Chantal Quinten

Patient Self-Reports of Symptoms and Clinician Ratings as Predictors of Overall Cancer Survival

BACKGROUND The National Cancer Institutes Common Terminology Criteria for Adverse Events (NCI-CTCAE) reporting system is widely used by clinicians to measure patient symptoms in clinical trials. The European Organization for Research and Treatment of Cancers Quality of Life core questionnaire (EORTC QLQ-C30) enables cancer patients to rate their symptoms related to their quality of life. We examined the extent to which patient and clinician symptom scoring and their agreement could contribute to the estimation of overall survival among cancer patients. METHODS We analyzed baseline data regarding six cancer symptoms (pain, fatigue, vomiting, nausea, diarrhea, and constipation) from a total of 2279 cancer patients from 14 closed EORTC randomized controlled trials. In each trial that was selected for retrospective pooled analysis, both clinician and patient symptom scoring were reported simultaneously at study entry. We assessed the extent of agreement between clinician vs patient symptom scoring using the Spearman and kappa correlation statistics. After adjusting for age, sex, performance status, cancer severity, and cancer site, we used Harrell concordance index (C-index) to compare the potential for clinician-reported and/or patient-reported symptom scores to improve the accuracy of Cox models to predict overall survival. All P values are from two-sided tests. RESULTS Patient-reported scores for some symptoms, particularly fatigue, did differ from clinician-reported scores. For each of the six symptoms that we assessed at baseline, both clinician and patient scorings contributed independently and positively to the predictive accuracy of survival prognostication. Cox models of overall survival that considered both patient and clinician scores gained more predictive accuracy than models that considered clinician scores alone for each of four symptoms: fatigue (C-index = .67 with both patient and clinician data vs C-index = .63 with clinician data only; P <.001), vomiting (C-index = .64 vs .62; P = .01), nausea (C-index = .65 vs .62; P < .001), and constipation (C-index = .62 vs .61; P = .01). CONCLUSION Patients provide a subjective measure of symptom severity that complements clinician scoring in predicting overall survival.

A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites.

The objective of this study was to examine the prognostic value of baseline health‐related quality of life (HRQOL) for survival with regard to different cancer sites using 1 standardized and validated patient self‐assessment tool.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients

BACKGROUND We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Health-Related Quality of Life in Non–Small-Cell Lung Cancer: An Update of a Systematic Review on Methodologic Issues in Randomized Controlled Trials

PURPOSE This study is an update of a systematic review of health-related quality-of-life (HRQOL) methodology reporting in non-small-cell lung cancer (NSCLC) randomized controlled trials (RCTs). The objective was to evaluate HRQOL methodology reporting over the last decade and its benefit for clinical decision making. METHODS A MEDLINE systematic literature review was performed. Eligible RCTs implemented patient-reported HRQOL assessments and regular oncology treatments for newly diagnosed adult patients with NSCLC. Included studies were published in English from August 2002 to July 2010. Two independent reviewers evaluated all included RCTs. RESULTS Fifty-three RCTs were assessed. Of the 53 RCTs, 81% reported that there was no significant difference in overall survival (OS). However, 50% of RCTs that were unable to find OS differences reported a significant difference in HRQOL scores. The quality of HRQOL reporting has improved; both reporting of clinically significant differences and statistical testing of HRQOL have improved. A European Organisation for Research and Treatment of Cancer HRQOL questionnaire was used in 57% of the studies. However, reporting of HRQOL hypotheses and rationales for choosing HRQOL instruments were significantly less than before 2002 (P < .05). CONCLUSION The number of NSCLC RCTs incorporating HRQOL assessments has considerably increased. HRQOL continues to demonstrate its importance in RCTs, especially in those studies in which no OS difference is found. Despite the improved quality of HRQOL methodology reporting, certain aspects remain underrepresented. Our findings suggest need for an international standardization of HRQOL reporting similar to the CONSORT guidelines for clinical findings.

Minimal important differences for interpreting health-related quality of life scores from the EORTC QLQ-C30 in lung cancer patients participating in randomized controlled trials

BackgroundThe aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in a subset of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) scales, which could be considered as clinically meaningful in patients with non-small-cell lung cancer (NSCLC).MethodsWHO performance status (PS) and weight change were used as clinical anchors to determine minimal important differences (MIDs) in HRQOL change scores (range, 0–100) in the EORTC QLQ-C30 scales. Selected distribution-based methods were used for comparison.FindingsIn a pooled dataset of 812 NSCLC patients undergoing treatment, the values determined to represent the MID depended on whether patients were improving or deteriorating. MID estimates for improvement (based on a one-category change in PS, 5 − <20% weight gain) were physical functioning (9, 5); role functioning (14, 7); social functioning (5, 7); global health status (9, 4); fatigue (14, 5); and pain (16, 2). The respective MID estimates for deterioration (based on PS, weight loss) were physical (4, 6); role (5, 5); social (7, 9); global health status (4, 4); fatigue (6, 11); and pain (3, 7).InterpretationBased on the selected QLQ-C30 scales, the MID may depend upon whether the patients’ PS is improving or worsening, but our results are not definitive. The MID estimates for the specified scales can help clinicians and researchers evaluate the significance of changes in HRQOL and assess the value of a health care intervention or compare treatments. The estimates also can be useful in determining sample sizes in the design of future clinical trials.

European enhanced surveillance of invasive pneumococcal disease in 2010: Data from 26 European countries in the post-heptavalent conjugate vaccine era

Streptococcus pneumoniae is a leading cause of severe infectious diseases worldwide. This paper presents the results from the first European invasive pneumococcal disease (IPD) enhanced surveillance where additional and valuable data were reported and analysed. Following its authorisation in Europe in 2001 for use in children aged between two months and five years, the heptavalent pneumococcal conjugate vaccine (PCV7) was progressively introduced in the European Union (EU)/European Economic Area (EEA) countries, albeit with different schemes and policies. In mid-2010 European countries started to switch to a higher valency vaccine (PCV10/PCV13), still without a significant impact by the time of this surveillance. Therefore, this surveillance provides an overview of baseline data from the transition period between the introduction of PCV7 and the implementation of PCV10/PCV13. In 2010, 26 EU/EEA countries reported 21 565 cases of IPD to The European Surveillance System (TESSy) applying the EU 2008 case definition. Serotype was determined in 9946/21565 (46.1%) cases. The most common serotypes were 19A, 1, 7F, 3, 14, 22F, 8, 4, 12F and 19F, accounting for 5949/9946 (59.8%) of the serotyped isolates. Data on antimicrobial susceptibility testing (AST) in the form of minimum inhibitory concentrations (MIC) were submitted for penicillin 5384/21565 (25.0%), erythromycin 4031/21565 (18.7%) and cefotaxime 5252/21565 (24.4%). Non-susceptibility to erythromycin was highest at 17.6% followed by penicillin at 8.9%. PCV7 serotype coverage among children <5 years in Europe, was 19.2%; for the same age group, the serotype coverage for PCV10 and PCV13 were 46.1% and 73.1%, respectively. In the era of pneumococcal conjugate vaccines, the monitoring of changing trends in antimicrobial resistance and serotype distribution are essential in assessing the impact of vaccines and antibiotic use control programmes across European countries.

Estimating HIV Incidence, Time to Diagnosis, and the Undiagnosed HIV Epidemic Using Routine Surveillance Data.

Background: Estimates of the size of the undiagnosed HIV-infected population are important to understand the HIV epidemic and to plan interventions, including “test-and-treat” strategies. Methods: We developed a multi-state back-calculation model to estimate HIV incidence, time between infection and diagnosis, and the undiagnosed population by CD4 count strata, using surveillance data on new HIV and AIDS diagnoses. The HIV incidence curve was modelled using cubic splines. The model was tested on simulated data and applied to surveillance data on men who have sex with men in The Netherlands. Results: The number of HIV infections could be estimated accurately using simulated data, with most values within the 95% confidence intervals of model predictions. When applying the model to Dutch surveillance data, 15,400 (95% confidence interval [CI] = 15,000, 16,000) men who have sex with men were estimated to have been infected between 1980 and 2011. HIV incidence showed a bimodal distribution, with peaks around 1985 and 2005 and a decline in recent years. Mean time to diagnosis was 6.1 (95% CI = 5.8, 6.4) years between 1984 and 1995 and decreased to 2.6 (2.3, 3.0) years in 2011. By the end of 2011, 11,500 (11,000, 12,000) men who have sex with men in The Netherlands were estimated to be living with HIV, of whom 1,750 (1,450, 2,200) were still undiagnosed. Of the undiagnosed men who have sex with men, 29% (22, 37) were infected for less than 1 year, and 16% (13, 20) for more than 5 years. Conclusions: This multi-state back-calculation model will be useful to estimate HIV incidence, time to diagnosis, and the undiagnosed HIV epidemic based on routine surveillance data.

Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial

Background:Little is known about whether changes in health-related quality of life (HRQoL) scores from baseline during treatment also predict survival, which we aim to investigate in this study.Methods:We analysed data from 391 advanced non-small-cell lung cancer (NSCLC) patients enrolled in the EORTC 08975 study, which compared palliative chemotherapy regimens. HRQoL was assessed at baseline and after each chemotherapy cycle using the EORTC QLQ-C30 and QLQ-LC13. The prognostic significance of HRQoL scores at baseline and their changes over time was assessed with Cox regression, after adjusting for clinical and socio-demographic variables.Results:After controlling for covariates, every 10-point increase in baseline pain and dysphagia was associated with 11% and 12% increased risk of death with hazard ratios (HRs) of 1.11 and 1.12, respectively. Every 10-point improvement of physical function at baseline (HR=0.93) was associated with 7% lower risk of death. Every 10-point increase in pain (HR=1.08) was associated with 8% increased risk of death at cycle 1. Every 10-point increase in social function (HR=0.91) at cycle 2 was associated with 9% lower risk of death.Conclusions:Our findings suggest that changes in HRQoL scores from baseline during treatment, as measured on subscales of the EORTC QLQ-C30 and QLQ-LC13, are significant prognostic factors for survival.

Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials

Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

Health-related quality of life in locally advanced and metastatic breast cancer: methodological and clinical issues in randomised controlled trials

Breast cancer is the leading cause of cancer death among women worldwide, and increasingly, randomised controlled trials of this disease are measuring the health-related quality of life of these patients. In this systematic Review, we assess the adequacy of methods used to report health-related quality of life (HRQOL) from 49 eligible randomised controlled trials of advanced breast cancer. We compare our findings with those from the literature to investigate whether the standard of HRQOL reporting in this field has changed. We conclude that the overall reporting of HRQOL has improved, but some crucial aspects remain problematic, such as the absence of HRQOL research hypotheses and the overemphasis on statistical rather than clinical significance. Additionally, new challenges are arising with the emergence of novel treatments and the advent of personalised medicine, and improved HRQOL tools are required to cover the range of side-effects of newer therapies.