Abstract 3273
Background
Limited stage small cell lung cancer (LS-SCLC) could be potentially curable with chemotherapy and radiation therapy. Notch pathway could be critically implicated with SCLC development, but there are few studies about its expression and clinical implications in SCLC. In this study, we evaluated the expression of Notch1, Notch2, and HES1 in LS-SCLC from clinical tumor tissue and their impact on PFS and OS.
Methods
A total of 75 patients with LS-SCLC, treated between 2010 and 2018, were enrolled, and their retrospective data were analyzed. Notch1, Notch2 and HES1 protein as Notch transcription factor were evaluated by immunohistochemistry. Staining was considered as low expression when 50% or less of the tumor cells expressed Notch1, Notch2, and HES1 with weak intensity.
Results
Among 75 patients, 42 patients (62.7%) received concurrent chemoradiotherapy, and 13 (17.3%) were diagnosed SCLC combined with NSCLC. Notch1, Notch2, and HES1 were identified in 50 (66.7%), 54 (72.0%), 24 (32.0%). There was no correlation of expression between Notch1 and HES1 (P = 0.115). Low expression of Notch1 or Notch2 was not associated with shorter PFS compared to high expression of them (median, 10.0 vs. 14.23, P = 0.172; 9.93 vs. 12.43, P = 0.759). Low expression of HES1 was tended to shorter PFS than high expression (8.40 vs. 13.57, P = 0.068). Low Notch1 expression was significantly associated with poor OS (median, 17.37 vs. 49.83, P = 0.022), but Notch2 and HES1 were not with OS (median; 21.73 vs. 18.40, P = 0.930; 15.37 vs. 27.90, P = 0.076). Of note, combined low expression of Notch1 and HES1 was significantly related with poor OS (median 15.37 vs. 28.63, P = 0.012). Multivariate Cox regression analysis showed that combined low expression Notch1 and HES1 was an independent poor prognostic factor for SCLC (HR = 1.23, P = 0.423).
Conclusions
Despite dramatic response rate of current standard treatment for LS-SCLC, more than half of patients experience failure within 2 years. It is clinically important to previse who the poor responder to the treatment is. In our study, low expression level of Notch1 and combined low expression of Notch1 and HES1 were related to poor overall survival, and these could be used as a prognostic biomarker for LS-SCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract
3887 - First Real Life Data on Durvalumab after definitive concomitant ChemoRadiotherapy (cCRT) in unresectable Stage (St) III Non-Small Cell Lung Cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) Temporary Authorization of Use (ATU)
Presenter: Virginie Avrillon
Session: Poster Display session 1
Resources:
Abstract
682 - EGFR Inhibitor Versus Chemotherapy as Adjuvant Treatment for Locally-advanced EGFR-mutant Non-Small Cell Lung Cancer
Presenter: Peng Xie
Session: Poster Display session 1
Resources:
Abstract
2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3300 - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis
Presenter: Daniel SW Tan
Session: Poster Display session 1
Resources:
Abstract
2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Presenter: Xiaohong Wang
Session: Poster Display session 1
Resources:
Abstract
5921 - Definition of an afatinib trough concentration threshold in the treatment of NSCLC
Presenter: Stephane Bouchet
Session: Poster Display session 1
Resources:
Abstract
2852 - A Phase Ib Trial of Neoadjuvant Chemoradiotherapy and Durvalumab(MEDI4736) for Potentially Resectable stage III Non-Small Cell Lung Cancer (NSCLC)
Presenter: Beung chul AHN
Session: Poster Display session 1
Resources:
Abstract
5141 - Mutational profiling of tumor tissue and sequential plasma illustrates emergent clones during treatment in late stage small cell lung cancer (SCLC)
Presenter: Stephanie Yaung
Session: Poster Display session 1
Resources:
Abstract