Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma.

J Thorac Oncol. 2012 Apr;7(4):716-22

Authors: Machtay M, Paulus R, Moughan J, Komaki R, Bradley JE, Choy H, Albain K, Movsas B, Sause WT, Curran WJ

Abstract
INTRODUCTION: Local-regional control (LRC) rates for non-small cell lung cancer after chemoradiotherapy were studied (using two different definitions of LRC) for the association between LRC and survival.
METHODS: Seven legacy Radiation Therapy Ooncology Group trials of chemoradiotherapy for locally advanced non-small cell lung cancer were analyzed. Two different definitions of LRC were studied: (1) freedom from local progression (FFLP-LRC), the traditional Radiation Therapy Oncology Group methodology, in which a failure is intrathoracic tumor progression by World Health Oorganization criteria; and (2) response-mandatory (strict-LRC), in which any patient not achieving at least partial response was considered to have failure at day 0. Testing for associations between LRC and survival was performed using a Cox multivariate model that included other potential predictive factors.
RESULTS: A total of 1390 patients were analyzed. The LRC rate at 3 years was 38% based on the FFLP-LRC definition and 14% based on the strict-LRC definition. Performance status, concurrent chemotherapy, and radiotherapy dose intensity (biologically equivalent dose) were associated with better LRC (using either definition). With the strict-LRC definition (but not FFLP-LRC), age was also important. There was a powerful association between LRC and overall survival (p, 0.0001) on univariate and multivariate analyses. Age, performance status, chemotherapy sequencing, and biologically equivalent dose were also significantly associated with survival. Histology and gender were also significant if the strict-LRC model was used.
CONCLUSIONS: LRC is associated with survival. The definition of LRC affects the results of these analyses. A consensus definition of LRC, incorporating functional imaging and/or central review, is needed, with the possibility of using LRC as a surrogate end point in future trials.

PMID: 22425920 [PubMed - indexed for MEDLINE]

Recurrence dynamics for non-small-cell lung cancer: effect of surgery on the development of metastases.

J Thorac Oncol. 2012 Apr;7(4):723-30

Authors: Demicheli R, Fornili M, Ambrogi F, Higgins K, Boyd JA, Biganzoli E, Kelsey CR

Abstract
INTRODUCTION: We study event rates over time (event dynamics) in patients undergoing surgery for early-stage non-small-cell lung cancer (NSCLC).
METHODS: Using a database of patients undergoing initial surgery for NSCLC, the event dynamics, based on the hazard rate, were evaluated. Events evaluated included time to any treatment failure, local recurrence, distant metastasis (DM), and development of a second primary lung cancer.
RESULTS: Among 1506 patients, time to any treatment failure dynamics demonstrated an initial surge in the hazard rate 9 months after surgery, followed by two smaller peaks at the end of the second and fourth years, respectively. This pattern was dominated by DM events. Two distinguishable peaks were noted for local recurrence in the first and second years. In contrast, the hazard rate for second primary lung cancer exhibited a more uniform pattern over time. The DM dynamics was analyzed by sex and three peaks emerged for both sexes. The timing of the first peak was similar for both sexes, at 7 to 9 months after surgery. The second peak occurred earlier in men (18-20 months) than women (24-26 months). For both sexes the third peak appeared during the fourth year.
CONCLUSIONS: Recurrence dynamics of resected early-stage NSCLC displays a multipeak pattern, which supports the hypothesis of a metastasis growth model previously described for early-stage breast cancer. The model assumes both cellular and micrometastatic tumor dormancy and a transient phase of acceleration of metastatic growth following surgical excision of the primary tumor.

PMID: 22425921 [PubMed - indexed for MEDLINE]

The impact of vitamin D deficiency on immune T cells in asthmatic children: a case-control study.

J Asthma Allergy. 2012;5:11-9

Authors: Maalmi H, Berraïes A, Tangour E, Ammar J, Abid H, Hamzaoui K, Hamzaoui A

Abstract
BACKGROUND: Vitamin D exerts profound effects on both adaptive and innate immune functions involved in the development and course of autoimmune and inflammatory diseases. As the incidence of vitamin D insufficiency is surprisingly high in the general population, experimental studies have started to investigate whether vitamin D levels (measured as serum 25 hydroxy vitamin D-25[OH]D) are correlated with immune cells and clinical parameters.
PURPOSE: The aim of the present research was to investigate serum vitamin D status in a case-control study in children with asthma and to study associations between vitamin D levels and certain immunological parameters.
MATERIALS AND METHODS: A case control study of thirty-nine children with clinically controlled asthma was enrolled to assess the relationship between serum vitamin D concentrations and disease activity. Vitamin D was assayed with a radioimmunoassay kit. We evaluated the relationship between vitamin D concentrations and forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), and the FEV(1)/FVC ratio. Correlations between inflammatory mediators, Th1, Th2, Th17, and regulatory T cells (Treg) and vitamin D were investigated.
RESULTS: Only 15.38% of our asthmatic children had a sufficient serum 25(OH)D (≥30 ng/mL) whereas 80% of healthy children expressed sufficient levels. Deficient values of vitamin D (<20 ng/mL) were observed in 17 (43.59%) asthmatic patients (14.40 ± 3.30 ng/mL; P = 0.0001). Deficiency was not observed in controls. Th1/Th2 ratio was significantly correlated to 25(OH) D level (r = 0.698; P = 0.0001). A significant negative correlation was observed between serum interleukin-17 and vitamin D levels in young asthmatics (r = -0.617; P = 0.001). A significant correlation was observed between CD25(+)Foxp3(+) Treg cells and vitamin D values in asthmatics (r = 0.368; P = 0.021).
CONCLUSION: Even in a southern Mediterranean country, hypovitaminosis D is frequent in children with asthma. Our findings suggest that vitamin D is an important promoter of T cell regulation in vivo in young asthmatics.

PMID: 22690128 [PubMed - in process]

Nasal polyposis in patients with asthma and allergic rhinitis.

J Laryngol Otol. 2012 Jun 12;:1-4

Authors: Ahmadiafshar A, Farjd HR, Moezzi F, Mousavinasab N

Abstract
Objective:This study aimed to determine the prevalence of nasal polyps in patients with allergic rhinitis and with asthma, and also to assess the impact of this condition on these disorders.Study design:Cross-sectional study.Methods:The presence of nasal polyps was assessed by rhinoscopy and endoscopic examination.Results:Nasal polyps were detected in 60 out of 250 patients (24 per cent) with documented asthma or allergic rhinitis. There was a statistically significant correlation between asthma severity and nasal polyposis prevalence (p = 0.007), but not between allergic rhinitis severity and nasal polyposis prevalence (p = 0.081). The prevalence of nasal polyps increased significantly with increasing patient age and rhinitis or asthma duration.Conclusion:The prevalence of nasal polyps in patients with allergic rhinitis or asthma was higher than previously reported. Given this high prevalence of nasal polyposis, nasal examination and concomitant treatment of this disorder are recommended.

PMID: 22691577 [PubMed - as supplied by publisher]