**5. Is there hope**

Primary brain tumors remain hard and challenging work despite the progress in understanding their genetics and technological progress that enabled safe and extensive tumor resection [3, 15, 17]. As gliomas include a variety of different histological tumor types and malignancy grades, contemporary achievements in terms of molecular imaging have given us a unique chance for a comprehensive interdisciplinary assessment of the glioma pathophysiology, with direct implications in terms of the medical and surgical treatment strategies available for patients [26]. The concept of individualized surgery in brain tumor neurosurgery, that is, specifically in neurooncology of glial tumors is actually based on the goal to provide as radical tumor resection as possible, without causing (additional) neurological deficit (**Figure 2**) [27].

Unfortunately, the prognosis of patients with grade IV malignant glioma particularly recurrent is dismal, and there is currently no effective therapy, but there are some promising agents as vaccine immunotherapy or recombinant nonpathogenic poliorhinovirus chimera (PVSRIPO) [28, 29]. Desjardins et al. have recently reported that overall survival among the patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among controls [29]. Extension of surgical excision is still an important predictor of outcome. Achieving a gross total resection of the tumor without significant complication requires a thorough understanding of available surgical approaches [15, 17, 30–32]. For majority of those patients, short-course radiotherapy with concurrent and adjuvant TMZ will bring a benefit, while gain from bevacizumab is limited [13]. There have been some ideas that certain antiepileptics also have a favorable effect on the outcome with glioma patients, but these studies have not given affirmative results [33]. To provide a highly personalized medicine, we will also have to make additional effort toward molecular neuropathology [30].

What do we want to see in the future? A patient from the supposed risk group will be scanned with MRI spectroscopy, 7T MRI, or similar MRI prototype. At the level of a robot medical center, needle biopsy of tumor will be performed, which will be followed by oncogenomic characterization of lesion, with gene map reading and defining. Research in the field of stem cells also has an important place and implications in the future. By way of stem cells, a specific

mapping (IEM) during awake craniotomy helps to maximize the extent of resection and to minimize the risk of permanent neurological morbidity, allowing a substantial increase in the

IDH, isocitrate dehydrogenase; NOS, not otherwise specified; RELA, reticuloendotheliosis viral oncogene homolog A [7].

† The last WHO classification of CNS tumors brought about some changes based on molecular findings.

**Table 1.** Simplified and modified from WHO 2016 classification of neuroepithelial tissue tumors.

WHO IV

WHO I

• WHO II • Ependymoma WHO II or III

• WHO III

WHO I

WHO III

• Ganglioglioma • Gangliocytoma

(Lhermitte-Duclos)

• Anaplastic ganglioglioma

**Ependymal tumors**

• Subependymoma

• Glioblastoma, IDH-wild type • Glioblastoma, IDH-mutant • Glioblastoma, NOS

• Myxopapillary ependymoma

• Anaplastic ependymoma

• Ependymoma, RELA fusion-positive

**Neuronal and mixed neuronal-glial tumors** • Diffuse leptomeningeal glioneuronal tumor

• Dysembryoplastic neuroepithelial tumor

• Dysplastic gangliocytoma of cerebellum

• Diffuse midline glioma, H3 K27M-mutant

Primary brain tumors remain hard and challenging work despite the progress in understanding their genetics and technological progress that enabled safe and extensive tumor resection [3, 15, 17]. As gliomas include a variety of different histological tumor types and malignancy grades, contemporary achievements in terms of molecular imaging have given us a unique

survival and quality of life of patients [14, 17, 25].

**Other astrocytic tumors (often referred as "circumscribed** 

6 Glioma - Contemporary Diagnostic and Therapeutic Approaches

• Oligodendroglioma, IDH-mutant and 1p/19q-codeleted†

**gliomas")** WHO I

WHO II

WHO III

WHO II

• Pilocytic astrocytoma

• Pleomorphic xanthoastrocytoma

**referred as "diffuse gliomas")**

• Diffuse astrocytoma, NOS

• Oligodendroglioma, NOS WHO III (anaplastic)

• Anaplastic astrocytoma, NOS

1p/19q-codeleted

• Diffuse astrocytoma, IDH-mutant • Diffuse astrocytoma, IDH-wild type

• Anaplastic astrocytoma, IDH-mutant • Anaplastic astrocytoma, IDH-wild type

• Anaplastic oligodendroglioma, NOS

• Anaplastic oligodendroglioma, IDH-mutant and

• Anaplastic pleomorphic xanthoastrocytoma **Diffuse astrocytic and oligodendroglial tumors (often** 

**5. Is there hope**

**Figure 2.** Contrast-enhanced axial T1 MRI scan of 54-year-old female patient with IDH-mutant glioblastoma. (A) Preoperative MRI and (B) 4 years after extensive surgical resection, followed with TMZ and radiotherapy treatment. Small part of recurrent tumor is visible 50 months after initial resection. Patient is still without any neurological deficit.

medicine will be produced, individualized for the particular patient, and in a microcapsule, it will be implanted into the brain zone affected by tumor, by way of robot surgery and injection needle. These are not at all unrealistic expectations in the next decade or two. Perhaps a bit futuristic, but it is also realistic to expect vaccination against glioma [28], that is, specific repair stem cells that will recognize the "glioma-damaged" part of the brain and thus preventively work on it, before the growth of tumor itself.

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Introductory Chapter: Glioma - Merciless Medical Diagnosis

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[7] Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathologica.

[8] Weller M, Van den Bent M, Tonn JC, et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. European Association for Neuro-Oncology (EANO) Lancet Oncology.

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[11] Brat DJ, Verhaak RGW, Aldape KD, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. The cancer genome atlas research network. The New England Journal of Medicine. 2015;**372**(26):2481-2498. DOI: 10.1056/NEJMoa1402121 [12] Baumert BG, Hegi ME, van den Bent MJ, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): A randomised, open-label, phase 3 intergroup study. The Lancet Oncology. 2016;**17**(11):1521-1532. DOI:

[13] Van den Bent MJ, Klein M, Smits M, et al. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): A randomised controlled phase 2 EORTC trial. The Lancet Oncology.

[14] Ghinda CD, Duffau H. Network plasticity and intraoperative mapping for personalized multimodal management of diffuse low-grade gliomas. Frontiers in Surgery. 2017;**4**:3.

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It is not too much to expect that the current generation of neurooncologists will resolve glioma problem for ever. We should bravely carry on. Time is brain.
