Search

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: The recognition of patient-reported outcomes for oral cancer is important in improving patients' quality of life. The aim of this study was to translate and validate the modified Sinhala version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oral Health Module (EORTC QLQ-OH15)., Methods: A cross-sectional study was conducted to validate the EORTC QLQ-OH15 that was modified after adding two questions to the original questionnaire. The two questions added were 'difficulty in opening the mouth wide' and 'trouble with talking' which affect oral health related quality of life (OHRQOL) of oral cancer patients receiving radiotherapy. The Sinhala translated modified EORTC QLQ-OH15 and already validated the core questionnaire EORTC QLQ-C30 were self-completed by 85 adult oral cancer patients who received initial anti-cancer treatment with radiotherapy with or without chemotherapy. Content and face validity were examined by an expert panel. Construct validity was confirmed by using factor analysis, multi-trait scaling analysis, and known group comparison. Reliability was assessed by internal consistency, test-retest reliability by Wilcoxon Signed Ranks Test and intra class correlation coefficient. Responsiveness to change was assessed., Results: The majority of participants (58%) were aged 50-69 years and 84% were males. Nearly 32% had cancer of the anterior two thirds of the tongue. Of the sample, 66% received chemo radiotherapy. Thirteen items were included for the factor analysis. They were loaded for four factors. Three scales 'Eating problem', 'Gum and Speech problem' and 'Soreness' loaded with 5, 4 and 3 items respectively and single item 'teeth' to a one factor with the total variance explained was 72.74%. Mann-Whitney U tests for all three scales were statistically significant confirming the ability of the modified EORTC QLQ-OH15 to detect expected differences in OHRQOL in clinically different groups. Cronbach's alpha for all the scales were more than 0.8. Wilcoxon Matched Paired Sign Rank Test showed highly significant results (p < 0.05) for all three scales revealing high responsiveness., Conclusions: The modified Sinhala version of the EORTC QLQ-OH15 is a valid, reliable tool that can be used to measure OHRQOL in oral cancer patients who receive radiotherapy with or without chemotherapy., (© 2022. The Author(s).)

Context: Patients with advanced cancer commonly suffer from both distressing symptoms and cognitive impairment, but the effect of cognitive impairment on the reliability and validity of symptom self-report is unknown., Objectives: To evaluate the reliability and validity of symptom self-report in cancer outpatients with and without mild to moderate cognitive impairment., Methods: This was an analysis of the longitudinal European Palliative Care Cancer Symptom study of adults with incurable cancer in specialized palliative care (30 centers across 12 countries). Patients who could not comply with the study because of severe cognitive impairment were excluded. Cognitive status on the Mini-Mental State Examination short version and nine symptoms (pain, tiredness, drowsiness, nausea, appetite, breathlessness, depression, anxiety, and well-being) using the revised Edmonton Symptom Assessment System were self-reported at baseline and one-month follow-up. Reliability was analyzed using intraclass correlation coefficients and validity using regression of each symptom with health-related quality of life (HrQoL) measured with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care., Results: A total of 1047 patients were included: mean age of 62.9 years; 54.4% women; main cancer types were of digestive organs (26.6%), breast (21.6%), and lungs (21.2%). Cognitive impairment was present in 181 (17.3%) at baseline and associated with worse self-reported tiredness, drowsiness, appetite, and depression. Reliability (intraclass correlation coefficient) and validity (associations with HrQoL) were similar between people with/without cognitive impairment across the nine symptoms, except breathlessness, which showed a weaker relation to HrQoL in patients with cognitive impairment. Findings were robust in sensitivity analyses and after controlling for potential confounders., Conclusion: In advanced cancer, self-report of nine major symptoms was reliable and valid also in people with mild-to-moderate cognitive impairment., Trial Registration: ClinicalTrials.gov database (NCT01362816)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Pain in cancer patients remains common and is often associated with insufficient prescribing of targeted analgesia. An explanation for undertreatment could be the failure to identify neuropathic pain mechanisms, which require additional prescribing strategies. We wanted to identify the prevalence of neuropathic mechanisms in patients with cancer pain to highlight the need for detailed assessment and to support the development of an international classification system for cancer pain. We searched for studies that included adult and teenage patients (age above 12 years), with active cancer and who reported pain, and in which a clinical assessment of their pain had been made. We found 22 eligible studies that reported on 13,683 patients. Clinical assessment methods varied, and only 14 studies reported confirmatory testing for either sensory abnormality or diagnostic lesion to corroborate a diagnosis of neuropathic pain. We calculated that the prevalence of patients with neuropathic pain (95% confidence interval) varied from a conservative estimate of 19% (9.4% to 28.4%) to a liberal estimate of 39.1% (28.9% to 49.5%) when patients with mixed pain were included. The prevalence of pain with a neuropathic mechanism (95% confidence interval) ranged from a conservative estimate of 18.7% (15.3% to 22.1%) to a liberal estimate of 21.4% (15.2% to 27.6%) of all recorded cancer pains. The proportion of pain caused by cancer treatment was higher in neuropathic pain compared with all types of cancer pain. A standardised approach or taxonomy used for assessing neuropathic pain in patients with cancer is needed to improve treatment outcomes., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Aim of this study was to validate the use of subjective average pain assessment over an 8-h time period to evaluate cancer pain intensity. A sample of 95 consecutive cancer inpatients were asked to score on 0-10 numerical scales the intensity of their pain at hourly intervals, and then, at the 8th hour, to rate their average pain intensity over the last 8h. Agreement between the average of the 8 hourly measures (8hA) and the single patient-rated average (PA8h) was examined with the intraclass correlation coefficient (ICC) and the absolute difference (AD) between the two measurements. Associations between AD, gender, age older than 70, somatic pain, visceral pain, neuropathic pain, pain on movement and the presence of pain exacerbations during the 8-h period, were also examined. Average pain intensity scores were very similar with the two measurement schedules: 3.4 for 8hA and 3.7 for PA8h, with a median AD of 0.44 points. Only six patients (6.3%) showed ADs higher than 2 points. Also the ICC (0.85) showed a substantial agreement between the two schedules. Among the examined variables, gender, age over 70years and presence of pain exacerbations showed a significant association with the agreement level. Overall, our results support the validity of a subjective average pain measurement over 8-h period in cancer patients., (Copyright (c) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Objectives: Patients with multiple myeloma (MM) often have pronounced symptoms and substantially reduced quality of life. The aims of treatment are to control disease, maximise quality of life and prolong survival. Hence, health-related quality of life (HRQOL) should be an important end-point in randomised controlled trials (RCTs) in addition to traditional endpoints. We wanted to evaluate whether trials reporting HRQOL outcomes have influenced clinical decision making and whether HRQOL was assessed robustly according to predefined criteria., Methods: A systematic review identified RCTs in MM with HRQOL assessment as a study end-point. The methodological quality of these studies was assessed according to a checklist developed for evaluating HRQOL outcomes in clinical trials. The impact of the HRQOL results on clinical decision making was assessed, using published clinical guidelines as a reference., Results: Fifteen publications presenting RCTs with HRQOL as a study end-point were identified. In 13 trials, the author stated that HRQOL results should influence clinical decision making. We found, however, that the HRQOL data only had a limited impact on published treatment guidelines for bisphosphonates, high-dose treatment, interferon, erythropoiesis-stimulating agents and novel agents., Conclusion: The present review indicates that the there are still few RCTs in MM including HRQOL as a study end-point. Systematic incorporation of HRQOL measures into clinical trials allows for a comparison of treatment arms that includes the patients' perspective. Before the full impact on clinical decisions can be realised, the quality and methodology of collecting HRQOL data must be further improved and the results rendered more comprehensible to clinicians.

The objective of this study was to assess the psychometric properties of the HDC-19, a module questionnaire for assessing symptoms and problems of patients undergoing stem cell transplantation (SCT) following high-dose chemotherapy (HDC). It consists of 19 questions and was developed for use in conjunction with EORTC QLQ-C30. Psychometric evaluations were performed according to guidelines recommended by the EORTC. The principal component analyses suggested that nine of the HDC-19 items could be reduced to four components (sexual functioning, future health perspectives, skin irritations and joint/muscle pain). Multitrait scaling analysis showed that most item-scale correlation coefficients met the standards of convergent (>0.40) and discriminant validity. Test-retest reliability coefficients between assessments at inclusion and admission were high, indicating that perceived health status remained virtually unchanged during this period. As expected, correlations between admission and one month after transplantation were considerably lower. The internal consistency of the multi-item scales was also satisfactory, (Cronbach's alpha 0.59-0.87). Overall, the known-groups comparisons showed smaller differences between designated groups than expected. As expected, changes in the HDC-19 mirrored changes in QLQ-C30 'global quality of life'. These results lend support to the validity of the HDC-19 as a supplementary questionnaire for assessing specific health-related quality of life (HRQOL) issues relevant for SCT patients.

Aim: The aim of this study was to estimate the association between objective cardiorespiratory fitness (CRF) and subjective self-reported physical function, taking into account the influence of mental distress. We hypothesized an association between these parameters, since they might be thought to measure parts of the same phenomenon., Methods: Approximately 1 month after discontinuation of all primary treatment, 90 cancer patients aged 18-50 years treated with chemotherapy were surveyed. CRF was determined by the Astrand-Ryhming indirect cycle ergometer test, which indicate peak VO2 in mL x kg(-1) x min(-1) (predicted VO2max). Self-reported physical function was assessed by The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The relation between VO2max and self-reported physical function was estimated by multiple linear regression. Mental distress (assessed by The Hospital Anxiety and Depression scale), age, gender, body mass index (BMI), time from treatment to physical test and diagnoses were included as potential confounders., Results: There was no association between predicted VO2max and self-reported physical function. Mental distress was negatively associated with self-reported physical function (P<0.001), but is not associated with predicted VO2max., Conclusions: The results suggest that predicted VO2max does not reflect self-reported physical function and vice versa in cancer patients after chemotherapy. If information about cardiac and/or pulmonary status is required, direct or indirect measures of VO2max should be used.

The most commonly encountered clinical conditions presenting with cognitive failure (CF) are delirium, dementia and amnestic disorders. Of these, delirium is probably the most prevalent in palliative care, and it is potentially reversible. Thus, improvement in diagnostics seems warranted. The objectives of this review were to examine the methods for assessment of CF and delirium in palliative care. Twenty-two studies were reviewed: 64% were published in 2000 or later. Twelve reports focused on delirium, six on CF, while the remaining four assessed confusion (2), hallucinations and general psychological morbidity. Median sample size was 100 (20393). Ten different instruments were used: The Mini Mental State Exam was used in 13 studies. Five studies were validation reports of new or existing instruments. The term CF is an imprecise description of a loss in one or more of the cognitive functions. The interchangeable use of CF as a description of specific diagnoses should be avoided, as this contributes to prevalence rates that are not representative. Assessment tools that discriminate between the different diagnostic entities presenting with CF should be used in future studies.

In cross-national comparisons based on questionnaires, accurate translations are necessary to obtain valid results. Differential item functioning (DIF) analysis can be used to test whether translations of items in multi-item scales are equivalent to the original. In data from 10,815 respondents representing 10 European languages we tested for DIF in the nine translations of the EORTC QLQ-C30 emotional function scale when compared to the original English version. We tested for DIF using two different methods in parallel, a contingency table method and logistic regression. The DIF results obtained with the two methods were similar. We found indications of DIF in seven of the nine translations. At least two of the DIF findings seem to reflect linguistic problems in the translation. 'Imperfect' translations can affect conclusions drawn from cross-national comparisons. Given that translations can never be identical to the original we discuss how findings of DIF can be interpreted and discuss the difference between linguistic DIF and DIF caused by confounding, cross-cultural differences, or DIF in other items in the scale. We conclude that testing for DIF is a useful way to validate questionnaire translations.

This study was conducted to explore treatment and disease-related effects on health-related quality of life (HRQoL) in patients with aggressive lymphoma, to identify predictors for impaired long-term HRQoL, and to analyze the prognostic value of pretreatment HRQoL. Ninety-five patients with aggressive lymphoma, constituting a subset of a randomized multicenter trial comparing CHOP and MACOP-B, entered a HRQoL study, using the EORTC QLQ-C30 questionnaire. Patient scores were compared to scores from an age- and gender-adjusted reference population sample, and evaluation of the prognostic value of pretreatment QoL scores in relation to clinical prognostic factors was performed. Before treatment, patients exhibited lower scores of global QoL, physical, role, and social functions, and more appetite loss, compared to the reference population. Role functioning improved compared to baseline, but remained depressed compared to the reference group more than 8 mo after end of treatment. By then, the patient group displayed no difference in other HRQoL variables compared to that of the reference population. No reliable predictor for impaired long-term HRQoL could be identified. In multivariate analysis, including the factors of the International Prognostic Index, pretreatment global QoL was an independent prognostic marker for overall survival. In conclusion, in this population with aggressive lymphoma and favorable prognostic features, HRQoL was not substantially affected during the first year after diagnosis. Pretreatment global QoL may constitute a significant prognostic factor, meriting further investigation in prospective studies.

Health-related quality of life (HRQOL) and occurrence of late intestinal side effects were assessed 3-4 years after pelvic radiotherapy for carcinoma of the endometrium and cervix. During 1988-1990, 143 women were included in a clinical trial to evaluate the effect of a low fat, low lactose diet on radiation-induced diarrhoea. Of 94 survivors, 79 (84%) answered the request. HRQOL was assessed by the EORTC QLQ-C36 and compared with population-based norms. The women scored lower than the general population on role functioning (81.5 versus 90.6 (p < 0.01)) and higher on diarrhoea (23.8 versus 9.5 (p < 0.01)). Compared with pre-treatment conditions, an increase in cases with pain in the lower back, hips and thighs was seen. Substantial pain and diarrhoea were associated with deterioration in HRQOL. In conclusion, few treatment and/or disease-related effects were detected 3-4 years after radiotherapy, with the exception of increased bowel frequency and pain in the lower back, hips and thighs.

Health-related quality of life (HRQOL) in leukemia and lymphoma patients treated with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT) stem cell transplantation or receiving combination chemotherapy (CT) was prospectively assessed by the EORTC QLQ-C30 and compared with reference data from a general population sample. One year after transplant, the SCT group had functional scores which were close to population values except for lower social (P < 0.0001) and role function (P = 0.0004). More symptoms and problems were reported, especially appetite loss (P = 0. 001) and financial difficulties (P = 0.0001). The ASCT patients reported a less than optimal HRQOL relative to the population 1 year post transplant. Cognitive, physical, role, and social function, dyspnoea, financial difficulties and global quality of life were most impaired (P < 0.001). In the CT group, physical, role and social function, dyspnoea and financial difficulties were impaired 1 year after start of chemotherapy, compared with the general population (P < 0.001). The EORTC QLQ-C30 was supplemented by a high-dose chemotherapy module, the HDC-19, at the 1-year assessment, but no consistent differences were found across groups. Fifteen to 34% of the patients expressed fears of relapse and worries about future health, while 24-30% indicated no participation in sexual activities.