Jianfei Shen

Prognostic Significance of Programmed Cell Death 1 (PD-1) or PD-1 Ligand 1 (PD-L1) Expression in Epithelial-Originated Cancer: A Meta-Analysis

AbstractThe expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients’ survival remains controversial.Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed.Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33–2.46, P < 0.001). Similarly, patients with PD-1 positive expression on TILs had significantly shorter OS than the PD-1 negative group (HR 2.53, 95% CI 1.22–5.21, P = 0.012). In analyses of PD-L1, all subgroups showed consistent trends toward unfavorable prognoses of patients with positive PD-L1 expression, regardless of antibodies and evaluation cutoffs. Subgroup analyses on PD-1 were not available due to limited data.PD-L1 or PD-1 expression status is a significant prognostic factor in epithelial-originated malignancies.

Choice of Surgical Procedure for Patients With Non-Small-Cell Lung Cancer ≤ 1 cm or > 1 to 2 cm Among Lobectomy, Segmentectomy, and Wedge Resection: A Population-Based Study.

PURPOSE According to the lung cancer staging project, T1a (≤ 2 cm) non-small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. METHODS We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. RESULTS OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC ≤ 1 cm. CONCLUSION Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.

Impact of examined lymph node count on precise staging and long-term survival of resected non-small-cell lung cancer: A population study of the US SEER database and a Chinese multi-institutional registry

Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non–small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institutional registry and the US SEER database on stage I to IIIA resected NSCLC (2001 to 2008) were analyzed for the relationship between the ELN count and stage migration and overall survival (OS) by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. The selected cut point was validated with the SEER 2009 cohort. Results Although the distribution of ELN count differed between the Chinese registry (n = 5,706) and the SEER database (n = 38,806; median, 15 versus seven, respectively), both cohorts exhibited significantly proportional increases from N0 to N1 and N2 disease (SEER OR, 1.038; China OR, 1.012; both P < .001) and serial improvements in OS (N0 disease: SEER HR, 0.986; China HR, 0.981; both P < .001; N1 and N2 disease: SEER HR, 0.989; China HR, 0.984; both P < .001) as the ELN count increased after controlling for confounders. Cut point analysis showed a threshold ELN count of 16 in patients with declared node-negative disease, which were examined in the derivation cohorts (SEER 2001 to 2008 HR, 0.830; China HR, 0.738) and validated in the SEER 2009 cohort (HR, 0.837). Conclusion A greater number of ELNs is associated with more-accurate node staging and better long-term survival of resected NSCLC. We recommend 16 ELNs as the cut point for evaluating the quality of LN examination or prognostic stratification postoperatively for patients with declared node-negative disease.

Evaluation of the efficacy and safety of anti-PD-1 and anti-PD-L1 antibody in the treatment of non-small cell lung cancer (NSCLC): a meta-analysis

BACKGROUND Currently, blockade of the programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling pathway has been proved one of the most promising immunotherapeutic strategies against cancer. Several antibodies have been developed to either block the PD-1 or its ligand PD-L1 are under development. So far, a series of phase I trials on PD-1/PD-L1 antibodies for non-small cell lung cancer (NSCLC) have been completed, without reports of results from phase II studies. Thus, we sought to perform a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of PD-1 or PD-L1 inhibition therapy. METHODS Electronic databases were searched for eligible literatures. Data of objective respond rate (ORR) and rate of adverse effects (AEs) with 95% confidence interval (CI) evaluated by immunohistochemistry (IHC) was extracted. The outcomes were synthesized based on random-effect model. Subgroup analyses were proposed. RESULTS In overall, ORR in the whole population with PD-1 blockage treatment is 22.5% (95% CI: 17.6% to 28.2%). Additionally, the rate of Grade 3-4 AEs is 16.7% (95% CI: 6.5% to 36.8%) and drug-related death rate is 2.5% (95% CI: 1.3% to 4.6%). As for patients with PD-L1 inhibition therapy, an overall ORR is 19.5% (95% CI: 13.2% to 27.7%). A higher rate of Grade 3-4 AEs (31.7%, 95% CI: 14.2% to 56.5%) is observed with a lower drug-related death rate (1.8%, 95% CI: 0.4% to 8.3%). In exploratory analyses of anti-PD-1 agents, we observed that greater ORR was presented in the median-dose cohort (3 mg/kg) than that of both low-dose (1 mg/kg) and high-dose (10 mg/kg) cohort (low-dose vs. median-dose: OR =0.12, P=0.0002; median-dose vs. high-dose: OR =1.47, P=0.18). CONCLUSIONS Anti-PD-1 and anti PD-L1 antibodies showed objective responses in approximately one fourth NSCLC patients with a tolerable adverse-effect profile. In addition, median-dose (3 mg/kg) might be a preferential dosage of anti-PD-1 agents.

Adjuvant Chemotherapy for the Completely Resected Stage IB Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis.

AbstractAdjuvant chemotherapy is recommended for postoperative stage II-IIIB nonsmall cell lung cancer patients. However, its effect remains controversial in stage IB patients. We, therefore, performed a meta-analysis to compare the efficacy of adjuvant chemotherapy versus surgery alone in stage IB patients.Six electronic databases were searched for relevant articles. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS). The time-to-event outcomes were compared by hazard ratio using log-rank test.Sixteen eligible trials were identified. A total of 4656 patients were included and divided into 2 groups: 2338 in the chemotherapy group and 2318 in the control group (surgery only). Patients received platinum-based therapy, uracil-tegafur, or a combination of them. Our results demonstrated that patients can benefit from the adjuvant chemotherapy in terms of OS (HR 0.74 95% CI 0.63–0.88) and DFS (HR 0.64 95% CI 0.46–0.89). Patients who received 6-cycle platinum-based therapy (HR 0.45 95% CI 0.29–0.69), uracil-tegafur (HR 0.71 95% CI 0.56–0.90), or a combination of them (HR 0.51 95% CI 0.36–0.74) had better OS, but patients who received 4 or fewer cycles platinum-based therapy (HR 0.97 95% CI 0.85–1.11) did not. Moreover, 6-cycle platinum-based therapy (HR 0.29 95% CI 0.13–0.63) alone or in combination with uracil-tegafur (HR 0.44 95% CI 0.30–0.66) had advantages in DFS. However, 4 or fewer cycles of platinum-based therapy (HR 0.89 95% CI 0.76–1.04) or uracil-tegafur alone (HR 1.19 95% CI 0.79–1.80) were not beneficial.Six-cycle platinum-based chemotherapy can improve OS and DFS in stage IB NSCLC patients. Uracil-tegafur alone or in combination with platinum-based therapy is beneficial to the patients in terms of OS, but uracil-tegafur seems to have no advantage in prolonging DFS, unless it is administered with platinum-based therapy.

Non-intubated resection and reconstruction of trachea for the treatment of a mass in the upper trachea

Tumors of the upper trachea are typically treated by tracheal resection and reconstruction via neck incision under general anesthesia. In recent years, non-intubated thoracic surgery has been widely applied for the treatment of lung diseases due to its advantages including quick postoperative recovery. In this article, we describe the application of non-intubated tracheal resection and reconstruction in one patient for the treatment of a mass in upper trachea.

High incidence of EGFR mutations in pneumonic-type non-small cell lung cancer.

Abstract To retrospectively identify computed tomography (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected pneumonic-type lung cancer (P-LC). A total of 953 consecutive patients with surgically resected lung cancer in the First Affiliated Hospital of Guangzhou Medical University from August 2011 to August 2013 were studied. The CT manifestations were reevaluated independently by 2 radiologists. The presence of pneumonic-type consolidation with pathological confirmed non-small lung cancer (NSCLC) was defined as P-LC. EGFR mutation was determined by direct DNA sequencing or amplification refractory mutation system-PCR. EGFR mutation rates as well as clinical and pathological manifestations between P-LC and control lung cancer patients were compared. P-LC was diagnosed in 85 patients. Among these patients, 82 were adenocarcinoma (including 78 cases of invasive adenocarcinoma and 4 cases of microinvasive adenocarcinoma), 2 were squamous carcinoma and 1 was other type. P-LC occurred more frequently in female (58.8% vs 37.1%, P < 0.01), nonsmoking (76.5% vs 56.5%, P = 0.001) and adenocarcinoma (58.8% vs 37.1%, P < 0.01) patients. Moreover, EGFR mutations were found in 39 of 52 P-LC patients (75%) and 263 of 542 non-P-LC NSCLC patients (48.5%). However, no difference was found on the mutation sites of EGFR. Histological type, sex, and radiological manifestations (P-LC vs non-P-LC) but not smoking or sequencing method can be served as the independent predictor of EGFR mutations. P-LC patients showed a significant higher incidence of EGFR mutations, which was independent of sex, histological type, and smoking history. The patients with imaging manifestation of pneumonic-type consolidation are highly suggested to perform EGFR mutation analysis to guide the sequential treatment.

Correlation between epidermal growth factor receptor mutations and nuclear expression of female hormone receptors in non-small cell lung cancer: a meta-analysis

BACKGROUND Compared with male, female non-small cell lung cancer (NSCLC) patients have better response when treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), suggesting a potential association between female hormones and EGFR mutation. However, the results provided by previous studies were inconclusive and controversial. We sought to examine the link between the expression of nuclear female hormone receptors and EGFR mutations in NSCLC. METHODS Electronic databases were used to search the relevant articles. The involved hormone receptors included estrogen receptor (ER) and progesterone receptor (PR). The primary endpoint was the occurrence of ER/PR expression and EGFR mutation in NSCLC patients. RESULTS Five studies fulfilled the criteria and were included in our analysis. Patients with high ER-β expression had higher positive EGFR mutation than low ER-β patients (44.2% vs. 23.7%), and there was a significant difference between the two groups [odds radio (OR) 3.44, 95% confidence interval (CI): 2.40-4.93, Z=6.72, P<0.001]. However, there is no significant correlation between EGFR mutations and ER-α (when included ER-α3, OR 1.20, 95% CI: 0.62-2.33, Z=0.55, P=0.58; and when included ER-α4, OR 1.18, 95% CI: 0.62-2.25, Z=0.51, P=0.61) or PR (OR 1.29, 95% CI: 0.40-4.10, Z=0.43, P=0.67). No significant publication bias was observed. CONCLUSIONS High nuclear expression of ER-β, but not ER-α or PR is correlated with EGFR mutations in NSCLC. The underlying mechanism and potential translational relevance warrant further investigation.

A meta-analysis of video-assisted thoracoscopic decortication versus open thoracotomy decortication for patients with empyema

BACKGROUND Thoracic pleural empyema is a collection of pus within a thoracic cavity. In stage 2 (fibrinopurulent) and stage 3 (organizational), decortication is the only choice. But there is no consensus on whether to choose video-assisted thoracoscopic decortication (VATD) or open thoracotomy decortication (OTD). We sought to answer this question by performing a meta-analysis. METHOD Six electronic databases were searched. Primary outcomes were operative time, postoperative hospital stay, prolonged air leak, chest tube duration, relapse rate, morbidity and mortality. Review Manager (RevMan) [Computer program]. Version 5.2, 2014 was used to pool the data. Subgroup analysis and publication bias analysis were also conducted. RESULT The operative time [mean difference -36.89; 95% confidence interval (CI), -60.96 to -12.82; P=0.003], postoperative hospital stay (mean difference -2.41; 95% CI, -3.74 to -1.09; P=0.0004), prolonged air leak (9.7% vs. 17.1%; RR 0.56; 95% CI, 0.33 to 0.94; P=0.03), chest tube duration (mean difference -1.52; 95% CI, -2.55 to -0.48; P=0.004), morbidity (16.4% vs. 24.5%; RR 0.62; 95% CI, 0.44 to 0.88; P=0.007) and mortality (4.1% vs. 6.2%; RR 0.47; 95% CI, 0.26 to 0.86; P=0.01) of VATD were statistically less than the OTD. In terms of relapse rate, there was no statistical significance between two surgical approaches (7.2% vs. 4.2%; RRN1.28; 95% CI, 0.39 to 4.15; P=0.68). CONCLUSIONS The present study summarized and compared the clinical outcomes of VATD versus OTD for the empyema patients. The current data showed that VATD might be comparable or even better than OTD in terms of operative time, postoperative hospital stay, chest tube duration, prolonged air leak rate, morbidity and mortality. But referring to the relapse rate, there was no statistical significance. The results from analysis was subject bias because of prospective randomized studies were not selected. However, VATD could be implemented safely as first-line management for most of empyema.

Choice of Surgical Procedure for Patients With NSCLC 1 to 2 cm Among Lobectomy, Segmentectomy, and Wedge Resection: A Population-Based Study

PURPOSE According to the lung cancer staging project, T1a (≤ 2 cm) non-small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. METHODS We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. RESULTS OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC ≤ 1 cm. CONCLUSION Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.