Treatment of glioblastoma in adults

Abstract

The diagnosis of a glioblastoma is mainly made on the basis of their microscopic appearance with the additional determination of epigenetic as well as mutational analyses as deemed appropriate and taken into account in different centers. How far the recent discovery of tumor networks will stimulate novel treatments is a subject of intensive research. A tissue diagnosis is the mainstay. Regardless of age, patients should undergo a maximal safe resection. Magnetic resonance imaging is the surrogate parameter of choice for follow up. Patients should receive chemoradiotherapy with temozolomide with the radiation schedule adapted to performance status, age and tumor location. The use of temozolomide may be reconsidered according to methylguanine DNA methyltransferase (MGMT) promoter methylation status; patients with an active promoter may be subjected to a trial or further molecular work-up in order to potentially replace temozolomide; patients with an inactive (hypermethylated) MGMT promoter may be counseled for the co-treatment with the methylating and alkylating compound lomustine in addition to temozolomide. Tumor-treating fields are an additive option independent of the MGMT status. Determination of recurrence is still challenging. Patients with clinical or radiographic confirmed progression should be counseled for a second surgical intervention, that is, to reach another macroscopic removal of the tumor bulk or to obtain tissue for an updated molecular analysis. Immune therapeutic approaches may be dependent on tumor types and molecular signatures. In newly diagnosed and recurrent glioblastoma, bevacizumab prolongs progression-free survival without affecting overall survival in an unselected population of glioblastoma patients. Whether or not selection can be made on the basis of molecular or imaging parameters remains to be determined. Some patients may benefit from a second radiotherapy. In our view, the near future will provide support for translating the amazing progress in understanding the molecular background of glioblastoma in to more complex, but promising therapy concepts

Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

“…In this regard, standard treatment for glioblastoma includes maximal surgical resection (whenever feasible), followed by radiotherapy and concurrent treatment with temozolomide plus additional 6 cycles of adjuvant temozolomide [13] . Despite such multimodal approach, the average survival of patients diagnosed with glioblastoma remains low (14-16 months), with better outcomes observed when tumors display O 6 -methylguanine Figure 1.…”

Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation

“…We also show that levels of sensory afferent input bidirectionally modulate tumor proliferation. Agents that stimulate GABAergic signalling may be tested to improve the efficacy of conventional anti-glioma treatments (Laub et al, 2018;Wick et al, 2018).…”

“…Despite advances in the last years (Ozdemir-Kaynak et al, 2018;Reitman et al, 2018), GBM remains one of the most difficult cancer to treat, with a median survival of 15 to 17 months and 5-year overall survival of 5% (Ostrom et al, 2016). Moreover, all the approved experimental treatments for high-grade glioma patients do not offer long-term benefits in symptom improvement or quality of life (Laub 3 et al, 2018;Wick et al, 2018). This devastating scenario strongly indicates a lack of knowledge in the biology of glioma and in its interaction with the peritumoral areas.…”

Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration

“…The causes of GB are under debate [2], 5% of the patients develop GB after a low grade astrocytoma [5] and the most frequent mutations include gain of function of EGFR (97%) and PI3K/AKT pathways (88%) [6]. The diagnosis, and therefore the treatment of GB, requires a mutations analysis taking into account the high frequency of clones within the same primary GB [7]. Temozolomide (TMZ) has emerged as an effective treatment for GB however, recent discoveries restrict the use of TMZ in GB patients depending on the methylation status of methylguanine DNA methytransferase (MGMT) [7].…”

“…The diagnosis, and therefore the treatment of GB, requires a mutations analysis taking into account the high frequency of clones within the same primary GB [7]. Temozolomide (TMZ) has emerged as an effective treatment for GB however, recent discoveries restrict the use of TMZ in GB patients depending on the methylation status of methylguanine DNA methytransferase (MGMT) [7]. Moreover, among other mutations, Isocitrate dehydrogenase (IDH) define the nature and features of GB [8] together with molecular alterations including 1p/10q deletions and tumour suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations [8,9].…”