scholarly journals PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Deirdre Cronin-Fenton ◽  
Tapashi Dalvi ◽  
Naimisha Movva ◽  
Lars Pedersen ◽  
Hanh Hansen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Nsclc Patients

AbstractProgrammed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001–2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ($$\ge$$ ≥  1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan–Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors—51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8–17.9) and 13.4 (95% CI = 9.5–16.3) in PD-L1+ and PD-L1− tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74–1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63–1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39–0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.

Abstract 4212: PD-L1 expression, EGFR and KRAS mutations in unresectable stage III non-small cell lung cancer (NSCLC) patients

2018 ◽  
Author(s):  
Deirdre Cronin-Fenton ◽  
Tapashi Dalvi ◽  
Elizabeth Hedgeman ◽  
Mette Norgaard ◽  
Lars Pedersen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Unresectable Stage ◽  
Nsclc Patients

Abstract A31: Predictive and prognostic value of KRAS mutations in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy

2012 ◽  
Vol 18 (3 Supplement) ◽  
pp. A31-A31
Author(s):  
Wouter W. Mellema ◽  
Anne-Marie C. Dingemans ◽  
Egbert F. Smit ◽  
Jules Derks ◽  
Daniëlle A.M. Heideman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Nsclc Patients ◽  
Predictive And Prognostic Value

scholarly journals Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2800
Author(s):  
Amir Onn ◽  
Teodor Gottfried ◽  
Amos Stemmer ◽  
Sarit Appel ◽  
Yaacov R. Lawrence ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact

Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.

scholarly journals Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5956
Author(s):  
Noriaki Sunaga ◽  
Yosuke Miura ◽  
Norimitsu Kasahara ◽  
Reiko Sakurai
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Evidence ◽  
Treatment Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Nsclc Patients ◽  
Major Progress

Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of KRAS-mutated NSCLC. In this review, we summarize the current understanding of KRAS mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting KRAS-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance.

scholarly journals Detection of Mitochondrial DNA Copy Number in Plasma Exosomes of Patients with Non-small Cell Lung Cancer

2022 ◽  
Author(s):  
Le Thi Thanh Nhan ◽  
Nguyen Thuy Quynh ◽  
Le Lan Phuong ◽  
Bui Phuong Thao ◽  
Nguyen Thi Tu Linh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Mtdna Copy Number ◽  
Pcr Assay ◽  
Nsclc Patients

For the prevalence of lung cancer and its poor diagnosis, the seeking of the efficient biomarkers for this disease is an urgent requirement, especially from non-invasive samples such as plasma. The mitochondria DNA (mtDNA) copy number change has been evaluated as a potential indicator of cancer risk, however, there have been few studies regarding mtDNA in plasma derived exosomes. In this study, the mtDNA copy number was measured on 29 plasma exosome samples of patients with non-small cell lung cancer (NSCLC) and 29 plasma exosome samples of cancer-free controls by real-time PCR assay, then being statistically analyzed to evaluate the relationship between these figures and several pathological features of NSCLC patients. As the results, the existence of mtDNA in exosomes isolated from plasma was detected through PCR assay using primers covering most of the mtDNA length. The relative mtDNA copy numbers determined in the exosomes of the disease and control groups were 1619.1 ± 2589.0 and 1207.0 ± 1550.0, respectively, whereas these values in two disease stages were 783.6 ± 759.3 (stage I-II) and 2647.0 ± 3584.0 (stage III-IV). Comparing among these groups, the difference was only statistically significant between the disease groups of stage I-II and stage III-IV (p<0.05), the group of stage III-IV and the control group (p<0.05). Indeed, the mtDNA copy number is associated with tumor stage and stage N (p<0.05). On the other aspect, the smoking habit of NSCLC patients could be an underlying reason behind the alteration in mtDNA copy number in the plasma exosomes. In short, our study demonstrates that the mtDNA copy number in exosomes resourced from plasma could be a potential biomarker for the detection and prognosis of NSCLC.

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