Virtual Library

Start Your Search

X. Liu



Author of

  • +

    MINI 06 - Quality/Prognosis/Survival (ID 111)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
    • +

      MINI06.11 - The Influence of Body Mass Index on Overall Survival following Surgical Resection of Non-Small Cell Lung Cancer (ID 2722)

      16:45 - 18:15  |  Author(s): X. Liu

      • Abstract
      • Presentation
      • Slides

      Background:
      Population studies suggest that high body mass index (BMI) correlates with a reduced risk of death from lung cancer. The aim of our study was to evaluate the influence of BMI on long term overall survival (OS) in surgical patients with non-small cell lung cancer (NSCLC).

      Methods:
      Study population consisted of 1935 patients who underwent surgical resection for lung cancer at MD Anderson Cancer Center between 2000-2014. Patients with perioperative mortality, 90-day mortality, intraoperative transfusion, postoperative ICU days, postoperative pneumonia, and postoperative transfusion were excluded. Study variables included both patient and treatment related characteristics. Univariable and multivariable Cox regression analyses were performed to identify variables associated with overall survival. Propensity matching was performed to compare patients with BMI <25 and BMI≥30 matching on type of surgery, age, gender, histology, and pathological stage.

      Results:
      On univariable analysis, significant predictors of improved survival were higher BMI, pathologic tumor stage (stage I vs II, III, or IV), type of surgery (lobectomy/pneumonectomy vs wedge resection/segmentectomy), younger age, female gender, and adenocarcinoma histology (vs squamous) (all p<0.05). Patients considered morbidly obese (BMI≥35) had a trend towards better outcomes than those classified as obese (BMI ≥30 and <35), overweight (BMI ≥25 and <30), or healthy weight (BMI<25) (HR 0.727, 0.848, 0.926, and 1, respectively, p=NS). On multivariate analysis, BMI remained an independent predictor of survival (p=0.02, see Table). Propensity matching analysis demonstrated significantly better OS (p=0.008) in patients with BMI≥30 compared to BMI <25 (Figure).

      Multivariate Cox Regression Model
      N (%) Overall Survival HR (95% CI)
      BMI <25 (Reference) ≥25 646 (33.4%) 1289 (66.7%) 1.000 0.833(0.713-0.975)
      Age Continuous variable Median 66 (13-88) 1.024 (1.015-1.032)
      Gender Female (Reference) Male 984 (50.9%) 951 (49.1%) 1.000 1.236 (1.061-1.441)
      Stage I (Reference) II III IV 1149 (59.4%) 431 (22.3%) 299 (15.5%) 56 (2.9%) 1.000 1.839 (1.570-2.271) 2.653 (2.182-3.225) 2.737 (1.934-3.873)
      Surgery Wedge/Segmentectomy (Reference) Lobectomy/Pneumonectomy 198 (10.2%) 1737 (89.8%) 1.000 0.602 (0.479-0.755)
      Pre-op therapy No (Reference) Yes 1604 (82.9%) 331 (17.2%) 1.000 1.399 (1.160-1.686)
      Histology Adenocarcinoma (Reference) Squamous Other 1252 (64.7%) 472 (24.4%) 211 (10.9%) 1.000 1.225 (1.035-1.451) 0.959 (0.747-1.231)
      Figure 1



      Conclusion:
      In a large, single center series, after controlling for disease stage and other variables, higher BMI was associated with improved OS following surgical resection of NSCLC. Further studies are necessary to define the complex relationship between BMI and treatment outcomes.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MINI 21 - Novel Targets (ID 133)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
    • +

      MINI21.02 - CCT68127 Is a Next Generation CDK2/9 Inhibitor with Potent Antineoplastic Activity Against Lung Cancer Cells (ID 554)

      16:45 - 18:15  |  Author(s): X. Liu

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung cancer growth was significantly repressed by the first generation CDK2/9/7 inhibitor seliciclib (R-roscovitine, CYC202, Cyclacel Ltd). This induced anaphase catastrophe and apoptosis to occur. Anaphase catastrophe happens when supernumerary centrosomes attempt mitosis by clustering extra centrosomes. If this clustering is inhibited, cells segregate chromosomes inappropriately and anaphase catastrophe occurs and leads to death of daughter cells. This study explored antineoplastic effects of a next generation CDK2/9 inhibitor: CCT68127 (Cyclacel) against lung cancer cells. CCT68127 inhibits CDK2/9 more potently and selectively than seliciclib (IC50s for CDK2 and CDK9 are 30nM and 110nM, respectively).

      Methods:
      Antineoplastic CCT68127 effects in murine (transgenic mouse-derived) and human lung cancer cells were compared to seliciclib using luminescent cell viability assays. Cell cycle arrest and apoptosis induction by CCT68127 were detected using fluorescence-based cell imaging after staining with propidium iodide (PI) and double-staining with Annexin V and PI. Multipolar anaphase cells were scored after a tubulin and DNA staining. RPPA (Reverse Phase Protein Assay) analyses were performed in CCT68127 and vehicle-treated lung cancer cells to uncover mechanisms engaged by CDK2/9 antagonism. Expression levels of nearly 200 key growth-regulatory proteins were examined before and after 6, 24, and 48 hours of CCT68127 versus vehicle treatments of murine: ED1 (wild-type KRAS) and LKR13 (mutant KRAS) and human lung cancer cells: H522 (wild-type KRAS) and Hop62 (mutant KRAS).

      Results:
      IC50s of CCT68127 in murine lung cancer cells (ED1, LKR13, and 393P) were <1µM while IC50 of seliciclib was >25µM. KRAS mutant murine lung cancer cells (LKR13 and 393P) were more sensitive to CCT68127 than the KRAS wild-type line (ED1). In contrast, growth inhibition in C10 immortalized murine pulmonary epithelial cells was negligible. IC50s in human lung cancer cell lines (Hop62, A549, H2122, H522, and H1703) were comparable to murine lung cancer cell lines. KRAS mutant lung cancer cells (Hop62, A549, and H2122) were more sensitive than KRAS wild-type lung cancer cell lines (H522 and H1703). Immortalized human bronchial epithelial cells (BEAS-2B) were resistant to CCT68127 treatment. CCT68127 triggered apoptosis in a dose-dependent manner in murine lung cancer cell lines and at much lower concentrations than seliciclib. CCT68127 caused G1 arrest. Its growth inhibition was partially reversed in washout experiments. CCT68127 also induced apoptosis in human lung cancer cells (Hop62, A549, H522, and H1703). A mechanism responsible for these effects was found. Anaphase catastrophe was triggered by CCT68127 treatment of murine and human lung cancer cell lines and was independent of KRAS mutation status. RPPA analyses uncovered distinct protein profiles after CCT68127 treatment. These included DNA repair, Hippo and Rab GTPase pathway members that were each markedly down-regulated.

      Conclusion:
      CCT68127 is a next generation CDK2/9 inhibitor that has more potent antineoplastic activity against KRAS mutant and wild-type lung cancer cells than the prior inhibitor, seliciclib. This occurred via induced anaphase catastrophe and was linked to changes in expressed growth regulatory proteins. Taken together, these findings implicate use of a next generation CDK2/9 inhibitor for human lung cancer cases.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.