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Background: Although early diagnosis and surgical resection of the tumor have been shown to be the most important predictors of lung cancer survival, long‐term survival for surgically‐resected early‐stage lung cancer remains poor. Aims: In this prospective study we aimed to investigate the survival and prognostic factors of surgically‐resected early‐stage non‐small cell lung cancer (NSCLC) in Central and Eastern Europe. Methods: We recruited 2052 patients with stage I‐IIIA NSCLC from 9 centers in Russia, Poland, Serbia, Czech Republic, and Romania, between 2007–2016 and followed them annually through 2020. Results: During follow‐up, there were 1121 deaths (including 730 cancer‐specific deaths). Median survival time was 4.9 years, and the 5‐year overall survival was 49.5%. In the multivariable model, mortality was increased among older individuals (HR for each 10‐year increase: 1.31 [95% CI: 1.21–1.42]), males (HR:1.24 [1.04–1.49]), participants with significant weight loss (HR:1.25 [1.03–1.52]), current smokers (HR:1.30 [1.04–1.62]), alcohol drinkers (HR:1.22 [1.03–1.44]), and those with higher stage tumors (HR stage IIIA vs. I: 5.54 [4.10 – 7.48]). However, education, chronic obstructive pulmonary diseases (COPD), and tumor histology were not associated with risk of death. All baseline indicators of smoking and alcohol drinking showed a dose‐dependent association with the risk of cancer‐specific mortality. This included pack‐years of cigarettes smoked (p‐trend = 0.04), quantity of smoking (p‐trend = 0.008), years of smoking (p‐trend = 0.010), gram‐days of alcohol drank (p‐trend = 0.002), frequency of drinking (p‐trend = 0.006), and years of drinking (p‐trend = 0.016). Conclusion: This study shows that the 5‐year survival rate of surgically‐resected stage I‐IIIA NSCLC is still around 50% in Central and Eastern Europe. In addition to non‐modifiable prognostic factors, lifetime patterns of smoking and alcohol drinking affected the risk of death and disease progression in a dose‐dependent manner in this population. [ABSTRACT FROM AUTHOR]

Background Because immune responses within the tumor microenvironment are important predictors of tumor biology, correlations of types of tumor infiltrating lymphocytes (TILs) with clinical outcomes were determined in 278 patients with head and neck squamous cell carcinoma (HNSCC). Methods Infiltrating levels of CD4 (helper T cells), CD8 (cytotoxic/suppressor T cells), FoxP3 (regulatory T cells), CD68 (myeloid-derived suppressor cells,) and CD1a (Langerhans) cells were measured in tissue microarrays (TMAs). Cox models tested associations with patient outcomes after adjusting for all known prognostic factors. Median follow-up was 36.6 months. Results Higher CD4 and CD8 TIL levels were associated with improved overall survival (OS; hazard ratio [HR] = 0.77; 95% confidence interval [CI] = 0.65-0.93; p = .005 and HR = 0.77; 95% CI = 0.64-0.94; p = .008, respectively), and relapse-free survival (RFS; p = .03 and .05, respectively). After controlling for prognostic factors, higher CD4 levels predicted improved OS and disease-specific survival (DSS; p = .003 and p = .004, respectively). Conclusion The findings suggest that TILs are a significant independent prognostic factor for HNSCC that differ by treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1074-1084, 2016 [ABSTRACT FROM AUTHOR]

Background: HPV-associated HNSCCs have a distinct etiologic mechanism and better prognosis than those with non-HPV associated HNSCCs. However, even within the each group, there is heterogeneity in survival time. Here, we test the hypothesis that specific candidate gene methylation markers (CCNA1, NDN, CD1A, DCC, p16, GADD45A) are associated with tumor recurrence and survival, in a well-characterized, prospective, cohort of 346 HNSCC patients.Methods: Kaplan-Meier curves were used to estimate survival time distributions. Multivariable Cox Proportional Hazards models were used to test associations between each methylation marker and OST/RPFT after adjusting for known or identified prognostic factors. Stratified Cox models included an interaction term between HPV and methylation marker to test for differences in the associations of the biomarker with OST or RPFT across HPV status.Results: Methylation markers were differentially associated with patient characteristics. DNA hypermethylation of NDN and CD1A was found to be significantly associated with overall survival time (OST) in all HNSCC patients (NDN hazard ratio (HR): 2.35, 95% CI: 1.40-3.94; CD1A HR: 1.31, 95% CI: 1.01-1.71). Stratification by HPV status revealed hypermethylation of CD1A was associated with better OST and recurrence/persistence-free time (RPFT) (OST HR: 3.34, 95% CI: 1.88-5.93; RPFT HR: 2.06, 95% CI: 1.21-3.49), while hypomethylation of CCNA1 was associated with increased RPFT in HPV (+) patients only (HR: 0.31, 95% CI: 0.13-0.74).Conclusions: This study is the first to describe novel epigenetic alterations associated with survival in an unselected, prospectively collected, consecutive cohort of patients with HNSCC. DNA hypermethylation of NDN and CD1A was found to be significantly associated with increased overall survival time in all HNSCC patients. However, stratification by the important prognostic factor of HPV status revealed the immune marker, CD1A, and the cell cycle regulator, CCNA1 to be associated with prognosis in HPV (+) patients, specifically. Here, we identified novel methylation markers and specific, epigenetic molecular differences associated with HPV status, which warrant further investigation. [ABSTRACT FROM AUTHOR]