glioblastoma_treatment

Glioblastoma treatment



Treatment for glioblastoma typically includes a combination of surgery, radiation therapy, and chemotherapy. Surgery is typically the first step in treatment, with the goal of removing as much of the tumor as possible. Radiation therapy and chemotherapy are often used after surgery to help kill any remaining cancer cells. In some cases, additional treatments such as targeted therapy or immunotherapy may also be used. It's important to note that treatment options and recommendations can vary depending on the individual case and the patient's overall health. Additionally, the development of new treatment options is an active area of research.


As the biological challenges and genetic basis of glioblastoma have become more understood, new therapeutic strategies may lead to more durable clinical responses and long-term remissions 1)

Due to the lack of consensus, there exists variability amongst surgeons and centers regarding glioblastoma treatment decisions. Though, objective data about the extent of this heterogeneity is still lacking. Gerritsen et al. aimed to evaluate and analyze the similarities and differences in neurosurgical practice patterns.

The survey was distributed to members of the neurosurgical societies of the Netherlands (NVVN), Europe (EANS), the United Kingdom (SBNS), and the United States (CNS) between January and March 2021 with questions about the selection of surgical modality and decision making in glioblastoma patients.

Survey respondents (224 neurosurgeons) were from 41 countries. Overall, the most notable differences observed were the presence and timing of a multidisciplinary tumor board; the importance and role of various perioperative factors in the decision-making process, and the preferred treatment in various glioblastoma cases case variants. Tumor boards were more common at academic centers. The intended extent of resection for glioblastoma resections in eloquent areas was limited more often in European neurosurgeons. They found a strong relationship between the surgeon's theoretical survey answers and their actual approach in presented patient cases. In general, the factors which were found to be theoretically the most important in surgical decision-making were confirmed to influence the respondents' decisions to the greatest extent in practice as well.

This survey illustrates the theoretical and practical heterogeneity among surgeons and centers in their decision-making and treatment selection for glioblastoma patients. These data invite further evaluations to identify key variables that can be optimized and may therefore benefit from consensus 2).

The gold standard for High-Grade Glioma treatment recommends beginning chemoradiation within 6 weeks after. glioblastoma surgery.

The standard of care management for newly diagnosed glioblastoma multiforme (Glioblastoma) includes surgery, radiation, temozolomide (TMZ) chemotherapy, and tumor treating fields 3).

From 2005 chemotherapy with temozolomide, according to Stupp protocol 4) , particularly in patients that demonstrate MGMT promoter methylation.

Conflicting reports have emerged regarding the importance of the time interval between these 2 treatments and there is no clear association between duration from surgery to initiation of chemoradiation on overall survival (OS). 5).


Treatment consists of maximal safe resection, radiotherapy, and chemotherapy. Trials of patients with newly diagnosed grade III glioma have shown survival benefit from adding chemotherapy to radiotherapy compared with initial treatment using radiotherapy alone. Both temozolomide and the combination of procarbazine, lomustine, and vincristine provide survival benefit. In contrast, trials that compare single modality treatment of chemotherapy alone with radiotherapy alone did not observe survival differences. Currently, for patients with grade III gliomas who require postsurgical treatment, the preferred treatment consists of a combination of radiotherapy and chemotherapy 6).


After treatment, all patients have to undergo brain magnetic resonance imaging procedure quarterly or half-yearly for 5 years and then on an annual basis. In patients with recurrent tumor, wherever possible re-resection or re-irradiation or chemotherapy can be considered along with supportive and palliative care. High-grade malignant glioma should be managed in a multidisciplinary center

The criteria used to assess extent of resection (EOR) have an impact on findings of association between EOR and survival. Current assessment of EOR mainly relies on pre and postoperative contrast-enhanced T1 weighted images (CE-T1WI).

This method is subject to several inherent limitations, including failure to evaluate nonenhancing components of glioma.

To solve this problem, fluid attenuated inversion recovery (FLAIR) imaging is added in the RANO criteria 7).


From the introduction of the first standard of care (SOC) established in 2005 in patients with a new diagnosis of Glioblastoma, 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 Glioblastoma 8).

Antiepileptic medications may increase radiosensitivity, and therefore improve clinical outcomes, specifically in glioblastoma multiforme patients 9).


The recommended treatment for MGMT promoter unmethylated glioblastoma (Glioblastoma) is radiation therapy with concurrent/adjuvant temozolomide (TMZ).

Although overall survival (OS) is the standard for determining Glioblastoma treatment efficacy, using OS as an endpoint when studying new therapeutic strategies can be problematic because of potential influence of therapies prior to or subsequently following the therapy being studied. For example, it is difficult to definitively conclude that bevacizumab has no efficacy in Glioblastoma when a large percentage of patients in the placebo arms in both III trials studying efficacy of bevacizumab (i.e. AVAglio and RTOG 0825) eventually crossed over and received bevacizumab (31% in AVAglio) 10) and 48% in RTOG-0825 11). If bevacizumab increased OS when given at any time during treatment, we may expect both treatment arms to have similar median OS since most patients eventually were treated with bevacizumab, disguising any therapeutic effects of the drug. Together, these results suggest OS may not be a suitable endpoint when studying new therapeutics or when there is a high chance of cross over in the control arm 12).

To overcome the limitations associated with using OS as the primary endpoint in studies involving new therapeutics, progression free survival (PFS) and objective response rate (ORR) should be considered important end points 13).


1)
Binder ZA, O'Rourke DM. Glioblastoma: The Current State of Biology and Therapeutic Strategies. Cancer Res. 2022 Mar 1;82(5):769-772. doi: 10.1158/0008-5472.CAN-21-3534. PMID: 35247893.
2)
Gerritsen JKW, Broekman MLD, De Vleeschouwer S, Schucht P, Jungk C, Krieg SM, Nahed BV, Berger MS, Vincent AJPE. Decision making and surgical modality selection in glioblastoma patients: an international multicenter survey. J Neurooncol. 2022 Jan 24. doi: 10.1007/s11060-021-03894-5. Epub ahead of print. PMID: 35067847.
3)
Stupp R, Taillibert S, Kanner A et al (2017) Effect of tumortreating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 318:2306–2316
4)
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. PubMed PMID: 15758009.
5)
Osborn VW, Lee A, Garay E, Safdieh J, Schreiber D. Impact of Timing of Adjuvant Chemoradiation for Glioblastoma in a Large Hospital Database. Neurosurgery. 2018 Nov 1;83(5):915-921. doi: 10.1093/neuros/nyx497. PubMed PMID: 29092047.
6)
van den Bent MJ, Smits M, Kros JM, Chang SM. Diffuse Infiltrating Oligodendroglioma and Astrocytoma. J Clin Oncol. 2017 Jul 20;35(21):2394-2401. doi: 10.1200/JCO.2017.72.6737. Epub 2017 Jun 22. Review. PubMed PMID: 28640702.
7)
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al: Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972, 2010
8)
Montemurro N. Glioblastoma Multiforme and Genetic Mutations: The Issue Is Not Over Yet. An Overview of the Current Literature. J Neurol Surg A Cent Eur Neurosurg. 2019 Sep 24. doi: 10.1055/s-0039-1688911. [Epub ahead of print] PubMed PMID: 31550738.
9)
Julie DAR, Ahmed Z, Karceski SC, Pannullo SC, Schwartz TH, Parashar B, Wernicke AG. An overview of anti-epileptic therapy management of patients with malignant tumors of the brain undergoing radiation therapy. Seizure. 2019 Jun 12;70:30-37. doi: 10.1016/j.seizure.2019.06.019. [Epub ahead of print] Review. PubMed PMID: 31247400.
10)
Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. doi: 10.1056/NEJMoa1308345. PubMed PMID: 24552318.
11)
Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. doi: 10.1056/NEJMoa1308573. PubMed PMID: 24552317; PubMed Central PMCID: PMC4201043.
12)
Ellingson BM, Wen PY, Cloughesy TF. Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials. Neurotherapeutics. 2017 Apr;14(2):307-320. doi: 10.1007/s13311-016-0507-6. Review. PubMed PMID: 28108885; PubMed Central PMCID: PMC5398984.
13)
Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, Robins HI, Lieberman FS, Fine HA, Fink KL, Junck L, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Hibberts J, Peterson PM, Prados MD; North American Brain Tumor Consortium. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol. 2008 Apr;10(2):162-70. doi: 10.1215/15228517-2007-062. Epub 2008 Mar 4. PubMed PMID: 18356283; PubMed Central PMCID: PMC2613818.
  • glioblastoma_treatment.txt
  • Last modified: 2023/01/19 12:51
  • by 127.0.0.1