Prognostic value of CD4+ T lymphopenia in non-small cell lung Cancer.

BACKGROUND: There is a paucity of data regarding the prognostic influence of peripheral blood CD4+ T lymphopenia in non-small cell lung cancer (NSCLC). Therefore, we investigated the prognostic value of T lymphopenia in NSCLC. MATERIALS: Treatment-naive patients with a pathological diagnosis of NSCLC, at clinical stage I to IV were included in the prospective TELOCAP1 study. Lymphocytes count was evaluated in peripheral blood by flow cytometry. CD4+ and CD8+ T lymphopenia were defined as an absolute count of < 500/µL and < 224/µL respectively. The prognostic value of T lymphopenia was analyzed in the whole population, in local/loco-regional (stage I-IIIB) and in advanced (stage IV) NSCLC disease, using the Kaplan-Meier method and Cox regression models for survival curves and multivariate analysis, respectively. RESULTS: Between July 2010 and January 2014, 169 evaluable patients with clinical stage I to IV NSCLC were prospectively enrolled. The prevalence of CD4+ and CD8+ T lymphopenia was similar in the study population (around 29%). Patients with CD4+ T lymphopenia showed lower overall survival than those with CD4+ T lymphocytes count > 500/µL (median overall survival (OS) 16.1 versus 21.7 months, hazard ratio (HR): 1.616 [95% CI: 1.1-2.36], p = 0.012). This association with OS was especially marked in local/loco-regional NSCLC stages (median OS, 21.8 versus 72 months, respectively, HR: 1.88 [95% CI: 0.9-3.8], p = 0.035). Multivariate analysis confirmed the worse prognosis associated with CD4+ T lymphopenia in local/loco-regional NSCLC, but not in metastatic patients (HR 2.028 [95% CI = 1.065-3.817] p = 0.02). Restricted cubic spline analysis showed that patients with CD4+ T lymphocytes count ≤500/µL displayed a high risk of death regardless of NSCLC clinical stage. There was no obvious relationship between CD8+ T lymphopenia and clinical outcome. CONCLUSION: We identified CD4+ T lymphopenia as an independent prognostic factor in local/loco-regional stages of NSCLC and CD4+ T lymphopenia is also associated with a high risk of death, regardless of NSCLC clinical stage. TRIAL REGISTRATION: EUDRACT: 2009-A00642-55.

Let us not underestimate the long-term risk of SPLC after surgical resection of NSCLC.

OBJECTIVES: Several studies have reported that patients operated on for non-small cell lung cancer (NSCLC) are at high risk of second primary lung cancer (SPLC). However, widely varying estimates of this risk have been reported, with very few studies taking into account that these patients are at particularly high competing risk of death, due to recurrence of the initial disease and to comorbidities. Risk factor evaluation over time has significant repercussions on the post-surgery surveillance strategy offered for NSCLC. This study primarily sought to measure the risk of SPLC in a long-term follow-up series, using statistical methods considering competing risks of death. MATERIALS AND METHODS: The cumulative SPLC risk was estimated using the cumulative incidence of patients with completely resected Stage I-III NSCLC diagnosed between 2002 and 2015 based on the Doubs and Belfort cancer registry (France). A proportional sub-distribution hazard model (sdRH) was used to investigate factors associated with SPLC risk in the presence of competing risks. RESULTS: Among the 522 patients, adenocarcinoma and Stage I or II disease accounted for 52.3% and 75.7% of patients, respectively. Overall, 84 patients developed SPLC (16.1%). The cumulative risk of SPLC was 20.2% at 10 years post-surgery (95% confidence interval [CI]: 15.3-23.2), and 25.2% (CI: 19.4-31.3) at 14 years post-surgery. On multivariate analysis, the SPLC risk was significantly higher in patients with postoperative thoracic radiotherapy (sdRH 2.79; 95% CI: 1.41-5.52; p = 0.003). CONCLUSION: This study using appropriate statistical methods to consider competing risks showed that after complete NSCLC resection, the cumulative incidence function of SPLC was high, with patients receiving postoperative thoracic radiotherapy at higher risk. These data support the need for life-long follow-up of patients who undergo NSCLC surgery, with the objective of screening for SPLC.

Rurality and survival differences in lung cancer: a large population-based multivariate analysis.

Several studies have suggested rural health disadvantages. In France, studies on rural-urban patterns of lung cancer survival have yielded conflicting results. The aim of this analysis was to determine whether rural residence was associated with poor survival in three French counties. The database consisted of all primary lung cancer cases diagnosed in 2000 and 2001 collected through the Doubs cancer registry. A degree of rurality, obtained from socio-demographic and farming parameters of the 1999 French census treated with factor analysis, was attributed to each patient according to his/her place of residence. Among the 802 patients, 21% resided in rural areas, 11% were semi-urban inhabitants and 68% were urban residents. Survival differed significantly between these three rurality categories (p=0.04), with 2-year survival rates of 18, 29 and 24%, respectively. Using a Cox model, rural areas were significantly correlated with poor survival as compared with semi-urban areas (OR=1.42; 95% confidence interval=1.06-1.90; p=0.02). There was no survival difference between semi-urban and urban patients (OR=1.18; 95% confidence interval=0.91-1.53; p=0.21). Patient and tumour characteristics, especially stage and staging procedures, as well as first line treatment, did not vary with the degree of rurality. In conclusion, rurality has to be considered as a strong prognostic factor. Several intricate factors might be hypothesized such as increasing time to diagnosis leading to heavier tumour burden, worse treatment compliance and socioeconomic status. Before practical interventions can be proposed, prospective studies are warranted with further definition of rural risk factors for decreased survival in rural lung cancer patients.