Papers by Andrew Bottomley
BMJ open, Jan 10, 2018
As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has inc... more As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated. Data will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for diffe...
Annals of palliative medicine, 2017
The aim of this study was to investigate the extent to which health-related quality of life (HRQO... more The aim of this study was to investigate the extent to which health-related quality of life (HRQOL) parameters have been reported in phase III trials with breast cancer patients (BCPs) who received radiation therapy (RT). We also examine the frequency and correlates of significant HRQOL gains. A systematic review was conducted. When HRQOL was a study endpoint, we extracted data on the instruments used for HRQOL analysis, assessing if there was formal statistical comparison between study groups and the results of such comparisons as reported by the authors of the studies. In result, 182 trials were included. HRQOL was considered as endpoint in 38 (20.8%) of the studies and it was used as primary endpoint in 10.9% of them. Of 22 trials that had a positive primary endpoint, 18 had a significant benefit in HRQOL, in favor of the experimental arm. Of 13 trials that had a negative primary endpoint, there were no differences in HRQOL among the study groups. With respect to HRQOL assessment...
Journal of Clinical Oncology
Journal of Clinical Oncology
Annals of palliative medicine, 2016
The aim of the present study was to conduct a cross-cultural adaptation (with translation into Br... more The aim of the present study was to conduct a cross-cultural adaptation (with translation into Brazilian Portuguese) and validation of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Bone Metastases-22 (EORTC QLQ-BM22). Ninety-five bone metastasis patients (31 men and 64 women, mean age 58.36±8.90 years) took part in the investigation. The translation guide of the EORTC was used to translate from English into Brazilian Portuguese and adapt the instrument culturally. The reliability and the face, content and construct validities were tested. Internal consistency was estimated using Cronbach's alpha for the total score, pain and functional subscales of the EORTC QLQ-BM22 (0.93, 0.86, 0.90). Reliability was analyzed by Pearson's correlation and intraclass correlation coefficients (ICCs). The correlations were higher than the recommended value of 0.75, which indicated good test-retest reliability. Construct validity was demonstrated b...
Lung Cancer, 2005
In our study 76% were male. mean and median age 74 (range 36-90). Mean performance status (P.S) a... more In our study 76% were male. mean and median age 74 (range 36-90). Mean performance status (P.S) at presentation was 1.87. Mean survival from ~agnosls was 231 days. with 20 patients remaining alive. 72% reported definite or possible asbestos fibre exposure, with 11% having no known exposure.
Journal of Clinical Oncology, 2008
Purpose A recent study identified a prognostic model for survival in metastatic colorectal cancer... more Purpose A recent study identified a prognostic model for survival in metastatic colorectal cancer patients which included WBC count, alkaline phosphatase (AP), number of metastatic sites, and patients’ self-reported social functioning. The aim of this research is to validate this model on data from an independent sample. Patients and Methods This validation study is based on a prospective randomized controlled trial in patients with metastatic colorectal cancer conducted by the European Organisation for Research and Treatment of Cancer (EORTC) Chronotherapy Group. Overall, 564 patients in 10 countries were enrolled. For the purpose of this independent validation, patients with health-related quality of life (HRQOL) baseline data were analyzed. HRQOL was assessed using the EORTC Quality of Life Questionnaire C30 (QLQ-C30). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. Results The previous model with an additional adj...
European Journal of Cancer, 2011
arm. The XP/FP arm showed a 5-point average improvement from baseline between Weeks 22−34. Role f... more arm. The XP/FP arm showed a 5-point average improvement from baseline between Weeks 22−34. Role functioning and fatigue scores were similar in both arms until Weeks 34 and 28, respectively, after which H+XP/FP showed sustained improvement over XP/FP. QLQ-STO22: HRQoL improved over time in both arms. Slight improvements from baseline in the dysphagia score were seen, notably after Week 19 until Weeks 31 (XP/FP) and 61 (H+XP/FP). Conclusions: In ToGA, adding H to XP/FP improved OS without compromising HRQoL; this effect was greater in patients with high HER2 expressing tumours in the H+XP/FP arm, where the time to deterioration in QoL was significantly longer. Consistent with these results, improved HRQoL was observed over time in this patient subgroup, with a sustained effect beyond CT administration when adding H to XP/FP.
European Journal of Cancer, 2001
PSA will be achieved at higher dose levels is not known. However, the modest effect on PSA observ... more PSA will be achieved at higher dose levels is not known. However, the modest effect on PSA observed to date suggests some biologic activity. Once MTD is reached, phase II trials of CW87 alone and in combination are planned.
Aims: Over the last decades, Health-related Quality of Life (HRQoL) end-points have become an imp... more Aims: Over the last decades, Health-related Quality of Life (HRQoL) end-points have become an important outcome of the randomised controlled trials (RCTs). HRQoL methodology in RCTs has improved following international consensus recommendations. However, no international recommendations exist concerning the statistical analysis of such data. The aim of our study was to identify and characterise the quality of the statistical methods commonly used for analysing HRQoL data in cancer RCTs. Methods: Building on our recently published systematic review, we analysed a total of 33 published RCTs studying the HRQoL methods reported in RCTs since 1991. We focussed on the ability of the methods to deal with the three major problems commonly encountered when analysing HRQoL data: their multidimensional and longitudinal structure and the commonly high rate of missing data. Results: All studies reported HRQoL being assessed repeatedly over time for a period ranging from 2 to 36 months. Missing data were common, with compliance rates ranging from 45% to 90%. From the 33 studies considered, 12 different statistical methods were identified. Twenty-nine studies analysed each of the questionnaire sub-dimensions without type I error adjustment. Thirteen studies repeated the HRQoL analysis at each assessment time again without type I error adjustment. Only 8 studies used methods suitable for repeated measurements.
Cancer, Jan 29, 2015
Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global... more Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global, double-blind, randomized, phase 3 trial of pazopanib 800 mg versus placebo as second-line or later treatment for patients with advanced soft tissue sarcoma (N = 369). In that trial, progression-free survival was significantly improved in the pazopanib arm (median, 4.6 vs 1.6 months; hazard ratio, 0.31; P < .001), and toxicity of pazopanib consisted mainly of fatigue, diarrhea, nausea, weight loss, and hypertension. HRQoL was assessed using the 30-item core European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol. The primary HRQoL endpoint was the EORTC QLQ-C30 global health status scale. Compliance with HRQoL assessments was good, ranging from 94% at baseline to 81% at week 12. Differences in scores on the EORTC QLQ-C30 global health statu...
Cancer, Jan 29, 2015
Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global... more Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global, double-blind, randomized, phase 3 trial of pazopanib 800 mg versus placebo as second-line or later treatment for patients with advanced soft tissue sarcoma (N = 369). In that trial, progression-free survival was significantly improved in the pazopanib arm (median, 4.6 vs 1.6 months; hazard ratio, 0.31; P < .001), and toxicity of pazopanib consisted mainly of fatigue, diarrhea, nausea, weight loss, and hypertension. HRQoL was assessed using the 30-item core European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol. The primary HRQoL endpoint was the EORTC QLQ-C30 global health status scale. Compliance with HRQoL assessments was good, ranging from 94% at baseline to 81% at week 12. Differences in scores on the EORTC QLQ-C30 global health statu...
Journal of Clinical Oncology, 2006
For malignant pleural mesothelioma (MPM) patients with a poor prognosis, maintaining health-relat... more For malignant pleural mesothelioma (MPM) patients with a poor prognosis, maintaining health-related quality of life (HRQOL) is important. This article compares the impact on HRQOL of first-line treatment with cisplatin versus raltitrexed and cisplatin. Patients with histologically-proven unresectable MPM, not pretreated with chemotherapy were randomly assigned to receive cisplatin 80 mg/m2 intravenously on day 1, with or without preceding infusion of raltitrexed 3 mg/m2. HRQOL was assessed with the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC Lung Cancer Module (QLQ-LC13) tools. Assessments were conducted at baseline, immediately before every treatment cycle, at the end of treatment, and every six weeks for 12 months. Two hundred fifty patients were randomly assigned, 80% were male with a median age of 58 years, WHO performance status 0, 1, and 2, in 25%, 62%, and 13% of cases. The clinical results found raltitrexed and cisplatin to be superior to cisplatin with regard to overall survival (P = .048). The global HRQOL scale was comparable at baseline on both treatment arms (P = .848); at no point was any significant difference apparent on this end point. Both treatments led to an improvement, over time, in dyspnoea. This effect is an important clinically meaningful reduction from baseline in the cisplatin/raltitrexed arm. However, the majority of scales of the EORTC QLQ-C30 or LC13 showed stabilization of HRQOL with few clinically significant differences between the treatment arms. This study provides important information about the HRQOL of chemotherapy-treated MPM patients.
Journal of Clinical Oncology, 2007
Malignant pleural mesothelioma (MPM) is a rare disease. Unlike other advanced cancer types, littl... more Malignant pleural mesothelioma (MPM) is a rare disease. Unlike other advanced cancer types, little is known about patient-reported symptoms or health-related quality of life (HRQOL) and their possible prognostic value. This study reports an evaluation of the prognostic value of these factors using data gathered from a recent randomized controlled trial. Patients were entered onto this trial if they had a histologically proven unresectable MPM, not pretreated with chemotherapy, WHO performance status &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 2, and adequate hematologic, renal, and hepatic function. Patients were randomly assigned to receive cisplatin 80 mg/m2 intravenously on day 1, without or with preceding infusion of raltitrexed 3 mg/m2. HRQOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/Lung Cancer 13 tool. The Cox proportional hazards regression model was used for the univariate and multivariate analyses of survival, along with a bootstrap validation technique. Included were the EORTC prognostic index (PI) composed of stage of disease, histology type, time since diagnosis, and WBC, and, in addition, 10 selected key symptoms and HRQOL scales. Two hundred fifty patients were randomly assigned (80% male; median age, 58 years; WHO performance status 0, 1, 2 in 25%, 62%, and 13% of cases, respectively). Two hundred twenty-nine patients (91.6%) had a valid HRQOL assessment. The final multivariate model retained the PI, pain (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001), and appetite loss (P = .0100) as independent prognostic indicators of survival. Results suggest that the PI, pain, and appetite loss may be independent prognostic factors in patients with advanced MPM.
Uploads
Papers by Andrew Bottomley
This manual explains in detail all the steps that are tobe followed when translating a QOL tool for use in international cancer clinical trials
the high prevalence of fatigue among cancer patients, its adverse effect on their quality of life, and the need to develop effective interventions to prevent or relieve it [1, 2]. This increased attention can be attributed, in part, to the development of instruments for the assessment of fatigue and their validation with cancer patients. These instruments have provided researchers with the tools necessary for quantifying and characterizing fatigue and exploring its etiology and treatment.