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A. Scherpereel



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    MO05 - Prognostic and Predictive Biomarkers II (ID 95)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO05.04 - A prospective study of innovative non-invasive tools to assess the response to anti-angiogenic therapies in non small cell lung cancer patients (ID 2676)

      16:15 - 17:45  |  Author(s): A. Scherpereel

      • Abstract
      • Presentation
      • Slides

      Background
      Therapies targeting tumor angiogenesis, such as anti-VEGF antibodies (bevacizumab), are a major step in the treatment of non small cell lung cancer (NSCLC) but are costly drugs and may be responsible for significant toxicities. The goal of our study was to assess the value of non-invasive tools evaluating early the response to bevacizumab in NSCLC.

      Methods
      56 consecutive patients with stage IIIB-IV non-squamous NSCLC were prospectively recruited. According to multidisciplinary committee advice, one group of patients (bevacizumab group, n =24) had a chemotherapy combined with bevacizumab, the second one (control group, n = 32) had a similar chemotherapy but without bevacizumab. Quantitative tumor perfusion was sequentially evaluated with CT-scan before (T0) and after 1 cycle (T1) and 3 cycles (T2) of chemotherapy. CT-scan parameters included: (a) tumor height and diameter; (b) tumoral blood volume (BV) and capillary permeability (CP). Blood biomarkers (Endocan, VEGF, Angiopoïetin-2, VEGFR-2, VE-cadherin) were measured at the same time points.

      Results
      We observed an early and quite specific decrease of BV, CP and blood levels of VEGF, Angiopoïetin-2 and VE-cadherin in the bevacizumab group compared to control group. In the bevacizumab group, the decrease of BV between T0 and T1 was more important in patients responding to treatment than in subjects with progression on clinical (ΔBVT0-1 =-2.72ml vs 0.32ml, p=0.004) or RECIST criteria (ΔBVT0-1 =-3.35ml vs 0.04ml, p=0.011). An initial high Endocan level appeared as a marker of bad prognosis (overall survival) (HR=1.469 [1.120-1.925]; p=0.005) using a cut-off value of 0.72ng/ml (HR=2.276 [1.074-4.82]; p=0.032). Moreover, in the bevacizumab group, a significant decrease of Endocan level between T0 and T1 was a marker of good prognosis (HR=0.141 [0.022-0.889]; p=0.037).

      Conclusion
      Whole tumor perfusion analysis by CT-scan exhibited a promising predictive value for patients treated by chemotherapy combined with anti-angiogenic drug, whereas blood Endocan appeared as the most interesting blood marker, having a significant prognostic value in the same patients. These two exciting non-invasive tools deserve further and larger studies to confirm their value in monitoring NSCLC patients with therapies targeting tumor angiogenesis.

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    O27 - Clinical Trials and Practice (ID 142)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Other Topics
    • Presentations: 1
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      O27.05 - Is primary tumor standardized uptake value (SUV) an independent prognostic factor for non-small cell lung cancer (NSCLC)? A meta-analysis based on individual patients data. (ID 3888)

      16:15 - 17:45  |  Author(s): A. Scherpereel

      • Abstract
      • Presentation
      • Slides

      Background
      [18]F-fluoro-2-deoxy-D-glucose positron emission tomography complements conventional imaging for staging lung cancer although its ability to predict outcome is less well established. Two literature-based meta-analyses suggest a prognostic value in univariate analysis. To assess FDG-PET value in predicting survival adjusted for some known prognostic factors, we carried out a meta-analysis based on individual patients data from multiple independent studies.

      Methods
      Following literature search, and after writing of a protocol for the meta-analysis, we contacted the authors of identified studies and requested individual patients data; we also tried to collect some unpublished data. Data analysis used Cox regression models stratified for the study with overall survival as primary outcome. SUV max was used as a binary covariate (median value for each study).

      Results
      Data were collected for 1526 patients (57% of the identified patients) from 11 publications and 1 unpublished series (median age : 64 years, 60% male patients, squamous cell in 34%, adenocarcinoma in 47%, stages I-II in 58%). Combined univariate hazard ratio (HR) was 1.43 (95% CI : 1.22-1.66); no statistically significant interaction between SUV and one of six additional freatures (age, gender, histology,stage, tumors size –in stages I-III patients- and surgical treatment), was found except for stage (p=0.05) with a decreased prognostic value of SUV for stage IV patients. Without considering SUV, multivariate analysis identified, in stage I-III patients, age, stage, tumor size and surgical treatment as independent prognostic factors. The addition of SUV improved that model : HR estimate for SUV effect was 1.58, statistically significant (95% CI : 1.27-1.96), p<0.0001. No interaction was found with SUV. When tumor size was not included in the tested covariates, we found SUV of additional value (adjustment for age, stage, surgical treatment) with a HR of 1.35 (95% CI : 1.15-158). Interaction between SUV and stage was detected, restricting the significant impact of SUV on survival to stage I-III patients.

      Conclusion
      Conclusions : Although suffering from selection bias and lack of homogeneous SUV assessment, these data suggest that SUV at the time of diagnosis is an independent prognostic marker for patients with stage I-III NSCLC. The utility of SUV in predicting survival in stage IV patients requires further studies.

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    O28 - Endoscopy (ID 124)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      O28.05 - An analysis of a prospective study from the European Lung Cancer Working Party (ELCWP) looking at predictive factors for response to chemotherapy (CT): limitations in translational cooperative research. (ID 1941)

      10:30 - 12:00  |  Author(s): A. Scherpereel

      • Abstract
      • Presentation
      • Slides

      Background
      Adequate tumour samplings for biological analyses are currently of major importance in treating oncological patients. Obtaining histological samplings from the primary lung cancer can be a challenge due to tumour accessibility, small biopsies or tolerance to bronchoscopy such as bleeding or dyspnoea in case of limited airflow capacity. The ELCWP developed a multicentre prospective study searching for predictive factors for response to chemotherapy based on genomic analyses. We aim to analyse the capability in obtaining adequate tumour samplings from the primary non small cell lung cancer (NSCLC) for studying the transcriptome (miRNA and mRNAs) with high throughput techniques.

      Methods
      All patients presenting with a suspected lung cancer were proposed participating to the study. To be evaluable for the primary endpoint of the study, patients needed to have a confirmed diagnosis of NSCLC treated with chemotherapy and assessable for response. During the diagnostic bronchoscopy, 3 biopsies were collected from the primary tumour, with a control sample from normally appearing bronchial mucosa. One was formalin fixed and paraffin embedded for pathological diagnosis. A second was used for transcriptome analysis and the third one was frozen and stored in a tissue bank. We are presenting the flow chart of the patients screened for entry in the ELCWP study and the limitations for obtaining tumour samplings in assessable patients.

      Results
      From 1/04/2009 to 12/06/2013, 307 patients suspected to have NSCLC were prospectively registered. Eleven are under evaluation for pending histological confirmation leaving 296 patients evaluable for the present analysis. In 25 cases, no lung cancer confirmation was obtained (other tumour n = 12, no pathological confirmation at all n = 6, benign lesion n = 6, other reason n = 1) and 6 further patients withdrew their initial consent. Among 265 pathologically confirmed lung cancer (samples obtained during bronchoscopy or by another technique), 38 small cell lung cancers (SCLC) and 227 NSCLC were diagnosed. In addition to the diagnostic biopsy, further samplings for genomic analyses could be obtained during the same bronchoscopy in 30/38 SCLC (79%) and 116/227 NSCLC (51%). Among 227 NSCLC, 107 were presenting with an advanced disease treated with a cisplatin-based chemotherapy and were assessable for response to chemotherapy (primary study endpoint). Among these 107 patients, 59 adequate tumour samplings could be obtained for transcriptome analysis (20% from the initial cohort and 55% among assessable patients).

      Conclusion
      This analysis of a prospective multicentre study is showing the difficulties and limitations in obtaining adequate tumour samplings for biological analyses when conducting translational cooperative research in non-small cell lung cancer.

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