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Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of TP53 and KRAS, KIF5B-RET fusion, copy number gains of PD-L1 and PD-L2, and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of EGFR and MDM2 and loss of PTPRD were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

The benefit of local ablative therapy (LAT) for oligo-recurrence has been investigated and integrated into the treatment framework. In recent decades, stereotactic body radiation therapy (SBRT) has been increasingly used to eliminate metastasis owing to its high rate of local control and low toxicity. This study aimed to investigate the outcomes of SBRT for patients with lung oligo-recurrence of non-small cell lung cancer (NSCLC) from our therapeutic center. Patients with lung oligo-recurrence of NSCLC treated with SBRT between December 2011 and October 2018 at Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) were reviewed. The characteristics, treatment-related outcomes, and toxicities of the patients were analyzed. Univariable and multivariable Cox regression were performed to identify the factors associated with survival. A total of 50 patients with lung oligo-recurrence of NSCLC were enrolled. The median follow-up period was 23.6 months. The 3-year local progression-free survival (LPFS), progression-free survival (PFS) and overall survival (OS) after SBRT were 80.2%, 21.9% and 45.3%, respectively. Patients in the subgroup with LAT to all residual diseases showed significantly improved OS and PFS. No treatment-related death occurred after SBRT. SBRT is a feasible option to treat patients with lung oligo-recurrence of NSCLC, with high rates of local control and low toxicity. LAT to all residual diseases was associated with better survival outcomes. Future prospective randomized clinical trials should evaluate SBRT strategies for such patients. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated.Methods: Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3' untranslated region (3'UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues.Results: Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade which contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo.Conclusions: Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic. [ABSTRACT FROM AUTHOR]

Background: Lobectomy is the standard treatment for patients with stage I non-small cell lung cancer (NSCLC). Recent studies have shown promising results of stereotactic body radiation therapy (SBRT) in these patients. We retrospectively compared the outcomes of lobectomy and SBRT in these patients from our therapeutic center.Methods: Patients who underwent lobectomy or SBRT for clinical T1-2a (T size≤5 cm), N0 M0, NSCLC between December 2011 and August 2016 were reviewed. Patient characteristics, treatment-related outcomes and toxicities were analyzed. Propensity score matching (PSM) was performed to improve comparability between the two groups.Results: Median follow-up period in the lobectomy (n = 246) and SBRT (n = 70) group was 31.4 months and 24.9 months, respectively. Three-year local recurrence-free survival (LRFS) was comparable in the two groups (97% vs. 91.7%, respectively; P = 0.768). Recurrence-free survival (RFS) at 3-year in the lobectomy and SBRT groups was 85.4 and 69.5%, respectively (P = 0.014). Three-year overall survival (OS) after lobectomy and SBRT was 88.2 and 79.7%, respectively (P = 0.027), while 3-year cancer-specific survival (CSS) was 91.3 and 82.5% (P = 0.022). After PSM (45 matched patients in each group), there was no significant between-group difference with respect to 3-year LRFS (89.6% vs. 87.5%, P = 0.635), RFS (77.6% vs. 67.3%, P = 0.446), OS (78.5% vs. 79.5%, P = 0.915) or CSS (86.4 and 79.5%, P = 0.551). In matched subgroup, 30-day mortality after lobectomy was 2.2%, and no treatment-related death occurred after SBRT.Conclusions: Treatment-related outcomes of SBRT and lobectomy were comparable. SBRT was well tolerated and had a very low toxicity profile in our study. SBRT is a promising alternative treatment option for stage I NSCLC patients. This study indicates that matching these disparate cohorts of patients is challenging. Clinical trials are essential to define the indications and relative efficacy of lobectomy and SBRT in a selected population. [ABSTRACT FROM AUTHOR]