURES REPRESENT UNIQUE MODELS OF GLIOBLASTOMA INTER-TUMOR HETEROGENEITY

Glioblastoma (GBM) is the most frequent primary malignant brain tumor. The invasive and heterogeneous nature of GBM stem cells (GSCs) provide the basis for extreme therapy resistance of GBM and the majority of patients survive less than one year from diagnosis. Relevant models of GBM are important for basic research and drug screening and development, and the current consensus in the field is that GSCs are most faithfully maintained under serum-free neural stem cell (NSC) conditions. We have used serum-free NSC media to explant 230 patient-derived GBM samples, and have in parallel also explanted the same samples in regular serum-containing media. We found, accordingly, that serum-free media was most effective in generating sustainable cultures (137/230, 60%), called serum-free (SF) cultures. Interestingly, we also found that that there was a subgroup of GBM specimens that could only be established in serum-containing media (31/230, 13%), called exclusive serum-containing (eSC) cultures. We characterized a number of the eSC cultures and found that they expressed typical GSC markers such as MSI-1, BMI-1, nestin, CD44 and SOX2. They also displayed all functional characteristics of GSCs, i.e. extended proliferation, sustained self-renewal and orthotopic tumor initiation. Molecular analyses showed that the eSC cultures were most closely related to but separated from mesenchymal subtype GBM. In summary we have established GSC cultures that would have evaded modeling under serum-free conditions, representing unique cell models of GBM inter-tumor heterogeneity. Key words: Glioblastoma, serum cultures, stem-like cells, GBM heterogeneity

Glioblastoma Multiforme and Genetic Mutations: The Issue Is Not Over Yet. An Overview of the Current Literature

Background and Objective Glioblastoma multiforme (GBM) is still a deadly disease with a poor prognosis and high mortality, despite the discovery of new biomarkers and new innovative targeted therapies. The role of genetic mutations in GBM is still not at all clear; however, molecular markers are an integral part of tumor assessment in modern neuro-oncology. Material and Methods We performed a Medline search for the key words “glioblastoma,” “glioblastoma multiforme,” and “genetic” or “genetics” from 1990 to the present, finding an exponential increase in the number of published articles, especially in the past 7 years. Results The understanding of molecular subtypes of gliomas recently led to a revision of the World Health Organization classification criteria for these tumors, introducing the concept of primary and secondary GBMs based on genetic alterations and gene or protein expression profiles. Some of these genetic alterations are currently believed to have clinical significance and are more related to secondary GBMs: TP53 mutations, detectable in the early stages of secondary GBM (found in 65%), isocitrate dehydrogenase 1/2 mutations (50% of secondary GBMs), and also O6-methylguanine-DNA methyltransferase promoter methylation (75% of secondary GBMs). Conclusion From the introduction of the first standard of care (SOC) established in 2005 in patients with a new diagnosis of GBM, a great number of trials have been conducted to improve the actual SOC, but the real turning point has never been achieved or is yet to come. Surgical gross total resection, with at least one more reoperation, radiation therapy plus concomitant and adjuvant temozolomide chemotherapy currently remains the current SOC for patients with GBM.

Aspekty leczenia pacjentów w starszym wieku z rozpoznaniem glejaka wielopostaciowego. Aspects of treatment of elderly patients with diagnosis of glioblastoma multiforme.

Glejak wielopostaciowy (glioblastoma multiforme, GBM) należy do najbardziej złośliwych nowotworów pierwotnych mózgu. Charakterystyczną cechą GBM jest jego naciekający wzrost, zdolność komórek do szerzenia się wzdłuż dróg nerwowych istoty białej oraz możliwość inwazji przeciwnej półkuli mózgu. Agresywna natura glejaka wielopostaciowego sprawia, że u nieleczonych pacjentów przeżycia wynoszą jedynie 3 - 6 miesięcy od rozpoznania choroby. Po 65 roku życia odnotowuje się gwałtowny wzrost przypadków glejaka wielopostaciowego. Obecnie na świecie około połowa pacjentów z tym nowotworem ma więcej niż 65 lat. Biorąc pod uwagę starzenie się społeczeństwa oblicza się, że coraz bardziej rosnąć będzie liczba nowo stwierdzanych przypadków GBM u pacjentów w podeszłym wieku, a problem odpowiedniego podejścia terapeutycznego do tej szczególnej grupy chorych będzie coraz istotniejszy. Przez wiele lat klinicyści odnosili się z niechęcią do wdrażania u osób starszych metod leczenia z powodzeniem stosowanych u młodych pacjentów. Tak więc poprzez samo kierowanie się wiekiem terapia starszych chorych z GBM była często suboptymalna. Tymczasem zmiana w podejściu do leczenia pacjentów w starszym wieku udowodniła, że najważniejszym czynnikiem branym pod uwagę przed rozpoczęciem leczenia powinien być stan ogólny chorego oceniony według powszechnie uznawanych skal (np. skali sprawności Karnofsky’ego). Wiele badań klinicznych potwierdziło, że zastosowanie technik operacyjnych, metod radioterapii i chemioterapii z temozolomidem przynosi również istotny zysk starszym pacjentom (wydłuża przeżycia całkowite, poprawia jakość życia), w tym nawet chorym po 80 roku życia. Glioblastoma multiforme (GBM) is one of the most malignant primary brain tumour.There is a rapid increase in the number of glioblastoma multiforme cases found in patients older than 65 years old. Currently about half of patients with this cancer are more than 65 years old. Taking into account the aging of the population it is calculated that the number of newly diagnosed GBM cases in older patients will grow more and more and the problem of an appropriate therapeutic approach to this specific group of patients will become more and more important. For many years clinicians were reluctant to implement in older patients methods of treatment successfully used in young patients. Thus by taking into consideration only the age the therapy of older patients with GBM was often suboptimal. Meanwhile, a change in the approach to the treatment of elders proved that the most important factor taken into account before starting treatment should be the general condition of the patient assessed according to commonly accepted scales (eg Karnofsky score). Many clinical trials have confirmed that the use of surgical techniques, radiotherapy methods and chemotherapy with temozolomide brings significant benefits to older patients (prolongs overall survival, improves quality of life), including those over 80 years old. Słowa kluczowe: glejak wielopostaciowy, starość, radioterapia, chirurgia, temozolomid Key words: glioblastoma multiforme, elderly, radiotherapy, surgery, temozolomide.

Evidence-based review of the role of reoperation in the management of malignant glioma

Using an evidence-based approach to available clinical studies, the authors examined the role of reoperation in the management of malignant glioma. A review of 1270 Medline-referenced articles spanning the period from 1966 through March 1998 was undertaken using the key words “glioblastoma” and “astrocytoma.” Using an evidence-based four-tiered grading system, the authors found only 14 articles that met their inclusion criteria. Of these, 11 were graded as Class III (retrospective case series) and three as Class II (prospective nonrandomized studies). There were no Class I reports (randomized clinical trials), and all Class IV reports (opinion reports) were excluded. The authors of 10 Class III and one Class II articles supported the role of reoperation in increasing survival time or quality of life in selected patients; however, the results of multivariate analysis in two Class II and one Class III article did not support prolonged survival. The authors conclude that there was insufficient evidence to support either a standard or a guideline for reoperation in malignant glioma given the current status of the literature. Selection bias was a major factor in these studies. With continued interest in clinical trials for recurrent malignant glioma, the role of reoperation needs to be addressed in case-controlled or randomized fashion to establish either standards or guidelines on this commonly debated issue.