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Radiation Oncology (London, England) Mar 2024Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival...
PURPOSE/OBJECTIVE(S)
Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT).
MATERIALS/METHODS
Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS.
RESULTS
Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies.
CONCLUSION
These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.
Topics: Humans; Glioblastoma; Temozolomide; Brain Neoplasms; Lymphopenia
PubMed: 38481255
DOI: 10.1186/s13014-023-02393-3 -
BMC Cancer Feb 2024Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.
METHODS
Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs).
RESULTS
A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities.
CONCLUSIONS
In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).
Topics: Humans; Temozolomide; Neuroendocrine Tumors; Response Evaluation Criteria in Solid Tumors; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38347461
DOI: 10.1186/s12885-024-11926-2 -
International Journal of Molecular... Nov 2023Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action.... (Meta-Analysis)
Meta-Analysis Review
Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol's anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol's effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect's weighted standardized difference in means was -2.046 (95%CI: -3.156 to -0.936; -value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models.
Topics: Humans; Rats; Mice; Animals; Temozolomide; Resveratrol; Cell Line, Tumor; Glioma; Brain Neoplasms; Models, Animal
PubMed: 38068922
DOI: 10.3390/ijms242316597 -
Journal of Neuro-oncology Aug 2023Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role.
METHODS
We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method.
RESULTS
Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53-0.75; p < 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6-41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4-21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (p < 0.001).
CONCLUSIONS
Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.
Topics: Humans; Glioblastoma; Temozolomide; Electric Stimulation Therapy; Brain Neoplasms; Combined Modality Therapy
PubMed: 37493865
DOI: 10.1007/s11060-023-04348-w -
Current Oncology (Toronto, Ont.) Feb 2023Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most... (Review)
Review
Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
Topics: Humans; Temozolomide; Retrospective Studies; Prospective Studies; Brain Neoplasms; Glioma; Chronotherapy; Randomized Controlled Trials as Topic
PubMed: 36826108
DOI: 10.3390/curroncol30020147 -
Journal of Neuro-oncology Nov 2022Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally... (Meta-Analysis)
Meta-Analysis
Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature.
PURPOSE
Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup.
METHODS
Hospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed.
RESULTS
41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80-90% were ECOG 0-1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0-2% Grade 3 radionecrosis rates.
CONCLUSION
HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.
Topics: Humans; Middle Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; COVID-19; Glioblastoma; Pandemics; Temozolomide
PubMed: 36355260
DOI: 10.1007/s11060-022-04151-z -
Neurology India 2022Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro...
OBJECTIVES
Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro ectodermal differentiation (GBM-PNET) with unknown behavior.
MATERIALS
We conducted a systematic review and individual patient data analysis of these rare GBM variants. We searched PubMed, google search, and Cochrane library for eligible studies till July 1 2016 published in English language and collected data regarding age, sex, subtype and treatment received, Progression Free Survival (PFS), Overall Survival (OS). Statistical Package for social sciences (SPSS) v16 software was used for all statistical analysis.
RESULTS
We retrieved data of 196 patients with rare GBM subtypes. Among these GBM-GC is commonest (51%), followed by GBM-R (19%), GBM-PNET (13%), GBM-SC (9%) and GBM-E (8%). Median age at diagnosis was 38, 40, 43.5, 69.5 and 18 years, respectively. Male: female ratio was 2:1 for GBM-E, and 1:3 for GBM-SC. Maximal safe resection followed by adjuvant local radiation was used for most of the patients. However, 6 patients with GBM-PNET, 3 each of GBM-E, GBM-SC received adjuvant craniospinal radiation. Out of 88 patients who received chemotherapy, 64 received Temozolomide alone or combination chemotherapy containing Temozolomide. Median PFS and OS for the entire cohort were 9 and 16 months. In univariate analysis, patient with a Gross Total Resection had significantly better PFS and OS compared to those with a Sub Total Resection [23 vs. 13 months (p-0.01)]. Median OS for GBM PNET, GBM-GC, GBM-SC, GBM-R and GBM-E were 32, 18.3, 11, 12 and 7.7 months, respectively (P = 0.001). Interestingly, 31.3%, 37.8% of patients with GBM-E, GBM-R had CSF dissemination.
CONCLUSION
Overall cohort of rarer GBM variant has equivalent survival compared to GBM not otherwise specified. However, epithelioid and Rhabdoid GBM has worst survival and one third shows CSF dissemination.
Topics: Humans; Male; Female; Glioblastoma; Temozolomide; Data Analysis; Brain Neoplasms; Retrospective Studies; Neuroectodermal Tumors, Primitive; Antineoplastic Agents, Alkylating
PubMed: 36352613
DOI: 10.4103/0028-3886.359222 -
Journal of Controlled Release :... Sep 2022Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated... (Review)
Review
Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated with glioma pathogenesis. Thus, miRNAs represent potential therapeutic agents for treating gliomas. However, miRNAs have not been established as part of the regular clinical armamentarium. This systemic review evaluates current molecular and pre-clinical studies with the aim of defining the most appealing supramolecular platform for administering therapeutic miRNA to patients with gliomas. An integrated analysis suggested that cationic lipid nanoparticles, functionalized with octa-arginine peptides, represent a potentially specific, practical, non-invasive intervention for treating gliomas. This supramolecular platform allows loading both hydrophilic (miRNA) and hydrophobic (anti-tumor drugs, like temozolomide) molecules. This systemic review is the first to describe miRNA delivery systems targeted to gliomas that integrate several types of molecules as active ingredients. Further experimental validation is warranted to confirm the practical value of miRNA delivery systems.
Topics: Arginine; Brain Neoplasms; Glioma; Humans; Liposomes; MicroRNAs; Nanoparticles; Peptides; Temozolomide
PubMed: 35905783
DOI: 10.1016/j.jconrel.2022.07.027 -
Neurology India 2022Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma. (Review)
Review
BACKGROUND
Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma.
OBJECTIVE
We conducted a systematic review to determine seizure outcomes in glioma patients treated with TMZ.
METHODS AND MATERIAL
We searched EMBASE and PubMed databases (January 1, 2003-August 26, 2021) by using search terms closely related to glioma, seizure, and temozolomide. Titles, abstracts, and full texts were screened and selected using previously established inclusion and exclusion criteria. The research team members reviewed potential articles and reached a consensus on the final articles to be included.
RESULTS
Nine studies containing data from three continents met our inclusion criteria. From several descriptive studies on low-grade gliomas (LGGs), the percentage of patients with partial seizure control after TMZ treatment ranged from 29% to 89.7%, and the percentage of patients with complete seizure control after TMZ ranged from 19.4% to 72%. In a retrospective cohort study of patients with LGGs, there was a marked difference in decreased seizure frequency between patients receiving TMZ and those who did not receive TMZ. In a randomized trial, TMZ seemed to have little effect on seizure control in elderly patients with glioblastoma.
CONCLUSIONS
At present, there are few high-quality and well-designed clinical studies on TMZ for gliomas-related seizures. In terms of the literature included in this review, TMZ has an inhibitory effect on epilepsy. More randomized controlled trials are needed to elucidate the clinical benefits of TMZ in the treatment of gliomas-related seizures.
Topics: Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Glioma; Humans; Randomized Controlled Trials as Topic; Retrospective Studies; Seizures; Temozolomide
PubMed: 35864610
DOI: 10.4103/0028-3886.349588 -
BMC Cancer Nov 2021Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that...
BACKGROUND
Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.
METHODS
We searched Medline and Embase (Jan 1994-Jan 2021) for studies evaluating the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Key data items included type of cell lines, temozolomide exposure duration in hours (hr), and cell viability measure (IC).
RESULTS
We included 212 studies from 2789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0-27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC, the median value for U87 at 24 h, 48 h and 72 h was 123.9 μM (IQR 75.3-277.7 μM), 223.1 μM (IQR 92.0-590.1 μM) and 230.0 μM (IQR 34.1-650.0 μM), respectively. The median IC at 72 h for patient-derived cell lines was 220 μM (IQR 81.1-800.0 μM).
CONCLUSION
Temozolomide sensitivity reported in comparable studies was not consistent between or within malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.
Topics: Animals; Antineoplastic Agents, Alkylating; Bias; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Glioma; Humans; In Vitro Techniques; Mice; Temozolomide
PubMed: 34794398
DOI: 10.1186/s12885-021-08972-5