**Gliomas**

VIII Preface

**Chapter 1**

**Provisional chapter**

**Current Trends in Glioblastoma Treatment**

**Current Trends in Glioblastoma Treatment**

DOI: 10.5772/intechopen.75049

Glioblastoma (also called glioblastoma multiforme – GBM) is a primary brain neoplasm, representing about 55% of all gliomas. It is a very aggressive and infiltrative tumor. Glioblastoma is usually highly malignant, with more than 90% 5-year mortality and a median survival of about 14.6 months. Compared to other cancers, the survival rate has not greatly changed over time and no current treatment is curative for this disease. Because the tumor has a heterogeneous cell population containing several types of cells, the treatment for GBM is one of the most challenging in clinical oncology. This chapter will discuss the current approaches in glioblastoma treatment, including resection tech-

**Keywords:** glioblastoma, surgical resection, intraoperative guidance, radiation therapy,

Glioblastoma is the most common primary brain malignancy in adults. It is the most aggressive of the gliomas, largely resistant to conventional therapies, having a very poor prognosis. The global incidence is 2–3 newly diagnosed cases per 100,000 people per year in the United States and Europe. According to Central Brain Tumor Registry of the United States, GBM accounts for 14.9% of all primary brain tumors and 55.4% of all gliomas. It represents the highest number of cases of all malignant tumors, with an estimated 12,390 new cases predicted in 2017. Currently, the standard of care (SoC) for patients with GBM consists of maximal

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Ligia Gabriela Tataranu, Vasile Ciubotaru, Tabita Larisa Cazac, Oana Alexandru,

Ligia Gabriela Tataranu, Vasile Ciubotaru, Tabita Larisa Cazac, Oana Alexandru,

Oana Stefana Purcaru, Daniela Elise Tache, Stefan Alexandru Artene and Anica Dricu

Oana Stefana Purcaru, Daniela Elise Tache,

Additional information is available at the end of the chapter

niques, chemotherapy and radiation therapy.

chemotherapy, intratumoral therapies, targeted therapy

Stefan Alexandru Artene and Anica DricuAdditional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.75049

**Abstract**

**1. Introduction**

#### **Chapter 1 Provisional chapter**

#### **Current Trends in Glioblastoma Treatment Current Trends in Glioblastoma Treatment**

DOI: 10.5772/intechopen.75049

Ligia Gabriela Tataranu, Vasile Ciubotaru, Tabita Larisa Cazac, Oana Alexandru, Oana Stefana Purcaru, Daniela Elise Tache, Stefan Alexandru Artene and Anica Dricu Ligia Gabriela Tataranu, Vasile Ciubotaru, Tabita Larisa Cazac, Oana Alexandru, Oana Stefana Purcaru, Daniela Elise Tache, Stefan Alexandru Artene and Anica DricuAdditional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.75049

#### **Abstract**

Glioblastoma (also called glioblastoma multiforme – GBM) is a primary brain neoplasm, representing about 55% of all gliomas. It is a very aggressive and infiltrative tumor. Glioblastoma is usually highly malignant, with more than 90% 5-year mortality and a median survival of about 14.6 months. Compared to other cancers, the survival rate has not greatly changed over time and no current treatment is curative for this disease. Because the tumor has a heterogeneous cell population containing several types of cells, the treatment for GBM is one of the most challenging in clinical oncology. This chapter will discuss the current approaches in glioblastoma treatment, including resection techniques, chemotherapy and radiation therapy.

**Keywords:** glioblastoma, surgical resection, intraoperative guidance, radiation therapy, chemotherapy, intratumoral therapies, targeted therapy

#### **1. Introduction**

Glioblastoma is the most common primary brain malignancy in adults. It is the most aggressive of the gliomas, largely resistant to conventional therapies, having a very poor prognosis. The global incidence is 2–3 newly diagnosed cases per 100,000 people per year in the United States and Europe. According to Central Brain Tumor Registry of the United States, GBM accounts for 14.9% of all primary brain tumors and 55.4% of all gliomas. It represents the highest number of cases of all malignant tumors, with an estimated 12,390 new cases predicted in 2017. Currently, the standard of care (SoC) for patients with GBM consists of maximal

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

safe surgical resection, followed by concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide (TMZ). New discoveries are being made in basic and translational research, novel therapeutic approaches have been tried and tested, some of them finding their way into clinical practice. Despite the synergistic multimodal strategies and individualized therapies, the available treatment is of limited utility, and patients have a poor prognosis, with a progression-free survival (PFS) of 7–8 months, a median survival of 14–16 months and 5-year overall survival (OS) of 9.8% [1]. This review focuses on the current treatment strategies and perspectives in the management of GBM.

a level of objectivity to diagnostic and should lead to improvements in determination of prognosis and treatment response. So, GBMs are further defined by the presence or absence of **isocitrate dehydrogenase (IDH) gene mutations**. IDH is an enzyme encoded by the IDH gene, whose mutations occur in gliomas. These mutations are oncogenic and they lead to a hypermethylation phenotype, as well as changes in cellular metabolism and response to hypoxic and oxidative stress [4, 5]. Mutated IDH can now be detected by immunohistochemistry and magnetic resonance spectroscopy (MRS). IDH mutation is identified as a genetic marker of secondary GBM. It can indicate a favorable prognosis and a relatively

Current Trends in Glioblastoma Treatment http://dx.doi.org/10.5772/intechopen.75049 5

**GBMs are divided into**: GBM, IDH-wildtype; GBM, IDH-mutant and GBM, NOS [6]. IDHwildtype GBM corresponds with clinically described primary or de novo GBM. It represents about 90% of GBMs. It arises without clinical, radiologic or histologic evidence of a pre-existing less malignant lesions, in elderly patients (median age of 62 years), usually supratentorial. The mean length of clinical history is 4 months and the median overall survival after conventional surgery, radiotherapy and chemotherapy is 15 months, the prognosis being poor [6, 7]. IDH-mutant GBM corresponds with secondary GBM (approximately 10% of GBMs). It typically develops from lower grade diffuse glioma. It occurs in younger patients (median age of 45 years), preferentially in the frontal lobe. The mean duration of the clinical history of secondary GBM is 15 months and the median overall survival after multimodal treatment (including surgical resection, radiotherapy and chemotherapy) is 31 months, a significantly better prognosis than primary GBM [6, 7]. Primary and secondary GBMs carry distinct genetic abnormalities. Other common genetic alterations in secondary GBMs include TP53 mutations (~65%), ATRX mutations (~65%) and loss of heterozygosity (LOH) on chromosome 19q (~50%). In primary GBMs, there is a high frequency of EGFR amplification (~35%), phosphatase and tensin homolog (PTEN) mutation (~25%) and LOH on chromosome 10 (LOH 10p ~50%, LOH 10q ~70%) [7, 8]. There is now increasing evidence that primary and secondary GBMs are in fact different tumor entities that develop from distinct cells of origin [7]. Despite the differences in their phenotypic and genotypic profiles, these two subtypes of GBM are histopathologically indistinguishable, except that extensive necrosis is more frequent in primary GBM and oligodendroglioma components are more frequent in secondary GBM [7]. Recent findings in pediatric GBMs regarding mutations in the histone H3F3A gene suggest that these tumors may represent a third major category of GBMs, separate from adult primary and secondary GBMs [9]. The terminology NOS (i.e., not otherwise specified) is used for GBM when molecular information is insufficient, either because testing cannot be fully performed or the

In the 2016 update of the WHO Classification of Tumors of the CNS, there are **three variants of IDH-wildtype GBMs**: giant cell GBM, gliosarcoma and epithelioid GBM. It is to be noted that variants are subtypes of accepted entities that are sufficiently well characterized pathologically and have potential clinical utility [6]. There are also **different patterns in GBMs**, including small cell GBMs, granular cell GBM and GBM with primitive neuronal component (previously referred as GBM with primitive neuroectodermal tumor (PNET)-like component). Patterns are histological features that are readily recognizable, but usually do not have

good response to radiation and/or alkylating chemotherapy.

results do not fit within a defined category.

clear clinicopathological significance [6].
