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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 -
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 -
Genes, Chromosomes & Cancer May 2023Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of...
Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of clear cell mesothelioma remained limited. In this study, we identified an index patient with clear cell mesothelioma, confirmed by immunohistochemical and ultrastructural studies. Targeted next-generation sequencing revealed the presence of an inactivating VHL mutation. We then systematically searched for VHL-mutant mesotheliomas in a comprehensive genomic profiling database of 1532 mesotheliomas. Collectively, we identified a cohort of four VHL-mutant clear cell mesotheliomas, including three peritoneal and one pleural tumors from three females and one male, with age range of 47-68 (median 63) years. Histologically, each tumor showed a microcystic to tubulopapillary architecture with prominent clear cells. By next-generation DNA sequencing, each of the four clear cell mesotheliomas harbored inactivating VHL mutations, while lacking other alterations typical of mesotheliomas such as BAP1, NF2, SETD2, CDKN2A, CDKN2B, TP53, and PTEN. By using low-pass whole genome sequencing on the index case and targeted next-generation sequencing on the remaining three cases, we identified extensive loss of heterozygosity throughout the genome but consistently sparing chromosomes 5, 7, and 20, characteristic of genomic near-haploidization. In summary, clear cell mesotheliomas were characterized by inactivating VHL mutations and genomic near-haploidization and appeared to represent a distinct clinicopathologic and molecular category of mesotheliomas. Our findings implicate VHL in the pathogenesis of a subset of mesotheliomas, particularly those with clear cell morphology.
Topics: Female; Male; Humans; Middle Aged; Aged; Haploidy; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mutation; Chromosome Aberrations; Genomics; Ubiquitin Thiolesterase; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 36515470
DOI: 10.1002/gcc.23119 -
BMJ Supportive & Palliative Care Mar 2020Malignant pleural effusion (MPE) results in breathlessness and impairment of health-related quality of life (HRQOL). This study reviews the existing literature on HRQOL...
BACKGROUND
Malignant pleural effusion (MPE) results in breathlessness and impairment of health-related quality of life (HRQOL). This study reviews the existing literature on HRQOL following invasive interventions in MPE.
METHODS
Five electronic databases were systematically searched and assessed three times during the review process and last completed on 15 June 2018. We included all studies evaluating HRQOL outcomes for the following interventions: therapeutic thoracocentesis, talc slurry (TS) pleurodesis, indwelling pleural catheter (IPC) insertion and thoracoscopic talc poudrage (TTP) pleurodesis. Meta-analysis was not performed due to substantial heterogeneity in the published data.
RESULTS
17 studies were included in the review reporting HRQOL outcomes in 2515 patients. TTP, TS and IPC were associated with modest but inconsistent improvements in HRQOL up to 12 weeks. No intervention was significantly different from another in HRQOL outcomes at any time point. The attrition to follow-up was 48.3% (664/1374) at 3 months. The overall quality of studies was inadequate.
CONCLUSION
TTP, TS and IPC seem to improve HRQOL in MPE over 4-12 weeks, but there are insufficient longer term data due to high attrition rates. Evidence on the most effective treatment strategy is limited by the small number of randomised or comparative studies.
TRIAL REGISTRATION NUMBER
CRD42016051003.
Topics: Aged; Catheterization; Catheters, Indwelling; Female; Humans; Male; Middle Aged; Pleural Effusion, Malignant; Pleurodesis; Quality of Life; Talc; Thoracentesis; Thoracoscopy; Treatment Outcome
PubMed: 31243020
DOI: 10.1136/bmjspcare-2018-001610 -
PloS One 2023Several prospective trials had been reported on chemotherapy with or without antiangiogenic agents in patients with advanced malignant pleural mesothelioma (MPM), with... (Meta-Analysis)
Meta-Analysis
Efficacy and safety profile of combining antiangiogenic agents with chemotherapy in patients with advanced malignant pleural mesothelioma: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVES
Several prospective trials had been reported on chemotherapy with or without antiangiogenic agents in patients with advanced malignant pleural mesothelioma (MPM), with diverse results. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of the combination regimen.
METHODS
We systematically identified trials in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts and ESMO Abstracts. All the randomized controlled trials (RCTs) about chemotherapy combined with antiangiogenic agents in advanced MPM were identified. Overall survival (OS) was the primary outcome, while progression-free survival (PFS), overall response rate (ORR) and serious toxicities were the secondary outcomes. Review Manager 5.3 was used to perform the statistical analyses. Stata 12.0 was used to assess the publication bias of egger's test.
RESULTS
5 randomized controlled trials containing 1250 patients were finally included in this analysis. Statistical analyses showed that the addition of antiangiogenic agents to chemotherapy could prolong OS [HR 0.79 (0.71-0.89), p<0.0001] and PFS [HR 0.75 (0.68-0.84), p<0.00001] in advanced MPM, especially in the epithelioid subgroup, with a tolerable toxicity profile. No significant difference was found in the analysis of ORR [HR 1.13 (0.95-1.35), p = 0.18]. Heterogeneity was found in the analyses of PFS and ORR, which might be caused by the limitation in uniform evaluation of tumor response.
CONCLUSIONS
The combination of antiangiogenic agents with chemotherapy showed superior over chemotherapy alone in patients with advanced MPM. More prospective trials should be warranted to identify patients who would most likely benefit from the combination regimen.
Topics: Humans; Angiogenesis Inhibitors; Mesothelioma, Malignant; Randomized Controlled Trials as Topic; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents
PubMed: 38127857
DOI: 10.1371/journal.pone.0295745 -
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 -
Surgery Today Jul 2021The prognosis of peritoneal carcinomatosis is poor. However, the emergence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) as a... (Review)
Review
The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan.
The prognosis of peritoneal carcinomatosis is poor. However, the emergence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) as a treatment option has prolonged survival and it can even potentially cure patients with peritoneal carcinomatosis. Randomized controlled studies and other observational studies indicated that this combined therapy potentially improved the prognosis of patients with colon, gastric, and ovarian cancers with acceptable morbidity and mortality rates. Even in rarer diseases, such as pseudomyxoma peritonei and malignant peritoneal mesothelioma, CRS + HIPEC markedly improved the prognoses over those with conventional treatment. Based on the accumulated evidence, clinical guidelines recommend CRS + HIPEC for selected patients with peritoneal carcinomatosis. However, several issues still need to be overcome. A standard method for HIPEC has not yet been established. Furthermore, the criteria employed for patient selection need to be clarified to achieve real benefits. The peritoneal cancer index, chemo-sensitivity and several biological markers are considered to be key factors.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Humans; Hyperthermic Intraperitoneal Chemotherapy; Japan; Male; Mesothelioma, Malignant; Middle Aged; Observational Studies as Topic; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Randomized Controlled Trials as Topic; Stomach Neoplasms
PubMed: 33185798
DOI: 10.1007/s00595-020-02180-7 -
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 -
BMC Cancer May 2020The CSC (cancer stem cell) markers often indicate poor prognosis and more cell invasion or migration of cancer patients. Podoplanin was assumed as a candidate CSC marker... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The CSC (cancer stem cell) markers often indicate poor prognosis and more cell invasion or migration of cancer patients. Podoplanin was assumed as a candidate CSC marker and predict poor prognosis among squamous cancers. Whereas, the prognostic value of podoplanin among lung squamous cancer (LUSC) patients remains controversial.
METHODS
A search of databases including PubMed, Embase and Web of Science was performed. Eligible articles studying the prognostic significance of podoplanin were selected. Odds ratio and HR (hazard ratio) were used to assess the relationships between podoplanin and clinical characteristics, as well as to quantify its prognostic role. The heterogeneity was estimated by I Statistic and P values from sensitivity analysis. Begg's funnel plots were used to estimate possible publication bias.
RESULTS
8 eligible studies containing 725 I-IV LUSC patients were included. Podoplanin expression showed no significant correlations with TNM stage, vascular invasion, lymphatic invasion, lymph node metastasis, pleural metastasis of tumor and gender of patients. However, podoplanin showed significant associations with better differentiation (pooled OR = 2.64, 95% CI 1.53-4.56, P = 0.0005, fixed effect) and better overall survival (HR = 2.14, 95% CI 1.45-3.15, P = 0.0001, fixed effect) and progression-free survival (HR = 1.73, 95% CI: 1.01-2.98, P = 0.05, fixed effect) of LUSC. Funnel plots illustrated no evidence of publication bias in our results.
CONCLUSIONS
Podoplanin could be a useful prognostic marker and indicates better differentiation for LUSC patients, and the value of PDPN expression as a marker for cancer stem cells in LUSC should be critically evaluated in future studies.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Humans; Lung Neoplasms; Membrane Glycoproteins; Prognosis
PubMed: 32408907
DOI: 10.1186/s12885-020-06936-9 -
Clinical Lung Cancer Sep 2019Tumor spread through air spaces (STAS) is a newly recognized invasion pattern in non-small-cell lung cancer (NSCLC). However, the clinical application value of STAS in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tumor spread through air spaces (STAS) is a newly recognized invasion pattern in non-small-cell lung cancer (NSCLC). However, the clinical application value of STAS in NSCLC remains to be clarified. We aimed to comprehensively explore the potential role of STAS as a prognostic indicator in NSCLC.
PATIENTS AND METHODS
A systematic search was performed in PubMed, Embase, Cochrane Library, and Web of Science until April 15, 2018. A quantitative meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 3231 patients from 8 studies were included. STAS was observed in 1204 cases (37.3%). A significant association was found between STAS and poor progression-free survival (PFS) (hazard ratio [HR], 1.789; P < .001) and overall survival (OS; HR, 1.488; P < .001). STAS was also an independent prognostic factor for PFS (HR, 1.632; P < .001) and OS (HR, 1.475; P < .001) without obvious heterogeneity. Subgroup analyses and meta-regression showed histology type, tumor, node, metastases (TNM) stage, publication year, sample size, region, and quality score did not alter prognostic value of STAS. Tumor STAS was associated with male sex (P < .001), history of smoking (P < .001), tumor budding (P = .038), vascular invasion (P < .001), lymphatic invasion (P < .001), pleural invasion (P < .001), T stage (P < .001), N stage (P < .001), and TNM stage (P < .001). The publication bias was observed. After adjustment using a nonparametric "trim-and-fill" method, corrected HRs had no significant change.
CONCLUSION
Tumor STAS is associated with clinicopathologically aggressive features and could be exploited as a novel prognostic predictor in NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasm Invasiveness; Prognosis; Survival Analysis
PubMed: 31230891
DOI: 10.1016/j.cllc.2019.05.012