Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.

Objective:To explore the appropriate radiotherapy time and method in the treatment of patients with brain metastases (BM) due to from non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation.Methods:Totally 69 EGFR-mutant NSCLC patients with BM treated in Zhongnan Hospital of Wuhan University from January 2014 to September 2018 were retrospectively reviewed. The patients were divided into two groups according to the time of brain radiotherapy, including the upfront radiotherapy group ( n=45) who received concurrent brain radiotherapy and EGFR-tyrosine kinase inhibitors(TKI)treatments and deferred radiotherapy group ( n=24) who received brain radiotherapy after intracranial progression during EGFR-TKI treatment. The upfront radiotherapy group was further divided into two groups, the group treated with WBRT concurrent with EGFR-TKI ( n=20) and the group treated with SRS concurrent with EGFR-TKI ( n=25). Overall survival (OS), progression-free survival (PFS) and intracranial progression-free survival (iPFS) time were evaluated. Results:The median OS of 69 patients was 31.2 months. For the upfront and deferred radiotherapy groups, the 1-, 2- year OS were 95%, 64% and 80%, 35%, the difference between the two groups was statistically significant. On subgroup analysis, the upfront WBRT, upfront SRS and deferred radiotherapy groups 1-, 2- year OS were 95%, 96%, 80% and 42%, 88%, 35%. Moreover, the upfront SRS group was associated with improved OS relative to the deferred radiotherapy group ( HR: 0.10, 95% CI: 0.23-0.46, P=0.003), but the upfront WBRT and deferred radiotherapy groups shared similar OS ( HR: 0.54, 95% CI: 0.21-1.32, P=0.180). There were no significant difference in iPFS and PFS between the upfront and deferred radiotherapy groups( P>0.05). Conclusions:Upfront brain radiotherapy prolonged the survival of BM patients metastasized from EGFR-mutant NSCLC. SRS concurrent with EGFR-TKI may be superior to WBRT concurrent with EGFR-TKI in the treatment of BM metastasized from EGFR-mutant NSCLC.

AbstractPurposeThe aim of the study was to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for pulmonary lesions in oligometastatic non‐small cell lung cancer (NSCLC) patients, to explore prognostic factors of progression‐free survival (PFS) and overall survival (OS), to validate improved survival contributed by SBRT in oligometastatic NSCLC patients.Patients and methodsA total of 71 oligometastatic NSCLC patients with 86 pulmonary lesions treated with SBRT in our institute between 2012 and 2018 were included. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were calculated using Kaplan‐Meier method. Prognostic factors of PFS and OS were analyzed using univariate and multivariate Cox analyses. Subgroup analyses were performed to investigate the impact of SBRT on PFS and OS during first line systemic treatment.ResultsAfter a median follow‐up of 17.6 months, 2‐year LC and OS rates were 82.6% and 55.3%, respectively. No grade 4 or more toxicities were observed. Multivariate analysis showed systemic treatment regimen before SBRT was an independent prognostic factor of PFS, but not for OS. Among this cohort, patients receiving first line target therapy could show a better PFS and OS than those undergoing first line chemotherapy (target therapy vs chemotherapy, PFS, 26.4 m vs 6.9 m; OS, 34.8 m vs 15.5 m).ConclusionsSBRT for pulmonary lesions was a feasible and tolerable option for oligometastatic NSCLC patients. Delivery of SBRT for pulmonary lesions improved outcomes of oligometastatic NSCLC patients. Finally, SBRT combined with first line target therapy might have optimal outcomes.

Objective To investigate postoperative recurrent pattern of the thoracic esophageal squamous cell carcinoma (TESCC),aiming to provide a basis for the delineation of postoperative radiotherapy volume for TESCC.Methods Clinical data of 66 TESCC patients who recurred after the radical esophagectomy in Zhongnan Hospital of Wuhan University from 2011 to 2017 were retrospectively analyzed.According to the AJCC 8th edition-defined classification of esophageal carcinoma,regional lymph node stations Ⅰ to 8M were defined as the upper-middle mediastinum region (UMMR),and stations 8Lo,9 and 15 were defined as the inferior mediastinum region (IMR),stations 16 to 20 were regarded as the upper abdominal lymph node region (UAR).Results Among all 66 patients,41 cases (62％) experienced locoregional recurrence alone,25 cases (38％) presented with distant metastasis alone.A total of 54 patients with 148 lymph node recurred after treatment.The highest risk region of lymph node recurrence was UMMR (118/148,80％),after that,followed by UAR (24/148,17％).With regard to 9 cases of UAR,6 patients had lower TESCC,and 8 patients (89％) were graded as ≥ pathological stage Ⅲ.Conclusions The highest risk region of lymph node recurrence is UMMR in TESCC patients undergoing radical esophagectomy,which should be considered as the target volume in postoperative radiotherapy.For patients with lower TESCC ≥ pathological stage Ⅲ,UAR might be the target volume with cautions.Anastomosis and IMR are probably not the routine treatment volumes.

Objective To analyze the clinical efficacy and prognosis of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases.Methods Medical records of 104 patients with SBRT for pulmonary oligometastases in our hospital between 2012 and 2018 were retrospectively reviewed.SBRT was performed by intensity modulated radiation therapy (IMRT) technique before December 2015,and by helical tomotherapy (HT) technique in others.The local control (LC),progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.Cox-regression was used for univariate analyses and multivariate analyses.The radiotherapy-related adverse events were evaluated by NCICTCAE V4.0.Results The 1-,2-and 3-year LC rates were 86.6％,75.9％ and 72.3％,respectively.The 1-,2-and 3-year PFS rates were 40.9％,28.4％ and 22.1％,respectively.The 1-,2-and 3-year OS rates were 75.9％,53.2％ and 43.53％,respectively.The median OS time was 26.6 months.Multivariate analyses showed that the pathologic type of primary tumor,the volume of lung oligometastases and the carcino-embryonic antigen (CEA) level before SBRT were the independent prognostic factors of LC (x2 =28.66,P＜0.05).The way of tumor progression after SBRT was the independent prognostic factor of OS (x2=40.01,P＜0.05).Meanwhile,there were no significant differences in the LC and OS between HTSBRT and IMRT-SBRT.Radiation pneumonitis was the major adverse event of SBRT (n =25,24.04％).Less than 7％ patients experienced grade 2 and above radiation pneumonitis.Conclusions SBRT shows high local control rates and tolerable adverse events in the treatment of pulmonary oligometastases.There were no significant differences in the clinical efficacy and adverse events between HT-SBRT and IMRT-SBRT,which means they are all suitable for clinical application.

Background: The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis.Methods: Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value < 0.05 was considered to be significant.Results: The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P < 0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P < 0.001), clinical stage (P < 0.001) and a reduced overall survival rate (P = 0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR = 2.244, P = 0.028).Conclusions: The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC.

Antisense oligonucleotide (ASODN) targeting specific gene can be capable of potently downregulating proliferation and invasion in human cancer cells. However, the underlying mechanisms are less well defined. Here the authors show that matrix metalloproteinase-7 (MMP-7) ASODN changes the ultrastructure of human A549 lung adenocarcinoma cells. Transfection of MMP-7 ASODN significantly lowered the expression of MMP-7 protein in A549 cells. Decreased microvilli, endoplasmic reticulum dilation, swelling of mitochondria, and formation of apoptotic bodies were observed by transmission electron microscope. Collectively, the findings identified the morphological mechanism that MMP-7 ASODN inhibited proliferation and invasion in A549 cells.

Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug.