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  • Bergqvist, Michael, et al. (författare)
  • Characteristics and Long-Term OS of Non-Small Cell Lung Cancer Patients Receiving EGFR Tyrosine Kinase Inhibitor Treatment
  • 2018
  • Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S419-S419
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are important therapeutic agents in treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. However, long-term follow-up and knowledge of clinical factors and TKI treatment patterns, which may be associated with longer OS, remains unclear. Using nationwide registry data, the aim was to investigate survival, prognostic factors for OS, and first line TKI treatment pattern of stage IIIB/IV NSCLC patients in Sweden.Method: In this cohort study, data on all patients diagnosed with stage IIIB-IV NSCLC during 2010—2015 from the nationwide Cancer Registry of Sweden were linked with data on dispensed EGFR-TKI drugs, comorbidity, and mortality data from Swedish national health registries. OS was defined as the interval from date of diagnosis until date of death. Survival rates were estimated using the Kaplan-Meier method. Assessment of predictive factors for OS was performed in multivariable Cox regression.Result: Of 9,992 stage IIIB/IV NSCLC patients (mean age 70 years, female 49%), 1419 (14%) received first-line TKI treatment. Overall, 59% of TKI treated patients (median age 68 years) were female, 44% had at least one comorbidity, 85% had adenocarcinoma, and 89% were stage IV. Median follow-up time was 15 months and median OS was 16 months; 1- and 3-years survival rates were 62% and 15%, respectively. Predictors of longer OS were younger age at diagnosis, adenocarcinoma, less advanced clinical stage, and less comorbid disease. Furthermore, patients included in the end of the period had a longer OS compared to earlier. TKI treatment switching/re-challenging, as well as prolonged TKI treatment, also predicted longer OS.Conclusion: This is the first nationwide study on NSCLC patients receiving first-line EGFR TKIs in routine clinical practice in Sweden. In addition to the reported prolonged TKI treatment length and TKI switching/re-challenging during the observation period, improvements and extension of EGFR testing targeting the appropriate NSCLC patient population may further have contributed to the observed relatively long overall survival.
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  • Edlund, Karolina, et al. (författare)
  • Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
  • 2019
  • Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 14:4, s. 628-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes.Methods: Cluster of differentiation (CD) 3 (CD3)-, CD8-, CD4-, forkhead box P3 (FOXP3)-, CD20-, CD79A-, and immunoglobulin kappa constant (IGKC)-positive immune cells, and tumor PD-L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan-Meier plots and uni- and multivariate Cox regression.Results: Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD-L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never-smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD-L1–positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients’ smoking history and histologic subtype.Conclusions: Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.
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