Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events. (Funded by Cancer Research U.K.; BC2001 Current Controlled Trials number, ISRCTN68324339.).

Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.

SummaryBackgroundAlthough survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens.MethodsThis open-label randomised trial was undertaken in 22 centres in the UK and Ireland and nine in Australia and New Zealand. Patients aged 1–18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk, intermediate-risk, and standard-risk groups on the basis of duration of first complete remission, site of relapse, and immunophenotype. All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed randomisation. Neither patients nor those giving interventions were masked. After three blocks of therapy, all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease (≥10−4 cells) received an allogenic stem-cell transplant. Standard-risk and intermediate-risk patients with postinduction low minimal residual disease (<10−4 cells) continued chemotherapy. The primary outcome was progression-free survival and the method of analysis was intention-to-treat. Randomisation was stopped in December, 2007 because of differences in progression-free and overall survival between the two groups. This trial is registered, reference number ISCRTN45724312.FindingsOf 239 registered patients, 216 were randomly assigned to either idarubicin (109 analysed) or mitoxantrone (103 analysed). Estimated 3-year progression-free survival was 35·9% (95% CI 25·9–45·9) in the idarubicin group versus 64·6% (54·2–73·2) in the mitoxantrone group (p=0·0004), and 3-year overall survival was 45·2% (34·5–55·3) versus 69·0% (58·5–77·3; p=0·004). Differences in progression-free survival between groups were mainly related to a decrease in disease events (progression, second relapse, disease-related deaths; HR 0·56, 0·34–0·92, p=0·007) rather than an increase in adverse treatment effects (treatment death, second malignancy; HR 0·52, 0·24–1·11, p=0·11).InterpretationAs compared with idarubicin, mitoxantrone conferred a significant benefit in progression-free and overall survival in children with relapsed acute lymphobastic leukaemia, a potentially useful clinical finding that warrants further investigation.FundingCancer Research UK, Leukaemia and Lymphoma Research, Cancer Council NSW, and Sporting Chance Cancer Foundation.

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BackgroundDevelopment of prognostic models enables identification of variables that are influential in predicting patient outcome and the use of these multiple risk factors in a systematic, reproducible way according to evidence based methods. The reliability of models depends on informed use of statistical methods, in combination with prior knowledge of disease. We reviewed published articles to assess reporting and methods used to develop new prognostic models in cancer.MethodsWe developed a systematic search string and identified articles from PubMed. Forty-seven articles were included that satisfied the following inclusion criteria: published in 2005; aiming to predict patient outcome; presenting new prognostic models in cancer with outcome time to an event and including a combination of at least two separate variables; and analysing data using multivariable analysis suitable for time to event data.ResultsIn 47 studies, prospective cohort or randomised controlled trial data were used for model development in only 33% (15) of studies. In 30% (14) of the studies insufficient data were available, having fewer than 10 events per variable (EPV) used in model development. EPV could not be calculated in a further 40% (19) of the studies. The coding of candidate variables was only reported in 68% (32) of the studies. Although use of continuous variables was reported in all studies, only one article reported using recommended methods of retaining all these variables as continuous without categorisation. Statistical methods for selection of variables in the multivariate modelling were often flawed. A method that is not recommended, namely, using statistical significance in univariate analysis as a pre-screening test to select variables for inclusion in the multivariate model, was applied in 48% (21) of the studies.ConclusionsWe found that published prognostic models are often characterised by both use of inappropriate methods for development of multivariable models and poor reporting. In addition, models are limited by the lack of studies based on prospective data of sufficient sample size to avoid overfitting. The use of poor methods compromises the reliability of prognostic models developed to provide objective probability estimates to complement clinical intuition of the physician and guidelines.

A substantial number of cancer outpatients report thoughts that they would be better off dead or thoughts of hurting themselves. Management of emotional distress and pain should be a central aspect of cancer care.

BackgroundAppropriate choice and use of prognostic models in clinical practice require the use of good methods for both model development, and for developing prognostic indices and risk groups from the models. In order to assess reliability and generalizability for use, models need to have been validated and measures of model performance reported. We reviewed published articles to assess the methods and reporting used to develop and evaluate performance of prognostic indices and risk groups from prognostic models.MethodsWe developed a systematic search string and identified articles from PubMed. Forty-seven articles were included that satisfied the following inclusion criteria: published in 2005; aiming to predict patient outcome; presenting new prognostic models in cancer with outcome time to an event and including a combination of at least two separate variables; and analysing data using multivariable analysis suitable for time to event data.ResultsIn 47 studies, Cox models were used in 94% (44), but the coefficients or hazard ratios for the variables in the final model were reported in only 72% (34). The reproducibility of the derived model was assessed in only 11% (5) of the articles. A prognostic index was developed from the model in 81% (38) of the articles, but researchers derived the prognostic index from the final prognostic model in only 34% (13) of the studies; different coefficients or variables from those in the final model were used in 50% (19) of models and the methods used were unclear in 16% (6) of the articles. Methods used to derive prognostic groups were also poor, with researchers not reporting the methods used in 39% (14 of 36) of the studies and data derived methods likely to bias estimates of differences between risk groups being used in 28% (10) of the studies. Validation of their models was reported in only 34% (16) of the studies. In 15 studies validation used data from the same population and in five studies from a different population. Including reports of validation with external data from publications up to four years following model development, external validation was attempted for only 21% (10) of models. Insufficient information was provided on the performance of models in terms of discrimination and calibration.ConclusionsMany published prognostic models have been developed using poor methods and many with poor reporting, both of which compromise the reliability and clinical relevance of models, prognostic indices and risk groups derived from them.

BackgroundWell-developed and well-tested patient-reported outcome measures for non–muscle-invasive bladder cancer (NMIBC) are required.ObjectiveTo test and adapt the scale structure and explore the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire for NMIBC.Design, setting, and participantsA total of 433 patients in the Bladder COX-2 Inhibition Trial (BOXIT) completed the EORTC QLQ-C30 and NMIBC questionnaires. BOXIT is evaluating the addition of celecoxib to standard treatment in high- and intermediate-risk NMIBC.Outcome measurements and statistical analysisMultitrait scaling investigated and adapted the questionnaire scale structure and evaluated the reliability and validity of the revised scales, as well as responsiveness to change.Results and limitationsA total of 410 patients (94.7%) (79.3% men, 74.6% high risk) returned baseline forms, and the questionnaire response rate was 88.2%. Multitrait scaling confirmed six scales and five single items. Scales and items demonstrated significant differences between patients with good and poor performance status scores (p < 0.001). Men reported better sexual function than women (p < 0.001). Scale and single-item module scores were not highly correlated with QLQ-C30 scores (evidence of discriminant validity), and the module was responsive to changes in health over time. International and test–retest data are required.ConclusionsThis study demonstrates the evidence-driven adapted scale structure and psychometric data of the EORTC QLQ-NMIBC24 module to use in clinical trials of patients with high- or intermediate-risk bladder cancer.