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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 -
Journal of Cancer Research and Clinical... Jan 2024Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive... (Review)
Review
BACKGROUND
Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive biomarker associated with improved overall survival (OS). In response to the clinical need, recent studies have focused on the development of non-invasive artificial intelligence (AI)-based methods for MGMT estimation. In this systematic review, we not only delve into the technical aspects of these AI-driven MGMT estimation methods but also emphasize their profound clinical implications. Specifically, we explore the potential impact of accurate non-invasive MGMT estimation on GBM patient care and treatment decisions.
METHODS
Employing a PRISMA search strategy, we identified 33 relevant studies from reputable databases, including PubMed, ScienceDirect, Google Scholar, and IEEE Explore. These studies were comprehensively assessed using 21 diverse attributes, encompassing factors such as types of imaging modalities, machine learning (ML) methods, and cohort sizes, with clear rationales for attribute scoring. Subsequently, we ranked these studies and established a cutoff value to categorize them into low-bias and high-bias groups.
RESULTS
By analyzing the 'cumulative plot of mean score' and the 'frequency plot curve' of the studies, we determined a cutoff value of 6.00. A higher mean score indicated a lower risk of bias, with studies scoring above the cutoff mark categorized as low-bias (73%), while 27% fell into the high-bias category.
CONCLUSION
Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.
Topics: Humans; Glioblastoma; Artificial Intelligence; Reproducibility of Results; DNA Methylation; Brain Neoplasms; DNA Modification Methylases; DNA Repair Enzymes; DNA; Tumor Suppressor Proteins
PubMed: 38291266
DOI: 10.1007/s00432-023-05566-5 -
International Journal of Molecular... Jan 2024High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT),... (Review)
Review
High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT), chemotherapy (CMT), and surgical resection. Despite the progress made in traditional treatments, the outlook for patients with HGGs remains bleak. Tumor metabolism is emerging as a potential target for glioma therapies, a promising approach that harnesses the metabolism to target tumor cells. However, the efficacy of therapies targeting the metabolism of HGGs remains unclear, compelling a comprehensive review. This study aimed to assess the outcome of present trials on HGG therapies targeting metabolism. A comprehensive search of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted until November 2023. The search method used pertinent Medical Subject Heading (MeSH) terminologies and keywords referring to "high-grade gliomas", "metabolism", "target therapies", "monoclonal antibodies", "overall survival", and "progression-free survival". The review analyzed studies that focused on therapies targeting the metabolism of HGGs in human subjects. These studies included both randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs). Out of 284 articles identified, 23 trials met the inclusion criteria and were thoroughly analyzed. Phase II trials were the most numerous (62%). Targeted metabolic therapies were predominantly used for recurrent HGGs (67%). The most common targeted pathways were the vascular endothelial growth factor (VEGF, 43%), the human epidermal growth factor receptor (HER, 22%), the platelet-derived growth factor (PDGF, 17%), and the mammalian target of rapamycin (mTOR, 17%). In 39% of studies, the subject treatment was combined with CMT (22%), RT (4%), or both (13%). The median OS widely ranged from 4 to 26.3 months, while the median PFS ranged from 1.5 to 13 months. This systematic literature review offers a thorough exploration of the present state of metabolic therapies for HGGs. The multitude of targeted pathways underscores the intricate nature of addressing the metabolic aspects of these tumors. Despite existing challenges, these findings provide valuable insights, guiding future research endeavors. The results serve as a foundation for refining treatment strategies and enhancing patient outcomes within the complex landscape of HGGs.
Topics: Humans; Glioma; Neuroglia; Aggression; Antibodies, Monoclonal; ErbB Receptors; Platelet-Derived Growth Factor
PubMed: 38255798
DOI: 10.3390/ijms25020724 -
Radiology. Artificial Intelligence Jan 2024Purpose To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase )... (Meta-Analysis)
Meta-Analysis
Purpose To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase ) status in grade 4 and lower-grade diffuse gliomas. Materials and Methods A systematic search was performed in the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases for relevant articles published between January 1, 2010, and July 7, 2021. Pooled sensitivity and specificity across studies were estimated. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2, and methods were evaluated using the radiomics quality score (RQS). Additional subgroup analyses were performed according to tumor grade, RQS, and number of sequences used (PROSPERO ID: CRD42021268958). Results Twenty-six studies that included 3280 patients were included for analysis. The pooled sensitivity and specificity of radiomics for the detection of mutation were 79% (95% CI: 76, 83) and 80% (95% CI: 76, 83), respectively. Low RQS scores were found overall for the included works. Subgroup analyses showed lower false-positive rates in very low RQS studies (RQS < 6) (meta-regression, = -1.9; = .02) compared with adequate RQS studies. No substantial differences were found in pooled sensitivity and specificity for the pure grade 4 gliomas group compared with the all-grade gliomas group (81% and 86% vs 79% and 79%, respectively) and for studies using single versus multiple sequences (80% and 77% vs 79% and 82%, respectively). Conclusion The pooled data showed that radiomics achieved good accuracy performance in distinguishing mutation status in patients with grade 4 and lower-grade diffuse gliomas. The overall methodologic quality (RQS) was low and introduced potential bias. Neuro-Oncology, Radiomics, Integration, Application Domain, Glioblastoma, IDH Mutation, Radiomics Quality Scoring Published under a CC BY 4.0 license.
Topics: Humans; Isocitrate Dehydrogenase; Radiomics; Glioma; Glioblastoma; Mutation
PubMed: 38231039
DOI: 10.1148/ryai.220257 -
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 -
Current Oncology (Toronto, Ont.) Nov 2023The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and... (Meta-Analysis)
Meta-Analysis Review
The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy.
Topics: Humans; Adult; Brain Neoplasms; Glioma; Biopsy; Combined Modality Therapy; Brain Stem
PubMed: 37999129
DOI: 10.3390/curroncol30110709 -
European Journal of Nuclear Medicine... Feb 2024Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [I]-metaiodobenzylguanidine (mIBG) is the standard imaging method;...
BACKGROUND
Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals.
METHODS
We searched the PubMed database for studies performing a head-to-head comparison between [I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([C]C-HED), F-18F-3,4-dihydroxyphenylalanine ([F]DOPA) [I]mIBG and Meta-[18F]fluorobenzylguanidine ([F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA).
RESULTS
Ten studies were selected: two regarding [C]C-HED, four [F]DOPA, one [I]mIBG, and three [F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies.
CONCLUSIONS
PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.
Topics: Child; Humans; 3-Iodobenzylguanidine; Dihydroxyphenylalanine; Neuroblastoma; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 37962616
DOI: 10.1007/s00259-023-06486-9 -
Neurosurgical Review Nov 2023Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to... (Review)
Review
Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.
Topics: Female; Humans; Pregnancy; Brain Neoplasms; Wakefulness; Craniotomy; Glioma; Anesthesia, General
PubMed: 37910275
DOI: 10.1007/s10143-023-02187-x -
Frontiers in Endocrinology 2023Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and... (Review)
Review
INTRODUCTION
Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature.
METHODOLOGY
We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs.
RESULTS
By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Prognosis; Epigenesis, Genetic; Neuroectodermal Tumors, Primitive
PubMed: 37908747
DOI: 10.3389/fendo.2023.1248575 -
International Journal of Molecular... Oct 2023Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients... (Review)
Review
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
Topics: Humans; Glioblastoma; Immune Checkpoint Inhibitors; Cancer Vaccines; Neoplasm Recurrence, Local; Glioma; Immunotherapy; Immunotherapy, Adoptive; Brain Neoplasms; Tumor Microenvironment
PubMed: 37894718
DOI: 10.3390/ijms242015037