Browsing Over 443 Presentations
49P - A Mendelian randomization study of the effects of Crohn’s disease on lung cancer
- J. Liu (Guangzhou, China)
- J. Liu (Guangzhou, China)
- H. Zhou (Guangzhou, China)
- Y. Zhang (Guangzhou, China)
- W. Fang (Guangzhou, China)
- Y. Yang (Guangzhou, China)
- S. Hong (Guangzhou, China)
- G. Chen (Guangzhou, China)
- S. Zhao (Guangzhou, China)
- J. Shen (Guangzhou, China)
- W. Xian (Guangzhou, China)
- Y. Huang (Guangzhou, China)
- H. Zhao (Guangzhou, China)
- L. Zhang (Guangzhou, China)
Abstract
Background
Crohn’s disease is associated with increased lung cancer risk in observational studies, but the causality of this association is uncertain. Here we conducted a two-sample Mendelian randomisation (MR) study to examine whether Crohn’s disease is causally related to lung cancer.
Methods
We used the summary data of the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC, 5,956 cases and 14,927 controls; European ancestry) and International Lung Cancer Consortium (ILCCO, 11348 lung cancer cases and 15861 controls; European ancestry). 52 single nucleotide polymorphisms (SNPs) associated with Crohn’s disease were used as instrumental variables in the MR analysis. We utilized various MR methods (inverse-variance weighting (IVW), MR Egger, weighted median regression) to explore the causality. To investigate whether the effect of Crohn’s disease is associated with the histology of lung cancer, we also performed similar analyses on two different histologic subtypes of lung cancer (adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).
Results
Crohn’s disease was not significantly associated with risk of lung cancer (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.97-1.04; p = 0.76, IVW method). Weighted median (OR, 1.03; 95% CI, 0.98-1.07; p = 0.26) and MR Egger analysis (OR, 1.03; 95% CI, 0.95-1.11; p = 0.49) showed similar effect estimates of Crohn’s disease on lung cancer. The MR-Egger regression analysis showed that there was no evidence for the presence of horizontal pleiotropy (intercept β=-0.005, p = 0.532). Our leave-one-out analysis revealed that no single SNP strongly drove the overall effect of Crohn’s disease on lung cancer. The similar causal trend was observed in both LUAD and LUSC (LUAD, OR 0.99, 95% CI 0.94-1.04, p = 0.67, IVW method; LUSC, OR 0.98, 95% CI 0.94-1.03, p = 0.47, IVW method).
Conclusions
Our findings indicated that Crohn’s disease might not be causally associated with lung cancer, although patients with Crohn’s disease were at increased lung cancer risk in observational studies. Our study suggested there might be other risk factors associated with lung cancer in patients Crohn’s disease, which needs to be confirmed in the further study.
Legal entity responsible for the study
The authors.
Funding
National Key R&D Program of China (2016YFC0905500).
Disclosure
All authors have declared no conflicts of interest.
Q&A
Meeting welcome and introductions
- V. Gregorc (Milan, Italy)
- V. Gregorc (Milan, Italy)
138P - PD-L1 confers primary resistance to EGFR-TKI in EGFR mutant non-small cell lung cancer via inducing EMT phenotype
- Y. Zhang (Suzhou, China)
- Y. Zhang (Suzhou, China)
- T. Liu (Suzhou, China)
- Y. Zeng (Suzhou, China)
- J. Zhu (Suzhou, China)
- W. Du (Suzhou, China)
- L. Zeyi (Suzhou, China)
- J. Huang (Suzhou, China)
Abstract
Background
There were approximately 30% of patients with epidermal growth factor receptor (EGFR)-activating mutations do not respond to EGFR- tyrosine kinase inhibitors (TKIs) (primary resistance). However, little is known about the molecular mechanism involved in primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer (NSCLC). Programmed death ligand-1 (PD-L1) (B7-H1, CD274) is an important immune co-signaling molecule from the B7/CD28 family, it not only negatively regulates T cell functions through its PD-1 and CD80 interactions, but also plays important regulatory roles in intracellular functions and leads to acquired resistance to EGFR-TKIs in NSCLC. Here, we investigated that mechanistic role of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant NSCLC.
Methods
The mRNA expression level of PD-L1 was detected using real-time quantitative reverse transcriptase PCR. Molecular manipulations (overexpression or silencing) were performed to investigate the effect of PD-L1 expression on sensitivity to gefitinib in vitro, and a xenograft mouse model was used for in vivo confirmation. Migration and invasion assay were used to determine EMT phenotype.
Results
The mRNA expression level of PD-L1 was consistent with IC50 value for gefitinib in H1975, HCC827 and PC-9 cell line. Overexpression of PD-L1 decreased the sensibility to gefitinib, in addition, knockdown of PD-L1 increased the sensibility to gefitinib in vitro. Furthermore, Overexpression of PD-L1 attenuated sensitivity to gefitinib in a xenograft mouse model. Overexpression of PD-L1 leaded to primary resistance to gefitinib through inducing EMT phenotype.
Conclusions
PD-L1 contributes to primary resistance to EGFR-TKI in EGFR mutant non-small-cell lung cancer, which may be mediated by inducing EMT phenotype.
Legal entity responsible for the study
The First Affiliated Hospital of Soochow University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
The pathologist’s point of view
- F. Lopez-Rios (Madrid, Spain)
- F. Lopez-Rios (Madrid, Spain)
Q&A
- E. Felip (Barcelona, Spain)
- E. Felip (Barcelona, Spain)
RECaN: What this project has taught us about advanced roles?
- D. Kelly (London, United Kingdom)
- D. Kelly (London, United Kingdom)
How to define it? How to treat it?
- A. Dingemans (Maastricht, Netherlands)
- A. Dingemans (Maastricht, Netherlands)
123P - Long term survival analysis of osimertinib in stage IV NSCLC patients harbored acquired EGFR T790M mutation: A real-word study in China
- S. Wang (Shanghai, China)
- S. Wang (Shanghai, China)
- B. Han (Shanghai, China)
Abstract
Background
Aura studies have demonstrated the efficacy of osimertinib in advanced NSCLC patients harbored acquired EGFR T790M mutation. However, the real word data remains rare in China.
Methods
This retrospective study was conducted in Shanghai Chest Hospital. We collected data form stage IV NSCLC patients diagnosed with acquired EGFR T790M mutation. The whole median overall survival (OS) and OS from osimertinib, progression free survival (PFS) of osimertinib were observed.
Results
A total of 584 patients were tested positive for EGFR T790M mutation either by tissue or blood from Jan 2012 to Dec 2017. Finally, 238 patients (60.1% female, 62.2% 19del, 19.7% smokers) received osimertinib and have enough data to analysis. The median whole OS and OS from osimertinib were 54.8 and 24.33 month, respectively. And PFS of osimertinib was 11.0 month. Patients with 19del have better PFS, OS and whole survival from osimertinb (12 vs 10month, P = 0.054; 24.4 vs 20.27month, P = 0.012; 42.7 vs 60.9month, P = 0.056). The therapy line and EGFR T790M mutation detection methods (tissue or blood) had no impacts on PFS and OS. Additionally, in 63 patients with brain metastases (BM), osimertinib plus local therapy could contribute to the OS (61.3 VS 47.8, p = 0.086). After osimertinib failure, 39 patients benefited from rebiopsy.
Conclusions
This study gave us information that osimertinib could be a standard therapy in patients with EGFR T790M mutation, these patients have a better prognosis and an indolent progress. In addition, although osimertinib showed good control of BM, local therapy although show be taken into consideration for patients with BM.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Importance of access to innovative treatments and their impact on patient reported outcomes
- M. Hennink (Utrecht, Netherlands)
- M. Hennink (Utrecht, Netherlands)
19P - FOXP3Δ3, the major isoform of FOXP3, promotes proliferation, migration, and invasion in non-small cell lung cancer
- H. JIA (Shatin, Hong Kong PRC)
- H. JIA (Shatin, Hong Kong PRC)
- H. Qi (Hong Kong, Hong Kong PRC)
- J. Peng (Hong Kong, Hong Kong PRC)
- M. Li (Hong Kong, Hong Kong PRC)
- G. Chen (Shatin, Hong Kong PRC)
Abstract
Background
Increasing evidence has shown that FOXP3 is not only expressed in immune cells but also in tumor cells. However, the results of tumor FOXP3 is inconsistent and even the opposite. Unlike mice, humans express multiple isoforms of FOXP3. However, the expression and role of FOXP3 isoforms in cancers are still largely unknown. The role of FOXP3 and FOXP3Δ3 in NSCLC remains unclear.
Methods
The expression of FOXP3 and four FOXP3 isoforms was analyzed using the RSEM method for 32 cancer types from TCGA databases. The correlation between the expression of FOXP3 and prognosis of NSCLC patients was analyzed (
Results
The expression of FOXP3 was upregulated in NSCLC tissues compared to adjacent non-tumor lung tissues. The FOXP3Δ3 was the most frequent FOXP3 isoform detected in NSCLC as well as in almost all types of cancers. The high expression of FOXP3 was correlated with poor prognosis in NSCLC. Tumor cells with FOXP3Δ3 were much more oncogenic than those without, and the ectopic expression of either FOXP3FL or FOXP3Δ3 could promote the proliferation, migration, and invasion of A549 and H23 cells. The ectopic expression of FOXP3 and FOXP3Δ3 downregulated E-cadherin and upregulated N-cadherin, snail, slug, MMP2, and MMP7.
Conclusions
FOXP3Δ3 is the major isoform of FOXP3 in NSCLC and it may be a predictive factor for NSCLC patients.
Legal entity responsible for the study
The Chinese University of Hong Kong.
Funding
Research Grants Council of the Hong Kong SAR (No: CUHK462613) and the National Natural Science Foundation of China (No: 81472742).
Disclosure
All authors have declared no conflicts of interest.
45P - Treatment (Tx) patterns and overall survival (OS) in patients (pts) with stage IIIB–IV NSCLC in Portugal: An IPO-PORTO database analysis from the I-O Optimise initiative
- M. Soares (Porto, Portugal)
- M. Soares (Porto, Portugal)
- L. Antunes (Porto, Portugal)
- P. Redondo (Porto, Portugal)
- M. Borges (Porto, Portugal)
- R. Hermans (London, United Kingdom)
- D. Patel (London, United Kingdom)
- F. Grimson (London, United Kingdom)
- R. Munro (London, United Kingdom)
- C. Chaib (Madrid, Spain)
- L. Lacoin (Ladeuze, Belgium)
- M. Daumont (Braine-L'Alleud, Belgium)
- J. Penrod (Princeton, NJ, United States of America)
- J. O'Donnell (Princeton, NJ, United States of America)
- M. Bento (Porto, Portugal)
- F. Goncalves (Porto, Portugal)
Abstract
Background
Understanding Tx patterns and related outcomes in the rapidly changing NSCLC landscape informs clinical decision-making. As part of I-O Optimise, a multinational research platform providing real-world insights into the management of lung cancers, Tx patterns and OS are reported for pts with NSCLC prior to immunotherapy reimbursement in Portugal.
Methods
IPO-Porto, Portugal’s largest oncology hospital, has a research database linked to the RORENO cancer registry, covering northern Portugal. This database has collected data on 1524 adult pts with NSCLC since 2012; the current analysis includes pts diagnosed at stage IIIB–IV from Jan 2015 (when systemic anticancer therapy [SACT] data became available) to Dec 2016 (follow-up to Jun 2017). Tx patterns are shown for the first 3 Tx lines. Kaplan–Meier methods were used for OS and time to next Tx or death (TTNT) from SACT initiation.
Results
Of 595 pts diagnosed at stages I–IV in 2015–2016, 54 (9.1%) had stage IIIB and 338 (56.8%) had stage IV NSCLC (median age, 65 yrs [range: 27–90; 9.2% ≥80]; male, 77.3%; brain metastases, 16.3%; non-squamous [NSQ], 73.7%; squamous [SQ], 21.2%). Of the 372 NSQ/SQ pts, 284 (76.3%) had 1st-line SACT; 101 (27.2%) had 2nd-line, and 20 (5.4%) had 3rd-line ( PD-1, programmed death-1; PD-L1, programmed death-ligand 1SACT regimen (%) Non-squamous Squamous 1st-line Tx n = 221 n = 63 Platinum-based chemotherapy 72.9 87.3 Non-platinum single agent 4.5 12.7 TKI (any) 22.6 0.0 Erlotinib 12.7 0.0 Crizotinib 2.3 0.0 Gefitinib 7.7 0.0 Anti-PD-1/anti-PD-L1 checkpoint inhibitors 0.0 0.0 2nd-line Tx n = 82 n = 19 Platinum-based chemotherapy 13.4 21.1 Non-platinum single agent 59.8 73.7 TKI (any) 24.4 0.0 Erlotinib 9.8 0.0 Crizotinib 11.0 0.0 Other TKI 3.6 0.0 Anti-PD-1/anti-PD-L1 checkpoint inhibitors 2.4 5.3 3rd-line Tx n = 17 n = 3 Platinum-based chemotherapy 35.3 0.0 Non-platinum single agent 41.2 100.0 TKI (any) 11.8 0.0 Erlotinib 5.9 0.0 Crizotinib 0.0 0.0 Anti-PD-1/anti-PD-L1 checkpoint inhibitors 11.8 0.0
Conclusions
Pts with advanced NSCLC have a high burden of disease, with most diagnosed at stage IV and a short OS from SACT initiation. Future analyses will assess the post-reimbursement impact of immunotherapies (and new TKIs) on Tx and OS in Portugal.
Editorial acknowledgement
Professional medical writing assistance was provided by Richard Daniel, PhD, of Parexel and funded by Bristol-Myers Squibb.
Legal entity responsible for the study
Bristol-Myers-Squibb.
Funding
Bristol-Myers-Squibb through an EU wide RWD initiative called IO-Optimize sponsored by BMS.
Disclosure
M.A.S. Soares: Advisory boards, talks: Roche; Lilly, BMS, MSD; Boehringer Ingelheim, Pfizer, AstraZeneca, Novartis, outsider the submitted work. L. Antunes, P. Redondo, M.J. Bento: Grants: IQVIA, during the conduct of the study. M. Borges: Grants: IQVIA to IPO Porto, during the conduct of the study. R. Hermans, F. Grimson, R. Munro: Employee: IQVIA Real-World Insight Solutions (vendor paid by BMS). D. Patel: Personal fees: BMS, during the conduct of the study. C. Chaib: Employee: Bristol-Myers Squibb. L. Lacoin: Consultant epidemiologist contracted by Bristol-Myers-Squibb. All other authors have declared no conflicts of interest.