Safety, efficacy and survival of patients with primary malignant brain tumours (PMBT) in phase I (Ph1) trials: the 12-year Royal Marsden experience.

BACKGROUND:Primary malignant brain tumours (PMBT) constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment options at relapse are limited. First-in-human solid tumour studies have historically excluded patients with PMBT due to the poor prognosis, concomitant drug interactions and concerns regarding toxicities. METHODS:Retrospective data were collected on clinical and tumour characteristics of patients referred for consideration of Ph1 trials in the Royal Marsden Hospital between June 2004 and August 2016. Survival analyses were performed using the Kaplan-Meier method, Cox proportional hazards model. Chi squared test was used to measure bivariate associations between categorical variables. RESULTS:100pts with advanced PMBT were referred. At initial consultation, patients had a median ECOG PS 1, median age 48 years (range 18-70); 69% were men, 76% had glioblastoma; 68% were on AEDs, 63% required steroid therapy; median number of prior treatments was two. Median OS for patients treated on a Ph1 trials was 9.3 months (95% CI 5.9-12.9) versus 5.3 months (95% CI 4.1-6.1) for patients that did not proceed with a Ph1 trial, p = 0.0094. Steroid use, poor PS, neutrophil-to-lymphocyte ratio and treatment on a Ph1 trial were shown to independently influence OS. CONCLUSIONS:We report a survival benefit for patients with PMBT treated on Ph1 trials. Toxicity and efficacy outcomes were comparable to the general Ph1 population. In the absence of an internationally recognized standard second line treatment for patients with recurrent PMBT, more Ph1 trials should allow enrolment of patients with refractory PMBT and Ph1 trial participation should be considered at an earlier stage

Association between fertility and HIV status: what implications for HIV estimates?

Background: Most estimates of HIV prevalence have been based on sentinel surveillance of pregnant women which may either under-estimate or over-estimate the actual prevalence in adult female population. One situation which can lead to either an underestimate or an overestimate of the actual HIV prevalence is where there is a significant difference in fertility rates between HIV-positive and HIV-negative women. Our aim was to compare the fertility rates of HIV-infected and HIV-uninfected women in Cameroon in order to make recommendations on the appropriate adjustments when using antenatal sentinel data to estimate HIV prevalence Methods: Cross-sectional, population-based study using data from 4493 sexually active women aged 15 to 49 years who participated in the 2004 Cameroon Demographic and Health Survey. Results: In the rural area, the age-specific fertility rates in both HIV positive and HIV negative women increased from 15-19 years age bracket to a maximum at 20-24 years and then decreased monotonically till 35-49 years. Similar trends were observed in the urban area. The overall fertility rate for HIV positive women was 118.7 births per 1000 woman-years (95% Confidence Interval [CI] 98.4 to 142.0) compared to 171.3 births per 1000 woman-years (95% CI 164.5 to 178.2) for HIV negative women. The ratio of the fertility rate in HIV positive women to the fertility rate of HIV negative women (called the relative inclusion ratio) was 0.69 (95% CI 0.62 to 0.75). Conclusion: Fertility rates are lower in HIV-positive than HIV-negative women in Cameroon. The findings of this study support the use of summary RIR for the adjustment of HIV prevalence (among adult female population) obtained from sentinel surveillance in antenatal clinics

Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit.

Background We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time. We have now reviewed the clinical outcomes of patients with relapsed malignant mesothelioma (MM) and propose a specific mesothelioma prognostic score (m-RPS) that can help identify patients who are most likely to benefit from early referral.Methods Patients who participated in 38 phase I trials between September 2003 and November 2015 were included in the analysis. Efficacy was assessed by response rate, median overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate analyses (MVA) were carried out to develop the m-RPS.Results A total of 65 patients with advanced MM were included in this retrospective study. The PFS was 2.5 months (95% confidence interval [CI] 2.0-3.1 months) and OS was 8 months (95% CI 5.6-9.8 months). A total of four (6%) patients had RECIST partial responses, whereas 26 (40%) patients had RECIST stable disease >3 months. The m-RPS was developed comprising of three different prognostic factors: a neutrophil: lymphocyte ratio greater than 3, the presence of more than two disease sites (including lymph nodes as a single site of disease) and albumin levels less than 35 from the MVA. Patients each received a score of 1 for the presence of each factor. Patients in group A (m-RPS 0-1; n = 35) had a median OS of 13.4 months (95% CI 8.5-21.6), whereas those in group B (m-RPS 2-3; n = 30) had a median OS of 4.0 months (95% CI 2.9-7.1, P < 0.0001). A total of 56 (86%) patients experienced G1-2 toxicities, whereas reversible G3-4 toxicities were observed in 18 (28%) patients. Only 10 (15%) patients discontinued phase I trials due to toxicity.Conclusions Phase I clinical trial therapies were well tolerated with early signals of antitumour activity in advanced MM patients. The m-RPS is a useful tool to assess MM patient suitability for phase I trials and should now be prospectively validated

The National Liver Transplantation audit: an overview of patients presenting for liver transplantation from 1994 to 1998. On behalf of the Steering Group of the UK Liver Transplantation Audit.

BACKGROUND: The aim of this study was to describe current clinical practice in liver transplantation in the UK and Ireland, to provide overall 1-year graft and patient survival rates, and to study some preoperative risk factors. METHODS: All patients receiving a liver transplant in the UK or Ireland between 1 March 1994 and 30 September 1998 were included. Data were collected on patients at the time of transplantation, 3 months after grafting and annually thereafter until the patient's death. The main outcome measures were graft and patient survival at 1 year. RESULTS: A total of 3102 liver transplants were carried out, of which 87 per cent were first transplants. The mean age at first transplantation was 42 (range 0-76) years. The most common indications for transplantation were primary biliary cirrhosis, alcoholic cirrhosis and posthepatitis C cirrhosis, but variations existed between sexes and centres. Risk factors associated with lower graft and patient survival were the presence of acute disease, being transplanted from hospital, and the need for renal and/or ventilatory support before operation. CONCLUSION: Donor and recipient demographics are consistent with data held by the European Liver Transplant Registry, as are 1-year graft and patient survival rates. Variation across centres in factors such as the primary indication for liver transplantation, population demographics, the clinical status of each patient, incidence of retransplantation and other risk factors contributes to the problem of adjusting for case mix

Can efficiency of follow-up for superficial bladder cancer be increased?

This study evaluated the efficiency with which follow-up cystoscopy was employed in a population-based cohort of patients with superficial bladder cancer. Subjects were 240 men, aged under 75 years, with superficial bladder cancer first diagnosed in 1982. The median duration of follow-up was 6.1 years. The median (interquartile range) number of follow-up cystoscopies was 8 (5-12) per patient with a patient-specific annual rate of 1.7 (1.2-2.2) per year. The median number of cystoscopies at which recurrent tumour was detected was 2 (0-5) per patient, patient-specific annual rate 0.4 (0.0-1.3) per year of follow-up. Among patients with a single tumour at diagnosis and a negative first check cystoscopy (MRC group 1), the proportion of positive cystoscopies was 0.1 (0.0-0.4). Comparison of observed intervals between cystoscopies with optimal intervals calculated using an optimisation model showed that patients in MRC group 1 were seen sooner in practice than the model predicted, while in practice other patients were seen later than the model predicted. These data support the suggestion that efficiency of follow-up for patients with superficial bladder cancer could be increased by dividing patients into groups with different risks of recurrence and differing follow-up requirements