Fan Yang

Video-assisted thoracoscopic surgery is more favorable than thoracotomy for administration of adjuvant chemotherapy after lobectomy for non-small cell lung cancer.

BackgroundVideo-assisted thoracoscopic surgery (VATS) lobectomy is a newly developed type of surgery for lung cancer and has been demonstrated obvious minimally-invasive advantages compared with traditional thoracotomy. Theoretically, that less trauma leads to quicker recovery and may facilitate administration of adjuvant chemotherapy. We tested this hypothesis in this study.MethodsOne hundred and ten NSCLC patients underwent lobectomy and adjuvant chemotherapy from June 2004 to June 2010 was analyzed. The baseline characteristic criteria, variables related to surgery and accomplishing status of chemotherapy were analyzed.ResultsAll 110 patients underwent lobectomy through VATS (n = 54) or thracotomy (n = 56) and adjuvant chemotherapy. There was no significant difference in patients age, preoperative pulmonary function, co-morbidity, pathologic staging between the two groups, whereas, blood loss, operation time and postoperative complications, chest tube duration and length of stay were less in VATS group. There were no significant differences in time to initiation chemotherapy. Cases in VATS group received more cycles of chemotherapy (3.6 vs. 3.0, p = 0.002). A higher proportion of patients received full dose on schedule in VATS group (57.4% vs. 33.9%, p = 0.013) and a higher proportion of patients completed ≥75% planed dose, (88.9% vs. 71.4%, p = 0.022); slightly higher proportion of patients in thoracotomy group had grade 3 or more toxicity (20.4% vs. 35.7%, p = 0.074).ConclusionsPatients underwent lobectomy by VATS have better compliance and fewer delayed or reduced dose on adjuvant chemotherapy than those by thoracotomy.

Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.

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

BackgroundThis study aimed at identifying risk factors of recurrence for completely resected pathologic T1aN0M0 lung adenocarcinomas.MethodsWe 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.ResultsThe 5-year recurrence-free rate was 83.7%. The LVI and new adenocarcinoma classification were significantly associated with 5-year RFS (Pu2009=u20090.012; Pu2009=u20090.022, 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 (Pu2009=u20090.005 versus Pu2009=u20090.181). 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, Pu2009=u20090.013), and is associated significantly more with male gender (adjusted OR 2.214, 95% CI: 1.050 to 4.668, Pu2009=u20090.037), and, with borderline significance, the presence of LVI (adjusted OR 2.091, 95% CI: 0.938 to 4.662, Pu2009=u20090.071).ConclusionsOur 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.

Indications for conversion of thoracoscopic to open thoracotomy in video-assisted thoracoscopic lobectomy

Backgroud:u2002 The study aims to discuss indications for conversion to thoracotomy in completely thoracoscopic lobectomy.

Influence on the behavior of lung cancer H1299 cells by silencing SLC35F2 expression.

BackgroundTo investigate the effects of RNA interference-mediated downregulation of Human Solute Carrier Family 35 member F2 (SLC35F2) expression on the biological behavior of lung cancer H1299 cells.MethodsThe lentiviral vector of small interfering RNA targeting SLC35F2 was introduced into H1299 cells by liposome-mediated transfection. Expression of the SLC35F2 protein was measured by western blot. The proliferation of H1299 cells was determined by Cell Counting Kit-8 assay. The migration of H1299 cells was measured by Transwell migration assay. Cell cycle analysis used fluorescence-activated cell sorting.ResultsSLC35F2 expression was markedly downregulated in H1299 cell clone (transfected with the lentiviral vector harboring small interfering RNA targeting SLC35F2). Proliferation decreased significantly compared with that of non-transfected H1299 cells. Transwell migration assay showed that fewer cells moved through the artificial basement membrane compared with untransfected H1299 cells (38.3u2009±u20095.7 vs. 113.5u2009±u20098.5, Pu2009<u20090.05). The cell cycle of H1299 cells was changed, the percentage of H1299 cells in S and G2/M phases being significantly decreased compared with untransfected H1299 cells (S phase: 15.3%u2009±u20093.0% vs. 27.0%u2009±u20095.4%, Pu2009>u20090.05; G2/M phase; 3.0%u2009±u20091.1% vs. 10.5%u2009±u20091.7%, Pu2009<u20090.05), whereas the percentage of H1299 cells in G0/G1 phase increased markedly (81.7%u2009±u20094.0% vs. 62.5%u2009±u20091.9%, Pu2009<u20090.05).ConclusionRNA interference-mediated downregulation of SLC35F2 expression by lentiviral vector can attenuate the proliferation, migration and invasion of H1299 cells.

Efficacy of intracellular immune checkpoint-silenced DC vaccine

BACKGROUND. DC-based tumor vaccines have had limited clinical success thus far. SOCS1, a key inhibitor of inflammatory cytokine signaling, is an immune checkpoint regulator that limits DC immunopotency. METHODS. We generated a genetically modified DC (gmDC) vaccine to perform immunotherapy. The adenovirus (Ad-siSSF) delivers two tumor-associated antigens (TAAs), survivin and MUC1; secretory bacterial flagellin for DC maturation; and an RNA interference moiety to suppress SOCS1. A 2-stage phase I trial was performed for patients with relapsed acute leukemia after allogenic hematopoietic stem cell transplantation: in stage 1, we compared the safety and efficacy between gmDC treatment (23 patients) and standard donor lymphocyte infusion (25 patients); in stage 2, we tested the efficacy of the gmDC vaccine for 12 acute myeloid leukemia (AML) patients with early molecular relapse. RESULTS. gmDCs elicited potent TAA-specific CTL responses in vitro, and the immunostimulatory activity of gmDC vaccination was demonstrated in rhesus monkeys. A stage 1 study established that this combinatory gmDC vaccine is safe in acute leukemia patients and yielded improved survival rate. In stage 2, we observed a complete remission rate of 83% in 12 relapsed AML patients. Overall, no grade 3 or grade 4 graft-versus-host disease incidence was detected in any of the 35 patients enrolled. CONCLUSIONS. This study, with combinatory modifications in DCs, demonstrates the safety and efficacy of SOCS1-silenced DCs in treating relapsed acute leukemia. TRIAL REGISTRATION. ClinicalTrials.gov NCT01956630. FUNDING. National Institute of Health (R01CA90427); the Key New Drug Development and Manufacturing Program of the “Twelfth Five-Year Plan” of China (2011ZX09102-001-29); and Clinical Application Research of Beijing (Z131107002213148).

Outcome of VATS Lobectomy for Elderly Non-Small Cell Lung Cancer: A Propensity Score-Matched Study.

PURPOSEnTo analyze the short-term and long-term outcome of video-assisted thoracic surgery (VATS) lobectomy for elderly patients with non-small cell lung cancer.nnnMETHODSn105 patients aged ≥75 years with resected non-small cell lung cancer were matched with 105 younger patients by propensity score. Survival rates were calculated by the Kaplan-Meier method. The cumulative incidence functions of conditional survival rate according to the age of the patients were calculated by competing risk analysis.nnnRESULTSnpatients ≥75 years was associated with higher postoperative complication rate (p <0.001), but similar perioperative death rate (p = 0.006). Patients ≥75 years were less likely to receive adjuvant chemotherapy (p <0.001). The 5-year overall survival rates were 54.6% for patients ≥75 years and 74.1% for patients <75 years (p = 0.001). No difference was seen in disease-free survival rate (59.5% vs. 71.9% respectively = 0.117). The cumulative incidence functions of 5-year cancer-specific death were similar between the two groups (28.7% vs. 24.6% respectively, p = 0.106). The cumulative incidence functions of 5-year non-cancer-specific death was significantly higher in the elderly group (18.7% vs. 1.0%, p <0.001).nnnCONCLUSIONSnVATS lobectomy for non-small-cell lung cancer in patients ≥75 years were feasible with increased morbidity but similar mortality. The resected elderly patients were more frequently associated with non-cancer-specific death.

Thoracic Lymphangiomatosis: Report of 3 Patients With Different Presentations

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.

Early metastasis detected in patients with multifocal pulmonary ground-glass opacities (GGOs)

Due to the prevalence of low-dose computed tomography (LDCT) screening, the detection rate of lung cancer presenting as multiple ground-glass opacities (GGOs) is increasing. In statements from thexa0Fleischner Society and the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, GGOs are considered as multiple primary lung cancers and at the early stage of tumorigenesis.1 2 Accumulating evidence supports the notion that metastasis in human cancer can occur at an early stage of disease progression. Whether multiple GGOs may represent intrapulmonary metastases remains unclear. In two patients with multiple GGOs, we found that two of the multiple GGOs in each patient shared somatic mutations based on exome sequencing, indicative of intrapulmonary metastasis. This finding, for the first time to our knowledge, shows that metastasis can occur among GGOs, even pure GGOs.nnThe two patients (P1 and P2) were both non-smokers. Detailed clinicopathological characteristics are summarised in (figure 1A). P1 was a 62-year-old woman who presented with nine GGOs including two in thexa0right middle lobe (RML), three in thexa0right lower lobe (RLL), three in thexa0left upper lobe (LUL) and one in thexa0left lower lobe (LLL) (figure 1B). She underwent RLL lobectomy and RML wedge resection in January 2015. The fivexa0resected nodules were all diagnosed as lung adenocarcinomas. Four months later she underwent LUL and LLL wedge resections. Three of the four resected nodules were diagnosed as lung adenocarcinomas. All eight malignant lesions were pathological T1–T2 tumours without lymphovascular invasion (onlinexa0supplementary figure 1). No lymph node metastasis was detected. P2 was a 44-year-old woman who presented with eight GGOs including six in thexa0right upper lobe (RUL) and two in thexa0LUL (figure 1C). Radiologically, all of the eight lesions were pure GGOs <15u2009mm (range 4–14u2009mm). She only underwent …

Plasma small ncRNA pair panels as novel biomarkers for early-stage lung adenocarcinoma screening

BackgroundLung cancer is a major cause of cancer-related mortality worldwide, and around two-thirds of patients have metastasis at diagnosis. Thus, detecting lung cancer at an early stage could reduce mortality. Aberrant levels of circulating small non-coding RNAs (small ncRNAs) are potential diagnostic or prognostic markers for lung cancer. We aimed to identify plasma small ncRNA pairs that could be used for early screening and detection of lung adenocarcinoma (LAC).ResultsA panel of seven small ncRNA pair ratios could differentiate patients with LAC or benign lung disease from high-risk controls with an area under the curve (AUC) of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage (which included 50 patients with early-stage LAC, 35 patients with benign diseases and 29 high-risk controls) and an AUC of 90.2%, a sensitivity of 91.5% and a specificity of 80.4% at the validation stage (which included 44 patients with early-stage LAC, 32 patients with benign diseases and 51 high-risk controls). The same panel could distinguish LAC from high-risk controls with an AUC of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage and an AUC of 89.5%, a sensitivity of 85.4% and a specificity of 83.3% at the validation stage. Another panel of five small ncRNA pair ratios (different from the first) was able to differentiate LAC from benign disease with an AUC of 82.0%, a sensitivity of 81.1% and a specificity of 78.1% in the training cohort and an AUC of 74.2%, a sensitivity of 70.4% and a specificity of 72.7% in the validation cohort.ConclusionsSeveral small ncRNA pair ratios were identified as markers capable of discerning patients with LAC from those with benign lesions or high-risk control individuals.