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J. Corral



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    MO11 - Screening and Epidemiology (ID 131)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      MO11.11 - IL-11 and CCL-1: Novel protein diagnostic biomarkers of lung adenocarcinoma in bronchoalveolar lavage (BAL) (ID 2876)

      17:15 - 17:20  |  Author(s): J. Corral

      • Abstract
      • Presentation
      • Slides

      Background
      Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are smoking related diseases and the presence of COPD increases itself the risk of developing lung cancer, probably due to underlying inflammation. LC is typically detected at late stages of the disease and carries a dismal prognosis. There is an unmet need for useful early detection methods of lung cancer in high risk subjects, such as smokers.

      Methods
      The expression of inflammatory proteins was studied in bronchoalveolar lavage samples (BAL) by antibody arrays in a prospective discovery cohort of 60 patients with the following inclusion criteria: age > 40 years, diagnostic broncoscopy due to hemoptysis or pulmonary nodule, smokers or ex-smokers pack of more than 30 pack-years, divided into four groups (control, LC, COPD, LC & COPD). Relevant biomarkers were validated by western blot. Additional validation was carried out by ELISA in two independent controlled cohorts of 139 (control, LC, COPD, LC & COPD) and 160 patients (control, all LC histological subtypes).

      Results
      CCL-1 and IL-11 were selectively expressed in samples of adenocarcinoma patients, with or without COPD (p<0•001) in the discovery cohort. These proteins exhibited a remarkable diagnostic performance for lung adenocarcinoma in an independent cohort of 139 patients. ROC curves showed that the optimum diagnostic cutoff value for IL-11 was 42 pg/mL (area under curve [AUC] 0•93 [95% CI 0•896-0•975], sensitivity 90%, specificity 86%), and for CCL-1 was 39•5 pg/ml (0•83 [95% CI 0•749-0•902], sensitivity 83%, specificity 74%). Further validation of the ELISA biomarkers at the mentioned cutoffs was performed in an additional cohort of 160 patients (20 controls, 66 LC, 74 LC & COPD). There was a significant correlation between BAL levels of IL-11 and CCL-1 (r2= 0•76, p<0•001), and the use of both biomarkers increased the diagnostic accuracy to 96,1% in the two validation cohorts. Appropriate diagnostic performance was observed for all subgroups regardless of stage at diagnosis, involvement of bronchial tract, pack-years smoked, and number of cells in BAL.

      Diagnostic performance of IL-11 and CCL-1 in the first validation cohort (N=139)
      Adenocarcinoma vs all patients AUC (95%IC) Sensivity (95%IC) Specificity (95%IC) PPV (95%IC) NPV (95%IC) Positive LR Negative LR
      IL-11 0.93 (0.896-0.975) 90.2% (79%-95.7%) 88.7% (80.6%-93.5%) 80.7% (68.7%-88.9%) 94.5% (87.8%-97.6%) 7.95 (4.53-13.98) 0.11 (0.05-0.26)
      CCL-1 0.83 (0.749-0.902) 80% (66.4%-87.7%) 74.1% (63.9%-82.2%) 72.1% (59.2%-73.4%) 86.3% (76.6%-92.4%) 3.02 (2.05-4.47) 0.29 (0.17-0.52)
      IL11 and CCL-1 71.2% (57.7%-81.7%) 94.4% (88.4%-97.4%) 86% (72.7%-93.4%) 87.2% (79.9%-92.1%) 12.8 (5.77-28.41) 0.31 (0.20-0.47)
      IL-11 and/or CCL-1 94.3% (84.6%-98.1%) 74.1% (65.1%-81.4%) 64.1% (53%-73.9%) 96.4% (89.9%-98.8%) 3.64 (2.63-5.04) 0.08 (0.03-0.23)
      Diagnostic performance of IL-11 and CCL-1 in the second validation cohort (N=160)
      Adenocarcinoma vs all patients AUC (95%IC) Sensivity (95%IC) Specificity (95%IC) PPV (95%IC) NPV (95%IC) Positive LR Negative LR
      IL-11 0.95 (0.92-0.98) 90.6% (79.7%-95.9%9 83% (86.8%-87.7%) 60.8% (49.7%-70.8%) 96.8% (92.7%-98.6%) 5.32 (3.81-7.41) 0.11 (0.05-0.26)
      CCL-1 0.91 (0.87-0.96) 91.7% (80.4%-96.7%) 77.5% (71.0%-82.9%) 51.2% (40.8%-61.4%) 97.3% (93.3%-99%) 4.08 (3.09-5.04) 0.11 (0.04-0.28)
      IL11 and CCL-1 71.2% (57.7%-81.7%) 96.3% (92.5%-98.2%) 84.1% (70.6%-92.1%) 92.3% (87.7%-95.3%) 19.1 (9-41.13) 0.3 (0.19-0.46)
      IL-11 and/or CCL-1 92.3% 82.6%-98.1%) 84% (78%-88.5%) 62.5% (51.5%-72.3%) 98.1% (94.6%-99.4%) 5.88 (4.21-8.22) 0.07 (0.02-0.20)

      Conclusion
      IL-11 and CCL-1 are highly specific biomarkers with great accuracy for the diagnosis of lung adenocarcinoma in BAL specimens. Further study of these proteins as markers for early diagnosis and screening in plasma and other biological materials is warranted.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-001 - Retrospective analysis of the clinico-pathological profile of ALK positive patients in the South of Spain (Andalusian Area) (ID 147)

      09:30 - 09:30  |  Author(s): J. Corral

      • Abstract

      Background
      The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with advanced non small cell lung cancer (NSCLC). ALK rearragement is detected in 2-7% of NSCLC patients. Fluorescence in situ hybridization (FISH) is the recommended method of detection. The clinical features of lung cancer that harbors ALK include light- or never-smokers, younger age, adenocarcinomas with acinar pattern or signet ring adenocarcinoma, and a lack of EGFR or KRAS mutations. Crizotinib has shown an important benefit in terms of overall response rate (ORR) and progression free survival (PFS) in the 2nd/3rd line setting. Treatment related adverse events were gastrointestinal and visual disorders.

      Methods
      Retrospective analysis of the clinico-pathological profile of ALK NSCLC patients between May 2011 and December 2012 in our Institution.

      Results
      10 cases (6,7%) were identified from 150 screened patients with adenocarcinoma histology and EGFR wild-type status. 7 (70%) patients were women. Median age at diagnosis was 62 years old (range=36-77). 90% patients were light-or-never smokers. All tumours were adenocarcinomas with EGFR wild type status: acinar growth pattern was detected in 4 cases (40%); 4 (40%) patients showed mucous cells and previous described signet-ring cells were detected in the last 2 (20%) cases. Only 5 (50%) patients received crizotinib therapy: 2 patients were treated during first line with partial response, 1 patient was treated in second line with stable disease and 2 patients received therapy in third line with partial response and no response, respectively. Only one patient required a dose reduction (200 mg bd) due to gastrointestinal toxicity.

      Conclusion
      Most of the patients with ALK rearregements in our serie have clinical and pathological characteristics to previously described. More women and older population were showed. In stead of the small sample size, pathological pattern based on acinar growth and mucous or signet-ring cells in adenocarcinomas with no EGFR mutation should guide the ALK screening process. ORR and toxicity profile confirmed Crizotinib benefit as soon as ALK status was detected.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-003 - Third-line therapy and beyond for patients with advanced/metastatic non-small cell lung cancer (NSCLC) (ID 294)

      09:30 - 09:30  |  Author(s): J. Corral

      • Abstract

      Background
      Lung cancer is the leading cause of cancer-related deaths globally, with a 15% 5-year survival rate. Platinum-based chemotherapy constitutes the main treatment modality, with a median overall survival (OS) of approximately 10-12 months. The current National Comprehensive Cancer Network (NCCN) guidelines recommend several options for first-line and second-line therapies but endorse only erlotinib/gefitinib as third-line therapy in unselected patients, as well as crizotinib in ALK-positive selected patients.The paucity of approved agents for third-line therapy and beyond for patients with non-small cell lung cancer (NSCLC) constitutes an important unmet medical need.

      Methods
      Retrospective analysis of 22 patients with advanced/metastatic NSCLC in progression after a minimum of 3 lines of therapy.

      Results
      Between January 2009 and October 2012, 22 patients were analysed. Median age at diagnosis was 62 years old. 15% of patients were never smokers and 72.7% had non squamous NSCLC histology. Stage at diagnosis resulted: 6 (27.3%) stage IIIA, 3 (13.6%) stage IIIB and 13 (59.1%) stage IV. 3 (13.6%) patients were EGFR mutation carriers and 1(1%) patient had ALK translocation. Third line therapy options resulted a clinical trial (27.3%), erlotinib (22.7%), paclitaxel/gemcitabine (13.6%), docetaxel (9.1%) and crizotinib (4.5%). Estimated median progression-free survival (PFS) between first and second line therapy was 5.3 months; PFS between second and third line resulted 4.4 months. Median PFS and overall survival (OS) beyond third line treatment has not been reached yet.

      Conclusion
      Currently, erlotinib/gefitinib and crizotinib, which target EGFR and ALK, are the only recommended agents for third-line therapy in patients with advanced/metastatic NSCLC. Real-world clinical practice reveals a variety of chemotherapeutic agents used in this setting. Additional systemic and/or targeted therapeutic under development, with complementary biomarker analysis, should be the key in identifying those patients most likely to benefit from newer agents.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-002 - New toxicity profile as radiological response marker in the context of mTOR therapy in advanced/metastatic non small cell lung cancer (NSCLC) (ID 293)

      09:30 - 09:30  |  Author(s): J. Corral

      • Abstract

      Background
      mTOR pathway plays a key role in most of solid tumors. Its blockage has shown clinical and survival benefit in the context of advanced/metastatic breast, kidney and neutroendocrine cancer. Multiple preclinical and early clinical trials are ongoing to demonstrate mTOR inhibition role as monotherapy as in chemo combo in NSCLC.

      Methods
      Retrospective analysis of advanced and/or metastatic NSCLC patients treated in our Institution with mTOR monotherapy or combined chemotherapy and correlation between radiological cavitation pattern mTOR therapy induced as early response marker.

      Results
      Four patients with advanced/metastastic NSCLC in progression after more or equal 2 lines of standard chemotherapy were treated in our center during 2012 in the context of early clinical trials. Three patients had squamous NSCLC and one patient adenocarcinoma. All ones were evaluated at 6-8 weeks by CT scan: cavitation as early response marker was seen in all of them but measurement by RECIST 1.1 criteria only showed stable disease.

      Conclusion
      Preliminary data suggest that cavitation may be a marker of stable disease by RECIST and the therefore, a therapeutic benefit. Overinfection and haemoptysis are currently complications in this context. Careful patient assessment should be undertaken while the drug is being administered.