Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

BACKGROUND: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score. METHODS: Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort. RESULTS: In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information. CONCLUSIONS: The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.

A telephone reminder intervention to improve breast screening information and access.

OBJECTIVES: In the UK, women aged 50-70 are offered breast cancer screening every three years. Screening participation rates in London have been particularly low. Low rates have been associated with low socio-economic status, and some ethnic groups have been observed to be underserved by cancer screening. This paper reports on a telephone reminder intervention in London Newham, an area of high deprivation and ethnic diversity. STUDY DESIGN: Observational study of planned intervention. METHODS: Women invited for breast screening were telephoned to confirm receipt of the invitation letter, remind invitees of their upcoming appointment, and to provide further information. Aggregate data at general practice level on invitation to and attendance at breast screening and on numbers reached by telephone were analysed by logistic regression. RESULTS: For the 29 participating GP practices (10,928 invitees) overall uptake in 2010 was higher compared to the previous screening round in 2007 (67% vs. 51%; p < 0.001). On average 59% of invitees were reached by the reminder calls. A 10% increase in women reached resulted in an 8% increase in the odds of women attending their screening appointment (95% CI: 5%-11%), after adjusting for 2007 attendance rates. Practices with a higher proportion of South Asian women were associated with a larger uptake adjusted for 2007 uptake and population reached by the telephone intervention, (4% increase in odds of attendance per 10% increase in South Asian population, CI 1%-7%, p = 0.003) while practices with a higher proportion of black women were associated with a smaller uptake similarly adjusted. (11% decrease in odds of attendance per 10% increase in black population, CI 9%-16%, p < 0.001). CONCLUSIONS: A language- and culture-sensitive programme of reminder calls substantially improved breast cancer screening uptake.

A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI).

BACKGROUND: There is increasing evidence that the presence of an ongoing systemic inflammatory response is a stage-independent predictor of poor outcome in patients with cancer. The aim of this study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), is associated with overall survival (OS) in patients with hepatocellular carcinoma (HCC). METHODS: All patients with a new diagnosis of HCC presenting to the Medical Oncology Department, Hammersmith Hospital between 1993 and 2011 (n=112) were included. Demographic and clinical data were collected. Patients in whom the combined albumin (g l(-1)) × total lymphocyte count × 10(9) l(-1) was ≥45, at presentation, were allocated a PNI score of 0. Patients in whom this total score was <45 were allocated a score of 1. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with OS. Independent predictors of survival identified on multivariate analysis were validated in an independent, stage-matched cohort of 68 patients. RESULTS: Univariate analyses showed that PNI (P=0.003), intrahepatic spread (P<0.001), the presence of extrahepatic disease (P=0.006), portal vein thrombosis (P=0.02), tumour multifocality (P=0.003), alfa-fetoprotein >400 ng ml(-1) (P<0.001) and Barcelona Clinic Liver Cancer score (P<0.01) were all predictors of OS in the training set. Multivariate analysis revealed the PNI (P=0.05), presence of extrahepatic disease (P<0.001) and degree of intrahepatic spread (P<0.001) as independent predictors of worse OS in this population. The PNI retained independent prognostic value in the validation set (P<0.001). CONCLUSION: The presence of a systemic inflammatory response, as measured by the PNI, is an independent and externally validated predictor of poor OS in patients with HCC.

Simple indices of inflammation as predictors of death from cancer or cardiovascular disease in a prospective cohort after two decades of follow-up.

BACKGROUND: Previous studies have identified sub-clinical inflammation as a potential factor in the pathogenesis of cancer and cardiovascular disease (CVD) but the possibility that simple, readily measured indices of sub-clinical inflammation might predict both CVD and cancer has not been tested in the context of a single, prospective analysis. AIM: To evaluate simply measured indices of inflammation as long-term predictors of death from either cancer or CVD. DESIGN: Prospective open cohort study. METHODS: A total of 1192 white males received measurements of a range of risk markers including the inflammation indices white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and serum globulin concentrations. Inflammation marker clustering was quantified as a factor-analysis-derived inflammation score and survival time to death from any cancer or CVD was modeled on baseline measures using the Cox proportional hazards model. RESULTS: A total of 1010 participants met inclusion criteria, of whom 94 died of cancer and 67 of CVD. Mean follow-up times among cases and survivors ranged from 18.2-21.9 years. Independently of established risk factors [age, body mass index (BMI), smoking, alcohol and exercise], WBC, ESR and globulin levels were all individually predictive of both cancer (hazard ratio 1.43, P = 0.002; 1.27, P = 0.02; 1.26, P = 0.02, respectively) and CVD mortality (1.29, P = 0.06; 1.43, P = 0.007; 1.50, P = 0.001). The inflammation score predicted both cancer mortality (1.35, P = 0.003) and CVD mortality (1.46, P = 0.002). Risks associated with high inflammation score were equivalent to and independent of smoking cigarettes for cancer or, for CVD, having a serum cholesterol concentration ≥6.2 mmol/l. CONCLUSIONS: Simple indices of inflammation predict death from cancer or CVD two decades later as strongly as smoking predicts cancer or cholesterol predicts CVD. Their measurement could contribute to evaluation of both cancer and CVD risk.

Genetic susceptibility to fibrocalculous pancreatic diabetes in Bangladeshi subjects: a family study.

Fibrocalculous pancreatic diabetes (FCPD) is an uncommon cause of diabetes, seen mainly in developing countries. A family-based study was carried out in 67 Bangladeshi families, consisting of a proband with FCPD and both parents, to determine whether an association exists between FCPD susceptibility and either the major histocompatiblity complex (MHC) or insulin gene (INS) loci. HLA-DQB1 typing was done using allele-specific primers, and INS was typed using the restriction enzyme HphI. Three microsatellites (TNFa, TNFc and TNFd), from within and flanking the TNF-LT locus, were used for MHC Class IV typing and a PCR-RFLP assay was used to define the -308G/A TNF promoter polymorphism. The extended transmission disequilibrium test (ETDT) was used for statistical analysis. An overall association was observed between FCPD and HLA-DQB1 (P = 0.003), that was largely due to a positive association with HLA-DQB1*0302 and a negative association with HLA-DQB1*0202. Although no association was found between FCPD and TNF-LT microsatellite markers a trend was observed for TNFc (P = 0.037, Pc = 0.15). No association was found between FCPD and INS (P = 0.26). This study confirms an association between FCPD and the MHC using a family-based study design and the stringent ETDT analysis; a novel protective association was found with HLA-DQB1*0202 in Bangladeshi FCPD subjects. The genetic susceptibility to FCPD has features both similar and dissimilar to T1DM.