Outcomes in Glioblastoma Patients: From Diagnosis to Palliation

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 10 September 2025 | Viewed by 10452

Special Issue Editors


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Guest Editor
Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
Interests: functional neurosurgery; cerebrovascular disease; neuro-oncology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Neurosurgery Unit, Department of Translational Medicine and for Romagna, University of Ferrara, Ferrara, Italy
Interests: neuro-oncology; pain treatment; functional neurosurgery; CSF physiology

Special Issue Information

Dear Colleagues,

One of the most challenging aspects in the treatment of high grade glioma (HGG) is the outcome assessment and the subsequent prognostic prevision. With the advancement of technical possibilities, it becomes fundamental to pursue a patient-tailored approach that takes into account a multitude of variables, including clinical, radiological, biomolecular and personal factors. This is particularly true for HGG patients that face the tremendous impact of such an aggressive tumor, as at each step of cure, a fundamental decision has to be made where every element is crucial. The most known example of a prognostic factor in HGG is the MGMT promoter methylation status and the response to alkylating agent chemotherapy, but many others are now under consideration in laboratory and clinical practice. From the first radiological evaluation to supportive end-of-life care, outcome assessment and prevision are of the utmost importance in HGG patient’s management to avoid both under or over treatments. This Special Issue will focus on the recent evidence on HGG’s Quoad vitam prognosis (prognostic radiological, clinical, biological, and genetical markers) and Quoad valetudinem prognosis (neurological and functional assessment of HGG patients, before and after therapy, including the psycho-social well-being of patients and caregivers).

Dr. Alba Scerrati
Dr. Giorgio Mantovani
Guest Editors

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Keywords

  • high-grade glioma
  • outcome assessment
  • prognostic factors
  • neuro-oncology
  • glioblastoma

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Published Papers (5 papers)

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Research

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11 pages, 1073 KiB  
Article
High-Grade Glioma Recurrence Is Delayed in Hispanic Patients despite Severe Social Vulnerability: A Retrospective Cohort Study
by Joshua A. Reynolds, Isabella L. Pecorari, Alexander Ledet and Vijay Agarwal
Cancers 2024, 16(8), 1579; https://doi.org/10.3390/cancers16081579 - 20 Apr 2024
Cited by 2 | Viewed by 1179
Abstract
High-grade gliomas (HGGs; WHO grade III or IV) are the most common and lethal brain malignancy. Patients of Hispanic ethnicity are diagnosed with HGGs earlier than non-Hispanic patients, but they exhibit improved HGG survival following diagnosis. Either environmental or biological factors could explain [...] Read more.
High-grade gliomas (HGGs; WHO grade III or IV) are the most common and lethal brain malignancy. Patients of Hispanic ethnicity are diagnosed with HGGs earlier than non-Hispanic patients, but they exhibit improved HGG survival following diagnosis. Either environmental or biological factors could explain this survival benefit. We aimed to determine if post-diagnosis advantages would still be present in Hispanic patients with high social vulnerability, an environmental condition predisposing patients to poor oncologic outcomes. HGG outcomes were retrospectively assessed in a cohort of 22 Hispanic patients and 33 non-Hispanic patients treated for HGGs from 2015 to 2020 at a single institution that serves a highly vulnerable region. Compared to non-Hispanic patients, Hispanic patients demonstrated higher social vulnerability index scores (96.8 + 0.7 vs. 76.3 + 4.6; *** p = 0.0002) and a 14-month longer interval between diagnosis and recurrence (19.7 + 5.9 (n = 13) vs. 5.5 + 0.6 months (n = 19); ** p = 0.001). In only those patients with more aggressive IDH-1 wildtype tumors (glioblastoma), Hispanic ethnicity still related to a longer time before recurrence (15.8 + 5.9 months (n = 9); 5.5 + 0.6 months (n = 18); * p = 0.034), and in a multivariate analysis, Hispanic ethnicity predicted time-to-recurrence (* p = 0.027) independent of patient age, functional status, MGMT gene methylation, or treatments received. Therefore, environmental factors, specifically social vulnerability, did not obscure the post-diagnosis benefits associated with Hispanic ethnicity. In future experiments, basic studies should be prioritized which investigate the cellular or genetic mechanisms underlying this ethnicity effect on HGG progression in the hopes of improving care for these devastating malignancies. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
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Review

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25 pages, 2438 KiB  
Review
Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
by Miguel Muñoz and Marisa Rosso
Cancers 2025, 17(3), 520; https://doi.org/10.3390/cancers17030520 - 4 Feb 2025
Viewed by 1147
Abstract
Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brainstem tumor. The median survival of DIPG is 16–24 months independent of the treatment received. Therefore, new therapeutic strategies against DIPG are urgently needed. Substance P (SP) peptide, through the neurokinin neurokinin-1 [...] Read more.
Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brainstem tumor. The median survival of DIPG is 16–24 months independent of the treatment received. Therefore, new therapeutic strategies against DIPG are urgently needed. Substance P (SP) peptide, through the neurokinin neurokinin-1 receptor (NK-1R), is involved in glioma progression. It induces glioma cell proliferation by activating MAPKs (p38 MAPK, ERK1/2, and JNK), c-Myc, AP-1, and NF-κB and induces antiapoptotic effects via PI3K/Akt/mTOR in glioma cells. SP favors glycogen breakdown that is essential for glycolysis. The SP/NK-1R system also regulates the migration and invasion of glioma cells, stimulates angiogenesis, and triggers inflammation which contributes to glioma progression. Moreover, all glioma cells express NK-1R, and NK-1R is essential for the viability of glioma cells and not of normal cells. In contrast, in glioma, NK-1R antagonists, such as the drug aprepitant, penetrate the brain and reach therapeutic concentrations, thereby inhibiting mitogenesis, inducing apoptosis, and inhibiting the breakdown of glycogen in glioma cells. In addition, they inhibit angiogenesis and exert antimetastatic and anti-inflammatory effects. The combination of radiotherapy with NK-1R antagonists produces radiosensitization and radioneuroprotection, reduces both peritumoral- and radiation-induced inflammation, and also provides antinausea and antivomiting effects. Objective: This review updates the involvement of the SP/NK-1R system in glioma promotion and progression and the potential clinical application of NK-1R antagonist drugs in DIPG therapy. Conclusions: NK-1R plays a crucial role in glioma progression and NK-1R antagonists such as aprepitant could be used in combination with radiotherapy as a potent therapeutic strategy for the treatment of patients with DIPG. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
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17 pages, 303 KiB  
Review
Glioblastoma: Clinical Presentation, Multidisciplinary Management, and Long-Term Outcomes
by David Sipos, Bence L. Raposa, Omar Freihat, Mihály Simon, Nejc Mekis, Patrizia Cornacchione and Árpád Kovács
Cancers 2025, 17(1), 146; https://doi.org/10.3390/cancers17010146 - 5 Jan 2025
Cited by 2 | Viewed by 2614
Abstract
Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, and poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy and concurrent [...] Read more.
Glioblastoma, the most common and aggressive primary brain tumor in adults, presents a formidable challenge due to its rapid progression, treatment resistance, and poor survival outcomes. Standard care typically involves maximal safe surgical resection, followed by fractionated external beam radiation therapy and concurrent temozolomide chemotherapy. Despite these interventions, median survival remains approximately 12–15 months, with a five-year survival rate below 10%. Prognosis is influenced by factors such as patient age, molecular characteristics, and the extent of resection. Patients with IDH-mutant tumors or methylated MGMT promoters generally have improved survival, while recurrent glioblastoma is associated with a median survival of only six months, as therapies in these cases are often palliative. Innovative treatments, including TTFields, add incremental survival benefits, extending median survival to around 20.9 months for eligible patients. Symptom management—addressing seizures, headaches, and neurological deficits—alongside psychological support for patients and caregivers is essential to enhance quality of life. Emerging targeted therapies and immunotherapies, though still limited in efficacy, show promise as part of an evolving treatment landscape. Continued research and clinical trials remain crucial to developing more effective treatments. This multidisciplinary approach, incorporating diagnostics, personalized therapy, and supportive care, aims to improve outcomes and provides a hopeful foundation for advancing glioblastoma management. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
22 pages, 377 KiB  
Review
Advances in Glioblastoma Diagnosis: Integrating Genetics, Noninvasive Sampling, and Advanced Imaging
by Ryan Gough, Randall W. Treffy, Max O. Krucoff and Rupen Desai
Cancers 2025, 17(1), 124; https://doi.org/10.3390/cancers17010124 - 2 Jan 2025
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Abstract
Glioblastoma is the most common primary brain tumor in adult patients, and despite standard-of-care treatment, median survival has remained less than two years. Advances in our understanding of molecular mutations have led to changes in the diagnostic criteria of glioblastoma, with the WHO [...] Read more.
Glioblastoma is the most common primary brain tumor in adult patients, and despite standard-of-care treatment, median survival has remained less than two years. Advances in our understanding of molecular mutations have led to changes in the diagnostic criteria of glioblastoma, with the WHO classification integrating important mutations into the grading system in 2021. We sought to review the basics of the important genetic mutations associated with glioblastoma, including known mechanisms and roles in disease pathogenesis/treatment. We also examined new advances in image processing as well as less invasive and noninvasive diagnostic tools that can aid in the diagnosis and surveillance of those undergoing treatment for glioblastoma. Our review is intended to serve as an overview of the current state-of-the-art in the diagnosis and management of glioblastoma. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
17 pages, 4664 KiB  
Review
Risk Factors of Distant Recurrence and Dissemination of IDH Wild-Type Glioblastoma: A Single-Center Study and Meta-Analysis
by Takahiro Tsuchiya, Daisuke Kawauchi, Makoto Ohno, Yasuji Miyakita, Masamichi Takahashi, Shunsuke Yanagisawa, Sho Osawa, Shohei Fujita, Takaki Omura and Yoshitaka Narita
Cancers 2024, 16(16), 2873; https://doi.org/10.3390/cancers16162873 - 18 Aug 2024
Cited by 1 | Viewed by 2432
Abstract
Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) is a highly aggressive brain tumor with a high recurrence rate despite adjuvant treatment. This study aimed to evaluate the risk factors for non-local recurrence of GBM. In the present study, we analyzed 104 GBMs [...] Read more.
Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) is a highly aggressive brain tumor with a high recurrence rate despite adjuvant treatment. This study aimed to evaluate the risk factors for non-local recurrence of GBM. In the present study, we analyzed 104 GBMs with a single lesion (non-multifocal or multicentric). Univariate analysis revealed that subventricular zone (SVZ) involvement was significantly associated with non-local recurrence (hazard ratio [HR]: 2.09 [1.08–4.05]). Tumors in contact with the trigone of the lateral ventricle tended to develop subependymal dissemination (p = 0.008). Ventricular opening via surgery did not increase the risk of non-local recurrence in patients with SVZ involvement (p = 0.190). A systematic review was performed to investigate the risk of non-local recurrence, and 21 studies were identified. A meta-analysis of previous studies confirmed SVZ involvement (odds ratio [OR]: 1.30 [1.01–1.67]) and O-6-methylguanine DNA methyltransferase promoter methylation (OR: 1.55 [1.09–2.20]) as significant risk factors for local recurrence. A time-dependent meta-analysis revealed a significant association between SVZ involvement and dissemination (HR: 1.69 [1.09–2.63]), while no significant association was found for distant recurrence (HR: 1.29 [0.74–2.27]). Understanding SVZ involvement and specific tumor locations associated with non-local recurrence provides critical insights for the management of GBM. Full article
(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation)
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