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Javier J. Zulueta
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-061 - Two Novel Protein-Based Prognostic Signatures Improve Risk Stratification of Early Lung ADC and SCC Patients (ID 9518)
09:30 - 09:30 | Author(s): Javier J. Zulueta
- Abstract
Background:
The development of robust, feasible and clinically useful molecular classifiers for early stage NSCLC patients to assess the risk of developing post-resection recurrence is an unmet medical need. Here we identified and validated the clinical utility of two different histotype-specific protein-based prognostic signatures to stratify the five-year risk of lung cancer recurrence or death in patients with either early lung adenocarcinoma (ADC) or early squamous cell carcinoma (SCC). The signatures are based on the immunohistochemical detection of three and five proteins, for ADC and SCC respectively
Method:
A total number of 562 lung cancer patients were included in this study (n=350 for ADC and n=212 for SSC). A training cohort was used to assess the value of the prognostic signatures based on immunohistochemical (IHC) detection (n=239 ADC and n=117 SSC). The prognostic signatures were developed by Cox regression analysis and were comprised of three and five proteins, respectively for ADC and SCC. Overfitting and optimism were quantified and calibrated by internal validation by applying shrinkage and bootstraping combination. The performance of the models was externally validated in a second cohort of 111 and 95 patients with stage I-II lung ADC and SCC, respectively.
Result:
The prognostic indexes (PIs) generated by the models were significant predictors of five-year outcome for disease-free survival: [P<0.001, HR=2.88 (95% CI, 1.77-4.69)] for ADC and [P<0.001; HR=2.97 (95% CI, 1.84-4.79)] for SCC; and overall survival: [P<0.001, HR=4.04 (95% CI, 2.30-7.10)] for ADC and [P=0.006; HR=1.86 (95% CI, 1.20-2.88)] for SCC, independently of other clinicopathological parameters. The prognostic ability of both PIs was externally validated in the second cohort of early stage lung cancer patients (P<0.05). The molecular classifiers added significant information to pathological stage. Combined models including both PIs and the pathological stage (CPIs) improved the risk stratification in both cases (P<0.001). Moreover, using the CPI value we were able to select the group of stage I-IIA patients who could obtain a benefit from platinum-based adjuvant chemotherapy treatment (P<0.05) in both histological subtypes.
Conclusion:
This study identifies and validates two protein-based prognostic signatures that accurately identify early lung cancer patients with high risk of recurrence or death. More importantly, the proposed models may be valuable tools to identify the subset of stage I-IIA patients for whom adjuvant chemotherapy could be beneficial.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-026 - Cell-CT® Differential Detection of Dysplastic Bronchial Epithelial Cells from Patient Explants (ID 10219)
09:30 - 09:30 | Author(s): Javier J. Zulueta
- Abstract
Background:
Chemoprevention could have a great impact on lung cancer prevention. While Iloprost treatment has shown a significant reduction of dysplasia in former smokers, the identification of patients who would benefit from the drug is seriously hampered due to the need to use invasive diagnostic procedures in patients who are typically asymptomatic. Published clinical data shows that non-invasive sputum analysis using the Cell-CT platform detects early stage lung cancer with high sensitivity (92%) and specificity (95%). This abstract reports the development of cell classifiers that distinguish cultured human lung dysplastic explants from malignant and normal sputum cells. This study represents a first important step toward developing a non-invasive diagnostic test for detecting patients with moderate to severe bronchial dysplasia who may then be treated with chemopreventive drugs such as Iloprost.
Method:
To achieve diagnostic classifications, sputum from patients without lung cancer (“normal cells”), small cell lung cancer and five adenocarcinoma cell lines, and cultured bronchial explants from three patients with moderate to severe dysplasia were analyzed using the Cell-CT.
Result:
15,000 normal cells from sputum, 500 malignant cells from each of the five lung cancer cell lines and 264 cells from patient dysplastic explants were analyzed using Cell-CT platform, measuring 704 structural biomarkers to sub-classify the cancer cells by abnormality and dysplastic status. Cell classifiers were operated to drive the highest specificity (avoidance of false positives). The area under ROC (aROC), sensitivity and specificity for each classifier were:Cell Classifiers aROC Sensitivity % Specificity % Lung Cancer cell lines 0.999 93% 99.99 Cells from patient dysplastic explants 0.995 86% 99.99
Conclusion:
These results show strong discrimination by the Cell-CT in classifying normal cells from sputum versus cells from lung dysplastic explants and lung cancer cell lines grown in culture. These data suggest that a non-invasive test using sputum liquid biopsy analyzed on the Cell-CT platform could enable the detection of dysplasia in patients who would benefit from chemoprevention drug therapy.
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P3.05 - Early Stage NSCLC (ID 721)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.05-002 - The Effect of Nodule Size on the Sensitivity of the LuCED® Test for Lung Cancer (ID 9597)
09:30 - 09:30 | Author(s): Javier J. Zulueta
- Abstract
Background:
The LuCED® test is based on analysis of sputum by the Cell-CT® platform that computes 3D images of cells with isometric resolution, allowing orientation-independent measurements of 704 3D structural biomarkers to generate a probabilistic score to identify abnormal cells. that was consistent by tumor histology and stage. Early stage tumors are generally smaller in size. One view is that smaller tumors might exfoliate fewer abnormal cells into sputum, making early stage tumor detection less likely. Here, we test the hypothesis that tumor size is a primary determinant of LuCED sensitivity.
Method:
Sputum samples from 74 biopsy confirmed non-small cell lung cancer cases were studied. The tumor size (mm) was characterized as the maximum tumor dimension supplied by the clinic. The numbers of bronchial epithelial cells and abnormal cells in sputum were measured and confirmed by cytological review. Tumor cell prevalence was characterized as (abnormal cells)/(bronchial epithelial cells) and plotted versus tumor size to assess any trend towards lower abnormal cell prevalence with decreasing tumor size.
Result:
The figures show the abnormal cell prevalence and the log of prevalence versus tumor size. Figure 1
Conclusion:
No trend was observed that might support the hypothesis that lower abnormal cell prevalence would occur with smaller tumor size. Moreover, variance in abnormal cell prevalence for any tumor size is large, suggesting that factors other than tumor size are more important in determining prevalence. There is no evidence to suggest that the LuCED test sensitivity decreases for smaller tumors, and this further suggests that early stage cancer, where tumors might be smaller, can still be detected. Published data shows that the LuCED test is 92% sensitive to stage 1 lung cancer.
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WS 01 - IASLC Supporting the Implementation of Quality Assured Global CT Screening Workshop (By Invitation Only) (ID 632)
- Event: WCLC 2017
- Type: Workshop
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/14/2017, 08:30 - 21:00, F203 (Annex Hall)
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WS 01.26 - COPD Integration into CT Screening – Patient Benefit? (ID 10671)
13:57 - 14:05 | Presenting Author(s): Javier J. Zulueta
- Abstract
Abstract not provided
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WS 02 - IASLC Symposium on the Advances in Lung Cancer CT Screening (Ticketed Session SOLD OUT) (ID 631)
- Event: WCLC 2017
- Type: Symposium
- Track: Radiology/Staging/Screening
- Presentations: 2
- Moderators:
- Coordinates: 10/14/2017, 09:00 - 18:15, F201 + F202 (Annex Hall)
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WS 02.08 - Session 2: Current Lung Cancer Screening Guidelines (Panel Discussion) (ID 10586)
12:00 - 12:00 | Presenting Author(s): Javier J. Zulueta
- Abstract
Abstract not provided
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WS 02.18 - Lung Cancer Screening and COPD – A Pneumologist’s Viewpoint (ID 10629)
16:15 - 16:45 | Presenting Author(s): Javier J. Zulueta
- Abstract
- Presentation
Abstract not provided
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