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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 -
Surgery Today Feb 2024Needle biopsy (NB) is used for the diagnosis of lung cancer, but there is still controversy about its effect on the prognosis after surgery. We conducted this... (Meta-Analysis)
Meta-Analysis Review
Needle biopsy (NB) is used for the diagnosis of lung cancer, but there is still controversy about its effect on the prognosis after surgery. We conducted this meta-analysis to compare the prognosis of lung cancer patients who underwent preoperative NB with that of those who did not. We systematically searched seven databases and Google Scholar for eligible studies. Recurrence-free survival (RFS) and overall survival (OS) were analyzed as primary outcome measures. Nine articles with a collective total of 13,541 patients (NB group, n = 4550; non-NB group, n = 8991) were included in our meta-analysis. OS [hazard ratio (HR) = 1.43 (0.96, 2.12), p = 0.08] and RFS (HR = 1.59 [1.25, 2.01], p = 0.0001) tended to be better in the non-NB group than in the NB group. Pleural recurrence (risk ratio (RR) = 2.40 [1.42, 4.07], p = 0.001) was significantly lower in the non-NB group than in the NB group. The recurrence analysis data did not reach significance, but the overall trend was better for the non-NB group. These findings demonstrate that NB is detrimental to the survival prognosis of lung cancer patients and increases the chance of pleural recurrence.
Topics: Humans; Lung Neoplasms; Prognosis; Proportional Hazards Models; Biopsy, Needle
PubMed: 36348163
DOI: 10.1007/s00595-022-02617-1 -
Clinical and Translational Science Jan 2023Indwelling pleural catheter (IPC) is widely used in patients with pleural effusion (PE). This meta-analysis aimed to comprehensively summarize the clinical complication... (Meta-Analysis)
Meta-Analysis
Indwelling pleural catheter (IPC) is widely used in patients with pleural effusion (PE). This meta-analysis aimed to comprehensively summarize the clinical complication from IPC. We searched four large electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane Library) for potentially relevant studies and assessed the included studies' quality using the methodological index for nonrandomized studies' criteria. Extracted data were used to pool rates, and to conduct subgroup and meta-regression analyses. Forty-one studies involving a cumulative 4983 patients with 5650 IPCs were included in this meta-analysis. The overall incidence of IPC complications was 20.3% (95% confidence interval [CI]: 15.0-26.3). The top four complications were: overall infection incidence 5.7% (95% CI: 0.7-2.4); overall catheter abnormality incidence 4.4% (95% CI: 2.8-6.3); pain incidence 1.2% (95% CI: 0.4-2.4); and overall loculation incidence 0.9% (95% CI: 0.1-2.1). Subgroup and meta-regression analyses for overall complications and infections by country, PE site, and PE type demonstrated these factors did not contribute significantly to heterogeneity. Further subgroup analyses for infection of benign PE showed that the overall infection incidence (12.6% [95% CI: 8.1-17.8] vs 0.7% [95% CI: 0.0-4.5]) and empyema incidence (9.1% [95% CI: 5.3-13.8] vs 0.0% [95% CI: 0.0-2.3]) of patients with liver-related PE were significantly higher than that of patients with heart-related PE. Our meta-analysis showed reliable pooled incidences of IPC-related complications, with infection being the most common. These results serve to remind clinicians about the incidence of IPC-related complications and emphasize the importance of taking corresponding preventive and therapeutic steps.
Topics: Humans; Catheterization; Catheters, Indwelling; Incidence; Pleural Effusion; Pleural Effusion, Malignant
PubMed: 36253892
DOI: 10.1111/cts.13430 -
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 -
Histopathology Mar 2023Tumour budding is an established prognostic factor in various solid tumours, including colorectal cancers and oral squamous cell carcinomas. However, its role is unclear... (Meta-Analysis)
Meta-Analysis Review
Tumour budding is an established prognostic factor in various solid tumours, including colorectal cancers and oral squamous cell carcinomas. However, its role is unclear and needs to be defined for squamous cell carcinoma of the lung (LSCC). Hence, we conducted a systematic review and meta-analysis investigating the prognostic role of tumour budding in LSCC. PubMed, Embase and Scopus were searched for peer-reviewed literature investigating the association between tumour budding and survival outcomes or clinicopathological variables in LSCC. The primary outcomes were pooled estimates for overall and recurrence-free survival with hazard ratio (HR) as the effect measure. The association between tumour budding and clinicopathological parameters was also investigated. Of 243 studies, nine were included, comprising 2546 patients. An increased risk of death [HR = 1.76, 95% confidence interval (CI) = 1.50-2.05, P < 0.00001] and recurrence (HR = 1.37, 95% CI = 1.12-1.68, P = 0.003) was evident in patients with high-grade tumour budding. Sensitivity and subgroup analyses revealed consistent results. Pathological stage II, lymph node metastasis, lymphovascular and pleural invasion were associated with high-grade tumour budding. Tumour budding is a new and promising prognostic factor in patients with LSCC. However, pervasive heterogeneity and publication bias reduces the credibility of these findings and the applicability of tumour budding in clinical practice. Future studies are required to standardise reporting on tumour budding in LSCC.
Topics: Humans; Prognosis; Carcinoma, Squamous Cell; Proportional Hazards Models; Mouth Neoplasms; Lung
PubMed: 36217904
DOI: 10.1111/his.14822 -
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 -
Mediterranean Journal of Hematology and... 2022Primary effusion lymphoma (PEL) is a large B-cell lymphoma growing within body-cavities caused by the Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8... (Review)
Review
Primary effusion lymphoma (PEL) is a large B-cell lymphoma growing within body-cavities caused by the Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (KSHV/HHV-8). It is mainly reported in HIV-infected patients. The uncommon occurrence in the elderly supports a form paralleling classic Kaposi sarcoma (KS), i.e. classic PEL, whose characteristics are relatively underexplored. To better understand the diagnostic modalities and clinical-epidemiological features of classic PEL, articles reporting cases of PEL were identified through MEDLINE/EMBASE databases (January 1998-July 2020) and screened according to PRISMA guidelines to extract individual-level data. A comparison was also performed between classic PEL and classic KS to evaluate similarities and differences. We identified 105 subjects (median age 77 years; 86% males), mainly from Mediterranean countries (52%, first Italy) and Eastern Europe (7%). Common comorbidities were heart failure (32%), cirrhosis (16%), and malignancy (20%) including lymphoid neoplasms. Pleural cavity was the commonest site (67%). PEL diagnosis was based on cytomorphology (89%), evidence of KSHV/HHV-8 infection (94%), EBV co-infection (28%) and clonality of IGH (59%), IGK (14%), TRG (9%) alone or in multiple combinations. Compared to KS, age (P<.001), gender-ratio (P=.08) and mortality (P<.001) were significantly higher in PEL, whereas the frequency of PEL as a second primary was similar (P=.44). This is the first systematic review of classic PEL case reports highlighting heterogeneity and lack of a uniform multidisciplinary approach at diagnosis, in the absence of specific guidelines as it happens for rare cancers. It is conceivable that classic PEL is still underdiagnosed in Mediterranean countries wherein KSHV/HHV-8 is endemic.
PubMed: 35444770
DOI: 10.4084/MJHID.2022.020 -
Thorax Apr 2023Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that... (Review)
Review
INTRODUCTION
Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval.
METHODS
Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed.
RESULTS
Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications.
CONCLUSION
Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose.
PROSPERO REGISTRATION NUMBER
CRD42019129002.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Cisplatin; Cytoreduction Surgical Procedures; Pleural Neoplasms; Combined Modality Therapy
PubMed: 35410957
DOI: 10.1136/thoraxjnl-2021-218214 -
European Journal of Cancer (Oxford,... May 2022Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomised controlled trials (RCTs) with systemic therapies for patients with pre-treated mesothelioma have reported equivocal efficacy results and generated a degree of clinical uncertainty about the choice of active treatment in this poor prognosis malignancy.
METHODS
To compare the effectiveness and safety and weigh the benefit of different systemic treatments in patients with pre-treated mesothelioma by systematic review, meta-analysis and network meta-analysis of RCTs. Full-text articles and abstracts were searched on PubMed, EMBASE, Cochrane Library and oncology conferences proceedings from 2005 through November 2021 for phase 2 and 3 RCTs. The protocol was submitted to the PROSPERO registry. Reporting followed the PRISMA guideline. Outcomes of interest were overall survival (OS) and progression-free (PFS), grade ≥3 treatment-related (Tr) adverse events (AEs), Tr-deaths and Tr-AEs leading to treatment discontinuation.
FINDINGS
Nine trials at low risk of bias by Cochrane Collaboration's methodology were included, encompassing 2789 patients. Five studies showed PFS benefit in the experimental treatment. In two studies, OS was prolonged by immunotherapy (versus placebo) or by adding an antiangiogenic agent to chemotherapy. Reported Tr-AE were lower with single-agent anti-PD1 compared with chemotherapy or placebo. The meta-analysis revealed a beneficial global effect on OS and PFS from experimental treatments (HR 0.86, 95% CI 0.77-0.96, p = 0.0083 and HR 0.79, 95% CI 0.72-0.86, p < 0.001), that for the PFS significantly favoured the comparison with non-active treatments (HR 0.73, 95% CI 0.66-0.81, p < 0.001). Younger patients (i.e. <65-70 years) appeared to benefit the most in OS (HR 0.71, 95% CI 0.55-0.92, p = 0.04). The risk of serious Tr-AEs and Tr-deaths was not significantly increased by experimental treatments (RR 1.38, 95% CI 0.81-2.35, p = 0.24 and RR 2.07, 95% CI 0.69-6.24, p = 0.19, respectively) that instead increased TrAEs leading to treatment discontinuation (RR 2.9, 95% CI 1.44-6.08, p = 0.003). The network meta-analysis did not identify any superior treatment in PFS.
INTERPRETATION
For patients with pre-treated MPM, single-agent anti-PD1 or chemotherapy ± the antiangiogenic agent can be considered active and safe systemic therapeutic options, particularly for younger patients.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Humans; Immunotherapy; Mesothelioma, Malignant; Network Meta-Analysis
PubMed: 35358809
DOI: 10.1016/j.ejca.2022.02.030 -
Frontiers in Oncology 2022Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the...
BACKGROUND
Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied.
METHODS
The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0.
RESULTS
The eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%-70%). The pooled OS rate was 94% (95% CI: 83%-100%) at 6 months, 87% (95% CI: 74%-96%) at 12 months, and 42% (95% CI: 16%-70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%).
CONCLUSIONS
Immune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.
PubMed: 35296019
DOI: 10.3389/fonc.2022.772509