early stage nsclc
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Author(s):  
J. Lorenz ◽  
D. Moghanaki ◽  
H. Keshava ◽  
D.H. Harpole ◽  
J.D. Bradley ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6139
Author(s):  
Michał Szczyrek ◽  
Anna Grenda ◽  
Barbara Kuźnar-Kamińska ◽  
Paweł Krawczyk ◽  
Marek Sawicki ◽  
...  

Background: Lung cancer is the leading cause of cancer-related deaths. Early diagnosis may improve the prognosis. Methods: Using quantitative methylation-specific real-time PCR (qMSP-PCR), we assessed the methylation status of two genes (in two subsequent regions according to locations in their promoter sequences) related to carcinogenesis, DICER and DROSHA, in 101 plasma samples (obtained prior to the treatment) of lung cancer patients and 45 healthy volunteers. Results: The relative level of methylation of DROSHA was significantly lower (p = 0.012 for first and p < 0.00001 for the second region) and DICER significantly higher (p = 0.029 for the first region) in cancer patients. The relative level of methylation of DROSHA was significantly (p = 0.037) higher in patients with early-stage NSCLC (IA-IIIA) and could discriminate them from healthy people with a sensitivity of 71% and specificity of 76% (AUC = 0.696, 95% CI: 0.545–0.847, p = 0.011) for the first region and with a sensitivity of 60% and specificity of 85% (AUC = 0.795, 95% CI: 0.689–0.901, p < 0.0001) for the second region. Methylation analysis of the first region of the DICER enabled the distinction of NSCLC patients from healthy individuals with a sensitivity of 96% and specificity of 60% (AUC = 0.651, 95% CI: 0.517–0.785, p = 0.027). The limitations of the study include its small sample size, preliminary nature, being an observational type of study, and the lack of functional experiments allowing for the explanation of the biologic backgrounds of the observed associations. Conclusion: The obtained results indicate that the assessment of DICER and DROSHA methylation status can potentially be used as a biomarker for the early detection of lung cancer.


2021 ◽  
Vol 10 (23) ◽  
pp. 5614
Author(s):  
Chun Ho Szeto ◽  
Walid Shalata ◽  
Alexander Yakobson ◽  
Abed Agbarya

Lung cancer is worldwide the most common malignancy. Standard of care treatments for early-stage non-small-cell lung cancer (NSCLC) include surgery and adjuvant chemotherapy. However, these patients continue to have poor prognosis due to systemic or local relapse. Immunotherapy has been considered as a novel approach to improve survival in patients with early-stage NSCLC. Since immune checkpoint inhibitors have transformed the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. In this review, we summarize reported and ongoing clinical trials of immunotherapy in both neoadjuvant and adjuvant settings. We also highlight unaddressed issues in this field of research, such as the predictive markers, the optimal combination therapy, and the need for adjuvant immunotherapy. More studies are needed to optimize the treatment regimen of immunotherapy in patients with early-stage NSCLC.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A53-A53
Author(s):  
Qianyun Luo ◽  
Edwin Parra ◽  
Marcelo Negrao ◽  
Neal Akhave ◽  
Erin Bayley ◽  
...  

BackgroundWhile the development of immunotherapies has improved the treatment of non-small cell lung cancer (NSCLC), most patients still fail to respond. Immune cell densities have been utilized to predict clinical responses but have largely failed to do so. However, the spatial distribution and interaction of these cells at the tissue level have been less studied. Here, we performed spatial analysis of the cells within the tumor immune microenvironment in order to evaluate their relationship with clinical outcomes in early-stage NSCLC.MethodsMultiplex immunofluorescence was performed on 123 early-stage NSCLC patients from the ICON (Immunogenomic profiling of non-small cell lung cancer) cohort including Cytokeratin (CK), CD3, CD8, CD45RO, FoxP3, CD68, CD20, CD57, Granzyme B (GzmB), PD-1, and PD-L1. Area under the curve (AUC) was calculated using Ripley’s L function, which evaluates the degree of spatial proximity of two cell populations, with a high AUC indicating clustering and low AUC indicating scattering. Findings were integrated with clinical parameters.ResultsAdenocarcinomas demonstrated CD3+PD1+ T cells were closer to CK+ tumor cells (n=60, p=0.035), and B cells were closer to cytotoxic T cells (n=43, p=0.03) than in squamous cell carcinoma. Higher AUC was observed between CD3+PD1+ T cells (n=56, p=0.035), with cytotoxic antigen-experienced T cells (CD45RO+GzmB+) closer to tumor cells (n=35, p=0.017) in stage I and II compared to stage III tumors. Untreated patient tumors exhibited higher proximity between CD20+ B cells and CD57+ NK cells (n=59, p=0.012), CD3+ T cells and PD-L1+ tumor cells (n=56, p=0.027), and CD68+ macrophages and PD-L1+ tumor cells (n=52, p=0.016) than neoadjuvant chemotherapy-treated patients. Patients with no recurrence presented higher AUC in antigen-experienced CD45RO+GzmB+ T cells and tumor cells (n=36, p=0.006), while those with improved survival demonstrated greater proximity between CD68+ macrophages and PD-L1+ tumors (n=52, p=0.016), CD20+ B cells and GzmB+ cells (n=49, p=0.03), and antigen-experienced CD45RO+GzmB+ T cells and tumor cells (n=36, p=0.047). Lastly, patients with improved survival also displayed greater proximity between CD3+CD8+ cytotoxic T cells and PD-L1- epithelial cells (n=76, p=0.04) in tumors versus matched adjacent lungs.ConclusionsOverall, our findings shed light on some of the potential cell interactions at play in the tumor microenvironment of early-stage NSCLC patients and suggest cell distributions could be utilized to predict clinical outcomes in early-stage NSCLC patients.


Author(s):  
Gudrun Absenger ◽  
Andreas Pircher

SummaryThis article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.


2021 ◽  
Vol 22 (5) ◽  
pp. 424-425
Author(s):  
Yasemin Benderli Cihan ◽  

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