A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

BackgroundNovel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.MethodsOur mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.ResultsUnique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context.ConclusionSupplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning

Health-related quality of life in KEYNOTE-010 : a phase II/III study of pembrolizumab versus docetaxel in patients with previously treated advanced, programmed death ligand 1-expressing NSCLC

Introduction: In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1-expressing (tumor proportion score >= 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here. Methods: Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m(2) every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ-Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain. Results: Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had "deteriorated" status and more had "improved" status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose. Conclusions: These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The relationship between quality of life (EORTC QLQ-C30) and survival in patients with gastro-oesopohageal cancer

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P < 0.01), tumour length (P < 0.0001), TNM stage (P<0.0001), weight loss (P<0.0001), dysphagia score (P<0.001), performance status (P<0.1) and treatment (P<0.0001) were significantly associated with cancer-specific survival. EORTC QLQ-C30, physical functioning (P<0.0001), role functioning (P<0.001), cognitive functioning (P<0.01), social functioning (P<0.0001), global quality of life (P<0.0001), fatigue (P<0.0001), nausea/vomiting (P<0.01), pain (P<0.001), dyspnoea (P<0.0001), appetite loss (P<0.0001) and constipation (P<0.05) were also significantly associated with cancer-specific survival. On multivariate survival analysis, tumour stage (P<0.0001), treatment (P<0.001) and appetite loss (P<0.0001) were significant independent predictors of cancer-specific survival. The present study highlights the importance of quality of life (EORTC QLQ-C30) measures, in particular appetite loss, as a prognostic factor in these patients

Psychosocial interventions for patients with head and neck cancer.

BACKGROUND: A diagnosis of head and neck cancer, like many other cancers, can lead to significant psychosocial distress. Patients with head and neck cancer can have very specific needs, due to both the location of their disease and the impact of treatment, which can interfere with basic day-to-day activities such as eating, speaking and breathing. There is a lack of clarity on the effectiveness of the interventions developed to address the psychosocial distress experienced by patients living with head and neck cancer. OBJECTIVES: To assess the effectiveness of psychosocial interventions to improve quality of life and psychosocial well-being for patients with head and neck cancer. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 17 December 2012. SELECTION CRITERIA: We selected randomised controlled trials and quasi-randomised controlled trials of psychosocial interventions for adults with head and neck cancer. For trials to be included the psychosocial intervention had to involve a supportive relationship between a trained helper and individuals diagnosed with head and neck cancer. Outcomes had to be assessed using a validated quality of life or psychological distress measure, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data and assessed the risk of bias, with mediation from a third author where required. Where possible, we extracted outcome measures for combining in meta-analyses. We compared continuous outcomes using either mean differences (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI), with a random-effects model. We conducted meta-analyses for the primary outcome measure of quality of life and secondary outcome measures of psychological distress, including anxiety and depression. We subjected the remaining outcome measures (self esteem, coping, adjustment to cancer, body image) to a narrative synthesis, due to the limited number of studies evaluating these specific outcomes and the wide divergence of assessment tools used. MAIN RESULTS: Seven trials, totaling 542 participants, met the eligibility criteria. Studies varied widely on risk of bias, interventions used and outcome measures reported. From these studies, there was no evidence to suggest that psychosocial intervention promotes global quality of life for patients with head and neck cancer at end of intervention (MD 1.23, 95% CI -5.82 to 8.27) as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This quality of life tool includes five functional scales, namely cognitive, physical, emotional, social and role. There was no evidence to demonstrate that psychosocial intervention provides an immediate or medium-term improvement on any of these five functional scales. From the data available, there was no significant change in levels of anxiety (SMD -0.09, 95% CI -0.40 to 0.23) or depression following intervention (SMD -0.03, 95% CI -0.24 to 0.19). At present, there is insufficient evidence to refute or support the effectiveness of psychosocial intervention for patients with head and neck cancer. AUTHORS' CONCLUSIONS: The evidence for psychosocial intervention is limited by the small number of studies, methodological shortcomings such as lack of power, difficulties with comparability between types of interventions and a wide divergence in outcome measures used. Future research should be targeted at patients who screen positive for distress and use validated outcome measures, such as the EORTC scale, as a measure of quality of life. These studies should implement interventions that are theoretically derived. Other shortcomings should be addressed in future studies, including using power calculations that may encourage multi-centred collaboration to ensure adequate sample sizes are recruited

Translation and validation of EORTC QLQ-C30 into Indonesian version for cancer patients in Indonesia.

The Indonesian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 can be used as a questionnaire to assess quality of life in Indonesian cancer patients with high-emetogenic treatments

Health-Related Quality of Life and Needs of Care and Support of Adult Tanzanians with Cancer: A Mixed-Methods Study.

Cancer is among the three leading causes of death in low income countries and the highest increase with regard to incidence figures for cancer diseases are found in these countries. This is the first report of the health-related quality of life (HRQOL) and needs of care and support of adult Tanzanians with cancer. A mixed-methods design was used. The study was conducted at Ocean Road Cancer Institute (ORCI) in Dar es Salaam, Tanzania. One hundred and one patients with a variety of cancer diagnoses treated and cared for at ORCI answered the Kiswahili version of the EORTC QLQ-C30 investigating HRQOL. Thirty-two of the patients participated in focus group interviews discussing needs of care and support. Data from focus group interviews were analyzed with content analysis. The findings show that the patients, both women and men, report a low quality of life, especially with regard to physical, role, and social function and a high level of symptoms and problems especially with financial difficulties and pain. Financial difficulties are reported to a remarkably high extent by both women and men. The patients, both women and men report least problems with emotional function. A content analysis of the interview data revealed needs of food and water, hygienic needs, emotional needs, spiritual needs, financial needs, and needs of closeness to cancer care and treatment services. The high score for pain points out that ORCI is facing severe challenges regarding care and treatment. However, when considering this finding it should be noted that the pain subscale of the Kiswahili version of the EORTC QLQ-C30 did not reach acceptable internal consistency and showed less than satisfactory convergent validity. This also applies to the subscales cognitive function and global health/quality of life. Attention should be drawn to meet the identified needs of Tanzanian cancer patients while hospitalized but also when at home. Increased accessibility of mosquito nets, pads, and pain-killers would help to fulfil some needs

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Comparison of 10-year overall survival between patients with G1 and G2 grade Ta bladder tumors

To compare long-term overall survival (OS) in patients with G1 and G2 grade Ta bladder cancer after transurethral resection of bladder tumors (TURBTs). Secondary aim was to investigate clinical and pathologic prognostic factors for OS of Ta patients, except G3/high grade (HG). A total of 243 patients, retrospectively selected, with Ta nonmuscle invasive bladder cancer (NMIBC) underwent TURBT between January 2006 and December 2008 (median follow-up 109 months). Inclusion criteria were: Ta at first manifestation, G1 or G2 grade with no associated carcinoma in situ (CIS). Seventy-nine patients were excluded due to concomitant CIS (1), G3/HG tumors (47), and lost to follow-up (31). Ethical approval was obtained from the Ethical Committee of the Mures County Hospital. Statistical analysis was performed using STATA 11.0. Following inclusion criteria, 164 patients with primary G1 or G2 Ta tumors, were enrolled. Recurrence was observed in 26 (15.8%) and progression in 5 (3%) patients. Ten-year survival in G1 patients was 67.8% (CI 54.3-78.1) and in G2 patients 59% (CI 49-67.3) (P=.31). Univariable and multivariable logistic regression analysis underlined that advanced age at diagnosis (hazard ratio [HR] 1.10) and no Bacillus Calmette-Guerin (BCG) treatment (HR 0.24 and 0.29) were independent predictors for death at 10 years after diagnosis. Long-term analysis confirms that patients with well differentiated (G1) and moderately well differentiated (G2) Ta tumors have similar OS. A longer OS was even reported in those who underwent BCG adjuvant therapy

Psychometric properties and measurement equivalence of the Multidimensional Fatigue Syndrome Inventory- Short Form (MFSI-SF) amongst breast cancer and lymphoma patients in Singapore.

BackgroundCurrently, several fatigue measurement instruments are available to evaluate and measure cancer-related fatigue. Amongst them, Multidimensional Fatigue Syndrome Inventory-Short Form (MFSI-SF) is a self-reported instrument and a multidimensional scale that aims to capture the global, somatic, affective, cognitive and behavioural symptoms of fatigue. This study examines the psychometric properties and measurement equivalence of the English and Chinese versions of MFSI-SF in breast cancer and lymphoma patients in Singapore.MethodsPatients were recruited from National Cancer Centre Singapore. Validity, reliability and responsiveness of MFSI-SF were evaluated in this study. Convergent validity was evaluated by correlating total and subscales of MFSI-SF to known related constructs in EORTC QLQ-C30. Known group validity was assessed based on patients' cancer stage, pain, insomnia and depression symptoms. Reliability was evaluated by Cronbach's α. Responsiveness analyses were performed with patients who have undergone at least one cycle of chemotherapy. Multiple regression was used to compare the total and subscale scores of MSFI-SF between the two language versions.ResultsData from 246 (160 English and 86 Chinese version) breast cancer and lymphoma patients were included in the study. Moderate to high correlations were observed between correlated MFSI-SF subscales and EORTC QLQ-C30 domains (|r| = 0.524 to 0.774) except for a poor correlation (r = 0.394) observed between MFSI-SF vigour subscale and EORTC QLQ-C30 role functioning subscale. Total MFSI-SF scores could differentiate between patients with higher depression, pain and insomnia status. Internal consistency of MFSI-SF was also high (α = 0.749 to 0.944). Moderate correlation was observed between change in total MFSI-SF score and change in fatigue symptom scale score and global QoL score on EORTC QLQ-C30 (|r| = 0.478 and 0.404 respectively). Poor correlations were observed between change in scores of hypothesised subscales (|r| = 0.202 to 0.361) except for a moderate correlation between change in MFSI-SF emotional fatigue score and change in EORTC QLQ-C30 emotional functioning domain score. Measurement equivalence was established for all subscales and total MFSI-SF score except for the emotional and vigour subscales.ConclusionsThis study supports the use of MFSI-SF as a reasonably valid scale with good internal consistency for measuring fatigue levels in the Singapore cancer population