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Frontiers in Immunology 2022A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to...
AIMS AND BACKGROUND
A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models.
METHODS
A systematic search for analyses of PPK models of eleven anti-PD-1 mAbs on the market that were carried out in humans was conducted using PubMed, Embase, and the Cochrane Library. The search covered the period from the inception of the databases to April 2022.
RESULTS
Currently, there are fourteen analyses on PPK models of anti-PD-1 mAbs summarized in this review, including seven models that refer to nivolumab, four referring to pembrolizumab, one referring to cemiplimab, one referring to camrelizumab, and one referred to dostarlimab. Most analyses described the pharmacokinetics of anti-PD-1 mAbs with a two-compartment model with time-varying clearance (CL) and a sigmoidal maximum effect. The estimated CL and volume of distribution in the central (V) ranged from 0.179 to 0.290 L/day and 2.98 to 4.46 L, respectively. The median (range) of interindividual variability (IIV) for CL and V was 30.9% (8.7%-50.8%) and 29.0% (4.32%-40.7%), respectively. The commonly identified significant covariates were body weight (BW) on CL and V, and albumin (ALB), tumor type, sex, and performance status (PS) on CL. Other less assessed significant covariates included lactate dehydrogenase (LDH), immunoglobulin G (IgG), ipilimumab coadministration (IPICO) on CL, and body mass index (BMI), malignant pleural mesothelioma (MESO) on V.
CONCLUSION
This review provides detailed information about the characteristics of PPK models of anti-PD-1 mAbs, the effects of covariates on PK parameters, and the current status of the application of the models. ALB, BW, specific tumor type, sex, and PS should be considered for the future development of the PPK model of anti-PD-1 mAbs. Other potential covariates that were assessed less frequently but still have significance (e.g., LDH, IgG, and IPICO) should not be ignored. Thus, further research and thorough investigation are needed to assess new or potential covariates, which will pave the way for personalized anti-PD-1 mAbs therapy.
Topics: Antibodies, Monoclonal, Humanized; Body Weight; Humans; Immunoglobulin G; Ipilimumab; Neoplasms; Nivolumab
PubMed: 35983041
DOI: 10.3389/fimmu.2022.871372 -
Journal of Thoracic Imaging Mar 2023To compare computed tomography (CT)-based radiologic features in patients, who are diagnosed with lung adenocarcinoma with the pathologically detected spread of tumor... (Meta-Analysis)
Meta-Analysis
To compare computed tomography (CT)-based radiologic features in patients, who are diagnosed with lung adenocarcinoma with the pathologically detected spread of tumor cells through air spaces (STAS positive [STAS+]) and those with no STAS. PubMed, Embase, and Scopus databases were systematically searched for observational studies (either retrospective or prospective) of patients with lung adenocarcinoma that had compared CT-based features between STAS+ and STAS-negative cases (STAS-). The pooled effect sizes were reported as odds ratio (OR) and weighted mean difference (WMD). STATA software was used for statistical analysis. The meta-analysis included 10 studies. Compared with STAS-, STAS+ adenocarcinoma was associated with increased odds of solid nodule (OR: 3.30, 95% CI: 2.52, 4.31), spiculation (OR: 2.05, 95% CI: 1.36, 3.08), presence of cavitation (OR: 1.49, 95% CI: 1.00, 2.22), presence of clear boundary (OR: 3.01, 95% CI: 1.70, 5.32), lobulation (OR: 1.65, 95% CI: 1.11, 2.47), and pleural indentation (OR: 1.98, 95% CI: 1.41, 2.77). STAS+ tumors had significant association with the presence of pulmonary vessel convergence (OR: 2.15, 95% CI: 1.61, 2.87), mediastinal lymphadenopathy (OR: 2.06, 95% CI: 1.20, 3.56), and pleural thickening (OR: 2.58, 95% CI: 1.73, 3.84). The mean nodule diameter (mm) (WMD: 6.19, 95% CI: 3.71, 8.66) and the mean solid component (%) (WMD: 24.5, 95% CI: 10.5, 38.6) were higher in STAS+ tumors, compared with STAS- ones. The findings suggest a significant association of certain CT-based features with the presence of STAS in patients with lung adenocarcinoma. These features may be important in influencing the nature of surgical management.
Topics: Humans; Adenocarcinoma of Lung; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prospective Studies; Retrospective Studies; Tomography; Tomography, X-Ray Computed; Observational Studies as Topic
PubMed: 36583661
DOI: 10.1097/RTI.0000000000000693 -
Biomedical Reports Dec 2020Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous... (Review)
Review
Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in , and experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This approach could represent an effort in the field of biomarker discovery for MM.
PubMed: 33149905
DOI: 10.3892/br.2020.1367 -
Medicine Jul 2021The influence of pre-treatment controlling nutritional status (CONUT) score on the prognosis of non-small cell lung cancer (NSCLC) patients is inconclusive. We performed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The influence of pre-treatment controlling nutritional status (CONUT) score on the prognosis of non-small cell lung cancer (NSCLC) patients is inconclusive. We performed this meta-analysis to evaluate the prognostic significance of CONUT score in NSCLC patients.
METHODS
A systematic literature review was conducted using PubMed, Embase, and the Cochrane Library databases. The hazard ratio (HR) and 95% confidence interval (CI) were extracted to assess the correlation between the CONUT score and the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), as well as the cancer-specific survival.
RESULTS
A total of 11 studies with 3029 patients were included in the analysis. Pooled results indicated that a high CONUT score was positively correlated with poor OS (HR: 1.63, 95%CI: 1.40-1.88, P < .001) and shortened DFS/RFS (HR: 1.65, 95%CI: 1.35-2.01, P < .001), but no significant relationship with the cancer-specific survival (HR: 1.28, 95%CI: 0.60-2.73, P = .517) was identified. The negative effect of high CONUT score on the OS and DFS/RFS was detected in every subgroup with varying treatment methods, cancer stage, CONUT cut-off values, sample size, and analysis methods of HR. Additionally, preoperative high CONUT score was an independent predictor of postoperative complications (odds ratio: 1.58, 95%CI: 1.21-2.06, P = .001) in NSCLC. Last but not least, high CONUT score was not significantly correlated with the patients' sex, smoking status, cancer stage, lymphatic invasion, vascular invasion, pleural invasion, and pathological cancer type.
CONCLUSION
These results demonstrate that high CONUT score is positively related to poor prognoses. The CONUT score may therefore be considered as an effective prognostic marker in NSCLC patients.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasm Staging; Nutritional Status; Postoperative Complications; Prognosis; Risk Factors
PubMed: 34190175
DOI: 10.1097/MD.0000000000026488 -
Frontiers in Immunology 2023In recent years, immune checkpoint inhibitors (ICIs) had extremely rapid growth in anti-cancer and improved outcomes of many malignancies, specifically lung cancer.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, immune checkpoint inhibitors (ICIs) had extremely rapid growth in anti-cancer and improved outcomes of many malignancies, specifically lung cancer. However, the incidence of ICIs-related adverse events also raised. Using this meta-analysis, ICIs-related respiratory disorders were investigated in lung cancer patients.
METHODS
Using Cochrane Library, Embase, and PubMed databases, we performed an integrated search for randomized controlled trials (RCTs) to compare respiratory disorders among different regimens. The data was prepared with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, and the quality of included studies was evaluated based on the Cochrane manual.
RESULTS
In total, 22 RCTs were involved in this meta-analysis. Compared with ICIs, chemotherapy reduced the risk of interstitial lung disease (p = 0.03; SMD: 2.81; 95% CI: 1.08, 7.27), pleural effusion (p = 0.002; SMD: 2.12; 95% CI: 1.32, 3.42), and pneumonitis (p < 0.00001; SMD: 9.23; 95% CI: 4.57, 18.64). ICIs plus chemotherapy could provide a higher probability for patients to suffer pneumonitis than chemotherapy (p = 0.01; SMD: 1.96; 95% CI: 1.17, 3.28). In addition, single ICI brought a lower likelihood for patients suffering pneumonitis than double ICIs (p = 0.004; SMD: 2.17; 95% CI: 1.27, 3.69).
CONCLUSION
ICIs-based treatment, such as ICIs alone, ICIs plus chemotherapy and double ICIs, can raise the incidences of some respiratory disorders in patients with lung cancer. It suggests that ICIs should be conducted based on a comprehensive consideration to prevent ICIs-related respiratory disorders. To a certain degree, this study might be provided to the clinician as a reference for ICIs practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022378901, identifier (CRD42022378901).
Topics: Humans; Immune Checkpoint Inhibitors; Randomized Controlled Trials as Topic; Respiration Disorders; Lung Neoplasms; Respiratory Tract Diseases
PubMed: 36926326
DOI: 10.3389/fimmu.2023.1115305 -
Thoracic Cancer Jan 2022Surgical resection of the thymus is indicated in the presence of primary thymic diseases such as thymoma. Video-assisted thoracoscopic surgery (VATS) and robot-assisted... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Surgical resection of the thymus is indicated in the presence of primary thymic diseases such as thymoma. Video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracic surgery (RATS) offer a minimally invasive approach to thymectomy. However, there is no clear conclusion whether RATS can achieve an equal or even better surgical effect when compared with VATS in treatment of thymoma. We performed this meta-analysis to explore and compare the outcomes of RATS versus VATS for thymectomy in patients with thymoma.
METHODS
PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases were searched for full-text literature citations. The quality of the articles was evaluated using the Newcastle-Ottawa Scale and the data analyzed using Review Manager 5.3 software. Fixed or random effect models were applied according to heterogeneity. Subgroup analysis was conducted.
RESULTS
A total of 11 studies with 1418 patients, of whom 688 patients were in the RATS group and 730 in the VATS group, were involved in the analysis. Compared with VATS, RATS was associated with less blood loss in operation, lower volume of drainage, fewer postoperative pleural drainage days, shorter postoperative hospital stay, and fewer postoperative complications. There was no significant difference in operative time and patients with or without myasthenia gravis between the two groups.
CONCLUSIONS
RATS has more advantages over VATS, indicating that RATS is better than VATS in terms of postoperative recovery. We look forward to more large-sample, high-quality randomized controlled studies published in the future.
Topics: Humans; Robotic Surgical Procedures; Thoracic Surgery, Video-Assisted; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 34806328
DOI: 10.1111/1759-7714.14234 -
Medicine Oct 2022Lobaplatin is a new platinum-based cytotoxic chemotherapeutic agent. Endostar is an endogenous angiogenic inhibitor with implicated anti-tumor activity. This study was... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Lobaplatin is a new platinum-based cytotoxic chemotherapeutic agent. Endostar is an endogenous angiogenic inhibitor with implicated anti-tumor activity. This study was to investigate the efficacy and safety of thoracic perfusion of lobaplatin combined with endostar in the treatment of malignant pleural effusions (MPE).
METHODS
We searched the databases of Pubmed, the Cochrane Library, Embase, WanFang Data, and CNKI to select the studies regarding the efficacy and safety of lobaplatin combined with endostar to treat MPE. A total of 10[3-12] randomized controlled trials with 651 patients were included.
RESULTS
The objective response rate (P < .001, odds ratio = 4.08) and disease control rate (P < .001, odds ratio = 3.69) of lobaplatin combined with endostar were significantly higher than lobaplatin alone. In addition, lobaplatin combined with endostar remarkably promoted the quality of life of patients (P < .001, odds ratio = 3.93) compared with lobaplatin alone. Lobaplatin combined with endostar also promoted the quality of life of patients (P < .05, odds ratio = 2.56) compared with cisplatin combined with endostar. At the same time, the leukopenia rate (P < .05, odds ratio = .40) and the incidence of nausea and vomiting (P < .05, odds ratio = .38) of lobaplatin combined with endostar were significantly lower than that of cisplatin combined with endostar.
CONCLUSIONS
The efficacy of lobaplatin combined with endostar was superior to lobaplatin alone. The safety was higher than cisplatin combined with endostar through thoracic perfusion in treating MPE, which indicated that lobaplatin combined with endostar could be the effective agent for controlling MPE.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclobutanes; Endostatins; Humans; Organoplatinum Compounds; Perfusion; Pleural Effusion, Malignant; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 36221355
DOI: 10.1097/MD.0000000000030749 -
AJR. American Journal of Roentgenology Nov 2019The purpose of this study was to perform a systematic review and meta-analysis regarding CT features of non-small cell lung cancer (NSCLC) with anaplastic lymphoma... (Meta-Analysis)
Meta-Analysis
The purpose of this study was to perform a systematic review and meta-analysis regarding CT features of non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. The PubMed and Embase databases were searched up to February 20, 2019. Studies that evaluated CT features of NSCLC with and without ALK rearrangement was included. Methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The association between CT features and ALK rearrangement was pooled in the form of the odds ratio (OR) or the mean difference (MD) using the random-effects model. Heterogeneity was examined using the inconsistency index (). Publication bias was examined using funnel plots and Egger tests. Sixteen studies were included, consisting of 3113 patients with NSCLC. The overall prevalence of patients with ALK rearrangement was 17% (528/3113). Compared with NSCLC without ALK rearrangement, on CT images those with ALK rearrangement were more frequently solid (OR = 2.86), central in location (OR = 2.72), and 3 cm or smaller (OR = 0.57); had lower contrast-enhanced CT attenuation (MD = -4.79 HU); more frequently had N2 or N3 disease (OR = 5.63), lymphangitic carcinomatosis (OR = 3.46), pleural effusion (OR = 1.91), or pleural metastasis (OR = 1.81); and less frequently had lung metastasis (OR = 0.66). Heterogeneity varied among CT features ( = 0-80%). No significant publication bias was seen ( = 0.15). NSCLC with ALK rearrangement had several distinctive CT features compared with that without ALK rearrangement. These CT biomarkers may help identify patients likely to have ALK rearrangement.
Topics: Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Gene Rearrangement; Humans; Lung Neoplasms; Tomography, X-Ray Computed
PubMed: 31414902
DOI: 10.2214/AJR.19.21485 -
Environmental Health : a Global Access... Aug 2019Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult...
BACKGROUND
Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult for pathologists, surgeons, oncologists and occupational physicians. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy except orchidectomy.
METHODS
A systematic literature review was conducted among the articles published in the English literature on primary MMTVT. Moreover four cases from the Apulia mesothelioma register are reported here.
RESULTS
Two hundred eighty-nine cases of MMTVT have been reported from 1943 to 2018. Overall asbestos exposure has been investigated only for 58% of all cases reported in this review, while in 41.8% this data are not available. Noteworthy is the fact that in many reports there is not an anamnestic reconstruction of any asbestos exposure. A history of direct occupational, environmental or familial asbestos exposure is found in 27.6% of the cases. The four cases from the Apulia mesothelioma register are all with ascertained occupational exposure to asbestos.
CONCLUSIONS
The true incidence of asbestos exposure in MMTVT is underestimated because of insufficient information reported in older literature. To establish a broad consensus on the causal relationship between asbestos and MMTVT in the scientific community its necessary to analyze the same variables in the epidemiological studies. In general it should be recommended that a positive history of exposure to asbestos or to asbestos-containing materials are at risk for the development of a MMTVT and should be monitored.
Topics: Asbestos; Humans; Incidence; Italy; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Occupational Diseases; Occupational Exposure; Registries; Testicular Neoplasms
PubMed: 31470859
DOI: 10.1186/s12940-019-0512-4 -
Medicine May 2024Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE.
METHODS
Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software.
RESULTS
A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RR = 1.40, 95%CI: 1.33 ~ 1.46, P < .001). And the combined use of LNT could increase the quality of life (RR = 1.45, 95%CI: 1.35 ~ 1.56, P < .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RR = 0.86, 95%CI: 0.78 ~ 0.94, P < .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias.
CONCLUSIONS
Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.
Topics: Humans; Cisplatin; Pleural Effusion, Malignant; Lentinan; Antineoplastic Agents; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38788041
DOI: 10.1097/MD.0000000000038032