Liqun Gong

The role of postoperative radiotherapy on stage N2 non-small cell lung cancer

BACKGROUND The clinical value of postoperative radiotherapy (PORT) in stage N2 nonsmall-cell lung cancer (NSCLC) is controversy. The aim of this study is to analyze the efficacy of PORT in subgroup of stage N2 NSCLC, which can help clinicians to choose proper patients for PORT. METHODS Clinical data of 359 patients with stage N2 NSCLC treated with radical surgery between Mar. 2000 and Jul. 2005 were retrospectively reviewed. Two hundred and seven patients received adjuvant chemotherapy and one hundred and four patients received adjuvant radiotherapy. First, the group of patients were analyzed to evaluate the factors affecting the overall survival. The all patients were divided based on tumor size and the number of lymph node metastasis station (single station or multiple station) so as to evaluate the role of PORT. The endpoint was overall survival (OS) and local recurrence-free survival (LRFS). Kaplan-Meier method was used to calculate the OS, LRFS and Log-rank was used to compare the difference in OS and LRFS between different groups. RESULTS The median duration of follow-up was 2.3 years. 224 patients died. The median survival was 1.5 years and 1, 3, 5-year survival were 78%, 38% and 26%. Univariate analysis showed tumor size, the number of lymph node metastasis station and PORT were correlated with OS. Among patients, 5-year survival rates in PORT and non-PORT were 29% and 24% (P=0.047) respectively. In subgroups, PORT was related with high survival in patients with multiple station N2 compared to non-PORT: 36% vs 20% (P=0.013) and 33% vs 15% (P=0.002) in patients in patients with tumor size>3 cm. Also, it was related with low local recurrence compared to non-PORT: 65% vs 48% (P=0.006) and 62% vs 48% (P=0.033). CONCLUSIONS PORT can improve overall survival for N2 NSCLC, especially the patients with the factors as follows: tumor size>3 cm and multiple station N2 can benefit from PORT more or less.

Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects

To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

[Research on Postoperative Radiotherapy for Non-small Cell Lung Cancer of Stage IIIA (N2) according to the Failure Patterns after Pulmonary Resection.].

BACKGROUND Postoperative radiotherapy (PORT) after complete resection of non-small cell lung cancer (NSCLC) has been introduced in order to reduce locoregional recurrence, but it remains controversy whether PORT can improve survival. Therefore, we want to investigate the effect of PORT and the relationship between failure patterns and primarily location of stage IIIA (N2) in NSCLC. METHODS This retrospective analysis included 233 patients who underwent resection of NSCLC, first recurrence involving a local-regional site. It illustrated the factors affecting local recurrence and the sites of failure on the basis of lobe of primary tumor. RESULTS Multivariable analysis demonstrated the number of positive lymph nodes (P=0.003), T stage (P<0.001), histological type (P=0.038), modus operandi (P=0.013) and the number of mediastinal lymph node stations involved (P=0.018) were the independent factors. For all patients, the most common site of failure was the bronchial stump/staple line, which was present more often in those who had a wedge resection than in those who had a more radical procedure (P<0.001). The local-region frequency of squamous was higher than adenocarcinoma carcinoma (P=0.025). The recurrence frequency of mediastinal lymph node among T1 and T2-3 were 36.4%, 62.0% (P=0.009) respectively. The localregion recurrence among primarily tumor location were different. CONCLUSIONS The number of positive lymph nodes, T stage, histological type, modus operations and the number of mediastinal lymph node stations involved were the independent factors in IIIA (N2) NSCLC.

Reappraisal of the role of postoperative radiation therapy in patients with pIIIa-N2 non-small cell lung cancer: A propensity score matching analysis

Reappraisal of the role of postoperative radiotherapy in pN2 non‐small cell lung cancer (NSCLC) patients according to N1 lymph node involvement.

Whole-exome sequencing identifies key mutated genes in T790M wildtype/cMET-unamplified lung adenocarcinoma with acquired resistance to first-generation EGFR tyrosine kinase inhibitors

PurposeLung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma harboring EGFR-activating mutations will inevitably acquire resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). EGFR T790M mutation and cMET amplification are common mechanisms. Further study is needed to explore unknown genomic alterations contributing to drug resistance.MethodsTumor and blood samples from 69 stage IIIB–IV NSCLC patients defined as acquired resistance to first-generation EGFR TKIs (gefitinib, erlotinib or ecotinib) were collected. The cobas® and Droplet digital PCR (ddPCR) were used to detect T790M mutations in tumor samples and plasma ctDNA. cMET amplification was evaluated by fluorescence in situ hybridization (FISH). Exome sequencing was performed in four T790M wildtype/cMET-unamplified samples.ResultsThe overall T790M-positive rate was 52.2% considering all testing methods. Out of 21 samples in which tumor re-biopsy was performed, 14 were T790M positive (66.7%). cMET amplification was identified in three out of seven T790M-negative samples. Exome sequencing in four T790M wildtype/cMET-unamplified samples and paired white blood cells identified a cohort of candidate key mutated genes including BRAF, FGFR1, PAK1, PCNT, PEBP4 and SOX3.ConclusionsEGFR T790M mutation and cMET amplification are main mechanisms leading to EGFR TKI resistance in lung adenocarcinoma. These key mutated genes identified in the present study would need further validation in large number of patients.

Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC

BACKGROUND Endostar (rh-endostatin) is a new recombinant human endostatin, which could inhibit cell proliferation, angiogenesis, and tumor growth. OBJECTIVE To explore anti-angiogenesis short-term efficacy combined with neoadjuvant chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify the potential predictive factors. METHODS We pathologically examined 26 patients diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or combined with Endostar, respectively. RESULTS Our results indicated that total clinical benefit rate (CBR) 87.5% and 64% (p= 0.76), respectively. The clinical benefit (CB) patients in the treatment group showed significant changes in endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF), blood flow (BF), permeability surface (PMS), and microvascular density (MVD) before and after treatment. Compared with CB patients in the control group, changes in EPC and MVD (only) before and after treatment were significant. The variation of EPC, PMS, and MVD before and after treatment in the treatment group showed positive correlation with tumor regression rate (TRR) and the variation of MVD, whereas those of EPC and PMS demonstrated positive correlations with variation of MVD before and after treatment. CONCLUSION Our findings suggested that PMS and EPC may be used as a predictive factor for the short-term efficacy of the combined therapy in NSCLC.

Alternative method for jejunostomy in Ivor-Lewis esophagectomy.

To supplement nutrition, jejunostomy has been widely adopted as an adjunct surgical procedure for Ivor‐Lewis esophagectomy. Most Chinese surgeons have a preference for parenteral nutrition even though it has some disadvantages compared with jejunostomy. In this report, we describe a new approach that allows the quick insertion of a feeding tube in Ivor‐Lewis esophagectomy. We retrospectively analyze cases that have applied this approach and compare the advantages and disadvantages of jejunostomy.