Efficacy of sequential radiation and chemotherapy in treating glioblastoma with poor performance status

Parr, Elsa; Baine, Michael J.; Shonka, Nicole; Wang, Tony J. C.; Zhang, Chi

doi:10.1007/s11060-020-03402-1

Cited by 4 publications

(2 citation statements)

References 11 publications

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“…Although the outcomes of the former study are getting more and more out of date and those of the latter have limitations related to a database review, both the Lamborn analysis and NCDP data showed negative results. [36,37] Notably, HRT was either not used or not evaluated. When SRT is used with concurrent chemotherapy, patients with KPS 70 have shown varying degrees of success in terms of survival.…”

Section: Discussionmentioning

confidence: 99%

A Review on the Role of Hypofractionated Radiotherapy in High-Grade Glioma Patients

Sakib¹

2022

Preprint

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High-grade gliomas (HGG) comprise WHO grade III anaplastic astrocytoma (AA) and WHO grade IV glioblastoma (GBM). Even WHO grade II, IDH-wild type gliomas may be categorized as HGG since genetic abnormalities are predictive. Surgery, radiation therapy (RT), chemotherapy, and combinations thereof are currently used to treat HGG. Patients with GBM and low-performance status who are elderly (defined here as age 60 or more) do far worse in terms of survival than younger patients. Surgery and chemoradiation are the mainstays of care for treating HGG. The best course of treatment for old and/or underperforming individuals, who typically have worse prognoses, is still up for debate. Elderly individuals treated with radiation therapy (RT) have better survival rates than those receiving only the best supportive care (BSC), but patients receiving both conventional RT and hypofractionated RT have equal survival rates.

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Section: Discussionmentioning

confidence: 99%

A Review on the Role of Hypofractionated Radiotherapy in High-Grade Glioma Patients

Sakib¹

2022

Preprint

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“…A logical solution to improve tolerance to therapy for these patients would be sequential delivery of treatment. The Lamborn analysis and NCDP data (21,86) both showed disappointing results although the results of the former study are increasingly dated and the latter one has the drawbacks associated with a database review. Of note, HRT was either not used or not assessed.…”

Section: Patients With Poor Performance Statusmentioning

confidence: 99%

Narrative review of palliative hypofractionated radiotherapy for high grade glioma

Saeed¹,

Tseng²

2021

Ann Palliat Med

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High grade gliomas (HGG) include World Health Organization (WHO) grade III anaplastic astrocytoma (AA) and WHO grade IV glioblastoma (GBM). As genomic alterations are prognostic, even WHO grade II, IDH-wildtype gliomas may be considered as HGG. Current management of HGG include best supportive care (BSC), surgery, radiation therapy (RT), chemotherapy, and a combination. Elderly patients (defined here as age ≥65) with GBM have significantly worse survival compared to younger patients.Similarly, patients with poor performance status [defined as Karnofsky performance status (KPS) <60 or ECOG performance status (PS) >2], regardless of age have worse outcomes. The standard of care for treatment of HGG involves surgery and chemoradiation. However, the optimal treatment in terms of efficacy, safety and maintaining quality of life (QoL), remains a matter of debate in the elderly and/or poor performing patients due to their worse prognosis. Less aggressive interventions are usually reserved for these patients despite surgery providing a survival and neurologic benefit. Improved survival has been noted in elderly patients treated with RT in comparison with those receiving best supportive care (BSC) alone, with similar survival for patients undergoing standard RT (60 Gy/30 fractions) and hypofractionated RT (25-40 Gy in 5-15 daily fractions). An alkylating agent, temozolomide (TMZ), represents a safe and effective option in select patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene. A recent phase III randomized trial for GBM patients (age ≥65 years, ECOG PS 0-2) demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS) with hypofractionated RT (40 Gy/15 fractions) with concurrent and adjuvant TMZ vs. RT alone, without adversely impacting either QoL or functional status. Despite chemoradiation becoming the recommended treatment in GBM patients who are elderly but fit, several questions remain unanswered. This includes the survival impact of chemoradiation in patients with severe comorbidities or with ECOG PS >2 or a combination of poor prognostic features such as male gender, poor neurocognition, biopsy only and lack of MGMT methylation.Personalized management of patients with HGG is warranted in the modern era as we attempt to balance the benefit of efficacious treatment with potential toxicity while appreciating the many nuances associated with multiple prognostic factors on anticipated survival. Here, we aim to review the palliative management options available for HGG patients with an emphasis on the role of RT.

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Preparation of transferrin-targeted temozolomide nano-micelles and their anti-glioma effect

Yu,

Xue

2024

PeerJ

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Objectives This study aims to develop brain-targeted temozolomide (TMZ) nanograins using the biodegradable polymer material PEG-PLA as a carrier. The model drug TMZ was encapsulated within the polymer using targeted nanotechnology. Key characteristics such as appearance, particle size, size distribution, drug loading capacity, in vitro release rate, stability, and anti-tumor effects were systematically evaluated through in vitro experiments. Methods Transmission electron microscopy (TEM) and Malvern size analyzer were employed to observe the morphological and particle size features of the TMZ nanospheres at various time points to assess stability. The effects of TMZ nanograins on glioma cell viability and apoptosis were evaluated using MTT assays and flow cytometry. Results The targeted TMZ nano-micelles were successfully synthesized. After loading and targeted modifications, the particle size increased from 50.7 to 190 nm, indicating successful encapsulation of TMZ. The average particle size of the nano-micelles remained stable around 145 ± 10 nm at 1 day, 15 days, and 30 days post-preparation. The release rate of the nano-micelles was monitored at 2 h, 12 h, 24 h, and 48 h post-dialysis, ultimately reaching 95.8%. Compared to TMZ alone, the TMZ-loaded PEG-PLA nano-micelles exhibited enhanced cytotoxicity and apoptosis in glioma cells. This was accompanied by increased mitochondrial membrane potential and reactive oxygen species (ROS) levels following treatment with the TMZ nano-micelles. Conclusions TMZ-loaded nano-micelles demonstrated a gradual release profile and significantly enhanced inhibitory effects on human glioma U251 cells compared to TMZ alone. The findings suggest that TMZ-loaded PEG-PLA nano-micelles may offer a more effective therapeutic approach for glioma treatment.

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Efficacy of sequential radiation and chemotherapy in treating glioblastoma with poor performance status

Cited by 4 publications

References 11 publications

A Review on the Role of Hypofractionated Radiotherapy in High-Grade Glioma Patients

A Review on the Role of Hypofractionated Radiotherapy in High-Grade Glioma Patients

Narrative review of palliative hypofractionated radiotherapy for high grade glioma

Preparation of transferrin-targeted temozolomide nano-micelles and their anti-glioma effect

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