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Cancer Radiotherapie : Journal de La... Apr 2021The efficacy of hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) without age restrictions remains unclear. The aim of this meta-analysis is to access the... (Meta-Analysis)
Meta-Analysis
PURPOSE
The efficacy of hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) without age restrictions remains unclear. The aim of this meta-analysis is to access the survival outcomes of HFRT in these patients.
METHODS
A comprehensive electronic literature search of PubMed, Web of Science and Cochrane Library was conducted up to June 1, 2020. The main evaluation data were the overall survival (OS) rate at 12 months and 24 months and the progression-free survival (PFS) rate at 6 and 12 months. The secondary evaluation data was the incidence of radionecrosis and adverse events. The study was performed using R "meta" package.
RESULTS
Eleven studies met the inclusion criteria, which totally contained 484 participants. The 12-month OS and 24-month OS rate of HFRT in GBM were 71.3% and 34.8%, while the 6-month PFS and 12-month rate were 74.0% and 40.8%. Compared to low-BED (biological equivalent dose) schedules (<78Gy), high-BED schedules may increase survival benefit both in PFS-6 (P=0.003) and PFS-12 (P=0.011), while the difference did not show on OS. Different dose per fraction had no significant effect on both OS and PFS. Incidence of radionecrosis was 14.2%. Although the overall incidence of adverse reactions cannot be quantified, the toxicity of HFRT was acceptable.
CONCLUSIONS
Compared with survival data for standard treatment, HFRT seemed to improve overall survival and progression-free survival, while high BED schedules may future increase benefit on PFS. Meanwhile, the toxicity of HFRT was tolerable. Further randomised controlled clinical studies are needed to confirm these findings.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Chemotherapy, Adjuvant; Glioblastoma; Humans; Incidence; Necrosis; Progression-Free Survival; Radiation Dose Hypofractionation; Radiation Injuries; Survival Rate; Temozolomide; Time Factors
PubMed: 33436285
DOI: 10.1016/j.canrad.2020.08.049 -
Advanced Drug Delivery Reviews Jan 2020Nanoparticles offer new opportunities for the treatment of skin diseases. The barrier function of the skin poses a significant challenge for nanoparticles to permeate...
Nanoparticles offer new opportunities for the treatment of skin diseases. The barrier function of the skin poses a significant challenge for nanoparticles to permeate into the tissue, although the barrier is partially compromised in case of injury or inflammation, as in the case of skin cancer. This may facilitate the penetration of nanoparticles. Extensive research has gone into developing nanoparticles for topical delivery; however, relatively little progress has been made in translating them to the clinic for treating skin cancers. We summarize the types of skin cancers and practices in current clinical management. The review provides a comprehensive outlook of the various nanoparticle technologies tested for topical therapy of skin cancers and summarizes the obstacles that impede its progress from the bench-to-bedside. The review also aims to provide an understanding of the pathways that govern nanoparticle penetration into the skin and a critical analysis of the approaches used to study nanoparticle interactions within the tissue.
Topics: Administration, Cutaneous; Antineoplastic Agents; Dacarbazine; Drug Carriers; Fluorouracil; Gold; Humans; Metal Nanoparticles; Nanoparticles; Skin Absorption; Skin Neoplasms; Skin Physiological Phenomena
PubMed: 32497707
DOI: 10.1016/j.addr.2020.05.011 -
Neuro-oncology Sep 2021The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade... (Meta-Analysis)
Meta-Analysis
MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review.
BACKGROUND
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade gliomas treated with temozolomide, however, there is no consensus on which test method, methylation sites, and cutoff values to use.
METHODS
We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included (i) adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; (ii) where MGMT status was determined in tumor tissue, and assessed by 1 or more technique; and (iii) where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios (HRs). Two or more methods were compared in 32 independent cohorts with 3474 patients.
RESULTS
Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP.
CONCLUSIONS
We cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Humans; Methylation; Promoter Regions, Genetic; Temozolomide; Tumor Suppressor Proteins
PubMed: 34467991
DOI: 10.1093/neuonc/noab105 -
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 -
Revista Espanola de Geriatria Y... 2024The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate...
INTRODUCTION
The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate dependence.
OBJECTIVE
To analyze by means of a systematic review the relationship between NCD and dependence with the risk of mortality in the elderly.
METHODS
A bibliographic search of longitudinal studies published in Pubmed and Scopus addressing the relationship between NCI, dependence for basic activities of daily living (ADL) and mortality published between 1995 and 2021 was performed. Of the 1040 articles found, 10 studies were selected.
RESULTS
It was observed that cohorts of elderly people with NCI presented mortality risk associated with ABVD impairment (Barthel test) and Mini-Mental State Examination scores following a significant linear trend. Other factors associated with mortality risk were low levels of education, living alone, and frailty.
CONCLUSIONS
The results underline the importance of performing assessments of cognitive and functional status using validated scales, since both areas are associated with mortality. The link between the three terms used in the search for this work is clear, but it is noteworthy that there are few longitudinal studies that analyze them together. The assessment of dependence and cognitive function in older adults should be considered in both research and clinical practice as it would provide information on their possible relationship with mortality.
Topics: Humans; Aged; Activities of Daily Living; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Hodgkin Disease; Vinblastine; Neurocognitive Disorders
PubMed: 37820397
DOI: 10.1016/j.regg.2023.101411 -
Medicine Nov 2019Glioblastoma (GB) is one of the most common malignancies with limited standard therapies such as surgery, radiotherapy (RT) plus temozolomide (TMZ). Molecularly targeted... (Comparative Study)
Comparative Study
BACKGROUND
Glioblastoma (GB) is one of the most common malignancies with limited standard therapies such as surgery, radiotherapy (RT) plus temozolomide (TMZ). Molecularly targeted drugs have been investigated among various clinical trials and are expected to develop in the field of tumor therapy, while the efficacy remains uncertain due to limited previous results. Thus, we focus on the evaluation of molecularly targeted drugs to clarify its overall effectiveness in terms of treating newly diagnosed GB.
METHODS
Electronic databases were searched for eligible literatures updated to April 2018. Randomized-controlled trials were included to assess the efficacy and safety of molecularly targeted drugs in patients with newly diagnosed GB. The main outcomes were further calculated including the following parameters: PFS (progression-free survival), OS (overall survival) as well as AEs (adverse events). All data were pooled along with their 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were evaluated quantitatively.
RESULTS
The combination of molecularly targeted drugs with TMZ + RT had no significant effects on OS (OR = 0.96, 95%CI = 0.89-1.04, P = .36). Meanwhile, the combination regimen significantly improved the PFS of patients with newly diagnosed GB (OR = 0.86 ,95% CI 0.75-0.98, P = .02). The rate of AEs (OR = 1.68,95%CI = 1.44-1.97, P < .00001) was higher in patients receiving molecularly targeted drugs, which was comparable to the contemporary group.
CONCLUSION
Longer PFS and a higher rate of AEs were observed with the addition of molecularly targeted drugs to standard chemoradiation in patients harboring newly diagnosed GB. Nevertheless, compared with the control arm, the regimen did not significantly prolong OS.
Topics: Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Humans; Male; Molecular Targeted Therapy; Prognosis; Randomized Controlled Trials as Topic; Survival Analysis; Temozolomide; Treatment Outcome
PubMed: 31702627
DOI: 10.1097/MD.0000000000017759