-
The Cochrane Database of Systematic... Nov 2014A major determinant of treatment offered to patients with non-small cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If the disease has not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A major determinant of treatment offered to patients with non-small cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If the disease has not spread to the ipsilateral mediastinal nodes, subcarinal (N2) nodes, or both, and the patient is otherwise considered fit for surgery, resection is often the treatment of choice. Planning the optimal treatment is therefore critically dependent on accurate staging of the disease. PET-CT (positron emission tomography-computed tomography) is a non-invasive staging method of the mediastinum, which is increasingly available and used by lung cancer multidisciplinary teams. Although the non-invasive nature of PET-CT constitutes one of its major advantages, PET-CT may be suboptimal in detecting malignancy in normal-sized lymph nodes and in ruling out malignancy in patients with coexisting inflammatory or infectious diseases.
OBJECTIVES
To determine the diagnostic accuracy of integrated PET-CT for mediastinal staging of patients with suspected or confirmed NSCLC that is potentially suitable for treatment with curative intent.
SEARCH METHODS
We searched the following databases up to 30 April 2013: The Cochrane Library, MEDLINE via OvidSP (from 1946), Embase via OvidSP (from 1974), PreMEDLINE via OvidSP, OpenGrey, ProQuest Dissertations & Theses, and the trials register www.clinicaltrials.gov. There were no language or publication status restrictions on the search. We also contacted researchers in the field, checked reference lists, and conducted citation searches (with an end-date of 9 July 2013) of relevant studies.
SELECTION CRITERIA
Prospective or retrospective cross-sectional studies that assessed the diagnostic accuracy of integrated PET-CT for diagnosing N2 disease in patients with suspected resectable NSCLC. The studies must have used pathology as the reference standard and reported participants as the unit of analysis.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data pertaining to the study characteristics and the number of true and false positives and true and false negatives for the index test, and they independently assessed the quality of the included studies using QUADAS-2. We calculated sensitivity and specificity with 95% confidence intervals (CI) for each study and performed two main analyses based on the criteria for test positivity employed: Activity > background or SUVmax ≥ 2.5 (SUVmax = maximum standardised uptake value), where we fitted a summary receiver operating characteristic (ROC) curve using a hierarchical summary ROC (HSROC) model for each subset of studies. We identified the average operating point on the SROC curve and computed the average sensitivities and specificities. We checked for heterogeneity and examined the robustness of the meta-analyses through sensitivity analyses.
MAIN RESULTS
We included 45 studies, and based on the criteria for PET-CT positivity, we categorised the included studies into three groups: Activity > background (18 studies, N = 2823, prevalence of N2 and N3 nodes = 679/2328), SUVmax ≥ 2.5 (12 studies, N = 1656, prevalence of N2 and N3 nodes = 465/1656), and Other/mixed (15 studies, N = 1616, prevalence of N2 to N3 nodes = 400/1616). None of the studies reported (any) adverse events. Under-reporting generally hampered the quality assessment of the studies, and in 30/45 studies, the applicability of the study populations was of high or unclear concern.The summary sensitivity and specificity estimates for the 'Activity > background PET-CT positivity criterion were 77.4% (95% CI 65.3 to 86.1) and 90.1% (95% CI 85.3 to 93.5), respectively, but the accuracy estimates of these studies in ROC space showed a wide prediction region. This indicated high between-study heterogeneity and a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a lack of precision. Sensitivity analyses suggested that the overall estimate of sensitivity was especially susceptible to selection bias; reference standard bias; clear definition of test positivity; and to a lesser extent, index test bias and commercial funding bias, with lower combined estimates of sensitivity observed for all the low 'Risk of bias' studies compared with the full analysis.The summary sensitivity and specificity estimates for the SUVmax ≥ 2.5 PET-CT positivity criterion were 81.3% (95% CI 70.2 to 88.9) and 79.4% (95% CI 70 to 86.5), respectively.In this group, the accuracy estimates of these studies in ROC space also showed a very wide prediction region. This indicated very high between-study heterogeneity, and there was a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a clear lack of precision. Sensitivity analyses suggested that both overall accuracy estimates were marginally sensitive to flow and timing bias and commercial funding bias, which both lead to slightly lower estimates of sensitivity and specificity.Heterogeneity analyses showed that the accuracy estimates were significantly influenced by country of study origin, percentage of participants with adenocarcinoma, (¹⁸F)-2-fluoro-deoxy-D-glucose (FDG) dose, type of PET-CT scanner, and study size, but not by study design, consecutive recruitment, attenuation correction, year of publication, or tuberculosis incidence rate per 100,000 population.
AUTHORS' CONCLUSIONS
This review has shown that accuracy of PET-CT is insufficient to allow management based on PET-CT alone. The findings therefore support National Institute for Health and Care (formally 'clinical') Excellence (NICE) guidance on this topic, where PET-CT is used to guide clinicians in the next step: either a biopsy or where negative and nodes are small, directly to surgery. The apparent difference between the two main makes of PET-CT scanner is important and may influence the treatment decision in some circumstances. The differences in PET-CT accuracy estimates between scanner makes, NSCLC subtypes, FDG dose, and country of study origin, along with the general variability of results, suggest that all large centres should actively monitor their accuracy. This is so that they can make reliable decisions based on their own results and identify the populations in which PET-CT is of most use or potentially little value.
Topics: Carcinoma, Non-Small-Cell Lung; Cross-Sectional Studies; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Multimodal Imaging; Positron-Emission Tomography; Prospective Studies; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 25393718
DOI: 10.1002/14651858.CD009519.pub2 -
Expert Review of Hematology Mar 2020: Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of diffuse large B-cell lymphoma. Approximately 10-30% of patients experience...
: Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of diffuse large B-cell lymphoma. Approximately 10-30% of patients experience refractory or relapsed PMBCL (rrPMBCL) after first-line therapy. Data and treatment guidelines for rrPMBCL are scarce, and management is based on clinical experience.: Two structured literature reviews were undertaken to determine the incidence, prevalence, and mortality rates associated with rrPMBCL, and to identify clinical practice guidelines and real-world patterns of care.: Epidemiology studies included reported lymphomas ( = 1), non-Hodgkin lymphoma ( = 1), lymphoid neoplasm ( = 1), PMBCL ( = 6), and rrPMBCL ( = 1). Of 12 published treatment guidelines, only four provided recommendations for rrPMBCL. Sixteen studies provided data on real-world treatment patterns, but most were single-center studies with small patient numbers. Chemotherapy/immunochemotherapy, followed by high-dose treatment (HDT) and stem cell transplantation, was a mainstay of salvage therapy in most studies; real-world care generally followed treatment guidelines.: Salvage chemotherapy (often with rituximab and radiotherapy), followed by HDT and stem cell transplantation, appears to be the standard real-world treatment for rrPMBCL. However, large prospective and retrospective studies are warranted to improve our knowledge of real-world treatment patterns.
Topics: Allografts; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Practice Guidelines as Topic; Recurrence; Salvage Therapy
PubMed: 31951774
DOI: 10.1080/17474086.2020.1716725 -
Surgical Oncology Dec 2020The optimal extent of lymphadenectomy for adenocarcinoma of the esophagogastric junction (AEG) has been continuously debatable. The study aimed to determine the... (Meta-Analysis)
Meta-Analysis
The optimal extent of lymphadenectomy for adenocarcinoma of the esophagogastric junction (AEG) has been continuously debatable. The study aimed to determine the incidence of lymph node metastasis at each station in Siewert types Ⅱ/Ⅲ AEG. PubMed was searched and publications reporting metastasis at each nodal station were eligible. Meta-analysis was performed using RevMan 5.3. Twenty-one studies involving 4662 patients were included. The incidence of lymph node metastasis was high (≥20%) in stations No. 3, 1, 2 and 7 in decreasing order, and moderate (10-20%) in stations No. 9, 19 and 110. The incidence did not exceed 10% in stations No. 10, 11p, 20, 8a, 4sa, 4 s b and 4d, was less than 5% in stations No. 5, 6, 11d, 12a, and even close to 0 in stations No. 107, 111 and 112. Compared with type Ⅲ tumors, type Ⅱ tumors had significantly lower incidence in some abdominal stations including No. 3, 4sa, 4 s b, 6, 8a and 10, while significantly higher in the lower mediastinal stations. The present analysis established a map of lymph node metastasis in Siewert types Ⅱ/Ⅲ AEG, which may serve as a valuable reference for the extent of lymphadenectomy.
Topics: Adenocarcinoma; Esophageal Neoplasms; Esophagogastric Junction; Humans; Incidence; Lymph Node Excision; Lymphatic Metastasis
PubMed: 32835903
DOI: 10.1016/j.suronc.2020.08.001 -
Annals of the American Thoracic Society Oct 2018Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) are commonly used for the diagnosis and mediastinal staging of lung cancer. Molecular markers... (Meta-Analysis)
Meta-Analysis
Adequacy of Samples Obtained by Endobronchial Ultrasound with Transbronchial Needle Aspiration for Molecular Analysis in Patients with Non-Small Cell Lung Cancer. Systematic Review and Meta-Analysis.
RATIONALE
Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) are commonly used for the diagnosis and mediastinal staging of lung cancer. Molecular markers are becoming increasingly important in patients with lung cancer to define targetable mutations suitable for personalized therapy, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species proto-oncogene (ROS1), and programmed death-ligand 1 (PD-L1).
OBJECTIVES
To evaluate the adequacy of EBUS-TBNA-derived tissue for molecular analysis.
METHODS
We searched the MEDLINE, LILACS, www.clinicaltrials.gov , and Epistemonikos databases through January 2018.
DATA EXTRACTION
Two independent reviewers performed the data search, quality assessment, and data extraction. We included both prospective and retrospective studies; risk of bias was evaluated using the ROBINS-I tool. The primary outcome was the proportion of adequate samples obtained by EBUS-TBNA for molecular analysis. Data were pooled by using a binary random effects model. Finally, evidence was rated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
RESULTS
A total of 33 studies including 2,698 participants were analyzed. In 28 studies that evaluated EBUS-TBNA for the identification of EGFR mutations, the pooled probability of obtaining a sufficient sample was 94.5% (95% confidence interval CI], 93.2-96.4%). For identification of ALK mutations, the pooled probability was 94.9% (95% CI, 89.4-98.8%). Finally, the prevalence of EGFR mutation was 15.8% (95% CI, 12.1-19.4%), and the prevalence of ALK mutation was 2.77% (95% CI, 1.0-4.8%). Data for ROS1 and PD-L1 mutations were not suitable for meta-analysis.
CONCLUSIONS
EBUS-TBNA has a high yield for molecular analysis of both EGFR and ALK mutations. However, the suitability of TBNA samples for next-generation sequencing is uncertain and should be explored in further studies. Clinical trial registered with PROSPERO (CRD42017080008).
Topics: Carcinoma, Non-Small-Cell Lung; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Lung Neoplasms; Mediastinum; Molecular Diagnostic Techniques; Proto-Oncogene Mas
PubMed: 30011388
DOI: 10.1513/AnnalsATS.201801-045OC -
Endocrine Nov 2023Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that...
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature.
METHODS
A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2 × 1.5 cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783 + 1G > A in the MEN1 gene was identified. We further searched PubMed and EMBASE for thymoma in association with MEN1.
RESULTS
A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted.
CONCLUSIONS
Besides carcinoid, other tumors, including thymoma, need to be identified for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Thymoma; Thymus Neoplasms; Carcinoid Tumor; Pancreatic Neoplasms
PubMed: 37668926
DOI: 10.1007/s12020-023-03440-5 -
Annals of the American Thoracic Society Nov 2019Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method used to diagnose suspected mediastinal lymph nodes or masses.... (Meta-Analysis)
Meta-Analysis
Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method used to diagnose suspected mediastinal lymph nodes or masses. However, the accuracy of the diagnosis in patients with suspected lymphoma is unclear. To evaluate the diagnostic yield of EBUS-TBNA in patients with suspected lymphoma. A literature search including EMBASE, MEDLINE, Cochrane Library, and Google Scholar was performed by two reviewers. Included articles were evaluated using the QUADAS-2 tool and meta-analysis with a binary method model to compare the sensitivity, specificity, and summary receiver operating characteristic curve in patients with suspected lymphoma. Fourteen studies (425 participants) were pooled in the analysis. EBUS-TBNA reported an overall sensitivity of 66.2% (confidence interval [CI], 55-75.8%; = 76.2%) and specificity of 99.3% (CI, 98.2-99.7%; = 40%). For a new diagnosis of lymphoma, 13 studies including 243 participants reported sensitivity of 67.1% (CI, 54.2-77.9%; = 66.8%) and specificity of 99.6% (CI, 99.1-99.8%; = 0%). For recurrence of lymphoma, 11 studies including 166 participants reported sensitivity of 77.8% (CI, 68.1-85.2%; = 20.2%) and specificity of 99.5% (CI, 98.9-99.8%; = 0%). In the recurrence group, we found the use of rapid onsite examination, sample size, and flow cytometry increased the sensitivity of EBUS-TBNA, albeit a potential source of heterogeneity. EBUS-TBNA has fair sensitivity for identifying a new diagnosis of lymphoma and fair to good sensitivity for identifying recurrence. PROSPERO CRD42018102773 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=102773.
Topics: Bronchoscopy; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Lung Neoplasms; Lymphatic Metastasis; Lymphoma; Mediastinal Neoplasms; Sensitivity and Specificity
PubMed: 31291126
DOI: 10.1513/AnnalsATS.201902-175OC -
Journal of Thoracic Oncology : Official... Jun 2019Confirmatory mediastinoscopy after negative endosonography findings is advised by the guidelines on patients with resectable NSCLC and suspected intrathoracic nodes on... (Meta-Analysis)
Meta-Analysis
Unforeseen N2 Disease after Negative Endosonography Findings with or without Confirmatory Mediastinoscopy in Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
INTRODUCTION
Confirmatory mediastinoscopy after negative endosonography findings is advised by the guidelines on patients with resectable NSCLC and suspected intrathoracic nodes on fludeoxyglucose F 18 positron emission tomography-computed tomography. Its role however is under debate owing to its limited nodal metastasis detection rate, morbidity, associated treatment delay, and unknown impact on survival.
METHODS
Systematic review and meta-analysis of studies on invasive mediastinal staging in patients with (suspected) NSCLC. The Medline, Embase, and Cochrane databases were searched until September 19, 2018, without year or language restrictions. The Quality Assessment Tool for Diagnostic Accuracy Studies, version 2, was used to evaluate the risk of bias and applicability of the included studies. Rates of unforeseen N2 disease were assessed for endobronchial ultrasound and/or endoscopic ultrasound staging strategies with or without confirmatory mediastinoscopy. Additionally, the complication rates of cervical video mediastinoscopy for mediastinal staging of NSCLC were investigated.
RESULTS
A total of 5073 articles were found, of which 42 studies or subgroups (covering a total of 3248 patients undergoing the surgical reference standard of treatment) were considered in the analysis. Random effects meta-analysis of endosonography with or without confirmatory mediastinoscopy showed rates of unforeseen N2 disease of 9.6% (95% confidence interval [CI]: 7.8%-11.7%, I = 30%) versus 9.9% (95% CI: 6.3%-15.2%, I = 73%), respectively. Random effects meta-analysis of mediastinoscopy (eight studies [1245 patients in total]) showed a complication rate of 6.0% (95% CI: 4.8%-7.5%), with laryngeal recurrent nerve palsy accounting for 2.8% (95% CI: 2.0%-4.0%).
CONCLUSION
The rate of unforeseen N2 disease after negative endosonography findings was similar in patients undergoing immediate lung tumor resection to those undergoing confirmatory mediastinoscopy first, at the cost of 6.0% rate of complications by mediastinoscopy.
Topics: Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Endosonography; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinoscopy; Neoplasm Staging; Observational Studies as Topic
PubMed: 30905829
DOI: 10.1016/j.jtho.2019.02.032 -
Minerva Chirurgica Oct 2018Bronchogenic carcinomas involving the carina or the tracheo-bronchial angle represents a challenging surgical procedure because of difficult surgical techniques and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Bronchogenic carcinomas involving the carina or the tracheo-bronchial angle represents a challenging surgical procedure because of difficult surgical techniques and complex ventilation procedures. Even though surgical outcomes for this type of procedure has improved over time, the need for surgical management of patients with metastatic mediastinal nodes, that is those that are graded N2 or higher according to the TNM classification, is still controversial.
EVIDENCE ACQUISITION
We searched PubMed, Embase, and CNKI for literature in English or Chinese reporting on this subject, with information on survival rates or survival curves for groups with different grades of nodal status. We then performed a meta-analysis by grouping N0 and N1 patients and compared the surgical outcomes to those graded as N2 or higher. Hazard Ratios for each study were derived from the Kaplan-Meier survival curve.
EVIDENCE SYNTHESIS
Seven studies were included in this meta-analysis. The calculated hazard ratios ranged from 0.146 to 0.455. The weighted average hazard ratio for the N0/N1 group as compared to the N2/N3 group was 0.261 (CI: 0.154-0.441). The Galbraith plot confirmed the homogeneity of the studies included.
CONCLUSIONS
Carinal resection and reconstruction remains a challenging surgical procedure and the rather poor surgical outcomes for patients graded as N2 or higher, according to nodal involvement points to the fact that better pre-operative management is required in terms of tumor grading, induction chemotherapy and radiotherapy to decrease the risks associated with metastatic mediastinal nodal status.
Topics: Bronchial Neoplasms; Carcinoma, Bronchogenic; Humans; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Invasiveness; Tracheal Neoplasms; Treatment Outcome
PubMed: 28565890
DOI: 10.23736/S0026-4733.17.07382-5 -
International Journal of Colorectal... Oct 2019It remains controversial whether patients benefit from adjuvant chemotherapy (ACT) after resection of pulmonary metastasis (PM) from colorectal cancer (CRC). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It remains controversial whether patients benefit from adjuvant chemotherapy (ACT) after resection of pulmonary metastasis (PM) from colorectal cancer (CRC). This meta-analysis was intended to evaluate the efficacy of ACT in patients after resection of PM from CRC.
METHODS
We systematically retrieved articles from PMC, PubMed, Cochrane Library, and Embase (up to March 5, 2019). Survival data, including overall survival (OS) and disease-free survival (DFS), were tested by hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS
We included 18 cohort studies with a total of 3885 patients. The meta-analysis showed that ACT had no significant effect on OS (HR = 0.78; 95% CI = 0.60-1.03; P = 0.077) and DFS (HR = 0.91; 95% CI = 0.74-1.11; P = 0.339) in patients after resection of PM from CRC. There was no significant difference in OS (HR = 0.79; 95% CI = 0.42-1.50; P = 0.474) in patients after resection of PM from CRC treated with bevacizumab (BV). Subgroup analysis showed that ACT did not improve OS (HR = 0.86; 95% CI = 0.57-1.29; P = 0.461) in patients who had undergone previous resection of extra PM. ACT did not improve OS in patients who had positive hilar/mediastinal lymph node metastasis (HR = 0.80; 95% CI = 0.57-1.14; P = 0.22).
CONCLUSION
In conclusion, ACT does not provide survival benefits for patients after resection of PM from CRC. ACT and targeted agents (BV) are not suggested for these patients.
Topics: Adult; Aged; Aged, 80 and over; Bevacizumab; Chemotherapy, Adjuvant; Cohort Studies; Colorectal Neoplasms; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Prognosis; Publication Bias; Regression Analysis; Survival Analysis
PubMed: 31446479
DOI: 10.1007/s00384-019-03362-7 -
Lung Cancer (Amsterdam, Netherlands) Dec 2018The primary objective of this study is to systematically review all pertinent literature related to the use of ultrasonographic features to predict malignancy in...
OBJECTIVES
The primary objective of this study is to systematically review all pertinent literature related to the use of ultrasonographic features to predict malignancy in mediastinal lymph nodes seen during endobronchial ultrasound (EBUS) procedures.
MATERIALS AND METHODS
Two independent reviewers completed the search and review (PubMed, EMBASE, Medline, and Cochrane databases) of the resulting titles and abstracts. Following full-text screening, thirteen articles met the inclusion criteria. Heterogeneity prevented any meta-analysis, instead a narrative review was completed. Results from each included article are categorized by the following ultrasonographic features: shape, echogenicity, margin status, central necrosis, short axis length, and central hilar structure. Diagnostic tools are also described in detail.
RESULTS
Absence of a central hilar structure and heterogeneous echogenicity were often associated with malignancy; however, consensus was not achieved amongst the included articles. The remaining ultrasonographic features were not consistently associated with malignancy or benign disease status, suggesting a need for prospective analysis. Four diagnostic tools were also assessed. These tools demonstrate that a combination of ultrasonographic features may accurately predict lymph node malignancy rather than a single feature.
CONCLUSION
Analysis of ultrasonographic features may prevent the need for repeat EBUS procedures when initial biopsy results are inconclusive. However, prospective external validation of these features is required to determine their true predictive capability. PROSPERO registration number: CRD42017068468.
Topics: Diagnosis, Differential; Endosonography; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mediastinum; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography
PubMed: 30527199
DOI: 10.1016/j.lungcan.2018.10.020