• Assessing the effectiveness of cervical screening.

      Wilson, S; Woodman, Ciaran B J; Centre for Cancer Epidemiology, Christie Hospital NHS Trust, Withington, Manchester, United Kingdom. (1995-09)
      The mathematic models used to assess the benefits and cost-effectiveness of cervical screening reveal little consistency in the definition of disease status, the basic assumptions made, or the data used in the model. Conclusions derived from the models often are model and data dependent. Several authors have used simplified models and unrealistic assumptions, such as the failure to differentiate between different grades of dysplasia, or 100% sensitivity for the screening test. The Markov process assumes that the rate of transfer between states is independent of the duration of time spent in one state, and this assumption may be unsound. The difficulty with all models is in interpreting the appropriateness of the parameter values. Some are well documented, for example, stage-specific survival rates for treated patients or attendance for screening. Many, however, cannot be given a fixed value. The large number of factors that appear implicated in the incidence of and mortality from cervical cancer can lead to many feasible sets of parameter values that generate output that approaches the observed data.
    • Health care system, cancer registration and follow-up of cancer patients in the United Kingdom.

      Wilson, S; Bell, J; Black, R; Coleman, M; Cummins, C; Lawrence, G; Page, M; Rider, L; Smith, J; Youngson, J; et al. (1995)
    • A recombinant modified vaccinia Ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer.

      Taylor, G; Jia, H; Harrington, K; Lee, Lip W; Turner, J; Ladell, K; Price, D; Tanday, M; Matthews, J; Roberts, C; et al. (2014-08-14)
      Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses.
    • Reliability of underlying incidence rates for estimating the effect and efficiency of screening for breast cancer.

      Prior, Pat; Woodman, Ciaran B J; Wilson, S; Threlfall, Anthony G; Centre for Cancer Epidemiology, Christie Hospital NHS Trust, Manchester, United Kingdom. (1996)
      The process of setting screening performance targets requires an estimate of what the incidence of breast cancer would have been in the population invited for screening if there had not been a screening programme. Before the introduction of the National Health Service breast screening programme in 1988 the incidence of breast cancer was already increasing in the population targeted for screening. To establish the incidence before screening the most recent complete data from all the regional cancer registries were collated. An age-period model was constructed to predict what these incidence rates might now have been if the screening programme had not been introduced. The model predicted that if prescreening trends continued (between 1987 and 1995) underlying incidence over this period would increase by 2.3 per 10,000 in women aged 50-54, 2.6 per 10,000 in women aged 55-59, and 2.9 per 10,000 in women aged 60-64. If the prescreening trends have continued then the use of a universal rate, applied across all calendar years and age groups, would seem to be inappropriate when setting targets.
    • Toxicity profile of bevacizumab in the UK neurofibromatosis type 2 cohort.

      Morris, K; Golding, J; Blesing, C; Evans, D; Ferner, R; Foweraker, K; Halliday, D; Jena, R; McBain, Catherine A; McCabe, Martin; et al. (2016-10-28)
      Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis type 2 (NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event (CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32 female), median age 24.5 years (range 11-66 years), were followed for a median of 32.7 months (range 12.0-60.2 months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24 %) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5 %) had proteinuria. Of 36 patients followed for 36 months, 78 % were free from hypertension and 86 % were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be independent predictors of development of hypertension with dose of 7.5 mg/kg 3 weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.