Icotinib, an EGFR tyrosine kinase inhibitor, as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma: a multicenter, open-label, single-arm, phase II study (ICAPE).

The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.

Prognostic significance of the combination of preoperative fibrinogen and the neutrophil-lymphocyte ratio in patients with non-small cell lung cancer following surgical resection.

The purpose of the present study was to evaluate the prognostic value of preoperative coagulation factor levels (including fibrinogen and D-dimer) and inflammatory indicators in patients with non-small cell lung cancer (NSCLC). The medical records of 456 patients with NSCLC who had undergone curative resection were retrospectively analysed. The recommended cut-off values for preoperative fibrinogen, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio and lymphocyte-monocyte ratio were determined using receiver operating characteristic curve analyses. The associations between preoperative fibrinogen or D-dimer levels and clinicopathological variables were analysed using the χ2 test. Univariate Kaplan-Meier analysis and a multivariate Cox proportional hazards model were applied to identify which prognostic variables were significantly associated with overall survival (OS) rates. Multivariate analyses revealed that lymph node metastasis (P<0.001), preoperative fibrinogen (P=0.024) and NLR (P=0.028) were effective independent prognostic variables associated with OS. Based on this result, a novel, single inflammation-based combination of fibrinogen and NLR (COF-NLR) score was proposed for the determination of prognosis. Patients with elevated fibrinogen and NLR levels were allocated a score of 2 (n=136), and those that demonstrated elevated levels of one or neither were allocated a score of 1 (n=152) or 0 (n=168), respectively. The 5-year OS rates were significantly poorer for patients with COF-NLR=2 compared with those with COF-NLR=1 or 0 (23.5% vs. 34.2% vs. 50.0%, P<0.001). A subgroup analysis demonstrated that the prognostic significance of COF-NLR was independent of histological subtype, lymph node metastasis and pathological stage. Therefore, COF-NLR has potential as a novel and useful blood marker for predicting tumour progression and the postoperative survival of patients with NSCLC. It may assist clinicians in risk stratification, prognosis predictions and facilitating individualised treatment.

Screening of specific nucleic acid aptamers binding tumor markers in the serum of the lung cancer patients and identification of their activities.

Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.