• Users Online: 295
  • Print this page
  • Email this page


 
 
Table of Contents
REVIEW
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 119-125

Advancement of clinical therapeutic research on glioma: A narrative review


Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China

Date of Submission27-May-2020
Date of Decision18-Jun-2020
Date of Acceptance14-Jul-2020
Date of Web Publication17-Oct-2020

Correspondence Address:
Dr. Zhiqiang Li
Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan 430071, Hubei Province
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_18_20

Rights and Permissions
  Abstract 

As theories evolve, the mechanism of glioma origination remains poorly understood. Understanding this mechanism promotes the clinical research on glioma therapeutic strategy and then improves the prognosis of patients with glioma. However, the overall survival of these patients is unsatisfactory. In the recent decade, a few novel therapies, such as tumor-treating fields and immunotherapy, have been introduced in clinic. Before they can be widely used, many key factors, including efficacy, safety, and benefit ratio, should be fully evaluated. Therefore, more clinical trials are required to corroborate the results and conclusions of basic research and improve the current treatment strategies. In this article, we searched relevant literature published in the past 5 years in PubMed and China National Knowledge Infrastructure and reviewed the advancements of clinical therapeutic research on glioma.

Keywords: Glioma, immunotherapy, radiochemotherapy, surgery, tumor-treating fields


How to cite this article:
Li F, Ma C, Xu C, Pan Z, Li Z. Advancement of clinical therapeutic research on glioma: A narrative review. Glioma 2020;3:119-25

How to cite this URL:
Li F, Ma C, Xu C, Pan Z, Li Z. Advancement of clinical therapeutic research on glioma: A narrative review. Glioma [serial online] 2020 [cited 2022 Nov 28];3:119-25. Available from: http://www.jglioma.com/text.asp?2020/3/3/119/298391


  Introduction Top


Gliomas are the leading primary malignant tumors of the central nervous system, with a morbidity of 7.3 cases per 100,000 people, comprising 85% of high-grade gliomas and 15% of low-grade gliomas.[1] This condition can happen to both children and adults. Its incidence and prognosis are closely linked to race, gender, and other patient-related factors.[2] In general, the first-line treatment for removing gliomas is surgery. Nevertheless, often, gliomas have already spread in the brain when diagnosed; thus, the recurrence rate remains high. To improve the patient's overall survival and progression-free survival (PFS), and to reduce the recurrence rate, physicians are trying to administer a combination of radiotherapy and chemotherapy, such as short-term radiotherapy and temozolomide, after surgery.[3],[4] However, considering that gliomas are highly invasive and heterogeneous and those glioma stem cells are resistant to various treatment options, the prognosis is generally extremely poor, as mainly manifested in cognitive function decline.[5],[6] With numerous studies that are currently conducted, malignancy-related glioma-specific molecules have been increasingly discovered;[7],[8],[9] hence, treatment schemes that are designed according to a series of molecular markers, including some drugs and the novel designing of the radiotherapy model, are essential to improve the survival rate of patients with gliomas. Research on the proliferation mechanism of glioma cells proposed that tumor-treating fields (TTF), diet therapy, and some other strategies improves the quality of postoperative recovery of patients to a greater extent.[10],[11] This review starts from various angles and discusses the practical effects and future directions of development concerning glioma treatment options.


  Database Search Strategy Top


We searched PubMed and China National Knowledge Infrastructure to identify multiple relevant studies published in the past 5 years. The terms included “glioma,” “glioblastoma,” “therapy,” “surgery,” “radiotherapy,” “chemotherapy,” and “tumor-treating fields.” More than 100 studies were found and some of them served as references. Some important reference data were listed for our thesis argument. We also simultaneously combined the authors' experience to review on the latest glioma treatment methods.


  Surgical Removal Top


In clinical practice, high-grade gliomas, diffuse low-grade gliomas, and recurrent gliomas are commonly treated by surgery. Maximum tumor resection is performed and is classified into gross-total resection, subtotal resection, partial resection, and biopsy. Identifying the extent of resection in each individual is generally difficult because the excision extension is closely related to the postoperative recovery of patients.[12] Each resection grade indicates a different prognosis. Compared with subtotal resection, gross-total resection can prolong the overall survival rate and PFS.[13] To effectively prevent postoperative permanent dysfunction, physicians routinely use auxiliary techniques such as intraoperative awakening and intraoperative brain function positioning, which aid in analyzing the impact of the resection site on the patient's sensory and motor functions.[5],[14] These techniques integrate a fluorescence-guided surgery, which can decrease tumor recurrence rate and prolong patient survival compared with white-light surgery.[15] A highly sensitive monoamine oxidase-A-specific probe-F1, which was recently designed by Fang et al.,[16] can clearly detect the boundary of the gliomas and paracancerous tissue with the aid of two-photon fluorescence microscopy, making F1 a hot spot with a broad prospect of application. In resecting high-grade gliomas, the imaging agent 5-aminolevulinic acid hydrochloride is frequently used to guide surgeons in performing accurate resection under a blue light. In a previous systematic analysis, 5-aminolevulinic acid hydrochloride can reduce the incomplete resection rate (level of evidence, low). In addition, the cost and benefit of this agent are satisfactory for patients.[17] In analyzing the blood perfusion status and grade of gliomas in real time, physicians can employ various ultrasound-based imaging techniques, such as B-mode, Doppler (power, color, and spectral), contrast-enhanced ultrasound, and elastosonography, intraoperatively to determine the maximum resection range.[18]

However, glioma resection surgery involves certain risks. It has a positive impact on complex attention, language, learning and memory tasks, and continuous follow-up improvement immediately after the operation, as indicated in a meta-analysis of 313 patients. Furthermore, the patients' attention, language fluency, object naming, and other neurocognitive functions are remarkably improved by the intraoperative awakening, but the patient's executive function has declined and even has a long-term downward trend.[19] Hence, surgery is not always the first treatment choice, depending on glioma type. Known for its extreme aggressiveness, diffuse intrinsic pontine glioma can spread to almost every important functional area of the brain. From the clinical viewpoint, selecting different surgical timing and operative duration does not remarkably improve the patient's overall survival.[20] To maximize the benefit of surgery to patients, researchers continually develop technology and improve the surgical procedures. As proposed by Li et al.,[21] a surgery guided by positron emission technology and optical dual-mode images can more sensitively locate the tumor for a more accurate removal; postoperatively, patients demonstrate an extended PFS, with no new neurological damage. In a clinical study by Schneider et al.,[22] lobectomy was used for temporal glioblastoma, resulting in a marked improvement of the patient's Karnofsky Performance Score, PFS, and overall survival compared with total resection.


  Radiochemotherapy Top


For some solid tumors such as gliomas, radiochemotherapy is often an integral part of the standard treatment plan proposed by clinical guidelines. However, some clinical problems, such as myelosuppression, chemoradiotherapy resistance, and toxicity to normal cells, have been observed.[23],[24] In radiotherapy, a certain dose of radiation is released, consequently breaking the double-strand DNA of tumor cells and then destroying the cell cycle. The formed DNA fragments can also induce apoptosis. Furthermore, 5-Iodo-2′-deoxyuridine can increase radiotherapy sensitivity.[25] However, considering the activation of the DNA repair system, the presence of glioma stem cells, and the increase in regulatory T cells with immunosuppressive effects caused by irradiation, cancer cells can escape death and continue the malignant proliferation, resulting in radioresistance.[26],[27] The main chemotherapy drug currently used for newly diagnosed and recurrent gliomas is temozolomide.[28] This drug can traverse the blood–brain barrier and invade the cerebrospinal fluid, thereby considering as a highly effective antitumor alkylating agent.[29] Under the physiological pH state of the systemic circulation, temozolomide is rapidly transformed into the active product 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC), which plays a cytotoxic role through the mismatch repair of methylated adducts.[30] To increase the rate of drug passing through the blood–brain barrier, scientists have tried to inhibit and even destruct the blood–brain barrier components, as guided by focused ultrasound with drug administration, to achieve superior results; as a result, the local concentration of temozolomide in the brain significantly increases.[31],[32] Similar to other cytotoxic drugs, temozolomide can cause several adverse events, such as nausea, vomiting, and hematological reactions (myelosuppression).[33] To reduce the incidence of adverse reactions and fully exert the antitumor effect of radiochemotherapy in patients with gliomas, physicians generally employ short-term radiotherapy combined with chemotherapy.[34]

Some scholars have conducted numerous clinical studies to analyze the effect of radiochemotherapy on glioma prognosis. For instance, compared with radiotherapy alone, short-term radiotherapy combined with temozolomide administration prolonged patient's overall survival, decreasing the mortality risk by 33% (9.3 months vs. 7.6 months; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.56–0.80; P < 0.001).[35] Chemotherapeutic drugs must reach an effective concentration in glioma cells to effectively exert the antitumor effect. These drugs can be efficiently guided to the target area through the barrier with the help of imaging analysis of the blood–brain barrier.[36] To analyze the impact of radiotherapy and chemotherapy individually and radiochemotherapy on patients, researchers have conducted numerous basic experiments and clinical trials. In a randomized open-label phase-three intergroup study, the investigators randomly divided 477 patients into the radiotherapy group (n = 240) and the chemotherapy group (temozolomide, n = 237), with a median follow-up of 48 months. Although the median PFS of the radiotherapy group was longer than that of the chemotherapy group (unadjusted HR, 1.16; 95% CI, 0.9–1.5; P = 0.22), PFS remained to be not significantly different between the two groups.[33] Conversely, in a clinical trial involving 251 eligible patients, the patient's 10-year PFS (21% vs. 51%) and overall survival (13.3 years vs. 7.8 years; HR, 0.59; P = 0.003) could be significantly improved in radiochemotherapy (mebendazole and cyclohexyl-nitrosourea) compared with those in radiotherapy alone, consistent with the results of other previous studies.[35],[37] In recent years, owing to the rapid advancement of biopharmaceutical technology, various monoclonal antibody types, such as the recombinant humanized monoclonal antibody bevacizumab, have been developed as anticancer drugs; bevacizumab can combine to vascular endothelial growth factor and inhibit the growth of blood vessels and the metastasis of various tumors.[38],[39],[40] Together with temozolomide, this drug is often used to treat recurrent glioma, but clinical studies have confirmed that bevacizumab and temozolomide combination has no significant difference in improving the overall survival compared with temozolomide alone. In contrast, bevacizumab may have a higher incidence of adverse reactions, such as hematological toxicity, neurological disorders, fatigue, and even treatment-related death.[41] To evaluate bevacizumab pretreatment in patients with glioma, the researchers selected a different set of representative radiophenotype markers according to pretreatment baseline MRI. By analyzing these markers, the overall survival and PFS after using bevacizumab could be substantially stratified.[42] Therefore, when formulating a plan for patients with glioma, the benefits and damages should be comprehensively considered, and the drug or radiation dose should be carefully selected to maximize the survival benefit of the patients.


  Immuno- and Bio-Therapy Top


The treatment options and prognosis of gliomas in children and adults are considerably different. Various molecular pathologic bases determine the differences in their treatment approaches, which must be considered when planning for treatment.[7],[43] In a meta-analysis of more than 1000 cases of high-grade and diffuse intrinsic pontine gliomas in children by Mackay et al.,[44] molecular changes mainly occurred in H3F3A (H3.3) and HIST1H3B (H3.1), including 67 cases of H3.3G34R/V (n = 63 G34R and n = 4 G34V), 316 cases of H3.3K27M, and 66 cases of H3.1/3.2K27M (n = 62 HIST1H3B, n = 2 HIST1H3C, and n = 2 HIST2H3C), and adult gliomas are distinguished by IDH1 and other molecular markers. The mutant IDH1 can promote the glioma progression in vivo, triggering seizures, and other nervous system syndromes.[45],[46] Therefore, in the past few years, scientists focused more on oncolytic virus. By modifying the E1A virus gene, Delta-24-RGD (DNX-2401) can selectively bind to glioma cells to promote chronic inflammatory cell activities, such as CD8+ T lymphocyte infiltration, and other immune reactions.[47],[48] Tejada et al.[49] initially used adenovirus DNX-2401 to treat an 8-year-old child with diffuse intrinsic pontine glioma; in the first few weeks, the patient well tolerated the injection of viral particles in situ during pathological biopsy, and radiation therapy could be performed after 2 weeks.

A human immune system consists of a class of receptors that can inhibit the activation and differentiation of T lymphocytes.[50] T lymphocytes lose its ability to induce cytotoxicity.[51] Normally, T lymphocytes have a protective effect on normal human cells and protect the body from autoimmune diseases. Inhibited T lymphocytes are regarded as the immune checkpoint. However, cunning cancer cells also use these immune checkpoints to evade recognition and poisoning by the immune system and proceed to unlimited proliferation of such immune checkpoints, including programmed death-1 (PD-1), programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4. The high expression of these molecules is often closely associated with patient survival.[52] According to this principle, scientists have designed various monoclonal antibody types to block the relevant immune checkpoint pathways and adequately inhibit tumor cell proliferation. The resulting immune checkpoint blockade therapy has helped millions of patients suffering from cancer.[53],[54],[55] Unfortunately, the use of inhibitors can result in resistance of tumor cells to treatment. Crafty cancer cells can counteract the pharmacological effects of monoclonal antibodies by producing exosomes expressing immune checkpoints.[56] Compared with chemotherapy, these inhibitors can significantly improve patients' overall survival and PFS, with a lower incidence of side effects. However, with the widespread use, rare but serious, or even life-threatening adverse events occur in patients.[57] For instance, a 66-year-old patient with lung adenocarcinoma using an anti-PD-1 monoclonal antibody developed myositis–myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis. Therefore, the patient's reaction should be closely observed, and symptomatic treatment of serious complications should be performed immediately.[58]

The impact of immune checkpoint inhibitors on the tumor microenvironment is extremely complex. These inhibitors can be used to treat various cancers because they can remodel the myeloid and lymphatic cavity, activate the differentiation of the mononuclear/macrophage system in the tumor, and restore the activity of cell subpopulations, such as antitumor T cells.[59] However, these inhibitors are hindered by the blood–brain barrier and immunosuppressive microenvironment; thus, sufficient drugs cannot reach the target area to exert their efficacy. Inspired by the theory that oncolytic viruses can efficiently cross the barrier and specifically bind to glioma cells, some scholars used the heoncolytic herpes simplex virus expressing PD-1 monoclonal antibody to examine the effect of combining these two agents on glioma, which can acquire a lasting memory immune response in a glioblastoma mouse model without any toxicity to normal neurons.[60],[61] With the advantages of specific binding to glioma cells and few side effects, oncolytic viruses can be combined with drugs such as temozolomide and monoclonal antibodies to effectively inhibit tumor cell proliferation, suggesting a great potential clinical research value.[62]


  Tumor-Treating Fields Top


TTF is a new type of cancer therapy; however, its anticancer mechanism has remained poorly understood, and the clinical efficacy requires further investigation. TTF uses a low-density, specific frequency electric field to function on the chromosome-related proteins of cancer cells to stimulate the erroneous separation of chromosomes; as a result, double-stranded DNA breaks, which in turn affects cell proliferation, and even induces apoptosis.[63] The antitumor effect is closely associated with the specific absorption rate of the cells to the electric field, the frequency of the electric field, and the commutation time.[64],[65] TTF can also induce a high expression of autophagy genes, thereby inhibiting tumor cell proliferation.[66] TTF efficacy is affected by various physical factors and the patient's constitution. To obtain an individualized treatment plan, physicians can use electric field-volume histograms and specific absorption rate-volume histograms to analyze various relevant factors and apply them clinically.[67] TTF can stimulate the body's antitumor immune effect and activate the macrophages by triggering the nuclear factor κB and mitogen-activated protein kinase pathways.[68] Moreover, TTF can effectively inhibit the malignant proliferation of glioma cells and has a great clinical potential; hence, it should be considered to be added to the standard treatment plan for patients with glioma.[10]

To analyze the effect of TTF combined with radiotherapy on cancer prognosis, Karanam et al. used non-small cell lung cancer cell lines and found that TTF has radiation sensitization. The reason is that TTF after radiotherapy can delay DNA damage repair after the irradiation of cancer cells.[69],[70],[71],[72] In addition, the electric field array of TTF does not affect the coverage of the target tumor by the rays.[73] Similarly, when combined with TTF and baseline temozolomide, tumor growth and neovascularization were inhibited, as revealed in early MRI analysis after treatment.[74] A clinical study involving 695 patients with glioblastoma who had completed initial radiochemotherapy confirmed that the median PFS of the group that received temozolomide combined with TTF was 6.7 months compared with 4 months in the group receiving only temozolomide chemotherapy; the difference was significant. Furthermore, the daily life ability and cognitive function of patients in the combined treatment group have been remarkably improved. In addition, the side effects caused by the electric field-related treatment may only be skin itching without headache, insomnia, and other adverse reactions; thus, the patient can tolerate well to TTF.[75],[76] However, the cost-effectiveness of using TTF is not relatively high. In a 3-health-state Markov model, the researchers analyzed the relationship between life-years gained using TTF and the corresponding cost, and they found that the benefit was extremely minimal (mainly because of the high cost of the device) and cannot be applied as the first-line treatment.[77] Moreover, certain requirements are needed for the duration for the patient to wear the electric field device. The duration is usually superior to 18 h and every 24 h, bringing inconvenience to the patient's daily life. Therefore, further research is needed to further simplify the treatment equipment and improve the penetration rate in patients.[10]


  Summary Top


Glioma, especially glioblastoma, greatly abbreviates the survival time of patients, with an extremely low quality of life. Although the maximum extent and safe surgical resection and radiochemotherapy are standard treatment options, glioma cannot significantly improve patient's quality of life. Another complicated problem is the rehabilitation of patients after treatment. Selecting treatment strategies is still tremendously challenging. Related research is still ongoing with the development of oncolytic viruses, TTF, and other treatments. Through the combined use of surgery, short-term radiotherapy, temozolomide, and TTF to a certain extent, the overall survival and PFS of patients can be prolonged, and the occurrence of adverse events may be reduced. At the same time, health-care professionals must also be alert to the occurrence of fatal complications related to immune checkpoint inhibitors. Furthermore, formulating prevention and emergency schemes in advance is essential as well.[59] The result of basic research and clinical trials do not always have a high degree of consistency.[42],[78] Therefore, these two types of studies should be closely combined and complement each other, so that the feasibility, safety, and clinical efficacy of the treatment plan can be fully evaluated to better serve patients with glioma.

Financial support and sponsorship

This work was supported by the Medical Science Advancement Program of Wuhan University of China (No. TFJC2018003, to ZL) and the National Health Commission of China (No. 2018ZX-07S-011, to ZL).

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Rasmussen BK, Hansen S, Laursen RJ, Kosteljanetz M, Schultz H, Nørgård BM, et al. Epidemiology of glioma: Clinical characteristics, symptoms, and predictors of glioma patients grade I-IV in the Danish Neuro-Oncology Registry. J Neurooncol 2017;135:571-9.  Back to cited text no. 1
    
2.
Ostrom QT, Cote DJ, Ascha M, Kruchko C, Barnholtz-Sloan JS. Adult glioma incidence and survival by race or ethnicity in the united states from 2000 to 2014. JAMA Oncol 2018;4:1254-62.  Back to cited text no. 2
    
3.
Lesueur P, Lequesne J, Grellard JM, Dugué A, Coquan E, Brachet PE, et al. Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol. BMC Cancer 2019;19:198.  Back to cited text no. 3
    
4.
Zhong L, Chen L, Lv S, Li Q, Chen G, Luo W, et al. Efficacy of moderately hypofractionated simultaneous integrated boost intensity-modulated radiotherapy combined with temozolomide for the postoperative treatment of glioblastoma multiforme: A single-institution experience. Radiat Oncol 2019;14:104.  Back to cited text no. 4
    
5.
Hameed NUF, Qiu T, Zhuang D, Lu J, Yu Z, Wu S, et al. Transcortical insular glioma resection: Clinical outcome and predictors. J Neurosurg 2018;131:706-16.  Back to cited text no. 5
    
6.
Hendriks EJ, Habets EJJ, Taphoorn MJB, Douw L, Zwinderman AH, Vandertop WP, et al. Linking late cognitive outcome with glioma surgery location using resection cavity maps. Hum Brain Mapp 2018;39:2064-74.  Back to cited text no. 6
    
7.
Chi AS, Tarapore RS, Hall MD, Shonka N, Gardner S, Umemura Y, et al. Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201. J Neurooncol 2019;145:97-105.  Back to cited text no. 7
    
8.
Ferrer VP, Moura Neto V, Mentlein R. Glioma infiltration and extracellular matrix: Key players and modulators. Glia 2018;66:1542-65.  Back to cited text no. 8
    
9.
Takahashi K, Proshin S, Yamaguchi K, Yamashita Y, Katakura R, Yamamoto K, et al. Sialidase NEU3 defines invasive potential of human glioblastoma cells by regulating calpain-mediated proteolysis of focal adhesion proteins. Biochim Biophys Acta Gen Subj 2017;1861:2778-88.  Back to cited text no. 9
    
10.
Burri SH, Gondi V, Brown PD, Mehta MP. The evolving role of tumor treating fields in managing glioblastoma: Guide for oncologists. Am J Clin Oncol 2018;41:191-6.  Back to cited text no. 10
    
11.
Woolf EC, Scheck AC. The ketogenic diet for the treatment of malignant glioma. J Lipid Res 2015;56:5-10.  Back to cited text no. 11
    
12.
Rossi M, Ambrogi F, Gay L, Gallucci M, Conti Nibali M, Leonetti A, et al. Is supratotal resection achievable in low-grade gliomas? Feasibility, putative factors, safety, and functional outcome. J Neurosurg 2019:1-4.  Back to cited text no. 12
    
13.
Yang K, Nath S, Koziarz A, Badhiwala JH, Ghayur H, Sourour M, et al. Biopsy versus subtotal versus gross total resection in patients with low-grade glioma: a systematic review and meta-analysis. World Neurosurg 2018;120:e762-e775.  Back to cited text no. 13
    
14.
Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, et al. Association of the extent of resection with survival in glioblastoma: A systematic review and meta-analysis. JAMA Oncol 2016;2:1460-9.  Back to cited text no. 14
    
15.
Uehara F, Hiroshima Y, Miwa S, Tome Y, Yano S, Yamamoto M, et al. Fluorescence-guided surgery of retroperitoneal-implanted human fibrosarcoma in nude mice delays or eliminates tumor recurrence and increases survival compared to bright-light surgery. PLoS One 2015;10:e0116865.  Back to cited text no. 15
    
16.
Fang H, Zhang H, Li L, Ni Y, Shi R, Li Z, et al. Rational design of a two-photon fluorogenic probe for visualizing monoamine oxidase a activity in human glioma tissues. Angew Chem Int Ed Engl 2020;59:7536-41.  Back to cited text no. 16
    
17.
Ontario Health (Quality). 5-Aminolevulinic Acid Hydrochloride (5-ALA)-Guided surgical resection of high-grade gliomas: A Health Technology Assessment. Ont Health Technol Assess Ser 2020;20:1-92.  Back to cited text no. 17
    
18.
Del Bene M, Perin A, Casali C, Legnani F, Saladino A, Mattei L, et al. Advanced ultrasound imaging in glioma surgery: Beyond Gray-Scale B-Mode. Front Oncol 2018;8:576.  Back to cited text no. 18
    
19.
Ng JCH, See AAQ, Ang TY, Tan LYR, Ang BT, King NKK. Effects of surgery on neurocognitive function in patients with glioma: A meta-analysis of immediate post-operative and long-term follow-up neurocognitive outcomes. J Neurooncol 2019;141:167-82.  Back to cited text no. 19
    
20.
Wijnenga MMJ, Mattni T, French PJ, Rutten GJ, Leenstra S, Kloet F, et al. Does early resection of presumed low-grade glioma improve survival? A clinical perspective. J Neurooncol 2017;133:137-46.  Back to cited text no. 20
    
21.
Li D, Zhang J, Chi C, Xiao X, Wang J, Lang L, et al. First-in-human study of PET and optical dual-modality image-guided surgery in glioblastoma using 68Ga-IRDye800CW-BBN. Theranostics 2018;8:2508-20.  Back to cited text no. 21
    
22.
Schneider M, Potthoff AL, Keil VC, Güresir Á, Weller J, Borger V, et al. Surgery for temporal glioblastoma: Lobectomy outranks oncosurgical-based gross-total resection. J Neurooncol 2019;145:143-50.  Back to cited text no. 22
    
23.
Ashby LS, Smith KA, Stea B. Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: A systematic literature review. World J Surg Oncol 2016;14:225.  Back to cited text no. 23
    
24.
Omuro A, Beal K, McNeill K, Young RJ, Thomas A, Lin X, et al. Multicenter phase IB trial of carboxyamidotriazole orotate and temozolomide for recurrent and newly diagnosed glioblastoma and other anaplastic gliomas. J Clin Oncol 2018;36:1702-9.  Back to cited text no. 24
    
25.
Bayart E, Pouzoulet F, Calmels L, Dadoun J, Allot F, Plagnard J, et al. Enhancement of IUdR radiosensitization by Low-Energy photons results from increased and persistent DNA damage. PLoS One 2017;12:e0168395.  Back to cited text no. 25
    
26.
Muroyama Y, Nirschl TR, Kochel CM, Lopez-Bujanda Z, Theodros D, Mao W, et al. Stereotactic radiotherapy increases functionally suppressive regulatory t cells in the tumor microenvironment. Cancer Immunol Res 2017;5:992-1004.  Back to cited text no. 26
    
27.
Sekhar KR, Wang J, Freeman ML, Kirschner AN. Radiosensitization by enzalutamide for human prostate cancer is mediated through the DNA damage repair pathway. PLoS One 2019;14:e0214670.  Back to cited text no. 27
    
28.
Sulman EP, Ismaila N, Armstrong TS, Tsien C, Batchelor TT, Cloughesy T, et al. Radiation therapy for glioblastoma: American society of clinical oncology clinical practice guideline endorsement of the american society for radiation oncology guideline. J Clin Oncol 2017;35:361-9.  Back to cited text no. 28
    
29.
Jackson S, Weingart J, Nduom EK, Harfi TT, George RT, McAreavey D, et al. The effect of an adenosine A (2A) agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma. Fluids Barriers CNS 2018;15:2.  Back to cited text no. 29
    
30.
Li X, Shao F, Sun J, Du K, Sun Y, Feng F. Enhanced copper-temozolomide interactions by protein for chemotherapy against glioblastoma multiforme. ACS Appl Mater Interfaces 2019;11:41935-45.  Back to cited text no. 30
    
31.
de Gooijer MC, de Vries NA, Buckle T, Buil LCM, Beijnen JH, Boogerd W, et al. Improved brain penetration and antitumor efficacy of temozolomide by inhibition of ABCB1 and ABCG2. Neoplasia 2018;20:710-20.  Back to cited text no. 31
    
32.
Liu HL, Huang CY, Chen JY, Wang HY, Chen PY, Wei KC. Pharmacodynamic and therapeutic investigation of focused ultrasound-induced blood-brain barrier opening for enhanced temozolomide delivery in glioma treatment. PLoS One 2014;9:e114311.  Back to cited text no. 32
    
33.
Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, et al. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): A randomised, open-label, phase 3 intergroup study. Lancet Oncol 2016;17:1521-32.  Back to cited text no. 33
    
34.
Muni R, Minniti G, Lanzetta G, Caporello P, Frati A, Enrici MM, et al. Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma. Tumori 2010;96:60-4.  Back to cited text no. 34
    
35.
Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, et al. Short-Course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 2017;376:1027-37.  Back to cited text no. 35
    
36.
Gao X, Yue Q, Liu Y, Fan D, Fan K, Li S, et al. Image-guided chemotherapy with specifically tuned blood brain barrier permeability in glioma margins. Theranostics 2018;8:3126-37.  Back to cited text no. 36
    
37.
Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. Radiation plus procarbazine, ccnu, and vincristine in low-grade glioma. N Engl J Med 2016;374:1344-55.  Back to cited text no. 37
    
38.
Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: Updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol 2015;16:1306-15.  Back to cited text no. 38
    
39.
Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): A multicentre, open-label, phase 3, randomised controlled trial. Lancet 2019;393:2404-15.  Back to cited text no. 39
    
40.
Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med 2017;377:1954-63.  Back to cited text no. 40
    
41.
van den Bent MJ, Klein M, Smits M, Reijneveld JC, French PJ, Clement P, 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. Lancet Oncol 2018;19:1170-9.  Back to cited text no. 41
    
42.
Grossmann P, Narayan V, Chang K, Rahman R, Abrey L, Reardon DA, et al. Quantitative imaging biomarkers for risk stratification of patients with recurrent glioblastoma treated with bevacizumab. Neuro Oncol 2017;19:1688-97.  Back to cited text no. 42
    
43.
Bockmayr M, Klauschen F, Maire CL, Rutkowski S, Westphal M, Lamszus K, et al. Immunologic profiling of mutational and transcriptional subgroups in pediatric and adult high-grade gliomas. Cancer Immunol Res 2019;7:1401-11.  Back to cited text no. 43
    
44.
Mackay A, Burford A, Carvalho D, Izquierdo E, Fazal-Salom J, Taylor KR, et al. Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell 2017;32:520-3700000.  Back to cited text no. 44
    
45.
Chen H, Judkins J, Thomas C, Wu M, Khoury L, Benjamin CG, et al. Mutant IDH1 and seizures in patients with glioma. Neurology 2017;88:1805-13.  Back to cited text no. 45
    
46.
Philip B, Yu DX, Silvis MR, Shin CH, Robinson JP, Robinson GL, et al. Mutant IDH1 promotes glioma formation in vivo. Cell Rep 2018;23:1553-64.  Back to cited text no. 46
    
47.
Lang FF, Conrad C, Gomez-Manzano C, Yung WKA, Sawaya R, Weinberg JS, et al. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: Replication and immunotherapeutic effects in recurrent malignant glioma. J Clin Oncol 2018;36:1419-27.  Back to cited text no. 47
    
48.
Martínez-Vélez N, Garcia-Moure M, Marigil M, González-Huarriz M, Puigdelloses M, Gallego Pérez-Larraya J, et al. The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Nat Commun 2019;10:2235.  Back to cited text no. 48
    
49.
Tejada S, Díez-Valle R, Domínguez PD, Patiño-García A, González-Huarriz M, Fueyo J, et al. DNX-2401, an oncolytic virus, for the treatment of newly diagnosed diffuse intrinsic pontine gliomas: A Case Report. Front Oncol 2018;8:61.  Back to cited text no. 49
    
50.
Marshall HT, Djamgoz MBA. Immuno-Oncology: Emerging targets and combination therapies. Front Oncol 2018;8:315.  Back to cited text no. 50
    
51.
Machicote A, Belén S, Baz P, Billordo LA, Fainboim L. Human CD8(+) HLA-DR(+) regulatory T cells, similarly to classical CD4(+) Foxp3(+) cells, suppress immune responses via PD-1/PD-L1 axis. Front Immunol 2018;9:2788.  Back to cited text no. 51
    
52.
Karihtala K, Leivonen SK, Brück O, Karjalainen-Lindsberg ML, Mustjoki S, Pellinen T, et al. Prognostic impact of tumor-associated macrophages on survival is checkpoint dependent in classical hodgkin lymphoma. Cancers (Basel) 2020;12:877.  Back to cited text no. 52
    
53.
Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, et al. First-Line nivolumab in stage iv or recurrent non-small-cell lung cancer. N Engl J Med 2017;376:2415-26.  Back to cited text no. 53
    
54.
Saha D, Martuza RL, Rabkin SD. Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade. Cancer Cell 2017;32:253-6700000.  Back to cited text no. 54
    
55.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. n engl J Med 2017;377:1345-56.  Back to cited text no. 55
    
56.
Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018;560:382-6.  Back to cited text no. 56
    
57.
Luo W, Wang Z, Tian P, Li W. Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: A meta-analysis of randomized controlled trials. J Cancer Res Clin Oncol 2018;144:1851-9.  Back to cited text no. 57
    
58.
Xing Q, Zhang ZW, Lin QH, Shen LH, Wang PM, Zhang S, et al. Myositis-myasthenia gravis overlap syndrome complicated with myasthenia crisis and myocarditis associated with anti-programmed cell death-1 (sintilimab) therapy for lung adenocarcinoma. Ann Transl Med 2020;8:250.  Back to cited text no. 58
    
59.
Gubin MM, Esaulova E, Ward JP, Malkova ON, Runci D, Wong P, et al. High-dimensional analysis delineates myeloid and lymphoid compartment remodeling during successful immune-checkpoint cancer therapy. Cell. 2018;175:1014-30 e19.  Back to cited text no. 59
    
60.
Nakashima H, Nguyen T, Kasai K, Passaro C, Ito H, Goins WF, et al. Toxicity and efficacy of a novel gadd34-expressing oncolytic hsv-1 for the treatment of experimental glioblastoma. Clin Cancer Res 2018;24:2574-84.  Back to cited text no. 60
    
61.
Passaro C, Alayo Q, De Laura I, McNulty J, Grauwet K, Ito H, et al. Arming an oncolytic herpes simplex virus type 1 with a single-chain fragment variable antibody against pd-1 for experimental glioblastoma therapy. Clin Cancer Res 2019;25:290-9.  Back to cited text no. 61
    
62.
Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, et al. Zika virus has oncolytic activity against glioblastoma stem cells. J Exp Med 2017;214:2843-57.  Back to cited text no. 62
    
63.
Mun EJ, Babiker HM, Weinberg U, Kirson ED, Von Hoff DD. Tumor-Treating Fields: A fourth modality in cancer treatment. Clin Cancer Res 2018;24:266-75.  Back to cited text no. 63
    
64.
Berkelmann L, Bader A, Meshksar S, Dierks A, Hatipoglu Majernik G, Krauss JK, et al. Tumour-treating fields (TTFields): Investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis. Sci Rep 2019;9:7362.  Back to cited text no. 64
    
65.
Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, et al. Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer cells. Sci Rep 2015;5:18046.  Back to cited text no. 65
    
66.
Kim EH, Jo Y, Sai S, Park MJ, Kim JY, Kim JS, et al. Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells. Oncogene 2019;38:6630-46.  Back to cited text no. 66
    
67.
Lok E, San P, Hua V, Phung M, Wong ET. Analysis of physical characteristics of tumor treating fields for human glioblastoma. Cancer Med 2017;6:1286-300.  Back to cited text no. 67
    
68.
Park JI, Song KH, Jung SY, Ahn J, Hwang SG, Kim J, et al. Tumor-Treating fields induce RAW264.7 macrophage activation via NK-κB/MAPK signaling pathways. Technol Cancer Res Treat 2019;18:1533033819868225.  Back to cited text no. 68
    
69.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444:756-60.  Back to cited text no. 69
    
70.
Giladi M, Munster M, Schneiderman RS, Voloshin T, Porat Y, Blat R, et al. Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells. Radiat Oncol 2017;12:206.  Back to cited text no. 70
    
71.
Karanam NK, Srinivasan K, Ding L, Sishc B, Saha D, Story MD. Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines. Cell Death Dis 2017;8:e2711.  Back to cited text no. 71
    
72.
Lopez Perez R, Nicolay NH, Wolf JC, Frister M, Schmezer P, Weber KJ, et al. DNA damage response of clinical carbon ion versus photon radiation in human glioblastoma cells. Radiother Oncol 2019;133:77-86.  Back to cited text no. 72
    
73.
Stachelek GC, Grimm J, Moore J, Huang E, Spoleti N, Redmond KJ, et al. Tumor-treating field arrays do not reduce target volume coverage for glioblastoma radiation therapy. Adv Radiat Oncol 2019;5:62-9.  Back to cited text no. 73
    
74.
Mohan S, Chawla S, Wang S, Verma G, Skolnik A, Brem S, et al. Assessment of early response to tumor-treating fields in newly diagnosed glioblastoma using physiologic and metabolic MRI: Initial experience. CNS Oncol 2016;5:137-44.  Back to cited text no. 74
    
75.
Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, et al. Effect of Tumor-Treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: A Randomized Clinical Trial. JAMA 2017;318:2306-16.  Back to cited text no. 75
    
76.
Taphoorn MJB, Dirven L, Kanner AA, Lavy-Shahaf G, Weinberg U, Taillibert S, et al. Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: A secondary analysis of a randomized clinical trial. JAMA Oncol 2018;4:495-504.  Back to cited text no. 76
    
77.
Bernard-Arnoux F, Lamure M, Ducray F, Aulagner G, Honnorat J, Armoiry X. The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma. Neuro Oncol 2016;18:1129-36.  Back to cited text no. 77
    
78.
Darge HF, Andrgie AT, Hanurry EY, Birhan YS, Mekonnen TW, Chou HY, et al. Localized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy. Int J Pharm 2019;572:118799.  Back to cited text no. 78
    



This article has been cited by
1 HOXA5 is amplified in glioblastoma stem cells and promotes tumor progression by transcriptionally activating PTPRZ1
Zhi-Cheng He, Qing Liu, Kai-Di Yang, Cong Chen, Xiao-Ning Zhang, Wen-Ying Wang, Hui Zeng, Bin Wang, Yu-Qi Liu, Min Luo, Lei Li, Qin Niu, Hui-Min Lu, Tao Luo, Xiao-Hong Yao, Hai-Tao Guo, Jia-Le Ji, Mian-Fu Cao, Yu Shi, Yi-Fang Ping, Xiu-Wu Bian
Cancer Letters. 2022; : 215605
[Pubmed] | [DOI]



 

Top
 
  Search
 
    Similar in PUBMED
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Database Search ...
Surgical Removal
Radiochemotherapy
Immuno- and Bio-...
Tumor-Treating F...
Summary
References

 Article Access Statistics
    Viewed3302    
    Printed102    
    Emailed0    
    PDF Downloaded190    
    Comments [Add]    
    Cited by others 1    

Recommend this journal