Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF) with epirubicin, cisplatin, 5-FU (ECF)

BACKGROUND: Health related quality of life (HRQOL) is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC) receiving either a standard or an experimental treatment. METHODS: Seventy-one patients have been treated in Cancer Institute (Tehran, Iran) with docetaxel, cisplatin, 5 FU (TCF) or epirubicin, cisplatin, 5-FU (ECF) and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy. RESULTS: The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001). Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups. CONCLUSION: Docetaxel based treatment (TCF) showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF). However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients

What Are the Real Procedural Costs of Bariatric Surgery? A Systematic Literature Review of Published Cost Analyses

This is the final version. Available on open access from Springer Verlag via the DOI in this recordThis review aims to evaluate the current literature on the procedural costs of bariatric surgery for the treatment of severe obesity. Using a published framework for the conduct of micro-costing studies for surgical interventions, existing cost estimates from the literature are assessed for their accuracy, reliability and comprehensiveness based on their consideration of seven ‘important’ cost components. MEDLINE, PubMed, key journals and reference lists of included studies were searched up to January 2017. Eligible studies had to report per-case, total procedural costs for any type of bariatric surgery broken down into two or more individual cost components. A total of 998 citations were screened, of which 13 studies were included for analysis. Included studies were mainly conducted from a US hospital perspective, assessed either gastric bypass or adjustable gastric banding procedures and considered a range of different cost components. The mean total procedural costs for all included studies was US$14,389 (range, US$7423 to US$33,541). No study considered all of the recommended ‘important’ cost components and estimation methods were poorly reported. The accuracy, reliability and comprehensiveness of the existing cost estimates are, therefore, questionable. There is a need for a comparative cost analysis of the different approaches to bariatric surgery, with the most appropriate costing approach identified to be micro-costing methods. Such an analysis will not only be useful in estimating the relative cost-effectiveness of different surgeries but will also ensure appropriate reimbursement and budgeting by healthcare payers to ensure barriers to access this effective treatment by severely obese patients are minimised.National Institute for Health Research (NIHR

Impact of question order on prioritisation of outcomes in the development of a core outcome set: a randomised controlled trial

BACKGROUND: Core outcome set (COS) developers increasingly employ Delphi surveys to elicit stakeholders' opinions of which outcomes to measure and report in trials of a particular condition or intervention. Research outside of Delphi surveys and COS development demonstrates that question order can affect response rates and lead to 'context effects', where prior questions determine an item's meaning and influence responses. This study examined the impact of question order within a Delphi survey for a COS for oesophageal cancer surgery. METHODS: A randomised controlled trial was nested within the Delphi survey. Patients and health professionals were randomised to receive a survey including clinical and patient-reported outcomes (PROs), where the PRO section appeared first or last. Participants rated (1-9) the importance of 68 items for inclusion in a COS (ratings 7-9 considered 'essential'). Analyses considered the impact of question order on: (1) survey response rates; (2) participants' responses; and (3) items retained at end of the survey. RESULTS: In total, 116 patients and 71 professionals returned completed surveys. Question order did not affect response rates among patients, but fewer professionals responded when clinical items appeared first (difference = 31.3%, 95% confidence interval [CI] = 13.6-48.9%, P = 0.001). Question order led to different context effects within patients and professionals. While patients rated clinical items highly, irrespective of question order, more PROs were rated essential when appearing last rather than first (difference = 23.7%, 95% CI = 10.5-40.8%). Among professionals, the greatest impact was on clinical items; a higher percentage rated essential when appearing last (difference = 11.6%, 95% CI = 0.0-23.3%). An interaction between question order and the percentage of PRO/clinical items rated essential was observed for patients (P = 0.025) but not professionals (P = 0.357). Items retained for further consideration at the end of the survey were dependent on question order, with discordant items (retained by one question order group only) observed in patients (18/68 [26%]) and professionals (20/68 [29%]). CONCLUSIONS: In the development of a COS, participants' ratings of potential outcomes within a Delphi survey depend on the context (order) in which the outcomes are asked, consequently impacting on the final COS. Initial piloting is recommended with consideration of the randomisation of items in the survey to reduce potential bias. TRIAL REGISTRATION: The randomised controlled trial reported within this paper was nested within the development of a core outcome set to investigate processes in core outcome set development. Outcomes were not health-related and trial registration was not therefore applicable

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

A core Outcome Set for Seamless, Standardized Evaluation of Innovative Surgical Procedures and Devices (COHESIVE)

OBJECTIVE: To develop a core outcome set (COS), an agreed minimum set of outcomes to measure and report in all studies evaluating the introduction and evaluation of novel surgical techniques. SUMMARY BACKGROUND DATA: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm. METHODS: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm. RESULTS: 7,972 verbatim outcomes were identified, categorized into 32 domains, and formatted into survey items/questions. 410 international participants (220 professionals, 190 patients/public) completed at least one round 1 survey item, of which 153 (69.5%) professionals and 116 (61.1%) patients completed at least one round 2 item. 12 outcomes were scored ‘consensus in’ (‘very important’ by ≥70% of patients and professionals) and 20 ‘no consensus’. A consensus meeting, involving 19 professionals and 10 patient/public representatives, led to agreement on a final 8-domain COS. Six domains are specific to a surgical innovation context: modifications, unexpected disadvantages, device problems, technical procedure success, whether the overall desired effect was achieved, surgeons’/operators’ experience. Two domains relate to intended benefits and expected disadvantages. CONCLUSIONS: The COS is recommended for use in all studies prior to definitive RCT evaluation to promote safe, transparent, and efficient surgical innovation

The iBRA (implant breast reconstruction evaluation) study: protocol for a prospective multi-centre cohort study to inform the feasibility, design and conduct of a pragmatic randomised clinical trial comparing new techniques of implant-based breast reconstruction.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK. The introduction of techniques to augment the subpectoral pocket has revolutionised the procedure, but there is a lack of high-quality outcome data to describe the safety or effectiveness of these techniques. Randomised controlled trials (RCTs) are the best way of comparing treatments, but surgical RCTs are challenging. The iBRA (implant breast reconstruction evaluation) study aims to determine the feasibility, design and conduct of a pragmatic RCT to examine the effectiveness of approaches to IBBR. METHODS/DESIGN: The iBRA study is a trainee-led research collaborative project with four phases:Phase 1 - a national practice questionnaire (NPQ) to survey current practicePhase 2 - a multi-centre prospective cohort study of patients undergoing IBBR to evaluate the clinical and patient-reported outcomesPhase 3- an IBBR-RCT acceptability survey and qualitative work to explore patients' and surgeons' views of proposed trial designs and candidate outcomes.Phase 4 - phases 1 to 3 will inform the design and conduct of the future RCT All centres offering IBBR will be encouraged to participate by the breast and plastic surgical professional associations (Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons). Data collected will inform the feasibility of undertaking an RCT by defining current practice and exploring issues surrounding recruitment, selection of comparator arms, choice of primary outcome, sample size, selection criteria, trial conduct, methods of data collection and feasibility of using the trainee collaborative model to recruit patients and collect data. DISCUSSION: The preliminary work undertaken within the iBRA study will determine the feasibility, design and conduct of a definitive RCT in IBBR. It will work with the trainee collaborative to build capacity by creating an infrastructure of research-active breast and plastic surgeons which will facilitate future high-quality research that will ultimately improve outcomes for all women seeking reconstructive surgery. TRIAL REGISTRATION: ISRCTN37664281

Feasibility of quality of life assessment in patients with upper gastrointestinal tract cancer

Quality of life (QOL) is an important outcome after treatment for upper gastrointestinal tract cancer but few studies report good accrual and subsequent attrition is usually high. This study investigated the feasibility of a nurse-led service to obtain longitudinal QOL assessments and explored how clinical and sociodemographic factors influence patients' need for help to complete questionnaires. Fully informed patients were invited into the study. Baseline hospital assessments were scheduled by telephone and thereafter by post unless patients' health indicated the need for a home visit. In all, 128 out of 140 (91%) baseline QOL assessments were performed. Follow-up questionnaire completion was good, with 114 patients (89%) completing all but one of the expected assessments. At baseline, 41 (32%) patients required a lot of help to complete questionnaires. Patients requiring help were more likely to be undergoing palliative treatment than treatment aimed at cure (68 vs 33%; odds ratio 3.48, P < 0.01). Patients' with advanced stage cancer of the upper gastrointestinal tract receiving palliative treatment require dedicated staff to ensure good compliance with longitudinal QOL data collection. It is essential to budget for this in clinical trails. © 2003 Cancer Research UK

Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial

Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery.The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches.Pilot parallel three-arm randomised controlled trial nested within feasibility work.Two UK NHS departments of upper gastrointestinal surgery.Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy.Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access.The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited.During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing, allowing a seamless transition into the definitive trial. Consequently, the database is unlocked at the time of writing and data presented here are for patients recruited by 31 August 2014. Random allocation achieved a good balance between the arms of the study, which, as a high proportion of patients underwent their allocated surgery (69/79, 87%), ensured a fair comparison between the interventions. Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind while pain was assessed during the first week post surgery. Postsurgical length of stay and risk of adverse events were within the typical range for this group of patients, with one death occurring within 30 days among 76 patients. There were good completion rates for the assessment of pain at 6 days post surgery (88%) and of the patient-reported outcomes at 6 weeks post randomisation (74%).Rapid recruitment to the pilot trial and the successful refinement of methodology indicated the feasibility of a definitive trial comparing different approaches to oesophagectomy. Although we have shown a full trial of open compared with minimally invasive oesophagectomy to be feasible, this is necessarily based on our findings from the two clinical centres that we could include in this small preliminary study.Current Controlled Trials ISRCTN59036820.This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 48. See the NIHR Journals Library website for further project information

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice

This is the final version. Available on open access from Wiley via the DOI in this recordBACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. METHODS: The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. RESULTS: The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).National Institute of Health Research Health Technology Assessment ProgrammeMedical Research Council (MRC

Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting):study protocol for a randomized controlled trial

Background: The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. Methods/Design: The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients’ motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients’ experiences of each trial arm. Discussion: The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on patient-reported, rather than disease-orientated, outcomes. Exploration of patient experience and health economic analyses will be integral to the assessment of benefit for patients and the NHS