Abstract Background Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host ...inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. Patients and methods Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. Results Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽2. A NLR ⩾3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06–1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02–1.56, P = 0.035) and hilar cancer: overall group ( N = 149) (HR-1.70, 95% CI; 1.10–2.50, P = 0.01) and advanced group ( N = 111) (HR-1.57, 95% CI; 1.04–2.44, P = 0.048). Conclusion Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials.
Abiraterone acetate (abiraterone) prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study's objective was to retrospectively identify ...factors associated with prostate-specific antigen (PSA) response to abiraterone and validate them in an independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR), thought to be an indirect manifestation of tumor-promoting inflammation, may be associated with response to abiraterone.
All patients receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March 2013 were reviewed. The primary end point was confirmed PSA response defined as PSA decline ≥50% below baseline maintained for ≥3 weeks. Potential factors associated with PSA response were analyzed using univariate and multivariable analyses to generate a score, which was then evaluated in an independent cohort from Royal Marsden (RM) NHS foundation.
A confirmed PSA response was observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%–50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate dehydrogenase, an NLR ≤ 5 and restricted metastatic spread to either bone or lymph nodes were each associated with PSA response. In multivariable analysis, only low NLR and restricted metastatic spread remained statistically significant. A score derived as the sum of these two categorical variables was associated with response to abiraterone (P = 0.007). Logistic regression analysis on an independent validation cohort of 245 patients verified that this score was associated with response to abiraterone (P = 0.003). It was also associated with OS in an exploratory analysis.
A composite score of baseline NLR and extent of metastatic spread is associated with PSA response to abiraterone and OS. Our data may help understand the role of systemic inflammation in mCRPC and warrant further research.
The androgen receptor (AR) is expressed frequently in breast cancer, but its prognostic significance is unclear. Preclinical data suggest that expression of AR may modify clinical outcomes in early ...breast cancer with improved prognosis in estrogen receptor (ER)-positive disease and poorer prognosis in ER-negative disease.
A systematic review of electronic databases was conducted to identify studies published between 1946 and July 2012 and to explore the association between AR expression and overall survival (OS) and disease-free survival (DFS) in women diagnosed with early breast cancer. The odds ratios (OR) for OS and DFS at 3 and 5 years were calculated and then weighted and pooled in a meta-analysis with Mantel-Haenszel random-effect modeling. All statistical tests were two-sided.
Nineteen studies with a total of 7693 women were included. AR expression was documented in 60.5% of patients. ER-positive tumors were more likely to express AR- than ER-negative tumors (74.8% vs 31.8%, χ(2) P < .001). Compared with tumors without AR expression, those expressing AR were associated with improved OS at both 3 and 5 years (OR = 0.47, 95% confidence interval CI = 0.39 to 0.58, P < .001; and OR = 0.40, 95% CI = 0.29 to 0.56, P < .001). The absolute differences in the probability of OS at 3 and 5 years were 6.7% (95% CI = 3.5% to 9.8%) and 13.5% (95% CI = 7.5% to 19.6%), respectively. Results for 3- and 5-year DFS were similar. Coexpression of the ER did not influence OS at 3 or at 5 years.
Expression of AR in women with breast cancer is associated with better OS and DFS irrespective of coexpression of ER.
Multiple factors can influence outcomes of patients receiving identical interventions in clinical trials and in routine practice. Here, we compare outcomes of men with metastatic castrate-resistant ...prostate cancer (mCRPC) treated with docetaxel and prednisone in routine practice and in clinical trials.
We reviewed patients with mCRPC treated with docetaxel at Princess Margaret Cancer Centre. Primary outcomes were overall survival and PSA response rate. Secondary outcomes were reasons for discontinuation and febrile neutropenia. Outcomes were compared for men treated in routine practice and in clinical trials, and with data from the TAX 327 study.
From 2001 to 2011, 438 men were treated, of whom 357 received 3-weekly docetaxel as first-line chemotherapy: 314 in routine practice and 43 in clinical trials. Trial patients were younger and had better performance status. Median survival was 13.6 months 95% confidence interval (95% CI) 12.1–15.1 months in routine practice and 20.4 months (95% CI 17.4–23.4 months, P = 0.007) within clinical trials, compared with 19.3 months (95% CI 17.6–21.3 months, P < 0.001) in the TAX 327 study. PSA response rates were 45%, 54%, and 53%, respectively (P = NS). Reasons for treatment discontinuation were similar although trial patients received more cycles (median: 6 versus 8 versus 9.5, P < 0.001). Rates of febrile neutropenia were 9.6, 0, and 3% (P < 0.001) while rates of death within 30 days of last dose were 4%, 0%, and 3%, respectively (P = NS).
Survival of patients with mCRPC treated with docetaxel in routine practice is shorter than for men included in trials and is associated with more toxicity.
An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing ...radical cystectomy (RC) is yet to be fully elucidated.
A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR.
The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR.
Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.
We investigated the value of the neutrophil–lymphocyte ratio (NLR) in patients with CRPC treated with chemotherapy in the phase III TROPIC trial. High NLR was associated with worse survival (OS) and ...reduced PSA and radiographic response. Conversion (high to low NLR) was associated with improved OS. NLR can be a useful biomarker to assess prognosis and response to treatment.
The neutrophil–lymphocyte ratio (NLR), proposed as an indicator of cancer-related inflammation, has known prognostic value in prostate cancer. We examine its association with survival (OS) and response in patients treated with second-line chemotherapy.
We analysed patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the TROPIC trial, evaluating cabazitaxel versus mitoxantrone. Cox regression models were used to investigate the association of baseline NLR (BLNLR) with OS and the significance of a change in NLR count with treatment. Logistic regression models were used to determine the association of BLNLR counts with prostate specific antigen (PSA) and RECIST responses. The optimal NLR cut-off was established based on the concordance index of different values.
Data from 755, 654 and 405 patients was available for OS, PSA and RECIST response analysis respectively. Median OS was 14.0 months 95% confidence interval (CI) 13.2–14.8. Median NLR was 2.9 (IQR: 1.9–5.1). BLNLR was associated with survival (HR 1.5, 95% CI 1.1–2.1,P = 0.011) in multivariable analysis (MVA) independently of variables included in the Halabi nomogram, treatment arm and corticosteroid use. The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival. BLNLR ≥3.0 was associated with lower PSA response (40.1% versus 59.9%;P < 0.001) and RECIST response (7.7% versus 15.6%,P = 0.022) in MVA. Conversion from high (≥3) to low (<3) NLR was associated with improved survival (HR 0.66; 95% CI 0.51–0.85;P = 0.001) and higher PSA response rates (66.4% versus 33.6%;P = 0.000). Use of corticosteroids at baseline did not modify the association between NLR and survival.
NLR is a valid prognostic biomarker in CRPC and is associated with survival, PSA and RECIST responses in patients treated with second-line chemotherapy. Changes in NLR counts with treatment may indicate benefit. NLR prognostic value is independent of prior use of corticosteroids.
NCT00417079.
Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for ...overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide.
Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set.
Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR–NYR), 34.2 months (31.5–NYR), and 21.1 months (17.5–25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14–0.29) and 0.40 (0.30–0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups.
Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design.
ClinicalTrials.gov: NCT01212991.
The derived neutrophil-to-lymphocyte ratio (dNLR) was prognostic for survival in men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy in two randomized phase III ...trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials.
The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy.
Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT.
In the training set, both dNLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11–1.50,P < 0.001 and HR 1.41; 95% CI 1.21–1.64,P < 0.001, respectively after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline. In the validation set, dNLR remained an independent prognostic factor for OS (HR 1.43; 95% CI 1.20–1.70,P < 0.001), whereas duration of initial ADT was not (HR 1.16; 95% CI 0.97–1.37,P = 0.10). In subgroup analyses of the TAX327 study, docetaxel improved OS irrespective of dNLR and duration of initial ADT.
The dNLR was prognostic for OS in men with mCRPC receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials and could be incorporated into prognostic nomograms.
NCT00519285.
Technologies for global health Howitt, Peter, MA; Darzi, Ara, Prof; Yang, Guang-Zhong, Prof ...
The Lancet (British edition),
08/2012, Letnik:
380, Številka:
9840
Journal Article
Recenzirano
Mechanical ventilation and intravenous sedation were initiated. Because of continuing spasms, intrathecal baclofen (1200 µg per day) was started on day 3 with a good clinical response. No ...recommendations about tetanus prophylaxis procedures for wound man agement in patients with blood diseases are available, except for bone-marrow transplantation.
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