Dynamic monitoring of circulating tumor DNA to analyze genetic characteristics and resistance profile of lorlatinib in ALK positive previously treated NSCLC.

BACKGROUND: To dynamically monitor the changes of genomic characteristics during lorlatinib treatment and analyze the resistance profile of lorlatinib in ALK-positive advanced Chinese patients with non-small cell lung cancer (NSCLC) with first- and second-generation ALK inhibitor resistance. METHODS: Ten eligible patients who were from a phase 2 study in China and admitted to the Fifth Medical Center of PLA General Hospital were analyzed. Blood samples were collected for next-generation sequencing (NGS) to characterize genetic variation at baseline, during treatment, and after disease progression. RESULTS: Among the 10 patients treated with lorlatinib, objective response rate (ORR) was 50%. The median progression-free survival (PFS) was 13.3 months, and median overall survival (OS) was 15.6 months. At baseline, the mutation frequency of ALK in circulating tumor DNA (ctDNA) was higher in the group who received two lines of previous anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), and a similar trend was observed for TP53. After one follow-up cycle, the decreased variant allele frequency (VAF) had a trend to be predictive for responses. In six patients in which blood samples had been taken after lorlatinib resistance, ALK compound mutations were found in three patients (50%), which were G1202R/L1196M, L1196M/D1203N, and G1202R/F1174C. The DNMT3A N403Tfs*4, ERCC3 E259D, and GNAS p.A436_P459del variants were only detected after progression in two of the other three patients without ALK compound mutations. CONCLUSIONS: The dynamic changes of genomic characteristics during lorlatinib treatment revealed the mutation landscape of Chinese patients with NSCLC after ALK-TKI resistance, indicated that the resistance profile of lorlatinib were heterogeneous, which laid the foundation for subsequent treatment to overcome lorlatinib resistance.

Efficacy of different sequential patterns after crizotinib progression in advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

BACKGROUND: The efficacy difference between the second- and third-generation of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) after crizotinib failure in advanced ALK-positive non-small cell lung cancer (NSCLC) has not been clarified. This study evaluates the efficacy of different sequential patterns after crizotinib progression. METHODS: Data of patients who met the study criteria were retrospectively analyzed. The Kaplan-Meier method was used to draw survival curves, log-rank method was used to compare the differences between groups, and Cox multivariate analysis was used to evaluate the significance of influencing factors. RESULTS: A total of 128 patients developed disease progression after crizotinib. The overall survival (OS) of 57 patients in the sequential second-generation ALK-TKIs group was significantly longer than that of 65 patients with other systemic treatment (58.5 months vs. 33.0 months, p < 0.001); The OS of the direct sequential lorlatinib group was significantly longer than the second-generation ALK-TKIs group (114.0 months vs. 58.5 months, p = 0.020). Similarly, of the 48 patients who developed disease progression after first- and second-generation ALK-TKIs treatment, 16 patients with sequential lorlatinib had significantly longer OS than the others (62.0 months vs. 43.0 months, p = 0.014). The progression-free survival (PFS) of second-line and third- or later-line lorlatinib were statistically different (20.0 months vs. 5.5 months, p = 0.011). CONCLUSIONS: The application of next-generation ALK-TKIs after crizotinib progression significantly prolonged survival, whereas direct sequencing lorlatinib seemed advantageous. Similarly, lorlatinib also prolonged survival in patients with first- and second-generation ALK-TKIs failure.

A Comparative Study on the Effects of Postoperative 125I Brachytherapy and Irradiation After Surgical Decompression and Stabilization for Metastatic Spinal Cancers.

PURPOSE: The study aims to investigate and compare the efficacy and safety of intraoperative 125I implantation and postoperative irradiation after surgical decompression and stabilization in the treatment of patients with metastatic epidural spinal cord compression (MESCC). METHODS: The study retrospectively enrolled 122 MESCC patients treated with surgical decompression and pedicle stabilization combined with 125I brachytherapy (the brachytherapy group) or postoperative radiotherapy (the irradiation group). Operation time, intraoperative blood loss, pain relief, postoperative ambulatory status, postoperative survival outcome, complications, and length of hospitalization were collected and compared between the two groups. Ten potential risk factors were analyzed for postoperative survival outcome. RESULTS: No significant difference was found in baseline characteristics between the two groups (P>0.05). Postoperative VAS score was significantly decreased, as compared with preoperative scores in both groups (P˂0.001). The VAS in the brachytherapy group was significantly lower than that in the irradiation group at postoperative 1 month, 3 months, and 6 months (P˂0.05). The postoperative ambulatory rates were 90.0% (54/60) in the brachytherapy group and 83.9% (52/62) in the irradiation group (P=0.32). The median overall survival time was similar between the two groups (7.43 months vs 7.27 months, P=0.37). Of all patients in the brachytherapy group, 25.0% (15/60) of patients suffered from complications, while 46.8% (29/62) of patients had complications in the irradiation group (P=0.0086). According to the multiple Cox regression, primary sites (P=0.038), ECOG performance status (P=0.014), and visceral metastases (P=0.0016) showed significance for postoperative survival outcome. CONCLUSION: Surgical decompression and spine stabilization combined with 125I brachytherapy is a relatively safe and useful method in MESCC patients.

Efficacy and Safety of Anlotinib in Advanced Non-Small Cell Lung Cancer: A Real-World Study.

PURPOSE: The ALTER0303 trial showed that anlotinib, a novel antiangiogenic tyrosine kinase inhibitor, administered as third-line or further treatment prolonged progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). This retrospective study investigated the efficacy and safety of anlotinib in real-world settings. PATIENTS AND METHODS: Medical records of patients with advanced NSCLC receiving anlotinib as third-line or further treatment were collected, and survival curves were derived using the Kaplan-Meier method. Univariate analysis was performed by log-rank testing. Cox regression analysis was used to evaluate the significance of factors obtained from the univariate analysis. RESULTS: Fifty-two patients with advanced NSCLC were included. The objective response rate was 16%, and the disease control rate was 80%. The median PFS was 4.5 months (95% confidence interval [CI]: 3.6-5.4), and the median OS was 9 months (95% CI: 6.5-11.5). Univariate analysis revealed that the group of patients with longer PFS and OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, ≤2 distant metastases, no liver metastases, ≤3 previous treatment lines, and ≤2 previous chemotherapy lines. Cox regression analysis demonstrated that only patients with ECOG PS ≤1 or no liver metastases had longer PFS and OS. Grade 3 treatment-related adverse events were reported in 14% of the patients, but no life-threatening adverse events were reported. CONCLUSION: Anlotinib was well tolerated and effective in patients with advanced NSCLC in real-world conditions. Patients with ECOG PS ≤1 or no liver metastases have longer PFS and OS.

Prognostic value of baseline hemoglobin-to-red blood cell distribution width ratio in small cell lung cancer: A retrospective analysis.

BACKGROUND: This study aimed to investigate the prognostic value of baseline hemoglobin-to-red blood cell distribution width ratio (HRR) in patients with small cell lung cancer (SCLC). METHODS: We retrospectively analyzed the medical records of patients with newly diagnosed SCLC who had received first-line chemotherapy at the Department of Pulmonary Oncology of the PLA 307 Hospital between January 2008 and October 2018. The optimal cutoff value of the continuous variables was determined using the X-tile software. Univariate and multivariate analyses were conducted using Cox proportional hazard models. The Kaplan-Meier method was used for survival analysis, with differences tested using the log-rank test. RESULTS: A total of 146 patients were included. The cutoff value for HRR was determined as 0.985. Statistically significant differences were observed in sex, smoking history, stage, radiotherapy combination, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, hemoglobin, and red blood cell distribution width between the high and low HRR groups. The median overall survival (OS) was nine and 17.5 months in the low and high HRR groups, respectively (P < 0.001). The median progression-free survival (PFS) was five and 8.5 months, respectively (P < 0.001). Univariate and multivariate analyses showed low HRR to be an independent predictor of a poor prognosis for OS (hazard ratio = 3.782; 95% confidence interval, 2.151-6.652; P < 0.001) and PFS (hazard ratio = 2.112; 95% confidence interval, 1.195-3.733; P = 0.01) in SCLC. CONCLUSION: Low HRR was associated with poorer OS and PFS in patients with SCLC and can be a potentially valuable prognostic factor for these patients. KEY POINTS: The prognostic value of the baseline hemoglobin-to-red blood cell distribution width ratio was evaluated in patients with small cell lung cancer. In this population, this ratio was an independent predictor of overall survival and progression-free survival. This ratio, an inexpensive and routine parameter, can be used as a prognostic factor in small cell lung cancer.

Exploratory study on application of MALDI­TOF­MS to detect serum and urine peptides related to small cell lung carcinoma.

Matrix­assisted laser desorption/ionization time­of­flight mass spectrometry (MALDI­TOF­MS) was employed to analyze differential serum and urine peptides in patients with small cell lung cancer (SCLC) and healthy individuals, and SCLC diagnostic classification models were constructed. Serum and urine samples from 72 patients with SCLC, age­ and gender­matched with 72 healthy individuals, were divided into training and testing sets in a 3:1 ratio. Serum and urine peptides were extracted using copper ion­chelating nanomagnetic beads, and mass spectra were obtained using MALDI­TOF­MS. Peptide spectra for the training set were analyzed, and the classification model was constructed using ClinProTools (CPT). The testing set was used for blinded model validation. For training­set sera, 122 differential peptide signal peaks with a mass of 0.8­10 kDa were observed, and 19 peptides showed significantly different expression [P<0.0005; area under curve (AUC) ≥0.80]. CPT screened 5 peptide peaks (0.8114, 0.83425, 1.86655, 4.11133 and 5.81192 kDa) to construct the classification model. The testing set was used for the blinded validation, which had 95.0% sensitivity and 90.0% specificity. For the training­set urine, 132 differential peptide signal peaks with m/z ratios of 0.8­10 kDa were observed, and 8 peptides had significantly different expression (P<0.0005; AUC ≥0.80). Then, 5 peaks (1.0724, 2.37692, 2.7554, 4.75475 and 4.7949 kDa) were used for classification model construction. The testing set was used for 36 blinded validation, which had 85.0% sensitivity and 80.0% specificity. Among the differential peptides, 3 had the same significant peaks at 2.3764, 0.8778 and 0.8616 kDa, identified as fibrinogen α, glucose­6­phosphate isomerase and cyclin­dependent kinase­1, respectively. The present study highlighted the differences that exist in serum and urine peptides between patients with SCLC and healthy individuals. Serum and urine peptide diagnostic classification models could be constructed using MALDI­TOF­MS, and showed high sensitivity and specificity.

Circulating plasma lncRNAs as novel markers of EGFR mutation status and monitors of epidermal growth factor receptor-tyrosine kinase inhibitor therapy.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations predict tumor response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, even patients with EGFR-sensitive mutations in NSCLC have limited efficacy with EGFR-TKI. Studies have shown that long noncoding RNA (lncRNA) is related to diagnosis and prognosis with NSCLC. This study aimed to explore the correlation between lncRNA in NSCLC patients with EGFR mutation status and EGFR-TKI efficacy. METHODS: The amplification-refractory mutation system method was used to test the EGFR mutation status in tumor tissues and pleural effusions of NSCLC patients. Three EGFR-mutant patients and three EGFR wild-type patients were selected. Differential lncRNA was performed on the pleural effusions of the two selected groups of patients using Clariom D Human chip technology. Five lncRNAs significantly associated with EGFR mutation status were screened by FC value and GO analysis, and then evaluated by real-time quantitative polymerase chain reaction in NSCLC patients' pleural effusions. Three were further analyzed in NSCLC patients' plasma. RESULTS: There were 61 significant differences in lncRNA between EGFR mutation-positive and wild-type patients. Among them, SCARNA7, MALAT1, NONHSAT017369, NONHSAT051892, and FTH1P2 were significantly associated with EGFR mutation status. SCARNA7, MALAT1, and NONHSAT017369 showed consistent results with plasma in pleural effusions compared to EGFR wild-type, all upregulated in the EGFR mutation group. CONCLUSION: This study shows that lncRNAs can be used not only as potential biomarkers for predicting the mutation status of EGFR and the efficacy of EGFR-TKI, but also for monitoring the efficacy of EGFR-TKI.

Single-nucleotide polymorphisms (rs342275, rs342293, rs7694379, rs11789898, and rs17824620) showed significant association with lobaplatin-induced thrombocytopenia.

This study aimed to investigate single-nucleotide polymorphisms (SNPs) associated with lobaplatin-induced thrombocytopenia in patients with advanced lung cancer in China. Thirty-nine patients who received lobaplatin-based chemotherapy in the 307 Hospitals of Chinese People's Liberation Army from April 2017 to March 2018 were enrolled as study subjects. Peripheral blood DNA was extracted, and 79 candidate SNP positions were selected. A Sanger sequencing platform was employed to measure genotypes for locating the SNP positions associated with lobaplatin-induced thrombocytopenia. Of the 79 candidate genes, SNPs rs342275 and rs7694379 were significantly associated with lobaplatin-induced decrease in platelet (PLT) count (P < 0.05). SNPs rs342275, rs342293, rs11789898, and rs17824620 showed significant association with lobaplatin-induced lowest PLT counts (P < 0.05). SNPs rs342275, rs342293, rs11789898, rs17824620, and rs7694379 can be used as predictors of thrombocytopenia induced by lobaplatin-based chemotherapy in patients with advanced lung cancer in China.

Detection of circulating tumor cells using oHSV1-hTERT-GFP in lung cancer.

BACKGROUND: This study was conducted to evaluate the clinical utility of the oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral blood of patients with lung cancer by comparing its sensitivity to the CellSearch CTC detection method. METHODS: The oHSV1-hTERT-GFP and CellSearch CTC detection methods were compared using peripheral blood samples of patients pathologically diagnosed with lung cancer. RESULTS: A total of 240 patients with lung cancer were recruited, including 89 patients who were newly diagnosed and 151 patients who had previously received treatment. Sixty-six newly diagnosed patients were evaluated using both methods. The CTC detection rates were 71.2% and 33.3% using the oHSV1-hTERT-GFP and CellSearch methods, respectively; this difference was statistically significant (P = 0.000). Among the entire cohort (n = 240), the CTC detection rate using the oHSV1-hTERT-GFP method was 76.3%, with a CTC count of 0-81. The CTC detection rates were 76.7%, 68.9%, and 76.3% in patients with squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, respectively. There was no statistically significant difference in the CTC detection rates between these different pathological subtypes (P = 0.738). The CTC detection rates of 79.8% and 74.4% in patients with stage I-III and IV lung cancer, respectively, were not significantly different (P = 0.427). CONCLUSION: The oHSV1-hTERT-GFP method is highly effective for detecting CTCs in patients with lung cancer, independent of pathological type and disease stage, and is ideal for large-scale clinical applications.

Circulating plasma microRNAs as potential markers to identify EGFR mutation status and to monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with advanced non-small cell lung cancer.

We aimed to identify a panel of circulating plasma microRNAs that can predict EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer. Microarrays were performed for the preliminary screening of dysregulated microRNAs in 9 EGFR mutation-positive patients versus healthy controls. MiR-107 was upregulated and miR-195 was downregulated in the exon 19 deletion versus wild-type group. The areas under the receiver operating characteristic curves for miR-107, miR-195, and a panel of these 2 microRNAs were 0.72, 0.75, and 0.74, with sensitivities and specificities of 64.7% and 76.6%, 71.8% and 69.1%, and 71.7% and 78.9%, respectively. MiR-122 was significantly upregulated in the p.L858R versus wild-type group. An area under the receiver operative characteristic curve of 0.75 suggests that miR-122 might be a specific biomarker for patients with the p.L858R mutation. In addition, dynamic changes in these 3 microRNAs were also found to correlate with responses to epidermal growth factor receptor-tyrosine kinase inhibitor treatment, indicating that circulating plasma microRNAs may represent potential biomarkers for monitoring epidermal growth factor receptor-tyrosine kinase inhibitor treatment. This study demonstrates the prospective application of circulating plasma microRNAs as potential non-invasive, convenient biomarkers for patients with EGFR-sensitive mutations.

Circulating microRNAs as novel biomarkers of ALK-positive nonsmall cell lung cancer and predictors of response to crizotinib therapy.

Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s rRNA as the most stable endogenous control gene using geNorm and NormFinder algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK-negative NSCLC patients (n = 32) were quantified using real-time reverse transcriptase quantitative polymerase chain reaction. The expression levels of miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%, respectively. Increased plasma levels of miR-660-5p after crizotinib treatment predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362-5p were significantly associated with progression-free survival (p = 0.015). Thus, in this preliminary investigation, we identified a potential panel of 3 microRNAs for distinguishing between patients with ALK-positive and ALK-negative NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for response to crizotinib treatment.

[Detection of Serum Peptides in Patients with Lung Squamous Cell Carcinoma by MALDI-TOF-MS and Analysis of Their Correlation with Chemotherapy Efficacy].

BACKGROUND: Treatment options for patients with squamous cell carcinoma of the lung (SCC) are limited in chemotherapy. However, not all patients could benefit form standard platinum regimen. Considering the dismal prognosis of patients with advanced SCC, a greater focus on selecting sensitive chemotherapy regimens remains of upmost importance to improve outcomes in this disease. In this study, we used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to detect pre-chemotherapy serum peptides in advanced lung squamous cell carcinoma patients accepting paclitaxel combined with platinum chemotherapy and to analyze the correlation between serum peptides and chemotherapy efficacy. METHODS: Patients with advanced lung squamous cell carcinoma received paclitaxel combining with platinum chemotherapy and evaluated the efficacy every two cycles. Evaluation of complete response (CR) or partial response (PR) patients defined as sensitive group, progressive disease (PD) patients defined as resistant group. Serum samples were collected from patients with lung squamous cell carcinoma. Eighty-one patients were randomly divided into training group (sensitive group I and resistant group I) and validation group (sensitive group II and resistant group II) according to the ratio of 3:1. Serum samples were pretreated and Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to detect serum peptide fingerprints. ClinProTools software was used to analyze the differences between the sensitive group I and the resistant group I. Three kinds of biological algorithms (SNN, GA, QC) built in CPT software were used to establish the curative effect prediction model respectively and the optimal algorithm was selected. The validation group was used for blind verification. RESULTS: Thirty sensitive patients and 31 resistant patients were enrolled in the training group. Ten sensitive patients and 10 resistant patients were included in the validation group. The training group had 96 differentially expressed peptides in the sensitive and resistant patients, with 16 statistically significant peptides (P<0.001). The predictive model was established by 5 polypeptides (1,897.75 Da, 2,023.93 Da, 3,683.36 Da, 4,269.56 Da, 5,341.29 Da). The recognition rate of this model was 89.18% and the cross validation rate was 95.11%. The accuracy of the model was 85%, the sensitivity was 90.0% and the specificity was 80.0%. The median PFS in the sensitive group was better than patients in the resistant group (7.2 months 95%CI: 4.4-14.5 vs 1.8 months 95%CI: 0.7-3.5). The results showed that the differential peptides 4,232.04 Da and 4,269.56 Da were correlated with PFS in patients with lung squamous cell carcinoma (P<0.001). CONCLUSIONS: MALDI-TOF-MS was used to detect the difference of serum peptides between sensitive and resistant groups. The preliminary curative effect prediction model was used to predict the efficacy of paclitaxel combined with platinum regimen. However, this model need further investigations to verify the accuracy and the sensitivity.

CD147 promotes the proliferation, invasiveness, migration and angiogenesis of human lung carcinoma cells.

Cluster of differentiation (CD) 147 is a transmembrane glycoprotein that is highly expressed at the tumor cell surface, which stimulates fibroblasts to produce a large number of matrix metalloproteinases and promotes tumor invasion and metastasis and tumor-induced angiogenesis. The present study investigated the functions and the role of CD147 in the human lung carcinoma A549 cell line. The present study constructed expression and interference [small interfering (si) RNA] lentiviral vectors of CD147, which established stable overexpression and low expression of CD147 in the A549 cell line, named A549-CD147 and A549-siCD147, respectively. The differences in biological features between various levels of CD147 expression in A549 cells was investigated by cell counting kit-8 (CCK-8), Transwell, scratch and lumen formation assays. The results of the CCK-8 assay revealed that A549-CD147 cell proliferation was significantly increased and A549-siCD147 cell proliferation was decreased compared with the control groups. The A549-CD147 cells had the largest number of cells penetrating the Matrigel in the Transwell assay, which indicates that upregulation of CD147 expression increases the infiltration capacity of cells. The scratch assay revealed that A549-CD147 cells have the highest capacity for migration, while A549-siCD147 cells have the lowest. Quantitative polymerase chain reaction and western blot analysis demonstrated that vascular endothelial growth factor (VEGF) expression was proportional to the expression level of CD147 at the mRNA and protein level. The lumen formation assay revealed that the number of vessel lumens that human umbilical vein endothelial cells formed in the A549-CD147 cell supernatant was increased compared with the A549-siCD147 cells. Collectively, the present results suggest that CD147 is important in the promotion of lung carcinoma cell proliferation, invasion and metastasis and the upregulation of VEGF, which stimulates the angiogenesis of lung carcinoma. In conclusion, CD147 may be a potential target in the treatment of lung carcinoma.

New imaging characteristics for predicting postoperative neurologic status in patients with metastatic epidural spinal cord compression. A retrospective analysis of 81 cases.

BACKGROUND CONTEXT: Several clinical features have been proposed for the prediction of postoperative functional outcome in patients with metastatic epidural spinal cord compression (MESCC). However, few articles address the relationship between preoperative imaging characteristics and the postoperative neurologic status. PURPOSE: This study aims to analyze the postoperative functional outcome and to identify new imaging parameters for predicting postoperative neurologic status in patients with MESCC. STUDY DESIGN: This study is a retrospective consecutive case series of patients with MESCC who were treated surgically. PATIENT SAMPLE: We assessed 81 consecutive patients who were treated with decompressive surgery for MESCC between 2013 and 2015. OUTCOME MEASURES: Eight imaging characteristics were analyzed for postoperative motor status by logistic regression models. Neurologic function was assessed using the Frankel grade preoperatively and postoperatively. METHODS: The following imaging characteristics were assessed for postoperative motor status: location of lesions in the spine, lamina involvement, retropulsion of the posterior wall, number of vertebrae involved, pedicle involvement, fracture of any involved vertebrae, T2 signal of the spinal cord at the compression site, and circumferential angle of spinal cord compression (CASCC). RESULTS: The postoperative neurologic outcome was better than the preoperative neurologic status (p<.01). In the entire group, 40.7% of the patients were non-ambulatory before the surgical procedure, whereas 77.8% of the patients could walk after surgery (p=.01). In the multivariate analysis, the location of the lesions (odds ratio [OR]: 3.89, 95% confidence interval [CI]: 1.19-12.77, p=.02) and CASCC (OR: 2.31, 95% CI: 1.44-3.71, p<.01) were significantly associated with postoperative neurologic outcome. A CASCC of more than 180° was associated with an increased OR that approached significance, and the larger the CASCC, the higher the risk of poor postoperative neurologic status. CONCLUSIONS: The postoperative neurologic status was dependent on the location of spine lesions and the CASCC. Patients with upper thoracic or cervicothoracic junction spine metastases or CASCC over 180° were at higher risk of relatively poor postoperative neurologic outcome. Timely, adequate surgical decompression is urgently warranted in these patients.

Percutaneous cementoplasty for painful osteolytic distal femur metastases: a case report.

Percutaneous cementoplasty has been shown to immediately restore the mechanical stability of affected bones, prevent further risk of bone fractures, and allow immediate weight bearing. It is emerging as one of the most promising procedures for patients with painful bone metastasis who are unsuitable for surgery or who show resistance to radiotherapy and/or analgesic therapies. This study aimed at describing the procedure, indications, and benefits of percutaneous cementoplasty for painful osteolytic distal femur metastases. We report the case of a painful metastatic lesion in the left distal femur secondary to non-small-cell lung cancer in a 58-year-old woman. The patient underwent percutaneous cementoplasty and experienced effective pain relief and recovery of knee function postoperatively. In addition, no perioperative complication was observed. Percutaneous cementoplasty for osteolytic distal femur metastases offers effective pain relief and restores impaired knee function. Although this method may be a safe option, larger samples of retrospective or prospective confirmation are warranted.

Lobaplatin for the treatment of SK-MES-1 lung squamous cell line in vitro and in vivo.

Lung squamous cell carcinoma is the second-largest histological subtype of lung cancer, which is the leading cause of cancer-related death worldwide. Lobaplatin, one of the third-generation platinum compounds, has shown encouraging anticancer activity in a variety of tumors. The aim of this study was to determine the therapeutic efficacy of lobaplatin on p53-mutant lung squamous cancer cells SK-MES-1. In order to evaluate the antitumor effect of lobaplatin, several in vitro and in vivo analyses were carried out, including Cell Counting Kit-8 (CCK-8), fluorescence-activated cell sorter, Western blot, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Findings showed that lobaplatin could inhibit cell proliferation and induce apoptosis of SK-MES-1 cells in vitro through both intrinsic and extrinsic apoptotic pathways in a time- and dose-dependent manner. In addition, lobaplatin could arrest cell cycle at S phase in SK-MES-1. Lobaplatin has obvious antitumor efficacy in human SK-MES-1 xenograft models; therefore, it seems to be a promising candidate in lung squamous cancer therapy.

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells.

Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.

Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells.

Ribosomal protein L34 (RPL34) was reported to be involved in the regulation of cell proliferation of prokaryotes, plant and animal cells. In the present study, we analyze the expression and function of RPL34 in NSCLC. Immunohistochemical analysis, qPCR and Western blot were used to detect the expression of RPL34 in NSCLC tissues and cells lines. Flow cytometry was used to detect cell activity of NSCLC cell line H1299 under lentivirus-mediated RNAi on RPL34. Cell proliferation and colony formation assays were used to analyze the role of RPL34 in NSCLC cell proliferation. We found that expression of ribosomal protein RPL34 was significantly up-regulated in NSCLC tissues compared to adjacent normal tissues. Lentivirus-mediated shRNA knockdown of RPL34 in NSCLC cell line H1299 resulted in a strong decrease of proliferation, and a moderate but significant increase of apoptosis and S-phase arrest. These data indicate that over-expressed RPL34 may promote malignant proliferation of NSCLC cells, thus playing an important role in development and progress of NSCLC.

A validated preoperative score predicting survival and functional outcome in lung cancer patients operated with posterior decompression and stabilization for metastatic spinal cord compression.

PURPOSE: This study aims to create and validate a score for survival and functional outcome of lung cancer patients with metastatic spinal cord compression (MSCC) after posterior decompressive surgery. METHODS: The entire cohort of 73 consecutive patients was randomly assigned to a test group (N = 37) and a validation group (N = 36). In the test group, we retrospectively analyzed 10 preoperative characteristics. Characteristics significantly associated with survival on multivariate analysis were included in the score. Patients in the validation group were used to confirm whether the score was reproducible. Postoperative functional outcome was analyzed both in the test and validation groups. RESULTS: On multivariate analysis, preoperative ambulatory status (P = 0.0017), visceral metastases (P = 0.0002), and time developing motor deficits (P = 0.0004) had significant impact on survival and were included in the scoring system. According to the prognostic scores, which ranged from 0 to 6 points, two risk groups were designed: 0-2 and 3-6 points and the median survival was 2.6 months (95 % CI, 1.0-3.8 months) and 10.7 months (95 % CI, 7.1-13.7 months), respectively (P < 0.0001). In the validation group, the corresponding median survival was 2.7 months (95 % CI, 1.6-5.5 months) and 10.8 months (5.8-13.6 months), respectively (P < 0.0001). In addition, the functional outcome was worse in patients with 0-2 points than in patients with 3-6 points both in the test (P = 0.0023) and validation groups (P = 0.0298). CONCLUSION: Patients with scores of 0-2 points, who have short survival time (life expectancy less than 3 months) and poor functional outcome, appear best treated with radiotherapy or best supportive care alone. Surgery may be no longer in consideration in most of the patients in this group. Patients with score of 3-6 points should be surgical candidates, because survival prognosis (life expectancy more than 10 months) and functional outcome are favorable after surgery.

Prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression from non-small cell lung cancer.

BACKGROUND: The aim of this study was to develop a scoring system for prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed nine preoperative characteristics for survival in a series of 64 patients with NSCLC who were operated with posterior decompression and spine stabilization for MSCC. Characteristics significantly associated with survival on multivariate analysis were included in the scoring system. The scoring point for each significant characteristic was derived from the hazard ratios on Cox proportional hazards model. The total score for each patient was obtained by adding the scoring points of all significant characteristics. RESULTS: Eastern Cooperative Oncology Group (ECOG) performance status, number of involved vertebrae, visceral metastases, and time developing motor deficits had significant impact on survival on multivariate analysis and were included in the scoring system. According to the prognostic scores, which ranged from 4 to 10 points, three prognostic groups were designed: 4-5 points (n = 22), 6-7 points (n = 23), and 8-10 points (n = 19). The corresponding 6-month survival rates were 95, 47 and 11%, respectively (P < 0.0001). In addition, the functional outcome was worse in the group of patients with 8-10 points compared with other two prognostic groups. CONCLUSIONS: The new scoring system will enable physicians to identify patient with MSCC from NSCLC who may be a candidate for decompression and spine stabilization, more radical surgery, or supportive care alone. Patients with scores of 4-5, who have the most favorable survival prognosis and functional outcome, can be treated with more radical surgery in order to realize better local control of disease and prevent the occurrence of local disease. Patients with scores of 6-7 points should be surgical candidates, because survival prognosis and functional outcome are acceptable after surgery, while patients with scores of 8-10 points, who have the shortest survival time and poorest functional outcome after surgery, appear to be best treated with radiotherapy or best supportive care.