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P. De Leyn
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MINI 01 - Pathology (ID 93)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:W.A. Franklin, A.G. Nicholson
- Coordinates: 9/07/2015, 10:45 - 12:15, Mile High Ballroom 2c-3c
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MINI01.11 - Transcriptome Sequencing of Tumor vs. Surrounding Non-Malignant Lung Tissue in Non-Small Cell Lung Cancer (ID 1765)
11:45 - 11:50 | Author(s): P. De Leyn
- Abstract
Background:
Both the response and the therapeutic ratio of targeted agents in NSCLC may depend on the expression of the target molecules in the tumor and the surrounding non-malignant lung tissue. We therefore performed transcriptome analysis and investigated correlations with histology, gender, age, CRP level and smoking status as well as evaluated the differential pathway expression in primary resected NSCLC and the surrounding non-malignant lung of the same patient.
Methods:
Transcriptome sequencing was performed on the primary tumor and distant lung tissue of the same patient from resection specimens of NSCLC patients. Differential gene expression between different conditions was identified using the statistical algorithms Cufflinks, EdgeR and DeSeq. Differential expression with P-values <0.05 after Benjamini-Hochberg correction was considered significant. Pathway analysis for overall tumor versus distant lung tissue was performed with the PANTHER gene classification platform using the Cufflinks, DeSeq and EdgeR differentially expressed gene sets as input.
Results:
Twenty-five patients were studied, 19 males and 6 females, with a median age of 69 years. Ten were current smokers, 14 former smokers (>4 weeks before surgery) and 1 non-smoker. Eleven patients had squamous cell carcinoma, 14 adenocarcinoma. A heat map with the results for the most commonly targeted genes in NSCLC is represented in figure 1. When compared to distant lung tissue, PD-L1 was downregulated in tumor tissue of adenocarcinoma and active smokers, but not in squamous cell carcinoma or ex-smokers. Internal control of tumor tissue of squamous vs. adenocarcinoma and ex-smokers vs. active smokers shows an important trend towards a higher expression of PD-L1 in squamous cell carcinoma and ex-smokers in both Cufflinks and EdgeR algorithms. Additional pathway analysis revealed 188 differentially regulated pathways. The most notable were downregulation of VEGF signaling, angiogenesis and B and T cell activation in tumor tissue when compared to distant lung tissue. Figure 1
Conclusion:
Our first results show a higher expression of PD-L1 in squamous tumors than in adenocarcinoma and a higher expression in tumors of ex-smokers than in those of active smokers. This may have consequences for the therapeutic ratio with anti-PD-L1 treatment. Downregulation of VEGFR-genes in tumor tissue was observed across almost all conditions. We will make this data more complete by adding methylation data as well as immunohistochemistry for protein localization.
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P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.02-022 - Sleeve Lobectomy Is a Safe and Effective Oncologic Procedure: A Single Center Experience over Three Decades (ID 896)
09:30 - 09:30 | Author(s): P. De Leyn
- Abstract
Background:
Sleeve lobectomy is a parenchyma-sparing technique suitable for treating central tumors, avoiding pneumonectomy. The aim of this study was to assess perioperative and long-term survival outcomes in patients treated by sleeve lobectomy.
Methods:
Data were analysed from a prospectively collected database. All consecutive cases of sleeve lobectomy/bilobectomy (1985 - 2013) were included. Cox-Regression was used to analyse survival outcomes. There were 300 patients available for analysis. Sleeve lobectomy was performed in 272 patients (RUL:153; RML:5; RLL:1; LUL:83; LLL:30), sleeve bilobectomy in 28 (RUM:17; RLM:11). In most patients a sleeve of the bronchus (n=219) or a reversed sleeve of the bronchus (n=19) was performed. Arterial (n=35) or combined arterial and bronchial sleeve (n=27) resections were less common. The most common operative indication was non-small cell lung cancer (254 cases, 85%), less commonly for carcinoid (n=27), small cell lung cancer (n=6) , pulmonary metastasis (n=9) and 4 others.
Results:
Patients were predominantly male (85%) with a mean age of 62.7 years (range 20.1-84.6). Postoperative course was uneventful (Dindo-grade 0/1) in 60%; with minor complications (Dindo-grade 2/3a) in 30% and major complications (Dindo-grade 3b/4) in 7.3%. In hospital mortality (Dindo-grade 5) was 2.7%. Overall median survival was 68 months, with a 5- and 10-year survival of 52.3% and 35.8%. A Cox-Regression model showed five independent prognosticators for survival: asymptomatic at presentation, age, pT, pN and neoadjuvant treatment (see table). Although neoadjuvant treatment showed to be a negative prognosticator for survival, complete responders (n=8 or 14.5% of neoadjuvant treated patients) showed a mean survival of 132 months and a 5-year survival of 80%. Figure 1
Conclusion:
Sleeve lobectomy can be safely performed as treatment for centrally-located lung tumours. A single-institution experience over 3 decades demonstrates acceptable morbidity and mortality rates. Overall survival seems to be mainly determined by oncologic variables (TNM-staging factors).
