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Lung Cancer (Amsterdam, Netherlands) Aug 2018Intra-pleural bacteria are effective pleurodesis agents in malignant pleural effusions. However, their relationship with survival is unclear.
BACKGROUND
Intra-pleural bacteria are effective pleurodesis agents in malignant pleural effusions. However, their relationship with survival is unclear.
OBJECTIVES
We undertook a comprehensive, structured evaluation of survival outcomes in adults with malignant pleural effusions treated with intra-pleural bacterial products.
DATA SOURCES
Medline, Embase, Cochrane library, Clinical Trials Registers and Open Grey.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Randomised controlled trials and non-randomised comparative studies were included, if the population included adults with malignant pleural effusions. Interventions of interest were any intra-pleural bacterial product, compared with placebo, alternative intra-pleural drug, or no treatment. Survival outcomes were collected.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two reviewers independently screened studies for eligibility, assessed papers for risk of bias and extracted data. Narrative synthesis was performed as high heterogeneity between studies precluded meta-analysis.
RESULTS
631 studies were identified, of which 14 were included. All were at high or unclear risk of bias in at least one domain. Six studies reported a survival benefit associated with intra-pleural bacterial products, whilst 8 reported no difference. Non-randomised studies and studies published prior to 2000 were more likely to report survival benefits.
LIMITATIONS
There was high heterogeneity between studies, which limited the generalisability of findings. Publication bias may have affected the review as five full-text papers were unobtainable, and survival outcomes were missing in a further five.
CONCLUSIONS
There is a lack of high quality evidence regarding the relationship between intra-pleural bacterial products and survival. Implications of key findings: Well-designed, prospective randomised trials are needed, to determine whether intra-pleural bacterial products can improve survival in pleural malignancy.
PROSPERO REGISTRATION NUMBER
CRD42017058067.
Topics: Adult; Antigens, Bacterial; Humans; Pleura; Pleural Effusion, Malignant; Pleurodesis; Publication Bias; Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 30032840
DOI: 10.1016/j.lungcan.2018.06.002 -
BMC Cancer Jul 2018Interleukin-2 (IL-2) is an important immunotherapy cytokine for various diseases including cancer. Some studies reported the efficacy and safety on cisplatin combined... (Meta-Analysis)
Meta-Analysis
Thoracic injection of low-dose interleukin-2 as an adjuvant therapy improves the control of the malignant pleural effusions: a systematic review and meta-analysis base on Chinese patients.
BACKGROUND
Interleukin-2 (IL-2) is an important immunotherapy cytokine for various diseases including cancer. Some studies reported the efficacy and safety on cisplatin combined with IL-2 versus cisplatin alone for treating malignant pleural effusion (MPE) through thoracic injection.
METHODS
We searched these studies from medical electronic database. A total of 18 studies that met the inclusion criteria were recruited in this meta-analysis. Pooled odds ratios (OR) with 95% confidence intervals (CI) were determined by the fixed effects model of meta-analysis.
RESULTS
The objective response rate (ORR) and disease control rate (DCR) of cisplatin plus IL-2 for controlling MPE was significantly higher than that of cisplatin alone (p < 0.001). In addition, compared with cisplatin alone, the presence of IL-2 improved the quality of life (QOL) of patients with MPE (p < 0.001). Although the use of IL-2 seemed to increase the probability of fever in patients (p = 0.001), it did not lead to extra other side effects (AEs) including myelotoxicity, nausea/vomiting and chest pain (p > 0.05).
CONCLUSIONS
The low-dose IL-2 improved the ORR, DCR and QOL of patients in the treatment of MPE. Although it may cause fever in patients, it did not increase other AEs.
Topics: Adult; Aged; Cisplatin; Female; Humans; Interleukin-2; Male; Middle Aged; Pleural Effusion, Malignant; Publication Bias; Quality of Life
PubMed: 29980186
DOI: 10.1186/s12885-018-4581-5 -
Journal of Visceral Surgery Dec 2018Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the literature and meta-analysis to investigate postoperative outcomes in these patients.
METHODS
Studies reporting outcomes after esophagectomy in patients with liver cirrhosis were searched in Medline, Embase, Cochrane Library, ISI Web of Science, and Scopus until June 2017, matching the terms "liver cirrhosis", "esophageal neoplasm" and/or "esophageal surgery". Extracted data included study characteristics, demographic and clinical patient characteristics, type of surgical procedure, and postoperative outcomes. A systematic review and Bayesian meta-analysis were performed.
RESULTS
Five observational, retrospective and single-arm studies with a total of 157 patients were included. The main cause of death was liver failure followed by pneumonia/sepsis and anastomotic leak. Ascites and pleural effusion were the most frequent postoperative complications (pooled rates 36% and 34%, respectively). The pooled morbidity rate was 74% (95% HPD=46-81%) while the pooled mortality was 18% (95% HPD=17-27%). Study heterogeneity (τ2) was low, ranging from 0.046 to 0.080. An incidental diagnosis of liver cirrhosis was reported in 15.6% of patients in one series. Five-year survival was similar between cirrhotic and non-cirrhotic patients but was statistically significantly higher in patients with MELD score<10.
CONCLUSIONS
Sound scientific evidence with regard to efficacy and outcomes of esophagectomy in patients with concomitant liver cirrhosis is lacking. There is a need to properly select these frail patients to reduce postoperative morbidity and mortality rates.
Topics: Bayes Theorem; Carcinoma; Cause of Death; Esophageal Neoplasms; Esophagectomy; Humans; Liver Cirrhosis; Monte Carlo Method; Observational Studies as Topic; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 29653854
DOI: 10.1016/j.jviscsurg.2018.03.014 -
The Cochrane Database of Systematic... Jan 2018Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal therapeutic strategies incorporating surgery, radiation therapy or photodynamic therapy and chemotherapy have been recommended for selected patients but there is no consensus about their effectiveness.
OBJECTIVES
To assess the benefits and harms of radical multimodal treatment options (including radical surgery ± radical radiotherapy ± photodynamic therapy ± systemic therapy) compared to each other or to palliative treatments, for people with malignant pleural mesothelioma.
SEARCH METHODS
We reviewed data from the Cochrane Lung Cancer group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase. We also checked reference lists of primary original studies, review articles and relevant conference proceedings manually for further related articles up to 21 March 2017.
SELECTION CRITERIA
We included parallel-group randomised controlled trials of multimodal therapy for people with malignant pleural mesothelioma (stages I, II or III) that measured at least one of the following endpoints: overall survival, health-related health-related quality of life, adverse events or progression-free survival. We considered studies regardless of language or publication status.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. Two review authors assessed the risk of bias in the included trials using pre-defined 'Risk of bias' domains. We assessed the methodological quality using GRADE.
MAIN RESULTS
We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated the evidence as moderate quality for overall survival and low quality for all other outcomes. One trial compared combined extrapleural pneumonectomy (EPP) plus neoadjuvant platinum-based chemotherapy plus postoperative high-dose hemithoracic radiotherapy with combined EPP plus platinum-based chemotherapy. The other trial compared EPP plus postoperative hemithoracic radiotherapy with standard (non-radical) therapy alone following platinum-based chemotherapy (patients in the standard therapy arm received continued oncological management according to local policy, which could include further chemotherapy or palliative radiotherapy).For the first trial, median overall survival calculated from registration was 20.8 months (95% confidence interval (CI) 14.4 to 27.8) in the no-radiotherapy group and 19.3 months (95% CI 11.5 to 21.8) in the radiotherapy group. For the second trial, median overall survival was 14.4 months (95% CI 5.3 to 18.7) for patients allocated to EPP and 19.5 months (95% CI 13.4 to time not yet reached) for patients randomised to standard non-radical therapy. In the second trial, 12 serious adverse events were reported during the study period: ten in the EPP group and two in the non-radical therapy group. Overall health-related quality of life scores were not different between the two arms in either study. We could not perform a meta-analysis of the two included trials due to clinical heterogeneity. We also identified three ongoing trials evaluating the topic of our review.
AUTHORS' CONCLUSIONS
The overall strength of the evidence gathered in this review is low and there is a lack of available evidence to support the use of radical multimodality therapy in routine clinical practice (particularly as one trial suggests greater harm). Given the added cost of multimodality treatment and the possible increase in risk of adverse effects, the lack of evidence of their effectiveness probably means that these interventions should currently be limited to clinical trials alone.
Topics: Antineoplastic Agents; Combined Modality Therapy; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Platinum Compounds; Pneumonectomy; Radiotherapy Dosage; Randomized Controlled Trials as Topic
PubMed: 29309720
DOI: 10.1002/14651858.CD012605.pub2 -
PloS One 2017Interleukin-17 (IL-17) plays an important role in cancer progression. Previous studies remained controversial regarding the correlation between IL-17 expression and lung... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Interleukin-17 (IL-17) plays an important role in cancer progression. Previous studies remained controversial regarding the correlation between IL-17 expression and lung cancer (LC) prognosis. To comprehensively and quantitatively summarize the prognostic value of IL-17 expression in LC patients, a systematic review and meta-analysis were performed.
METHODS
We identified the relevant literatures by searching the PubMed, EMBASE, Cochrane Library, SinoMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases, up until April 1, 2017. Overall survival (OS), disease free survival (DFS) and clinicopathological characteristics were collected from relevant studies. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated to estimate the effective value of IL-17 expression on clinical outcomes.
RESULTS
Six studies containing 479 Chinese LC patients were involved in this meta-analysis. The results indicated high IL-17 expression was independently correlated with poorer OS (HR = 1.82, 95% CI 1.44-2.29, P < 0.00001) and shorter DFS (HR = 2.41, 95% CI 1.42-4.08, P = 0.001) in LC patients. Further, when stratified by LC histological type (non-small cell lung cancer and small cell lung cancer), tumor stage (Ⅰ-Ⅲ,Ⅰ-Ⅳ and Ⅳ), detection specimen (serum, intratumoral tissue and pleural effusion), test method (immunological histological chemistry and enzyme linked immunosorbent assay), and HR estimated method (reported and estimated), all of the results were statistically significant. These data indicated that elevated IL-17 expression is correlated with poor clinical outcomes in LC. The meta-analysis did not show heterogeneity or publication bias.
CONCLUSIONS
The present meta-analysis revealed that high IL-17 expression was an indicator of poor prognosis for Chinese patients with LC. It could potentially help to assess patients' prognosis and estimate treatment efficacy in therapeutic interventions.
Topics: China; Gene Expression Regulation, Neoplastic; Humans; Interleukin-17; Lung Neoplasms; Prognosis
PubMed: 28934305
DOI: 10.1371/journal.pone.0185168 -
Radiotherapy and Oncology : Journal of... Oct 2017Malignant pleural mesothelioma (MPM) is a devastating disease with limited treatment options and a dismal prognosis. Attempts to employ radical radiotherapy in this... (Review)
Review
Malignant pleural mesothelioma (MPM) is a devastating disease with limited treatment options and a dismal prognosis. Attempts to employ radical radiotherapy in this disease have been limited by the complex shape of the pleura and the dose restrictions necessitated by the close proximity of radiosensitive structures. Recent shifts towards a 'lung sparing' surgical approach in MPM have further heightened these challenges. The aim of this systematic review is to assess recent advances in radiotherapy planning and delivery, to ascertain how these developments have impacted on the feasibility of delivering photon-based, high-dose radiotherapy with radical intent in MPM. Three electronic databases were searched and a total of 249 articles reviewed. The challenge of generating high quality, practice-defining data for diseases such as MPM was highlighted by the identification of just two randomised studies. Much of the literature consisted of low quality, retrospective data with small cohorts and inconsistent reporting on radiotherapy techniques and dosimetry. Nevertheless, a number of prospective phase II studies were identified to suggest that radical doses of radiotherapy can be delivered safely after a lung sparing procedure in MPM, reporting encouraging survival data and acceptable levels of toxicity.
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 28859932
DOI: 10.1016/j.radonc.2017.08.003 -
Respiration; International Review of... 2017The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established.
OBJECTIVES
This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE.
METHODS
The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies.
RESULTS
Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94.
CONCLUSIONS
In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Humans; Keratin-19; Mucin-1; Pleural Effusion, Malignant; Sensitivity and Specificity
PubMed: 28427079
DOI: 10.1159/000468545 -
British Journal of Cancer Mar 2017Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural... (Review)
Review
BACKGROUND
Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic.
METHODS
A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies. Two independent researchers read the abstracts and used the Quality in Prognostic Studies tool to assess the quality of the evidence.
RESULTS
Forty-five studies were identified from the current literature. Twenty studies investigated the role of serum soluble mesothelin with majority suggesting that it has variable utility as a baseline test but when measured serially correlates with treatment response and prognosis. Several studies demonstrated that serum osteopontin correlated with survival at baseline. Other biomarkers have shown prognostic utility in individual studies but are yet to be reproduced in large cohort studies.
CONCLUSIONS
From the available literature no serum or pleural fluid biomarker was identified that could be recommended currently for routine clinical practice. However, a falling serum soluble mesothelin might correlate with treatment response and improved survival.
Topics: Biomarkers, Tumor; Humans; Mesothelioma; Pleural Neoplasms; Prognosis
PubMed: 28170372
DOI: 10.1038/bjc.2017.22 -
Medicine Jan 2017Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used to treat malignant ascites or as a preventive strategy for microscopic carcinomatosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely used to treat malignant ascites or as a preventive strategy for microscopic carcinomatosis following surgical resection of abdominal tumors, application of hyperthermic intrathoracic chemotherapy (HITHOC) in the treatment of malignant pleural effusion is limited. The objective of the current study was to conduct a systematic review and meta-analysis on the application of HITHOC in the palliative treatment of malignant pleural effusion.
METHODS
After thorough searching of online databases, total 27 articles were included into qualitative systematic review and 5 of them were used to conduct qualitative meta-analysis.
RESULTS
It was found that most of HITHOC was used in combination of cytoreductive surgery (CRS) including pleurectomy/decortication or after surgical resection of primary tumors, which mainly were lung cancer, thymoma or thymic carcinoma, breast cancer, and ovarian cancer. Patients who received HITHOC had significantly longer median survival length compared to the patients without HITHOC (Hedges g = 0.763, P < 0.001). In addition, HITHOC therapy was favored (Hedges g = 0.848, P < 0.001) in terms of median survival length, tumor-free survival rate, with tumor survival rate or Karnofsky performance status (KPS) scale.
CONCLUSION
HITHOC is a safe and effective therapy in controlling pleural effusion and increasing patient's survival rate.
Topics: Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Neoplasm Staging; Palliative Care; Pleural Effusion, Malignant; Survival Analysis; Thoracic Cavity; Thoracic Surgical Procedures
PubMed: 28072694
DOI: 10.1097/MD.0000000000005532 -
Physiological Reports Dec 2016Conventional methods may fail to identify the cause of pleural effusion (PE), thus establishing reliable biomarkers is deemed necessary. This study aimed at examining... (Meta-Analysis)
Meta-Analysis Review
Conventional methods may fail to identify the cause of pleural effusion (PE), thus establishing reliable biomarkers is deemed necessary. This study aimed at examining the role of vascular endothelial growth factor (VEGF) as a biomarker in the differentiation between malignant and benign PEs in adults. A comprehensive literature search in PubMed (Medline), Scopus (ELSEVIER), and Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted using keywords. We included studies that evaluated pleural and/or serum levels of VEGF among patients presenting with undiagnosed PE and the association between these levels and the final diagnosis. We performed a meta-analysis to calculate the summary effect using the random effects model. Statistical analysis was performed with the statistical package for meta-analysis Comprehensive Meta-Analysis. Twenty studies were included in the systematic review, while 11 of them in the meta-analysis. Pleural fluid VEGF levels among patients with malignant PE were increased by 1.93 ng/mL as compared to patients with benign PE (95% CI: 1.32-2.54, Q = 173, df (Q): 10, I = 94.2%, P < 0.05). Serum VEGF levels among patients with malignant PE were increased respectively by 1.90 ng/mL (95% CI: 0.93-2.88, Q = 182, df (Q): 6, I = 96.7%, P < 0.05). This study showed that malignant PEs were associated with higher levels of both pleural fluid and serum VEGF VEGF appears to represent a promising biomarker for the differential diagnosis between benign and malignant PEs.
Topics: Biomarkers, Tumor; Female; Humans; Male; Pleural Effusion, Malignant; Vascular Endothelial Growth Factor A
PubMed: 28039396
DOI: 10.14814/phy2.12978