ERK inhibitor: A candidate enhancing therapeutic effects of conventional chemo-radiotherapy in esophageal squamous cell carcinoma.

For patients with esophageal squamous cell carcinoma (ESCC), standard therapeutic methods (cisplatin and radiotherapy) have been found to be ineffective and severely toxic. Targeted therapy emerges as a promising solution for this dilemma. It has been reported that targeted therapies are applied alone or in combination with standard conventional therapies for the treatment of a variety of cancers. To the best of our knowledge, in patients with ESCC, the combinational methods containing standard therapy and ERK-targeted therapy have yet to be explored. To analyze the prognostic role of p-ERK in ESCC patients, the Kaplan-Meier analysis and Cox regression model were used. To assess the effects of ERK-targeted therapy (GDC0994) on ESCC cells, in vitro studies including CCK-8 assay, colony formation assay, and scratch wound healing assay were conducted. In addition, the changes in cell cycle distribution and apoptosis were analyzed by flow cytometry. Besides, to assess the efficacy of different therapies in vivo, the xenograft tumor models were established by subcutaneously inoculating tumor cells into the flank/leg of mice. In patients with ESCC, a strong correlation between the high expression level of p-ERK and the poor prognosis (p < 0.01, Log-Rank test) has been identified. By analyzing the results from CCK-8 and scratch wound healing assays, we demonstrated that the ERK inhibitor repressed the viability and migration of ESCC cells. In addition, following the treatment of GDC0994, the volumes of xenograft tumors significantly decreased (p < 0.001, one-way ANOVA). Furthermore, blocking the mitogen-activated protein kinase (MAPK/ERK) pathway enhanced the therapeutic efficacy of both cisplatin and radiotherapy (p < 0.05). These findings imply the role of p-ERK in the prognosis of ESCC patients and the therapeutic value of ERK inhibitors in ESCC.

Skip metastasis in mediastinal lymph node is a favorable prognostic factor in N2 lung cancer patients: a meta-analysis.

BACKGROUND: Skip metastasis is a common lymph node metastatic pattern in non-small cell lung cancer (NSCLC). The relationship between skip metastasis and specific clinicopathologic factors and the prognostic value of skip metastasis are controversial. METHODS: A systematic search and analysis of skip metastasis in NSCLC was conducted in the databases of PubMed, EMBASE, and Web of Science up to Dec 2019. Summarized hazard ratio (HR), mean difference (MD), and odds ratio (OR) with associated 95% confidence intervals (CI) were evaluated to investigating the relationship between skip metastasis and overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and clinicopathological features in NSCLC. RESULTS: 29 studies with a total of 1,806 skip and 4,670 non-skip N2 patients were included. The upper lobe tumor showed a higher rate of skip metastasis compared with lower lobe one (RR =1.16, 95% CI: 1.00-1.34, P=0.044, I2=39.8%). The presence of skip metastasis correlated with superior overall survival (HR =0.74, 95% CI: 0.66-0.83, P<0.001, I2=48.2%) and DFS or RFS (HR =0.71, 95% CI: 0.61-0.84, P<0.001, I2=18.2%). Further subgroup analyses indicated similar results in articles that reported intrapulmonary lymph node dissection (HR =0.67, 95% CI: 0.57-0.77, P<0.001, I2=0). CONCLUSIONS: The results indicate that the presence of skip metastasis is associated with a marked increase in survival of NSCLC patients compared to patients with non-skip N2 metastasis. These results suggest that skip metastasis might be a distinct subgroup for purposes of N staging of NSCLC patients, and intrapulmonary lymph node assessment is needed.

Lobe-Specific Node Dissection Can Be a Suitable Alternative to Systematic Lymph Node Dissection in Highly Selective Early-Stage Non-Small-Cell Lung Cancer Patients: A Meta-Analysis.

PURPOSE: Whether the lobe-specific lymph node dissection is an alternative to systematic lymph node dissection for early-stage non-small-cell lung cancer remains controversial. An elaborate meta-analysis was conducted to evaluate the effects of lobe-specific lymph node dissection in early-stage patients. METHODS: A systematic literature search was conducted up to February 19, 2020 in PubMed, Ovid, Web of Science, and China National Knowledge Infrastructure databases. The outcomes including overall survival (OS), complications, and recurrence rate were extracted and analyzed. RESULTS: Nine studies including one randomized controlled trial (RCT) and eight retrospective cohort studies with 8499 non-small-cell lung cancer patients were included. The results indicated that lobe-specific lymph node had a lower rate of postoperative complication (relative risk [RR]: 0.83, 95% confidence interval [CI]: 0.72-0.95, P = 0.006). No significant difference was observed between lobe-specific lymph node and systematic lymph node dissection in OS (hazard rate = 1.12, 95% CI: 0.81-1.54, P = 0.501) with high heterogeneity (I2 = 71.9%). CONCLUSION: Lobe-specific lymph node can reach a comparable long-term prognosis in some highly selected patients. However, these results should be viewed cautiously with the existence of high heterogeneity. Due to the high heterogeneity, a strict patient selection process by experienced thoracic surgeons was recommended before validating lobe-specific lymph node.

The Favorable Prognostic Factors for Superior Sulcus Tumor: A Systematic Review and Meta-Analysis.

Background: Superior sulcus tumor is a rare non-small cell lung cancer with poor prognosis. Exploring the potential prognostic factors of patients with superior sulcus tumor and adopting individualized treatment for patients with different prognostic factors are of great significance for the prolongation of patients' lives. To figure out the prognostic factors of upper sulcus tumors, a meta-analysis was conducted. Method: We searched all the articles published until January 2020 in PubMed, Embase, and Web of Science databases, and the search strategy included the following terms, combining superior sulcus tumor and prognosis. Hazard ratio (HR) with associated confidential interval (CI) was evaluated for the purpose of investigating prognostic factors for superior sulcus tumor. STATA 16.0 was used for analysis of extracted data and assessment of publication bias. Result: Fifteen eligible studies, which had 1,009 patients with superior sulcus tumor, were included in this meta-analysis. The studies were published between 1994 and 2018, and the patient recruitment periods ranged from 1974 to 2016. The median follow-up time ranged from 18 to 95 months. The meta-analysis indicated that lower T stage (HR, 1.63; 95% CI, 1.35-1.97), lower N stage (HR, 3.08; 95% CI: 2.37-3.99), negative surgical margin (HR, 0.25; 95% CI, 0.17-0.38), and pathologic complete response (HR, 0.55; 95% CI, 0.39-0.77) were favorable prognostic factors. Conclusion: We found that T stage, N stage, surgical margin, and pathologic complete response are prognostic factors for superior sulcus tumor. To reach a better long-term survival, patients with these negative prognostic factors may need a more aggressive treatment, while more studies should be conducted to further validate these results and explore a more effective treatment.

Does percutaneous transthoracic needle biopsy increase the risk of pleural recurrence in patients with stage I lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: does percutaneous transthoracic needle biopsy (PTNB) increase the risk of pleural recurrence in patients with stage I lung cancer? Altogether, 298 papers were found using the reported search, of which 7 cohort studies and 1 meta-analysis represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Four cohort studies suggested an association between PTNB and pleural recurrence in patients with stage I lung cancer, while the other 3 cohort studies found that PTNB had no impact. One meta-analysis (the largest study) including 5 of the cohort studies above concluded that PTNB increased the risk of pleural recurrence among patients with stage I lung cancer with subpleural lesions. Based on the available evidence, it was suggested that there may be an association between PTNB and pleural recurrence in patients with stage I lung cancer, especially for patients with subpleural lesion.