Persistent Neutrophil to Lymphocyte Ratio >3 during Treatment with Enzalutamide and Clinical Outcome in Patients with Castration-Resistant Prostate Cancer.

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8-90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7-4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5-9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5-14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2-20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07-1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10-1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients.

Association Between Early PSA Increase and Clinical Outcome in Patients Treated with Enzalutamide for Metastatic Castration Resistant Prostate Cancer.

OBJECTIVE: Prostate-specific antigen (PSA) decline by 50 % from the baseline to 12 weeks (PSA50w12) is currently used to predict response to treatment and clinical outcome of patients with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the association between PSA changes at 4 weeks and clinical outcome. PATIENTS AND METHODS: Eligible patients had PSA levels assessed at baseline, and monthly during enzalutamide treatment. Early PSA increase was defined as an increased PSA level at 4 weeks ≥20 % (PSA + 20w4) from baseline. Early PSA decline was defined as a PSA response at 4 weeks ≥30 % (PSA30w4) and ≥50 % (PSA50w4) from baseline. Progression-free survival (PFS), overall survival (OS) and their 95 % confidence intervals (CI) were evaluated by the Kaplan-Meier method and compared with the log-rank test. The impact of early PSA increase and decline on PFS and OS was evaluated by Cox regression analyses. RESULTS: We assessed 193 patients with median age of 73 years (range 43-91 years). The median follow-up was 11.7 months (range 0.5-27.4 months). PSA + 20w4 predicted both PFS and OS [HR 6.50 (95 % CI 2.63-16.07; p < 0.0001) and HR 10.54 (95 % CI 4.02-27.64; p < 0.0001), respectively], whereas PSA30w4 and PSA50w4 predicted only PFS [HR 0.37 (95 % CI 0.21-0.67; p = 0.0009) and HR 0.34 (95 % CI 0.19-0.60; p = 0.0003), respectively]. CONCLUSIONS: An early PSA increase, defined as a PSA level at 4 weeks ≥20 % (PSA + 20w4), could be useful to quickly identify patients unlikely to benefit from enzalutamide. Larger studies are needed to confirm PSA + 20W4 as an early biomarker of primary resistance to enzalutamide.

Do New Zealand children with non-cystic fibrosis bronchiectasis show disease progression?

BACKGROUND: There is minimal literature available on the long-term outcome of pediatric non-cystic fibrosis (CF) bronchiectasis. AIM: To document 5-year outcomes of children with chest computerized tomography (CT) scan diagnosed bronchiectasis from a tertiary New Zealand (NZ) respiratory clinic. METHODS: Review of a clinical database identified 91 children. Demographics, clinical data, lung function, chest X-ray (CXR), sputum, presumed etiology, admission data, and the NZ deprivation index (NZDep) were collected. Univariate and multivariate regression were used to correlate clinical findings with lung function data and CXR scores using the Brasfield Scoring System. RESULTS: Of the 91 children, 53 (59%) were Pacific Island, 22 (24%) Maori, 14 (15%) European, and 2 (2%) Other. The median follow-up period was 6.7 years (range 5.0-15.3 years) and median age at diagnosis was 7.3 years (range 11 months-16 years). Lung function data (n = 64) showed a mean decline of -1.6% predicted/year. In 30 children lung function declined (mean FEV(1) -4.4% predicted/year, range 1-17%), remained stable in 13 and improved in 21 children (mean FEV(1) of +3% predicted/year, range 1-15%). Reduced lung function was associated with male gender, chronic Haemophilus influenzae infection, longevity of disease, and Maori and Pacific Island ethnicity. There was a significant correlation with FEV(1) and CXR score at beginning (n = 47, r = 0.45, P = 0.001) and end (n = 26, r = 0.59, P = 0.002) of the follow-up period. The only variable consistently related to CXR score was chronic Haemophilus influenzae infection occurring in 27 (30%) (r(2) = 0.52, P = <0.0001). Only four children were chronically infected with Pseudomonas species. Six children died. CONCLUSION: In our experience despite management in a tertiary multidisciplinary bronchiectasis clinic, progression of lung disease continues in a group of children and young adults.