Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial.

Importance: Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective: The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants: This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions: There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures: First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results: A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance: This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration: isrctn.org Identifier: ISRCTN44687907.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: main results of a cluster preference randomised controlled trial.

PURPOSE: The patient concerns inventory (PCI) is a prompt list allowing head and neck cancer (HNC) patients to discuss issues that otherwise might be overlooked. This trial evaluated the effectiveness of using the PCI at routine outpatient clinics for one year after treatment on health-related QOL (HRQOL). METHODS: A pragmatic cluster preference randomised control trial with 15 consultants, 8 'using' and 7 'not using' the PCI intervention. Patients treated with curative intent (all sites, disease stages, treatments) were eligible. RESULTS: Consultants saw a median (inter-quartile range) 16 (13-26) patients, with 140 PCI and 148 control patients. Of the pre-specified outcomes, the 12-month results for the mean University of Washington Quality of Life (UW-QOLv4) social-emotional subscale score suggested a small clinical effect of intervention of 4.6 units (95% CI 0.2, 9.0), p = 0.04 after full adjustment for pre-stated case-mix. Results for UW-QOLv4 overall quality of life being less than good at 12 months (primary outcome) also favoured the PCI with a risk ratio of 0.83 (95% CI 0.66, 1.06) and absolute risk 4.8% (- 2.9%, 12.9%) but without achieving statistical significance. Other non-a-priori analyses, including all 12 UWQOL domains and at consultant level also suggested better HRQOL with PCI. Consultation times were unaffected and the number of items selected decreased over time. CONCLUSION: This novel trial supports the integration of the PCI approach into routine consultations as a simple low-cost means of benefiting HNC patients. It adds to a growing body of evidence supporting the use of patient prompt lists more generally.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: baseline results in a cluster preference randomised controlled trial.

PURPOSE: The main aim of this paper is to present baseline demographic and clinical characteristics and HRQOL in the two groups of the Patient Concerns Inventory (PCI) trial. The baseline PCI data will also be described. METHODS: This is a pragmatic cluster preference randomised control trial with 15 consultant clusters from two sites either 'using' (n = 8) or 'not using' (n = 7) the PCI at a clinic for all of their trial patients. The PCI is a 56-item prompt list that helps patients raise concerns that otherwise might be missed. Eligibility was head and neck cancer patients treated with curative intent (all sites, stage of disease, treatments). RESULTS: From 511 patients first identified as eligible when screening for the multi-disciplinary tumour board meetings, 288 attended a first routine outpatient baseline study clinic after completion of their treatment, median (IQR) of 103 (71-162) days. At baseline, the two trial groups were similar in demographic and clinical characteristics as well as in HRQOL measures apart from differences in tumour location, tumour staging and mode of treatment. These exceptions were cluster (consultant) related to Maxillofacial and ENT consultants seeing different types of cases. Consultation times were similar, with PCI group times taking about 1 min longer on average (95% CL for the difference between means was from - 0.7 to + 2.2 min). CONCLUSION: Using the PCI in routine post-treatment head and neck cancer clinics do not elongate consultations. Recruitment has finished but 12-month follow-up is still ongoing.

Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: a cluster preference randomized controlled trial.

BACKGROUND: The consequences of treatment for Head and Neck cancer (HNC) patients has profound detrimental impacts such as impaired QOL, emotional distress, delayed recovery and frequent use of healthcare. The aim of this trial is to determine if the routine use of the Patients Concerns Inventory (PCI) package in review clinics during the first year following treatment can improve overall quality of life, reduce the social-emotional impact of cancer and reduce levels of distress. Furthermore, we aim to describe the economic costs and benefits of using the PCI. METHODS: This will be a cluster preference randomised control trial with consultants either 'using' or 'not using' the PCI package at clinic. It will involve two centres Leeds and Liverpool. 416 eligible patients from at least 10 consultant clusters are required to show a clinically meaningful difference in the primary outcome. The primary outcome is the percentage of participants with less than good overall quality of life at the final one-year clinic as measured by the University of Washington QOL questionnaire version 4 (UWQOLv4). Secondary outcomes at one-year are the mean social-emotional subscale (UWQOLv4) score, Distress Thermometer (DT) score ≥ 4, and key health economic measures (QALY-EQ-5D-5 L; CSRI). DISCUSSION: This trial will provide knowledge on the effectiveness of a consultation intervention package based around the PCI used at routine follow-up clinics following treatment of head and neck cancer with curative intent. If this intervention is (cost) effective for patients, the next step will be to promote wider use of this approach as standard care in clinical practice. TRIAL REGISTRATION: 32,382. Clinical Trials Identifier, NCT03086629 . PROTOCOL: Version 3.0, 1st July 2017.

Evaluating public involvement in research design and grant development: Using a qualitative document analysis method to analyse an award scheme for researchers.

PLAIN ENGLISH SUMMARY: The National Institute for Health Research (NIHR) Research Design Service (RDS) for Yorkshire and Humber has been running a public involvement funding scheme since 2008. This scheme awards researchers a small amount of money to help them get involvement from patients and/or the public. Involvement activities take place at the time when researchers are planning studies, and when they are completing application forms to request funding for a proposed research project. After the public involvement activities researchers are asked to write a report for the RDS describing what they did with the public involvement funding. This study analysed those reports using an approach which included members of a public involvement panel in the data analysis process. The aim of the work was to see what the views and experiences of researchers who received funding were, and what might be learned for the future of the scheme. Twenty five reports were analysed. Four main themes were identified, these described: the added value of public involvement; aspects to consider when planning and designing public involvement; different roles of public contributors; and aspects of valuing public member contributions. The group approach to analysis was successful in enabling involvement of a variety of individuals in the process. The findings of the study provide evidence of the value of public involvement during the development of applications for research funding. The results also indicate that researchers recognise the variety in potential roles for the public in research, and acknowledge how involvement adds value to studies. ABSTRACT: Background A regional Research Design Service, funded by the National Institute for Health Research, introduced a small grant in 2008, to support public involvement (often known as patient and public involvement [PPI]) activities during the development of applications for research funding. Successful applicants are requested to submit a report detailing how the grant money was used, including a description of the aims and outcomes of the public involvement activities. The purpose of this study was to analyse the content of these reports. We aimed to find out what researcher views and experiences of public involvement activities were, and what lessons might be learned. Methods We used an innovative method of data analysis, drawing on group participatory approaches, qualitative content analysis, and Framework Analysis to sort and label the content of the reports. We developed a framework of categories and sub-categories (or themes and sub-themes) from this process. Results Twenty five documents were analysed. Four main themes were identified in the data: the added value of public involvement; planning and designing involvement; the role of public members; and valuing public member contributions. Within these themes, sub-themes related to the timing of involvement (prior to the research study/intended during the research study), and also specific benefits of public involvement such as: validating ideas; ensuring appropriate outcomes; ensuring the acceptability of data collection methods/tools and advice regarding research processes. Other sub-themes related to: finding and approaching public members; timing of events; training/support; the format of sessions; setting up public involvement panels: use of public contributors in analysis and interpretation of data; and using public members to assist with dissemination and translation into practice. Conclusions The analysis of reports submitted by researchers following involvement events provides evidence of the value of public involvement during the development of applications for research funding, and details a method for involving members of the public in data analysis which could be of value to other researchers The findings of the analysis indicate recognition amongst researchers of the variety in potential roles for public members in research, and also an acknowledgement of how involvement adds value to studies.

Establishing a large prospective clinical cohort in people with head and neck cancer as a biomedical resource: head and neck 5000.

BACKGROUND: Head and neck cancer is an important cause of ill health. Survival appears to be improving but the reasons for this are unclear. They could include evolving aetiology, modifications in care, improvements in treatment or changes in lifestyle behaviour. Observational studies are required to explore survival trends and identify outcome predictors. METHODS: We are identifying people with a new diagnosis of head and neck cancer. We obtain consent that includes agreement to collect longitudinal data, store samples and record linkage. Prior to treatment we give participants three questionnaires on health and lifestyle, quality of life and sexual history. We collect blood and saliva samples, complete a clinical data capture form and request a formalin fixed tissue sample. At four and twelve months we complete further data capture forms and send participants further quality of life questionnaires. DISCUSSION: This large clinical cohort of people with head and neck cancer brings together clinical data, patient-reported outcomes and biological samples in a single co-ordinated resource for translational and prognostic research.