[Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors].

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

[The efficacy and influence factors analysis of EGFR TKIs on patients with lung adenosquamous carcinoma].

Objective: To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors. Methods: From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%. Results: Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P>0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS (P>0.05), while EGFR mutation is the only influencing factor of OS (P<0.05) in the current study. Conclusions: EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.

Genetic diversity of Toona sinensis Roem in China revealed by ISSR and SRAP markers.

Toona sinensis Roem has an important value as a type of traditional vegetable and Chinese medicinal herb, and is also a valuable source of wood in China. In this study, we used the inter-simple sequence repeat (ISSR) and sequence-related amplified polymorphism (SRAP) markers to assess the level and pattern of genetic diversity in five domesticated T. sinensis populations in China. Our results indicated a relatively low level of genetic diversity both at species (Hs = 0.1662, 0.2098, respectively) and population levels (Hs = 0.0978, 0.1145, respectively). Molecular variance analyses revealed a relatively high degree of differentiation among populations (GST = 0.3901, 0.4498), and low levels of gene flow (Nm = 0.7816 and 0.6116). We divided the five populations into two groups by cluster analysis: group one consists of populations collected from the south part of China (e.g., Yuxi, Yunan Province and Zuanjiang, Chongqing Municipality), and group two contains those cultivated in north part of China (e.g., Hengshui, Hebei Province, Jinan and Rizhao, Shandong Province). The correlation of genetic relationships among populations fits well with their geographical distribution (Mantel test; r = 0.7236 and 0.6789, respectively). Asexual propagation, limited gene flow and geographic isolation are most likely the key factors associated with the observed genetic structure of T. sinensis grown in China. The present study indicated that both ISSR and SRAP markers were effective and reliable for assessing the degree of T. sinensis genetic variations.

[Retrospective analysis of albumin-bound paclitaxel in the treatment of elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: To observe the safety and short-term efficacy of sigle drug albumin-bound paclitaxel (ABP) in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 23 elderly patients with advanced NSCLC who received weekly ABP regimen (130 mg/m(2)/week) in our hospital from October 2011 to March 2014 were retrospectively evaluated. The short-term efficacy, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median treatment period was 4 cycles (2-10 cycles). Partial response, stable disease, progressive disease, overall response rate, and disease control rate were 26.1%, 43.5%, 30.4%, 26.1% and 69.6%, respectively. The median PFS was 5.33 months (95% CI: 2.95-7.70 months), while the median OS was 40.33 months (95% CI: 29.82-50.83 months). Major adverse events included leucopenia (82.6%), neutropenia (78.3%), nausea or vomiting (56.5%), fatigue (52.2%), peripheral neuropathy (26.1%), myalgia/arthralgia (30.4%), thrombocytopenia (13.0%) and arrhythmia (4.3%). The patients accompanied with chronic diseases had significantly higher incidence rate of peripheral neuropathy and myalgia/arthralgia compared with the patients without accompanied chronic diseases (50.0% vs. 9.1% and 66.7% vs. 9.1%, P<0.05 for both). CONCLUSION: The weekly single drug ABP regimen is effective and well-tolerated in elderly patients with advanced NSCLC.