Publications by authors named "Kezhong Chen"

25 Publications

  • Page 1 of 1

Development and Validation of Machine Learning-based Model for the Prediction of Malignancy in Multiple Pulmonary Nodules: Analysis from Multicentric Cohorts.

Clin Cancer Res 2021 Apr 24;27(8):2255-2265. Epub 2021 Feb 24.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Purpose: Nodule evaluation is challenging and critical to diagnose multiple pulmonary nodules (MPNs). We aimed to develop and validate a machine learning-based model to estimate the malignant probability of MPNs to guide decision-making.

Experimental Design: A boosted ensemble algorithm (XGBoost) was used to predict malignancy using the clinicoradiologic variables of 1,739 nodules from 520 patients with MPNs at a Chinese center. The model (PKU-M model) was trained using 10-fold cross-validation in which hyperparameters were selected and fine-tuned. The model was validated and compared with solitary pulmonary nodule (SPN) models, clinicians, and a computer-aided diagnosis (CADx) system in an independent transnational cohort and a prospective multicentric cohort.

Results: The PKU-M model showed excellent discrimination [area under the curve; AUC (95% confidence interval (95% CI)), 0.909 (0.854-0.946)] and calibration (Brier score, 0.122) in the development cohort. External validation (583 nodules) revealed that the AUC of the PKU-M model was 0.890 (0.859-0.916), higher than those of the Brock model [0.806 (0.771-0.838)], PKU model [0.780 (0.743-0.817)], Mayo model [0.739 (0.697-0.776)], and VA model [0.682 (0.640-0.722)]. Prospective comparison (200 nodules) showed that the AUC of the PKU-M model [0.871 (0.815-0.915)] was higher than that of surgeons [0.790 (0.711-0.852), 0.741 (0.662-0.804), and 0.727 (0.650-0.788)], radiologist [0.748 (0.671-0.814)], and the CADx system [0.757 (0.682-0.818)]. Furthermore, the model outperformed the clinicians with an increase of 14.3% in sensitivity and 7.8% in specificity.

Conclusions: After its development using machine learning algorithms, validation using transnational multicentric cohorts, and prospective comparison with clinicians and the CADx system, this novel prediction model for MPNs presented solid performance as a convenient reference to help decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-4007DOI Listing
April 2021

Minimally invasive surgery versus thoracotomy for resectable stage II and III non-small-cell lung cancers: a systematic review and meta-analysis.

Eur J Cardiothorac Surg 2021 May;59(5):940-950

Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China.

:

Objectives: The study aimed to compare the long-term oncological efficacy and perioperative outcomes of patients with locally advanced non-small-cell lung cancers who underwent minimally invasive surgery (MIS) or thoracotomy.

Methods: Cochrane Library, PubMed and EMBASE databases, ClinicalTrials.gov and reference lists were searched for relevant studies. Two reviewers independently assessed the quality of the studies. Recurrence-free survival (RFS) and overall survival (OS) and perioperative outcomes were synthesized. Random-effects models were used to summarize hazard ratios (HRs), relative risks and standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Results: Twenty-three retrospective cohort studies were reviewed with a total of 3281 patients, of whom 1376 (41.9%) received MIS and 1905 (58.1%) received thoracotomy. Meta-analysis showed no significant differences in both RFS (HR, 1.02; 95% CI, 0.89-1.17; P = 0.78) and OS (HR, 0.91; 95% CI, 0.80-1.03; P = 0.15) between MIS versus thoracotomy approaches. Similar results were observed in propensity score matched studies (RFS, HR, 0.94; 95% CI, 0.73-1.20; P = 0.62; OS, HR, 0.96; 95% CI, 0.72-1.30; P = 0.81). No significant difference was found in lymph node clearance and margin positivity. As for perioperative outcomes, MIS was associated with a significant reduction in postoperative complications (relative risk, 0.83; P = 0.01), intraoperative blood loss (standardized mean difference, -0.68; P = 0.007), chest tube drainage (standardized mean difference, -0.38; P = 0.03) and length of hospital stay (standardized mean difference, -0.79; P = 0.002) when compared with thoracotomy.

Conclusions: The use of MIS for resectable stage II and III non-small-cell lung cancers is an eligible alternative to conventional thoracotomy without compromising the long-term survival and short-term outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ejcts/ezaa437DOI Listing
May 2021

Surgical Prognosis of Synchronous Multiple Primary Lung Cancer: Systematic Review and Meta-Analysis.

Clin Lung Cancer 2020 Nov 5. Epub 2020 Nov 5.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China. Electronic address:

Background: We evaluated the long-term prognosis of synchronous multiple primary lung cancer (SMPLC) patients after surgical treatment and explored prognostic factors for overall survival (OS).

Materials And Methods: A systematic review and meta-analysis was performed regarding the surgical prognosis of SMPLC. A literature search was performed using online databases. All studies were rigorously categorized following the 8th edition of the tumor, node, metastasis classification (TNM) staging rules for multiple lung cancers: SMPLC and multifocal ground-glass/lepidic (GG/L) lung cancers. Five-year OS after surgery was pooled, and hazard ratios (HRs) for prognostic factors were synthesized. Specific subgroup analysis and sensitivity analysis were conducted (PROSPERO registration CRD42019142420).

Results: An analysis of 26 studies including 1788 patients was performed. The pooled 5-year OS was 45% (95% confidence interval [CI], 37-53) of true SMPLC patients and 62% (95% CI, 57-67) of patients with pathologic stage I disease, which was different from the 5-year OS of 93% (95% CI, 85-100) of patients with multifocal GG/L lung cancers. Poor prognostic factors for SMPLC were lymph node metastasis (HR = 2.36; 95% CI, 1.75-3.20; P < .001) and pneumonectomy (HR = 2.96; 95% CI, 1.36-6.45; P = .006], whereas histology (HR = 1.11; 95% CI, 0.82-1.50; P = .508), laterality (HR = 1.16; 95% CI, 0.93-1.44, P = .190), sublobar resection (HR = 1.29; 95% CI, 0.90-1.84; P = .159), and adjuvant therapy (HR = 1.07; 95% CI, 0.64-1.80; P = .791) were not found to influence the outcome.

Conclusion: The long-term prognosis of SMPLC patients after surgery is acceptable, especially in patients with early-stage disease. Sublobar resection can be applied, although pneumonectomy should be avoided. Advanced criteria are needed to diagnose SMPLC and distinguish it from multifocal GG/L lung cancer to perform accurate surgical evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2020.10.022DOI Listing
November 2020

Clinical characteristics and management of primary mediastinal cysts: A single-center experience.

Thorac Cancer 2020 09 17;11(9):2449-2456. Epub 2020 Jul 17.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Background: In this study we aimed to assess the clinical outcomes of performing video-assisted thoracic surgery (VATS) to treat primary mediastinal cysts (PMCs) and investigate the clinical factors which increase the difficulties associated with VATS.

Methods: The medical records of all consecutive PMC patients, who underwent surgical resection from April 2001 to July 2016, were reviewed and 282 patients were included. Clinical characteristics, imaging features, and surgical outcomes were analyzed. Follow-up data were successfully obtained from 230 PMC patients by telephone or outpatient clinic annually. The latest follow-up was July 2019.

Results: VATS was performed in 278 patients and four patients were converted into thoracotomy. The mean operation time and intraoperative bleeding were 102.4 ± 40.9 minutes (range 25-360 minutes) and 52.4 ± 75.1 mL (range 5-600 mL), respectively. The intra- and postoperative complication rates were 2.8 and 5.7%, respectively. Seven patients with bronchogenic cysts showed severe cyst adhesion to vital mediastinal structures and thus had incomplete resection. Multivariable logistic analysis revealed that a maximal cyst diameter greater than 5 cm was significantly associated with increased risks of operation time extension (OR = 2.106; 95% CI: 1.147-3.865, P = 0.016) and intraoperative blood loss increase (OR = 4.428; 95% CI: 1.243-16.489, P = 0.022). A total of 230 patients had follow-up data. The median follow-up time was 70 months (range, 36-210 months). No local recurrence was observed.

Conclusions: Surgical resection by VATS may be recommended for PMC management as a primary therapeutic strategy. Cysts with a maximum diameter greater than 5 cm or cysts adjacent to vital mediastinal structures can increase the surgical difficulties.

Key Points: • Significant findings of the study A diameter >5 cm and adhesions significantly increased the risk of operation time extension together with increased blood loss. • What this study adds Cysts with a diameter >5 cm or those adjacent to vital mediastinal structures increased the potential for surgical difficulties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471030PMC
September 2020

Perioperative Dynamic Changes in Circulating Tumor DNA in Patients with Lung Cancer (DYNAMIC).

Clin Cancer Res 2019 12 22;25(23):7058-7067. Epub 2019 Aug 22.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Purpose: No study has investigated the precise perioperative dynamic changes in circulating tumor DNA (ctDNA) in any patients with early-stage cancer. This study (DYNAMIC) investigated perioperative dynamic changes in ctDNA and determined the appropriate detection time of ctDNA-based surveillance for surgical patients with lung cancer. Consecutive patients who underwent curative-intent lung resections were enrolled prospectively (NCT02965391). Plasma samples were obtained at multiple prespecified time points including before surgery (time A), during surgery after tumor resection (time B-time D), and after surgery (time P1-time P3). Next-generation sequencing-based detection platform was performed to calculate the plasma mutation allele frequency. The primary endpoint was ctDNA half-life after radical tumor resection.

Results: Thirty-six patients showed detectable mutations in time A. The plasma ctDNA concentration showed a rapid decreasing trend after radical tumor resection, with the average mutant allele fraction at times A, B, C, and D being 2.72%, 2.11%, 1.14%, and 0.17%, respectively. The median ctDNA half-life was 35.0 minutes. Patients with minimal residual disease (MRD) detection had a significant slower ctDNA half-life than those with negative MRD (103.2 minutes vs. 29.7 minutes, = 0.001). The recurrence-free survival of patients with detectable and undetectable ctDNA concentrations at time P1 was 528 days and 543 days, respectively ( = 0.657), whereas at time P2 was 278 days and 637 days, respectively ( = 0.002).

Conclusions: ctDNA decays rapidly after radical tumor resection. The ctDNA detection on the third day after R0 resection can be used as the baseline value for postoperative lung cancer surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-19-1213DOI Listing
December 2019

Monitoring of circulating tumor DNA and its aberrant methylation in the surveillance of surgical lung Cancer patients: protocol for a prospective observational study.

BMC Cancer 2019 Jun 13;19(1):579. Epub 2019 Jun 13.

Peking University People's Hospital, Beijing, People's Republic of China.

Background: Detection of circulating tumor DNA (ctDNA) is a promising method for postoperative surveillance of lung cancer. However, relatively low positive rate in early stage patients restricts its application. Aberrant methylation of ctDNA can be detected in blood samples, and may provide a more sensitive method. This study is designed to systematically evaluate and compare the detection of aberrant methylation and mutations in ctDNA among surgical non-small cell lung cancer (NSCLC) patients, aiming to investigate the feasibility of ctDNA detection as a means of lung cancer surveillance.

Methods: This is a prospective observational study. Consecutive surgical NSCLC patients will be recruited. Blood samples will be collected both before and after surgery (during the follow-up period), while matching tumor tissues and tumor-adjacent normal tissues will be collected during surgery. Quantitative analysis of aberrant methylation and mutations of ctDNA will be conducted in combination with a three-year follow-up data.

Discussion: This is the first registered prospective study designed to investigate the feasibility of ctDNA methylation detection as a means of postoperative lung cancer surveillance. We will systematically evaluate and compare the quantitative detection of ctDNA mutations and ctDNA methylation in surgical NSCLC patients, combining with the follow-up information. By integrating genetic and epigenetic information of ctDNA, more effective strategies for postoperative surveillance may be defined.

Trial Registration: This study (MEDAL, MEthylation based Dynamic Analysis for Lung cancer) was registered on ClinicalTrials.gov on 08/05/2018 (NCT03634826; Pre-results).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-019-5751-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567563PMC
June 2019

Application of circulating tumor DNA for dynamic monitoring of advanced non-small cell lung cancer treatment response: An open-label, multicenter, prospective, observational study protocol.

Thorac Cancer 2019 05 13;10(5):1310-1315. Epub 2019 Apr 13.

Department of Oncology IV, First Hospital of Shijiazhuang, Shijiazhuang, China.

Response Evaluation Criteria in Solid Tumors version 1.1 is currently considered the indicator to assess the curative effect of cancer. However, radiographic measurements often fail to detect tiny lesions or changes in the tumor burden, while tumor biomarkers possess low sensitivity and stability. Circulating tumor DNA (ctDNA) is a potential noninvasive approach that can be used to make an earlier diagnosis, monitor disease progress, and determine treatment efficacy. Previous studies of non-small cell lung cancer (NSCLC) have not clearly determined the optimum time to monitor ctDNA. Hence, the appropriate time to evaluate ctDNA to determine the curative effects of treatment in advanced NSCLC compared to conventional imaging and tumor markers should be explored in order to prevent unnecessary side effects and to avoid continuing ineffective therapies. This protocol outlines a prospective clinical trial in which advanced NSCLC patients will be recruited and longitudinal changes in ctDNA levels with changes in radiographic tumor size or tumor biomarkers will be assessed. ctDNA will be quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using multigene next-generation sequencing assay. Conclusions will be drawn from data collection and analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501042PMC
May 2019

Liquid biopsy in newly diagnosed patients with locoregional (I-IIIA) non-small cell lung cancer.

Expert Rev Mol Diagn 2019 05 3;19(5):419-427. Epub 2019 Apr 3.

a Department of Thoracic Surgery , Peking University People's Hospital , Beijing , P.R. China.

Introduction: Liquid biopsy is a promising method for the management of lung cancer, but previous studies focused mainly on patients with advanced-stage disease. As the methodology has progressed for the detection of circulating tumor DNA (ctDNA) and its aberrant methylation, researchers are gradually investigating the utility of liquid biopsy in early-stage patients. As a result, liquid biopsy has shown its potential for the application in patients with early- and locally advanced-stage non-small cell lung cancer (NSCLC). Areas covered: This review summarizes the utility of liquid biopsy in NSCLC and provide an outlook for future development. We focus on the role of ctDNA and its aberrant methylation in patients with stage IA to stageⅢA NSCLC, in the field of early detection and screening, perioperative management, and postoperative surveillance. Expert opinion: Liquid biopsy has shown the potential for clinical application of early-stage patients but has not been routinely applied yet. The utilization of liquid biopsy will be promoted by improved detection methods and data from well-designed clinical trials. With the development of precision medicine, liquid biopsy will likely play an increasingly important clinical role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14737159.2019.1599717DOI Listing
May 2019

Multiple primary lung cancers: clinical and genetic features.

J Thorac Dis 2018 Dec;10(12):E832-E834

Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2018.11.130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344728PMC
December 2018

The Video-Assisted Thoracic Surgery for Mediastinal Bronchogenic Cysts: A Single-Center Experience.

World J Surg 2018 11;42(11):3638-3645

Department of Thoracic Surgery, Peking University People's Hospital, No. 11 Xizhimen South Avenue, Xicheng District, Beijing, 100044, People's Republic of China.

Objective: The aim of this study was to evaluate the outcomes of video-assisted thoracic surgery (VATS) for mediastinal bronchogenic cyst (MBC) excision and investigate the surgical indication for MBC.

Methods: We retrospectively reviewed all consecutive MBC patients who underwent surgical excision between April 2001 and June 2016. One hundred and nineteen patients were enrolled with a median age of 45.4 years and divided into two groups: anterior mediastinum group (n = 48), and middle and posterior mediastinum group (n = 71). VATS technique was initially performed for each patient. The cyst should be resected completely as far as possible. Follow-up was completed by telephone or outpatient clinic every year. The deadline of follow-up was June 2017.

Results: One hundred and eighteen patients underwent VATS, and only one patient converted to open thoracotomy. The average operative time was 103.8 ± 41.6 min (40-360 min). The average intraoperative blood loss was 56.6 ± 86.6 ml (5-600 ml). The intraoperative complication rate was 3.4%, and the incomplete excision rate was 5.9%. The multivariate logistic analysis showed that maximal diameter >5 cm was significantly associated with risk of operation time extension (OR = 3.968; 95% CI 1.179-13.355, p = 0.026) and bleeding loss increasing (OR = 12.242; 95% CI 2.420-61.933, p = 0.002). No serious postoperative complications were observed. Follow-up was performed in 102 patients, and the mean follow-up time was 45 months (12-194 months). There was no local recurrence.

Conclusions: The maximal diameter >5 cm increased risk of operation time extension and bleeding loss increasing. Early surgical excision of MBC by VATS is recommended to establish histopathological diagnosis, relieve symptoms, and prevent surgery-related complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-018-4660-4DOI Listing
November 2018

Dynamic changes of circulating tumour DNA in surgical lung cancer patients: protocol for a prospective observational study.

BMJ Open 2018 02 6;8(2):e019012. Epub 2018 Feb 6.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Introduction: Circulating tumour DNA (ctDNA) has potential applications in cancer management. Most previous studies about ctDNA focused on advanced stage cancer patients. We have completed a clinical prospective study (NCT02645318) and showed the feasibility and clinical application of ctDNA detection in early stage non-small cell lung cancer (NSCLC) patients. The aim of this study is to investigate the elimination rate of ctDNA level after surgery. This is the first prospective study to evaluate the perioperative dynamic changes of ctDNA in surgical lung cancer patients.

Methods And Analysis: This is a prospective observational study to determine the elimination rate of circulating tumour DNA after surgery. Consecutive patients with suspected lung cancer who undergo curative-intent lung resection will be enrolled. 10 mL blood samples are taken by intravenous puncture. Plasma samples are obtained before surgery (time A) and at a series of scheduled time-points (2 min to 72 hours, time B to F) after tumour resection. DNA is prepared from 4 mL of purified plasma. A multiplex assay based on circulating single-molecule amplification and resequencing technology (cSMART) is used to simultaneously detect and quantitate hot spot EGFR, KRAS, BRAF, ERBB2, PIK3CA, TP53, ALK, RET and MET plasma DNA variants. Positive plasma mutations are validated in tumour tissue and normal lung tissue by targeted sequencing.

Ethics And Dissemination: Ethical approval has been obtained from the Peking University People's Hospital Medical Ethics Committee (2016PHB156-01). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.

Trial Registration Number: NCT02965391; Pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2017-019012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829675PMC
February 2018

Clinical features, diagnosis and thoracoscopic surgical treatment of thymic cysts.

J Thorac Dis 2017 Dec;9(12):5203-5211

Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing 100044, China.

Background: Thymic cysts are rare benign developmental anomalies and there is no consensus management for thymic cysts. The aim of this study was to disclose the efficacy of perioperative diagnosis for thymic cysts by chest computerized tomography (CT) and to elucidate the surgical procedure by video-assisted thoracic surgery (VATS) in the management of thymic cysts.

Methods: We retrospectively reviewed 108 consecutive thymic cyst patients who underwent VATS at our institution between April 2001 and August 2015. All patients received chest CT preoperatively and underwent VATS treatment. Clinical characteristics, imaging features and surgical exploration were taken into consideration to determine the surgical extent.

Results: Multivariate logistic regression analysis showed that a diameter ≤3 cm [risk ratio (RR) =4.525; 95% confidence interval (CI), 1.027-20.000; P=0.046] and an unenhanced CT value >20 Hounsfield unit (Hu) (RR =7.043; 95% CI, 1.750-28.345; P=0.006) were independent factors of incorrect diagnosis of chest CT. Three different surgical procedures were performed, which included thymectomy (n=49), cyst resection and partial thymectomy (n=46), and extended thymectomy (n=13). No serious postoperative complications were observed. The median follow-up-time was 60.6 months (range, 12.0-168.0 months) with no late complications or recurrences.

Conclusions: A diameter ≤3 cm and an unenhanced CT value >20 Hu were independent factors of incorrect diagnosis of chest CT. VATS is a reliable approach for the surgical resection of thymic cysts. We think that local resection is adequate for simple thymic cysts. However, thymectomy is necessary when there is suspicion of a thymoma or multilocular thymic cyst, and radical thymectomy is advisable for patients with autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2017.10.148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756969PMC
December 2017

Favorable prognosis and high discrepancy of genetic features in surgical patients with multiple primary lung cancers.

J Thorac Cardiovasc Surg 2018 01 5;155(1):371-379.e1. Epub 2017 Oct 5.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China. Electronic address:

Objective: Multiple primary lung cancers are detected with increasing frequency, but the ideal strategy for diagnosis and treatment remains disputable. This study evaluated both clinical characteristics and genetic alterations to investigate the appropriate strategy for patients with multiple primary lung cancer.

Methods: A total of 96 patients in our practice were diagnosed with multiple primary lung cancer over 7 years by clinical-pathologic criteria. According to consolidation/tumor ratio, they were classified into 3 groups: group A (multiple ground-glass opacity-dominant nodules, consolidation/tumor ratio ≤0.5), group B (1 solid-dominant nodule, consolidation/tumor ratio >0.5 with other ground-glass opacity-dominant nodules), and group C (2 solid-dominant nodules). A series of somatic genetic mutations and fusions were analyzed in a portion of the patients.

Results: There were 24, 35, and 37 patients in groups A, B, and C, respectively. During follow-up, 23 patients had recurrence. The 5-year recurrence-free survival was 100% in patients with multiple ground-glass opacity, 68% in those with 1 solid lesion, and 51.4% in those with 2 solid tumors (P = .001). Eighteen patients died of lung cancer. The 5-year overall survival was 100% in group A, 80.5% in group B, and 59.9% in group C (P = .002). A total of 77 driver mutations were detected in 61 of the 82 lesions. A high rate of discordance of genetic alterations (89.7%) was found between cancers within individual patients. Two patients in group C had concordant driver mutations between the 2 lesions, and both of them harbored tumor recurrence.

Conclusions: A high discordance of driver mutations between tumors in individual patients and a favorable prognosis were identified in patients with multiple primary lung cancers diagnosed by clinical-pathologic criteria, which support different strategies from those with metastatic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2017.08.141DOI Listing
January 2018

Comparison of plasma to tissue DNA mutations in surgical patients with non-small cell lung cancer.

J Thorac Cardiovasc Surg 2017 09 24;154(3):1123-1131.e2. Epub 2017 May 24.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China. Electronic address:

Objective: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non-small cell lung cancer (NSCLC), but previous work focused on patients with advanced-stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC.

Method: Consecutive patients with suspected lung cancer who underwent curative-intent lung resection were enrolled prospectively in this study. Targeted DNA sequencing with a next-generation sequencing platform was used to identify a series of somatic mutations in matched tumor tissue DNA (tDNA) and plasma ctDNA samples. Plasma was collected before, during, and after surgery. Concordance was defined as matched tDNA and ctDNA with the same identified mutations or with no mutations.

Results: In the enrolled 76 patients with lung cancer who were included, 31 had concordant mutations and 21 had no mutation in both ctDNA and tDNA, yielding an overall concordance of 68.4%. ctDNA samples obtained before and during surgery had the same mutations with a low variance in mutation frequency (1.2%) that was reduced to an average of 0.28% after surgery (P < .001). More patients were positive as assayed by ctDNA (48; 63.2%) than with serum tumor protein markers (36; 49.3%). The area under the curve was greater in ctDNA (0.887, 95% confidence interval [CI], 0.788-0.986) than for the 2 prediction models (0.803, 95% CI, 0.647-0.959; 0.69, 95% CI, 0.512-0.869) for estimating malignancy of solitary pulmonary nodules.

Conclusion: ctDNA mutation analysis for stage I-III surgical patients with NSCLC is feasible. More studies are needed to investigate its clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2017.04.073DOI Listing
September 2017

Validation of the Eighth Edition of the TNM Staging System for Lung Cancer in 2043 Surgically Treated Patients With Non-small-cell Lung Cancer.

Clin Lung Cancer 2017 11 12;18(6):e457-e466. Epub 2017 Apr 12.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, P.R. China. Electronic address:

Purpose: The International Association for the Study of Lung Cancer has proposed a revision of the Tumor, Node, Metastasis (TNM) classification for lung cancer. The purpose of this study is to evaluate the prognostic value of the eighth edition of the TNM staging system in surgically treated patients with non-small-cell lung cancer.

Methods: Data from 2043 consecutive patients with non-small-cell lung cancer who underwent surgical treatment in our single center between January 2006 and September 2015 were collected and analyzed retrospectively. Cox proportional hazard models were used to assess the prognostic significance of the T and N descriptors.

Results: The reversed overall survival curves of stage IIA and stage IIB in the seventh edition were corrected in the eighth edition. Better prognostic value in predicting overall survival, including a higher log rank test of trend χ statistic (433.6 vs. 414.2), a smaller Akaike Information Criterion value (4759.6 vs. 4768.2), a higher Harrell C-index (0.776 vs. 0.769), and a lower integrated Brier score (0.092 vs. 0.093), was observed for the eighth edition relative to the seventh edition. Recurrence-free survival analysis of subsets of patients stratified by T and N descriptors showed a stepwise deterioration. Significant differences were found between patients of subdivided stage IA (IAI vs. IA2; P = .003 and IA2 vs. IA3; P = .004).

Conclusion: The eighth edition of the TNM staging system for lung cancer has prognostic value superior to that of the seventh edition. It was able to predict recurrence-free survival well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2017.04.001DOI Listing
November 2017

Propensity-matched comparison of video-assisted thoracoscopic with thoracotomy lobectomy for locally advanced non-small cell lung cancer.

J Thorac Cardiovasc Surg 2017 04 15;153(4):967-976.e2. Epub 2016 Dec 15.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China. Electronic address:

Objective: We evaluated whether video-assisted thoracoscopic lobectomy for locally advanced non-small cell lung cancer could be performed safely and with acceptable long-term outcomes by our improved technique and compared with standard thoracotomy lobectomy in a well-balanced population.

Methods: Patients with clinical stage II and III A non-small cell lung cancers who received lobectomy were reviewed. Video-assisted thoracoscopic lobectomies were all performed with Wang's technique by the surgeons who had overcome the learning curve and achieved proficiency. By using propensity-matched analysis, perioperative outcomes and long-term survival were compared.

Results: Matching based on propensity scores produced 120 patients in each group. Conversion rate to thoracotomy was 11.7%. After thoracoscopic lobectomy, hospital length of stay was shorter compared with thoracotomy (9.2 vs 12 days; P = .014) despite similar rates of postoperative complications (30/125 [25%] vs 34/125 [28.3%]; P = .56). Disease-free survival (49.1% vs 42.2%; P = .40) and overall survival (55.0% vs 57.1%; P = .73) at 5 years were similar between groups. Although advanced pathologic stage (hazard ratio [HR], 2.018; 95% confidence interval [CI], 1.330-3.062) and no postoperative chemotherapy (HR, 1.880; 95% CI, 1.236-2.858) were independently associated with increased hazard of death in multivariable Cox regression at each time point in follow-up, thoracoscopic lobectomy was not (HR, 1.075; 95% CI, 0.714-1.620; P = .73).

Conclusions: With continued experience and optimized technique, video-assisted thoracoscopic lobectomy can be performed in the majority of cases without compromising perioperative outcomes and oncologic efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2016.12.008DOI Listing
April 2017

[Clinical features and treatment outcome of multiple primary lung cancer patients with different imaging performance].

Zhonghua Wai Ke Za Zhi 2015 Oct;53(10):731-6

Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China; Email:

Objective: To analyze the clinical characteristics and follow up record of patients with synchronous multiple lung cancers (SMLC).

Methods: The medical records of 1 868 lung cancer patients who underwent surgical treatments From January 2007 to December 2014 were reviewed, in which 103 patients were diagnosed SMLC by Martini and American College of Chest Physicians modified guideline. The average age was 60.5 years, including 34 male and 69 female patients. According to consolidation/tumor ratio (CTR) on thin-section computed tomography, 103 cases were classified into three groups: group A (multiple ground-glass opacities, CTR ≤ 50%), group B (with one solid dominant nodules, CTR > 50%), group C (with two solid dominant nodules). The surgical procedure was determined according to CT findings and respiratory function. The Kaplan-Meier method was used to analyze the duration of recurrence-free survival (RFS) and over-all survival (OS), and differences were assessed using the Log-rank test. Multivariate analysis using the Cox proportional hazards models was used to assess the potential independent effects on RFS or OS.

Results: There were 38 patients in group A (36.9%), 40 patients in group B (38.8%) and 25 patients (24.3%) in group C. More female (73.7% vs. 48.0%, χ² = 4.291, P = 0.038), less smoker (21.1% vs. 44.0%, 2 = 3.770, P = 0.052), younger (56.2 years old vs. 65.9 years old, t = -4.172, P = 0.000) and less tumor size (1.24 cm vs. 2.31 cm, t = -4.573, P = 0.000) patients in group A than in group C. The 3, 5-year RFS were 80.3% and 64.9% for all patients, respectively. The 3, 5-year OS were 87.3% and 68.6% for all patients, respectively. The 3, 5-year RFS were 100% and 100% in group A, 77.7% and 51.8% in group B, 59.6% and 44.7% in group C (P = 0.029). No significance were found in OS between the three groups (P = 0.214). Multivariate Cox analysis demonstrated that size of dominant nodule larger than 2 cm (HR = 4.475, 95% CI: 1.138 to 17.604, P = 0.032) is associated with poor prognosis, whereas postoperative chemotherapy did not affect RFS.

Conclusions: Multifocal ground-glass opacities and multiple solid lung cancers are different in nature. RFS of patients with SMLC is strongly affected tumor size. Surgical resection is effective and should be performed specifically to patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2015

Risk factors of recurrence for resected T1aN0M0 invasive lung adenocarcinoma: a clinicopathologic study of 177 patients.

World J Surg Oncol 2014 Sep 13;12:285. Epub 2014 Sep 13.

Department of Thoracic Surgery, Peking University People's Hospital, 11 Xizhimen Nan Ave, Beijing 100044, China.

Background: This study aimed at identifying risk factors of recurrence for completely resected pathologic T1aN0M0 lung adenocarcinomas.

Methods: We reviewed the records of 177 T1aN0M0 invasive adenocarcinoma patients, and re-classified achieved surgical specimens according to the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. Impact on recurrence-free survival (RFS) for age, gender, smoking history, lymphovascular invasion (LVI) and new classification was analyzed by log-rank test and Cox regression. Two existing prognostic grouping schemes of new classification were compared, and subsequently, the correlation of high-grade group in the better prognostic grouping model with clinical data was investigated statistically.

Results: The 5-year recurrence-free rate was 83.7%. The LVI and new adenocarcinoma classification were significantly associated with 5-year RFS (P = 0.012; P = 0.022, respectively). The designation of papillary predominant subtype in the low-grade group, along with lepidic- and acinar predominant subtype had more prognostic significance than the model of combining papillary-, solid- and micropapillary predominant subtypes as the high-grade group (P = 0.005 versus P = 0.181). This high-grade group has increased risk of recurrence in a multivariate Cox regression (adjusted HR 2.815, 95% CI: 1.239 to 6.397, P = 0.013), and is associated significantly more with male gender (adjusted OR 2.214, 95% CI: 1.050 to 4.668, P = 0.037), and, with borderline significance, the presence of LVI (adjusted OR 2.091, 95% CI: 0.938 to 4.662, P = 0.071).

Conclusions: Our results showed that the solid- and micropapillary predominant subtype of IASLC/ATS/ERS classification remains the only risk factor for post-operative recurrence of T1aN0M0 adenocarcinomas, suggesting that they can be indicators of aggressive tumor behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1477-7819-12-285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168167PMC
September 2014

Development and validation of a clinical prediction model for N2 lymph node metastasis in non-small cell lung cancer.

Ann Thorac Surg 2013 Nov 30;96(5):1761-8. Epub 2013 Aug 30.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, People's Republic of China.

Background: The true incidence of occult N2 lymph node metastasis in patients with clinical N0 non-small cell lung cancer (NSCLC) remains controversial. Estimation of the probability of N2 lymph node metastasis can assist physicians when making diagnosis and treatment decisions.

Methods: We reviewed the medical records of 605 patients (group A) and 211 patients (group B) with computed tomography-defined N0 NSCLC that had an exact tumor-node-metastasis stage after surgery. Logistic regression analysis of group A's clinical characteristics was used to estimate the independent predictors of N2 lymph node metastasis. A prediction model was then built and internally validated by using cross validation and externally validated in group B. The model was also compared with 2 previously described models.

Results: We identified 4 independent predictors of N2 disease: a younger age; larger tumor size; central tumor location; and adenocarcinoma or adenosquamous carcinoma pathology. The model showed good calibration (Hosmer-Lemeshow test: p = 0.96) with an area under the receiver operating characteristic curve (AUC) of 0.756 (95% confidence interval, 0.699 to 0.813). The AUC of our model was better than those of the other models when validated with independent data.

Conclusions: Our prediction model estimated the pretest probability of N2 disease in computed tomography-defined N0 NSCLC and was more accurate than the existing models. Use of our model can be of assistance when making clinical decisions about invasive or expensive mediastinal staging procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2013.06.038DOI Listing
November 2013

A primary pulmonary glomus tumor complicated with hyperpyrexia and anemia.

Ann Thorac Surg 2013 Feb;95(2):e29-31

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, PR China.

Pulmonary glomus tumors are extremely rare, with only 19 cases having been reported worldwide. The glomus body is considered to be related to the regulation of body temperature, but the reported cases were not associated with hyperpyrexia. Here, we describe a 28-year-old man with hyperpyrexia and anemia complicated with a coin lesion of the right lung. After resection of the upper lobe of the right lung by video-assisted thoracoscopic surgery, all of the patient's symptoms disappeared. The pathologic analysis reported a rare pulmonary glomus tumor. The disease had not recurred by 1 year after operation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2012.08.117DOI Listing
February 2013

Thoracic lymphangiomatosis: report of 3 patients with different presentations.

Ann Thorac Surg 2012 Dec;94(6):2111-3

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Lymphangiomatosis originates from congenital multiple malformations of the lymphatic vessel system. It is a benign lesion with malignant behavior. No radical treatment is indicated for this disease. The first patient presented initially with multiple bone cysts suggestive of multiple myeloma, the second with pleural effusion, and the third with mild shortness of breath. The lesions in these 3 patients were mainly located in the upper mediastinum, the parietal pleura, and the lung, respectively. Without any further treatment, their symptoms and radiographic images showed no progression of these conditions after a follow-up time of 7 to 42 months.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2012.04.056DOI Listing
December 2012

[Modified Restriction Enzyme-based Detection of EGFR Mutations in Lung Cancer].

Zhongguo Fei Ai Za Zhi 2011 Aug;14(8):637-41

Department of Thoracic Surgery, People's Hospital, Peking University, Beijing 100044, China.

Background: Epidermal growth factor receptor (EGFR) gene mutation in lung cancer is a reliable predictor of the efficacy of tyrosine kinase inhibitors, so detection of gene mutation has very important clinical significance. The aim of this study is to optimize conditions for restriction enzyme-based mutant enriched detection of EGFR mutation in lung cancer specimens.

Methods: EGFR somatic mutations identified in DNA specimens from 251 lung adenocarcinomas with modified mutant enriched method and direct sequencing were compared. The sensitivity of the modified method was determined by serial dilution of mutant-carrying lung cancer cells in wild-type cells.

Results: 46 deletion mutations in exon 19 and 26 point mutations in exon 21 were found by sequencing, while modified method identified another 78 deletions in exon 19 and 57 substitutions in exon 21 with a mutation rate of 53.8%. Sensitivity of this modified method was 0.5% (mutant/wild type) in serial diluted cells.

Conclusions: The modified restriction enzyme-based method is convenient for clinical EGFR mutation screening in non-small cell lung cancer for its simpleness, cost-saving and high sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3779/j.issn.1009-3419.2011.08.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999627PMC
August 2011

Learning curves and long-term outcome of simulation-based thoracentesis training for medical students.

BMC Med Educ 2011 Jun 22;11:39. Epub 2011 Jun 22.

Department of Thoracic Surgery, Peking University People’s Hospital, No 11, Xizhimen South Street, Beijing 100044, China.

Background: Simulation-based medical education has been widely used in medical skills training; however, the effectiveness and long-term outcome of simulation-based training in thoracentesis requires further investigation. The purpose of this study was to assess the learning curve of simulation-based thoracentesis training, study skills retention and transfer of knowledge to a clinical setting following simulation-based education intervention in thoracentesis procedures.

Methods: Fifty-two medical students were enrolled in this study. Each participant performed five supervised trials on the simulator. Participant's performance was assessed by performance score (PS), procedure time (PT), and participant's confidence (PC). Learning curves for each variable were generated. Long-term outcome of the training was measured by the retesting and clinical performance evaluation 6 months and 1 year, respectively, after initial training on the simulator.

Results: Significant improvements in PS, PT, and PC were noted among the first 3 to 4 test trials (p < 0.05). A plateau for PS, PT, and PC in the learning curves occurred in trial 4. Retesting 6 months after training yielded similar scores to trial 5 (p > 0.05). Clinical competency in thoracentesis was improved in participants who received simulation training relative to that of first year medical residents without such experience (p < 0.05).

Conclusions: This study demonstrates that simulation-based thoracentesis training can significantly improve an individual's performance. The saturation of learning from the simulator can be achieved after four practice sessions. Simulation-based training can assist in long-term retention of skills and can be partially transferred to clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1472-6920-11-39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144014PMC
June 2011