The number of resected lymph nodes is associated with the long-term survival outcome in patients with T2 N0 non-small cell lung cancer.

OBJECTIVE: For the patients with pathologic T2 N0 non-small cell lung cancer (NSCLC), the extent of lymph node (LN) removal required for survival is controversial. We aimed to explore the prognostic significance of examined LNs and to identify how many nodes should be examined. METHODS: We reviewed 549 patients who underwent pulmonary or pneumonectomy surgery or plus lymphadenectomy who were confirmed as T2 stage and LN negative by postoperative pathological diagnosis. According to Martingale residuals of the Cox model, the patients were classified into four groups by the number of examined LNs (1-2 LNs, 3-7 LNs, 8-11 LNs, and ≥12 LNs). Kaplan-Meier analysis and Cox regression analysis were used to evaluate the association between survival and the number of examined LNs. RESULT: Compared with the 1-2 LNs, 3-7 LNs, and 8-11 LNs groups, the survival was significantly better in the ≥12 LNs group. The 5-year cancer-specific survival rate was 60.5% for patients with 1-2 negative LNs, compared with 68.7%, 72.6%, and 78.4% for those with 3-7, 8-11, and >11 LNs examined, respectively. The 7-year cancer-specific survival rate was 52.9% for patients with 1-2 negative LNs, compared with 63.7%, 63.8%, and 70.8% for those with 3-7, 8-11, and >11 LNs examined, respectively (P=0.045). There was a significant drop in mortality risk with the examination of more LNs. The lowest mortality risk occurred in those with 32 or more LNs examined. Multivariate analysis showed that age and the number of examined LNs were strong independent predictors of survival. CONCLUSION: The number of examined LNs is a strong independent prognostic factor. Our study demonstrates that patients with T2 N0 NSCLC should have at least 12 LNs examined and that the results of this study may provide information for the optimal number of resected LNs in surgery.

The role of plasma miRNAs in the diagnosis of pulmonary nodules.

BACKGROUND: In this study, we aimed to assess the clinical utility of detection of plasma microRNAs (miRNAs) in the diagnosis of pulmonary nodules. METHODS: Fifty-seven patients with pulmonary nodules who had undergone surgery were enrolled in our study from July 2016 to July 2017 at Sun Yat-sen University Cancer Center. We measured the expression levels of 12 miRNAs (miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210) in plasma samples of 57 patients, including 15 benign pulmonary nodules patients and 42 malignant pulmonary nodules patients. The levels of these miRNAs were detected by Real-time quantitative polymerase chain reaction (RT-PCR). The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of plasma miRNAs for non-small cell lung cancer (NSCLC). RESULTS: The expression levels of plasma miRNA-17, -146a, -200b, -182, -155, -221, -205, -126, -7, -21, -145, and miRNA-210 are not associated with gender, age, pTNM stage, differentiation grade. The levels of miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miRNA-210 in NSCLC patients are significantly higher than those in benign pulmonary nodules patients (P<0.05). However, there are no significant differences for the expression levels of miRNA-155 and miRNA-126. For diagnosing NSCLC, the sensitivity and specificity was 66.7% and 80.0% for miRNA-17, 54.8% and 86.7% for miRNA-146a, 64.3% and 86.7% for miRNA-200b, 83.3% and 73.3% for miRNA-182, 54.8% and 80.0% for miRNA-221, 73.8% and 80.0% for miRNA-205, 78.6% and 73.3% for miRNA-7, 78.6% and 60.0% for miRNA-21, 78.6% and 73.3% for miRNA-145, 76.2% and 73.3% for miRNA-210. CONCLUSIONS: Plasma miRNAs (miRNA-17, -146a, -200b, -182, -221, -205, -7, -21, -145, and miRNA-210) have relatively high sensitivity and specificity for the diagnosis of NSCLC. These plasma miRNAs may be the potential biomarkers for early diagnosis of lung cancer.

Tumor-stroma ratio (TSR) in non-small cell lung cancer (NSCLC) patients after lung resection is a prognostic factor for survival.

BACKGROUND: In recent years, the tumor-stroma ratio (TSR) has been considered to a new and independent predictive variable for the prognosis of some kinds of neoplasms. The objective of this study was to assess the prognostic significance of the TSR in non-small cell lung cancer (NSCLC). METHODS: A cohort of 261 NSCLC patients who underwent radical surgery of lung cancer were included in the present study. Two independent observers visually estimated the TSR on hematoxylin-eosin (H&E) stained tissue pathological slices. According to the proportion of stroma ≥50% or <50%, We separate the patients into two groups: those with stroma-poor and those with stroma-rich tumors. RESULTS: Both univariate and multivariate analyses disclosed that the TSR was associated with overall survival (OS) [hazard ratio (HR), 1.741; 95% confidence intervals (CI), 1.040-2.913 and HR, 1.904; 95% CI, 1.132-3.202, respectively]. The HR values for disease-free survival (DFS) were 1.795 (95% CI, 1.073-3.005) and 2.034 (95% CI, 1.210-3.420). The OS and DFS of patients with stroma-poor tumors were better than those with stroma-rich tumors. CONCLUSIONS: These results demonstrated that the TSR is a new prognostic factor for NSCLC. Stroma-poor tumors were associated with longer disease-free period and better prognosis than were stroma-rich tumors in NSCLC patients. The TSR may contribute to the development of individualized treatment for NSCLC in the future.

The role of postoperative adjuvant chemotherapy for lymph node-positive esophageal squamous cell carcinoma: a propensity score matching analysis.

The prognosis of patients with lymph node-positive esophageal squamous cell carcinoma (ESCC) who primarily receive radical esophagectomy remains poor. In this study, we aimed to retrospectively investigate the role of postoperative adjuvant chemotherapy with docetaxel- or paclitaxel-based regimens in these patients. A total of 434 consecutive patients were included in this study who underwent radical esophagectomy and were pathologically confirmed to have lymph node-positive ESCC from January 2005 to December 2010 in our institution. Among these patients, 113 patients received postoperative adjuvant chemotherapy (Group SC), and 321 patients underwent surgery alone (Group S). Propensity score matching and multivariate analyses were used to compensate for differences in some baseline characteristics. After matching, Group SC had significantly longer median disease-free survival (DFS) than that in Group S (23.63 months vs. 16.70 months; p = 0.006); further subset analysis revealed that a benefit regarding DFS was only associated with patients with N1 stage and with tumor length <4.5 cm. The median overall survival (OS) was similar between the two groups (38.57 months for Group SC vs. 25.27 months for Group S; p = 0.05). Multivariate analysis showed that postoperative chemotherapy, length of the tumor, T status, and N category were significantly independent predictive factors of tumor recurrence (p < 0.05). Our data suggested that adjuvant chemotherapy with docetaxel- or paclitaxel-based regimens could significantly improve DFS for patients with N1 stage and tumor length <4.5 cm ESCC and that it could potentially prolong OS for patients with lymph node-positive ESCC after surgery, compared with surgery alone. These results warrant further confirmation in prospective, randomized trials.

Effect of metabolic syndrome and its components on recurrence and survival in early-stage non-small cell lung cancer.

Previous studies have indicated that clustering of components of metabolic syndrome (MetS) increases the risk for the development of several cancers such as colon, prostate, and breast cancer. However, the prognostic role of MetS in early-stage non-small cell lung cancer (NSCLC) has not been well defined. We reviewed the clinical data and pre-treatment information of MetS of 545 patients with NSCLC who underwent radical surgery and were pathologically diagnosed as stage IB of NSCLC. The influence of MetS and/or its components on survival outcome was examined using Kaplan-Meier and Cox proportional hazards analyses. The patients with MetS showed no difference in survival outcome regarding overall survival (OS) and disease-free survival (DFS) compared with patients without MetS in univariate, multivariate, and stratification analyses. However, in univariate analysis, a high high density lipoprotein level was a good prediction factor for DFS (median DFS with vs. without MetS: 124.3 vs. 115.1 months P = 0.036). Other single MetS components showed no association with OS and DFS in early-stage NSCLC. For other clinical characteristic, the age and adjuvant therapy were the independent prognostic factors of OS in univariate and multivariate analyses. MetS and/or its components do not have significant prognostic value in early-stage NSCLC.

Concurrent oncogene mutation profile in Chinese patients with stage Ib lung adenocarcinoma.

Molecular characteristics in lung cancer are associated with carcinogenesis, response to targeted therapies, and prognosis. With concurrent oncogene mutations being reported more often, the adjustment of treatment based on the driver gene mutations would improve therapy. We proposed to investigate the distribution of concurrent oncogene mutations in stage Ib lung adenocarcinoma in a Chinese population and find out the correlation between survival outcome and the most frequently mutated genes in EGFR and KRAS in Chinese population. Simultaneously, we tried to validate the Sequenom method by real time fluoresce qualification reverse transcription polymerase chain reaction (RT-PCR) in oncogene detection. One hundred fifty-six patients who underwent complete surgical resection in our hospital between 1999 and 2007 were retrospectively investigated. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined. Genetic mutations occurred in 86 of 156 patients (55.13%). EGFR was most frequently gene contained driver mutations, with a rate of 44.23%, followed by KRAS (8.33%), PIK3CA (3.84%), KIT (3.20%), BRAF (2.56%), AKT (1.28%), MET (0.64%), NRAS (0.64%), HRAS (0.64%), and ERBB2 (0.64%). No mutations were found in the RET, PDGFRA, FGFR1, FGFR3, FLT3, ABL, CDK, or JAK2 oncogenes. Thirteen patients (8.3%) were detected in multiple gene mutations. Six patients had PIK3CA mutations in addition to mutations in EGFR and KRAS. EGFR mutations can coexist with mutations in NRAS, KIT, ERBB2, and BRAF. Only one case was found to have a KRAS mutation coexisting with the EGFR T790M mutation. Otherwise, mutations in EGFR and KRAS seem to be mutually exclusive. There is no survival benefit in favor of EGFR/KRAS mutation. Several concomitant driver gene mutations were observed in our study. None of EFGR/KRAS mutation was demonstrated as a prognostic factor. Polygenic mutation testing by time-of-flight mass spectrometry was validated by RT-PCR, which can be an alternative option to test for multiple mutations and can be widely applied to clinical practice and help to guide treatment.

Time-varying pattern of postoperative recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC): results of a single-center study of 994 Chinese patients.

BACKGROUND: The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy. PATIENTS AND METHODS: This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function. RESULTS: The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups. CONCLUSIONS: The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy.