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Cancers Jul 2023Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited... (Review)
Review
Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL.
PubMed: 37509289
DOI: 10.3390/cancers15143628 -
JMIR Dermatology Nov 2023Rosacea is a chronic inflammatory skin condition that predominantly manifests as facial flushing, irritation, and acne. Rosacea and cancer are thought to be linked by... (Review)
Review
BACKGROUND
Rosacea is a chronic inflammatory skin condition that predominantly manifests as facial flushing, irritation, and acne. Rosacea and cancer are thought to be linked by the commonality of inflammatory and immune response dysfunction. Studies that have looked into this possible association have reported mixed results.
OBJECTIVE
Given the conflicting literature on this topic, our study sought to evaluate the overall association between rosacea and several cancers commonly investigated in the literature.
METHODS
A systematic review was conducted using the Cochrane, PubMed, Embase, and Ovid databases. Studies were screened independently for inclusion of rosacea and glioma and breast, thyroid, hepatic, or skin cancers. Using information from the articles, rosacea and each cancer were categorized as having a positive, negative, or unclear association.
RESULTS
Our systematic review included 39 full-text studies that investigated the association between rosacea and various malignancies. Among the malignancies of concern, 41% (16/39) of the studies reported an association with basal cell carcinoma, with 2 cohorts revealing an adjusted risk ratio (RR) of 1.50 (95% CI 1.35-1.67) and 0.72 (95% CI 0.56-0.93). In total, 33% (13/39) of the studies reported an association with squamous cell carcinoma, with 2 cohorts revealing an adjusted RR of 1.4 (95% CI 1.02-1.93) and 1.30 (95% CI 0.90-1.88). A total of 8% (3/39) of the studies reported an association between breast cancer and melanoma, with breast cancer cohorts revealing an adjusted RR of 8.453 (95% CI 1.638-43.606), 1.03 (95% CI 0.89-1.20), and 1.36 (95% CI 1.18-1.58) and melanoma cohorts revealing an adjusted RR of 1.10 (95% CI 0.95-1.27), 0.63 (95% CI 0.47-0.85), and 0.96 (95% CI 0.57-1.62). A total of 5% (2/39) of the studies reported an association among nonmelanoma skin cancers, hepatic cancer, and thyroid carcinomas, with nonmelanoma skin cancer cohorts revealing an adjusted RR of 1.36 (95% CI 1.26-1.47) and 2.66 (95% CI 1.53-4.61), hepatic cancer cohorts revealing an adjusted RR of 1.42 (95% CI 1.06-1.90) and 1.32 (95% CI 0.89-1.95), and thyroid carcinoma cohorts revealing an adjusted RR of 1.06 (95% CI 0.68-1.65) and 1.59 (95% CI 1.07-2.36). Only 1 cohort reported an association with glioma, revealing an adjusted RR of 1.36 (95% CI 1.18-1.58). According to our review, patients with rosacea were statistically more likely to have nonmelanoma skin cancers, breast cancer, and glioma. Rosacea was not found to be substantially associated with melanoma. The associations between rosacea and hepatic and thyroid cancers were unclear because of conflicting results.
CONCLUSIONS
The current literature shows that rosacea is significantly associated with increased odds of nonmelanoma skin cancers, glioma, and breast cancer. Rosacea does not appear to be associated with melanoma. Further studies should be conducted to clarify the association between thyroid and hepatic cancers and rosacea.
PubMed: 37938876
DOI: 10.2196/47821 -
Frontiers in Pharmacology 2023To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas. Electronic databases including Pubmed, Embase, Cochrane Library and...
To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas. Electronic databases including Pubmed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials (RCT) related to high-grade gliomas. The inclusion of qualified literature and extraction of data were conducted by two independent reviewers. The primary clinical outcome measures of network meta-analysis were overall survival (OS) while progression-free survival (PFS), objective response rate (ORR) and adverse event of grade 3 or higher were secondary measures. 22 eligible trials were included in the systematic review, involving 3423 patients and 30 treatment regimens. Network meta-analysis included 11 treatments of 10 trials for OS and PFS, 10 treatments of 8 trials for ORR, and 8 treatments of 7 trials for adverse event grade 3 or higher. Regorafenib showed significant benefits in terms of OS in paired comparison with several treatments such as bevacizumab (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.21-0.73), bevacizumab plus carboplatin (HR, 0.33; 95%CI, 0.16-0.68), bevacizumab plus dasatinib (HR, 0.44; 95%CI, 0.21-0.93), bevacizumab plus irinotecan (HR, 0.4; 95%CI, 0.21-0.74), bevacizumab plus lomustine (90 mg/m) (HR, 0.53; 95%CI, 0.33-0.84), bevacizumab plus lomustine (110 mg/m) (HR, 0.21; 95%CI, 0.06-0.7), bevacizumab plus vorinostat (HR, 0.42; 95%CI, 0.18-0.99), lomustine (HR, 0.5; 95%CI, 0.33-0.76), and nivolumab (HR, 0.38; 95%CI, 0.19-0.73). For PFS, only the hazard ratio between bevacizumab plus vorinostat and bevacizumab plus lomustine (90 mg/m) was significant (HR,0.51; 95%CI, 0.27-0.95). Lomustine and nivolumab conferred worse ORR. Safety analysis showed fotemustine as the best and bevacizumab plus temozolomide as the worst. The results suggested that regorafenib and bevacizumab plus lomustine (90 mg/m) provide improvements in terms of survival but may have poor ORR in patients with recurrent high-grade glioma.
PubMed: 37324487
DOI: 10.3389/fphar.2023.1191480 -
Neuro-oncology Advances 2022Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have...
BACKGROUND
Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have been characterized, their application to AYA populations is less clear. There is a major need to develop more robust evidence-based practices for managing AYA glioma patients.
METHODS
A systematic review using PRISMA methodology was conducted using multiple databases with the objective of identifying demographic, clinical, molecular and treatment factors influencing AYA glioma outcomes.
RESULTS
40 Studies met inclusion criteria. Overall survival was highly variable across studies depending on glioma grade, anatomic compartment and cohort characteristics. Thirty-five studies suffered from high risk of bias in at least one domain. Several studies included older adults within their cohorts; few captured purely AYA groups. Despite study heterogeneity, identified favorable prognosticators included younger age, higher functional status at diagnosis, low-grade pathology, oligodendroglioma histology and increased extent of surgical resection. Though isocitrate dehydrogenase (IDH) mutant status was associated with favorable prognosis, validity of this finding within AYA was compromised though may studies including older adults. The prognostic influence of chemotherapy and radiotherapy on overall survival varied across studies with conflicting evidence.
CONCLUSION
Existing literature is heterogenous, at high risk of bias, and rarely focused solely on AYA patients. Many included studies did not reflect updated pathological and molecular AYA glioma classification. The optimal role of chemotherapy, radiotherapy, and targeted agents cannot be determined from existing literature and should be the focus of future studies.
PubMed: 36479061
DOI: 10.1093/noajnl/vdac168 -
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 Neuroimaging : Official... May 2022Angiocentric gliomas (AGs) are epileptogenic low-grade gliomas in young patients. We aimed to investigate the MRI findings of AGs and systematically review previous... (Review)
Review
BACKGROUND AND PURPOSE
Angiocentric gliomas (AGs) are epileptogenic low-grade gliomas in young patients. We aimed to investigate the MRI findings of AGs and systematically review previous publications and three new cases.
METHODS
We searched PubMed, Elsevier's abstract and citation database, and Embase databases and included 50 patients with pathologically proven AGs with analyzable preoperative MRI including 3 patients from our institution and 47 patients from 38 publications (median age, 13 years [range, 2-83 years]; 35 men). Two board-certified radiologists reviewed all images. The relationships between seizure/epilepsy history and MRI findings were statistically analyzed. Moreover, clinical and imaging differences were evaluated between supratentorial and brainstem AGs.
RESULTS
Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain parenchymal atrophy were observed in 23 out of 50 (46.0%), 10 out of 50 (20.0%), and 14 out of 50 (28.0%) patients, respectively. Intratumoral T1-weighted high-intensity areas were observed significantly more frequently in patients with stalk-like signs (positive, 9/10 vs. negative, 14/40, p = .0031) and regional atrophy (13/14 vs. 10/36, p = .0001). There were significant relationships between the length of seizure/epilepsy history and presence of intratumoral T1-weighted high-intensity area (median 3 years vs. 0.5 years, p = .0021), stalk-like sign (13.5 vs. 1 year, p < .0001), and regional atrophy (14 vs. 0.5 years, p < .0001). Patients with brainstem AGs (n = 7) did not have a seizure/epilepsy history and were significantly younger than those with supratentorial AGs (median, 5 vs. 13 years, p < .0001, respectively).
CONCLUSIONS
Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain atrophy were frequent imaging features in AG. We also found that affected age was different between supratentorial and brainstem AGs.
Topics: Adolescent; Atrophy; Brain Neoplasms; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Neuroimaging; Seizures
PubMed: 35201652
DOI: 10.1111/jon.12983 -
Frontiers in Neurology 2021Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses...
Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses to immune checkpoint inhibitors. Treatment-related lymphopenia has been associated with poor survival in patients with various tumors. This meta-analysis evaluated the risk and impact of lymphopenia in patients with glioma. The PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched. Eligible studies were included if they reported the incidence and risk factors of lymphopenia and the impact of lymphopenia on survival. Stata 16.0 was used for this meta-analysis. A total of 21 studies were included in the final systematic review and 20 were included in the quantitative analysis. The overall incidence of grade III/IV lymphopenia was 31.6% [95% confidence interval (CI), 22.3-40.8%]. Pooled results based on pathology of glioma revealed that the incidence in astrocytoma and astrocytoma oligodendroglioma patients was 20.2% (95% CI:5.9-34.4%), and the incidence in glioblastoma patients was 27.6% (95% CI:16.2-38.9%). Lymphopenia was associated with poor overall survival (hazard ratio, 1.99; 95% CI, 1.74-2.27; < ) compared to no lymphopenia. Brain receiving radiation dose of 20 or 25 Gy, female sex, older age, lower baseline lymphocyte count, and dexamethasone dose > 2 mg instead of baseline use were risk factors for lymphopenia. Treatment-related lymphopenia was associated with decreased survival in patients with glioma. Optimization of chemoradiation regimens, particularly in patients with concurrent risk factors, can reduce lymphopenia and potentially improve survival in the era of immunotherapy.
PubMed: 35058869
DOI: 10.3389/fneur.2021.726561 -
Neuro-oncology Advances 2021Cranial radiation therapy is essential in treating many pediatric cancers, especially brain tumors; however, its use comes with the risk of developing second... (Review)
Review
BACKGROUND
Cranial radiation therapy is essential in treating many pediatric cancers, especially brain tumors; however, its use comes with the risk of developing second malignancies. Cranial radiation-induced gliomas (RIGs) are aggressive high-grade tumors with a dismal prognosis, for which no standard therapy exists. A definitive molecular signature for RIGs has not yet been established. We sought to address this gap by performing a systematic review and meta-analysis of the molecular features of cranial RIGs.
METHODS
A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles and case reports that described molecular analyses of cranial radiation-induced high-grade gliomas were identified and evaluated, and data extracted for collation.
RESULTS
Of 1727 records identified, 31 were eligible, containing 102 unique RIGs with molecular data. The most frequent genetic alterations in RIGs included or mutations, or amplifications, and deletion, along with 1q gain, 1p loss and 13q loss. Of note, mutations in , , , , , , or the promoter were not observed. A comparative analysis revealed that RIGs are molecularly distinct from most other astrocytomas and gliomas and instead align most closely with the pedGBM_RTK1 subgroup of pediatric glioblastoma.
CONCLUSIONS
This comprehensive analysis highlights the major molecular features of RIGs, demonstrates their molecular distinction from many other astrocytomas and gliomas, and reveals potential genetic drivers and therapeutic targets for this currently fatal disease.
PubMed: 34859225
DOI: 10.1093/noajnl/vdab109 -
British Journal of Cancer Jan 2013Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of in vivo glioma models in predicting clinical efficacy.
METHODS
We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias.
RESULTS
We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74-2.03) and reduced tumour volume by 50.4% (41.8-58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias.
CONCLUSION
These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental in vivo glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine.
Topics: Animals; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Disease Models, Animal; Glioma; Mice; Rats; Survival Analysis; Temozolomide; Treatment Outcome; Xenograft Model Antitumor Assays
PubMed: 23321511
DOI: 10.1038/bjc.2012.504 -
Acta Neurochirurgica Jan 2017Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In... (Review)
Review
BACKGROUND
Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.
METHODS
We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.
RESULTS
The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.
CONCLUSIONS
5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.
Topics: Aminolevulinic Acid; Animals; Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Neurosurgical Procedures; Photosensitizing Agents
PubMed: 27878374
DOI: 10.1007/s00701-016-3028-5