Hong Jian

Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients

The objective of this study is to explore clinical risk factors for venous thromboembolism (VTE) in postoperative lung cancer patients in order to provide a basis for the prevention and treatment of postoperative VTE.

Predictive significance of bone sialoprotein and osteopontin for bone metastases in resected Chinese non-small-cell lung cancer patients: A large cohort retrospective study

BACKGROUND Bone is one of the most common sites of metastasis in patients with non-small-cell lung cancer (NSCLC). Over-expression of bone sialoprotein (BSP) and osteopontin (OPN) in tumour samples has shown prognostic significance in bone metastasis (BM) of breast and prostate cancer, respectively. However, their importance in BM of NSCLC has not been verified. Therefore, we planned a large cohort retrospective study to investigate the relationship between the expression of these two biomarkers (BSP and OPN) and BM in surgically resected NSCLC patients. METHODS 180 completely resected NSCLC patients were included in this study. 40 patients subsequently developed BM. Paraffin-embedded primary tumour tissues of patients were supplied to produce a tissue microarray, and immunohistochemistry method was used for evaluation of the expression of BSP and OPN. Different expressions of these two biomarkers among BM group and non-BM group were estimated by chi(2) test. BM-free survival was analyzed by Kaplan-Meier method. The prognostic impact of clinicopathologic variables and biomarker expression was evaluated by Cox proportional hazards model. RESULTS BSP expression was associated with BM (p=0.007), whereas OPN expression did not reach statistical significance (p=0.245). Univariate analysis showed that expression of BSP (p=0.010) and N staging (p<0.005) was associated with BM-free survival. Multivariate analyses showed BSP expression (HR=3.322, p=0.003), N staging (HR=1.879, p=0.001), and T staging (HR=1.618, p=0.024) were independent prognostic factors for BM. CONCLUSIONS BSP protein expression in the primary resected NSCLC is strongly associated with BM and could be used to identify high-risk patients. Correlation of OPN protein expression and BM needs further investigation.

Prognostic value of MMP9 activity level in resected stage I B lung adenocarcinoma.

The clinical outcomes of patients with early‐stage non‐small cell lung cancer (NSCLC) have remained unsatisfactory after complete surgical resection. The objective of this study was to explore the prognostic value of matrix metalloproteinase 9 (MMP9) activity level in Chinese patients with stage I B lung adenocarcinoma. A sensitive and validated method was employed for determining the activity of MMP9 in human lung adenocarcinoma cells in vitro. Then, the association was examined between the level of MMP9 enzymatic activity and clinical outcomes. A total of 104 cases were stratified according to the IASLC/ATS/ERS classification scheme and activity of MMP9 was analyzed by SensoLyte® assay kit. The results showed that the MMP9 activity was the highest in solid predominant and micropapillary predominant subtypes, intermediate in acinar predominant and papillary predominant subtypes, and the lowest in lepidic predominant subtype. Multivariate analysis revealed that pathological subtype and activity of MMP9 were independent prognostic factors for disease‐free survival (DFS), respectively (P = 0.005 and 0.029). Significant relationship existed between enzyme activity of MMP9 and prognosis. And the 30 months DFS of high‐ and low‐level MMP9 activity tumors was 44.2% and 84.1% (P < 0.0001), respectively. High‐level MMP9 activity is correlated with aggressive tumor behaviors and poor clinical outcomes in early‐stage lung adenocarcinoma after complete resection.

A Cost-Effectiveness Analysis of Docetaxel versus Pemetrexed in Second-Line Chemotherapy for Stage IIIb or IV Non-Small Cell Lung Cancer in China

Background: To study the cost-efficacy of docetaxel and pemetrexed as single agents versus platinum-based combination agents in second-line treatment of stage IIIb or IV non-small cell lung cancer (NSCLC) patients by evaluating chemotherapeutic indexes and medical costs. Methods: Treatment responses were evaluated by progression-free survival (PFS), overall survival (OS), hematological and gastrointestinal toxicities. Results: Two hundred and seven stage IIIb or IV NSCLC patients were recruited to this clinical observation retrospective study. Thirty-four subjects were treated with docetaxel (group A), 98 with platinum-based doublet chemotherapy with docetaxel (group B), 42 with pemetrexed (group C), and 33 patients with platinum-based doublet combination therapy with pemetrexed (group D). The average PFS of groups A and B was 3.28 and 4.58 months, respectively (p = 0.042). The mean PFS of groups C and D was 3.1 and 4.98 months, respectively (p = 0.017). The mean OS of these groups was 12.88, 13.17, 12.40 and 13.04 months, respectively, without significant differences. The total medical costs in these four groups amounted to USD 5,533, 7,745, 8,569 and 15,291, respectively. Conclusions: Platinum-based doublet chemotherapy with docetaxel or pemetrexed could significantly increase PFS, however, without significant OS improvement in comparison with using them as single agents. The medical expenses associated with doublet therapy were much higher than those associated with single therapy with a significant portion of the medical expenses spent on treating hematological and gastrointestinal toxicity.

AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling

Most tumors develop resistance to targeted cancer drugs, even though these drugs have produced substantial clinical responses. Here we established anaplastic lymphoma kinase (ALK)‐positive drug‐resistant lung cancer cell lines, which are resistant to ceritinib (LDK378). We found that ceritinib treatment resulted in robust upregulation of SRC activity, as measured by the phosphorylation of the SRC substrate paxillin. Knockdown of SRC alone with siRNA effectively sensitized ceritinib resistance in ALK‐positive cells. Furthermore, SRC inhibition by AZD0530 was effective in ALK‐resistant cancer cells. Thus, ALK inhibition by ceritinib may lead to upregulation of SRC signaling, and AZD0530 could serve as a potential drug in the clinic to treat ALK‐resistant lung cancer patients.

Intercalating and maintenance gefitinib plus chemotherapy versus chemotherapy alone in selected advanced non-small cell lung cancer with unknown EGFR status

Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m2) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15–25 of each cycle until disease progress (n = 109). Progression-free survival (PFS) was 9.7 vs. 4.2 month in the gefitinib vs. control arm (HR: 0.41, 95% CI: 0.31–0.56; P < 0.001). Overall survival (OS) was also longer in the gefitinib arm (20.1 vs. 15.4 months; HR: 0.68; 95% CI 0.48–0.97; P = 0.0323). Adverse events, including diarrhea, dermal reaction and thrombocytopenia, were more common in the gefitinib arm. In conclusion, intercalating and maintenance gefitinib treatment is a viable option for advanced NSCLC patients with unknown EGFR mutation status in subpopulations with high EFGR mutation rate.

Endostar in combination with postoperative adjuvant chemotherapy prolongs the disease free survival of stage IIIA NSCLC patients with high VEGF expression

Purpose The aim of this study is to compare the therapeutic effect between endostar plus adjuvant chemotherapy and adjuvant chemotherapy alone in the patients with completely resected non-small cell lung cancer (NSCLC) at stage IB to IIIA. Experimental Design This is an open, multicenter, randomized (1:1) study with 250 NSCLC patients. Completely resected NSCLC patients at stages IB to IIIA were randomized to receive adjuvant NP plus endostar (Vinorelbine 25 mg/m2 on day 1 and day 8 plus Cisplatin 75 mg/m2 on day 1, and plus endostar 7.5 mg/m2 per day iv for consecutive 14 days) or NP regimen alone. Every 21 days were set as one cycle for 4 cycles. The primary endpoint was disease-free survival (DFS). Secondary endpoints included tumor response rate, overall survival and safety. Results The two groups had no significant difference in the incidence of toxicity reaction. Endostar plus NP prolonged the DFS of patients with completely resected NSCLC at stage IIIA (19.33±3.73 vs 17.10±9.68 months) but with no statistical difference compared to NP alone. In the endostar plus NP group, those cases with high expression of vascular endothelial growth factor (VEGF) showed a significantly better DFS than those with low VEGF expression (48.45±3.52 vs 40.18±4.54 months, P<0.05). Conclusions Vascular targeted therapy with endostar plus NP prolongs the DFS of patients with complete resectable NSCLC in stage IIIA and significantly extends the DFS of NSCLC patients with high VEGF expression, but does not show benefits in OS for stage IB−IIIA.

Oral 1.03. Frequent PD-L1 expression in thymic squamous cell carcinoma of Chinese patients

Background A recent publication reported diffuse high intensity PD-L1 staining in thymic epithelial tumor (TET). The PD-L1 scores and histology were significantly correlated, with higher intensity staining in WHO classification B2/B3/C TET. Among B2/B3/C TET, thymic squamous cell carcinoma (TSQCC) has morphological features of squamous cell carcinoma as seen in other organs. Unlike thymomas, it generally lacks resemblance to the normal thymic cytoarchitecture. Here we examine PD-L1 expression in a TSQCC of Chinese patients.

Long-term results of a randomized controlled trial evaluating preoperative chemotherapy in resectable non-small cell lung cancer

Objective We aimed to evaluate whether preoperative chemotherapy provides benefits in the survival and prognosis of patients with non-small cell lung cancer (NSCLC) in resectable stages I to IIIA, except T1N0. Methods In this randomized, controlled trial, 356 patients with stage I (except for T1N0), II and IIIA NSCLC were assigned to either the preoperative chemotherapy plus surgery arm (179 patients) or the primary surgery arm (177 patients). Both treatments were followed by adjuvant chemotherapy. The end point of this study included overall survival (OS), progression-free survival (PFS), and survival rate associated with clinical remission. Results Statistical survival difference was found between the preoperative chemotherapy plus surgery arm and the surgery-alone arm. However, the median survival time (MST) in the preoperative chemotherapy arm was lower than that of surgery-alone arm (MST, 45.42 months vs 57.59 months) (P = 0.016). When comparing the effect of preoperative chemotherapy at each stage of NSCLC, a statistical survival difference was found in stage II NSCLC but not in stage I and IIIA (MST 40.86 months vs 80.81 months) (P = 0.044). However, no statistically significant difference in PFS was noticed between the two arms, except for stage I NSCLC (hazard radio [HR] = 0.87; 95% CI, 0.561–1.629; P = 0.027). The survival rate was higher for patients who had clinical remission after preoperative chemotherapy, but the differences did not reach statistical significance (MST 42.10 months vs 35.33 months) (P = 0.630). Conclusion Preoperative chemotherapy did not show benefits in OS and PFS for stage I–IIIA NSCLC patients.