Barry Main

Enhanced recovery after surgery (ERAS) for head and neck oncology patients

To describe the development of an enhanced recovery after surgery (ERAS) protocol for people undergoing surgery for head and neck cancer.

A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery: the BARIACT project

Background Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials—the BARIACT Study. Methods and Findings Outcomes identified from systematic reviews and patient interviews informed a questionnaire survey. Patients and health professionals were surveyed three times and asked to rate the importance of each item on a 1–9 scale. Delphi methods provided anonymised feedback to participants. Items not meeting predefined criteria were discarded between rounds. Remaining items were discussed at consensus meetings, held separately with patients and professionals, where the COS was agreed. Data sources identified 2,990 outcomes, which were used to develop a 130-item questionnaire. Round 1 response rates were moderate but subsequently improved to above 75% for other rounds. After rounds 2 and 3, 81 and 14 items were discarded, respectively, leaving 35 items for discussion at consensus meetings. The final COS included nine items: “weight,” “diabetes status,” “cardiovascular risk,” “overall quality of life (QOL),” “mortality,” “technical complications of the specific operation,” “any re-operation/re-intervention,” “dysphagia/regurgitation,” and “micronutrient status.” The main limitation of this study was that it was based in the United Kingdom only. Conclusions The COS is recommended to be used as a minimum in all trials of bariatric and metabolic surgery. Adoption of the COS will improve data synthesis and the value of research data. Future work will establish methods for the measurement of the outcomes in the COS.

The metastatic potential of head and neck cutaneous malignant melanoma: is sentinel node biopsy useful?

Results from a large multicentre trial suggest that sentinel lymph node biopsy examination may benefit disease-free survival in patients with cutaneous malignant melanoma of intermediate thickness, but this is controversial. We recorded the outcomes of patients with these lesions in the head and neck with specific reference to regional lymph node metastases, to find out whether routine sentinel lymph node biopsy examination would have been beneficial. We reviewed pathology databases, multidisciplinary outcomes, and notes for all patients managed by a regional melanoma service between 2004 and 2009, and recorded key characteristics of the tumours. Details on patients with malignant melanoma of intermediate thickness (1.2-3.5mm) were further analysed for the development of nodal metastases in the neck over a 3-year postoperative period. We compared our data with the rate of predicted nodal metastases generated from the trial. Of 132 patients with malignant melanoma of the head and neck, 33 (25%) had lesions of intermediate thickness, and nodal metastases developed in only one. The remaining 32 remained free of neck disease during the study period. Although trial data predicted that 16% (n=5 in this sample) would show signs of metastasis and require neck dissection, on the basis of our data, practice in our unit will not change. Sentinel node biopsy examination for melanoma remains controversial because the natural history of metastatic spread of disease is not fully understood.

RE: Recommended Patient-Reported Core Set of Symptoms to Measure in Adult Cancer Treatment Trials

We read with interest the editorial (1) and four linked papers (2–5) exploring the important issue of core sets in cancer trials. The editorial highlights the need for a clear rationale for core outcome sets (COS) and for better approaches to their development. We welcome this attention to core outcome sets and here refer to the rationale and approach promoted by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative (www.comet-initiative.org) (6). The primary justification for developing and using COS in oncology is the need for consensus in the selection, measurement, and reporting of outcomes in trials to improve data synthesis, reduce outcome reporting bias, and optimize the relevance of evidence for decision-making. Currently, the heterogeneity of outcome reporting in all cancer types prevents meaningful comparisons of data (7), but the mandatory use of a minimal set of outcomes (including both clinical and patient-reported outcomes) for specific cancer types should address these issues. However, careful consideration needs to be given to the scope of any COS, including whether it is to apply to one or all modes of treatment for the particular condition. Whilst we agree that consensus methods are required to define a COS, the methods used in the linked papers do not fully address how patients can be involved (8). For example, Chera et al. state that, “experts on this panel agreed that these symptoms and health-related quality of life (HRQoL) domains are relevant to most head and neck cancer patients” (2). The panel, however, included only one patient representative. It is recommended that real canvassing of the opinion of a representative sample of people who have been treated for the disease is required to justify inclusion of items in a COS. Whether symptom prevalence equates to symptoms that patients prioritize is unknown, and we consider that the emphasis given to patients’ views should be in similar or greater proportions to those of health professionals. Core outcome sets represent an important step in improving the quality, reporting, and understanding of the results of clinical trials. It is essential to optimize methods for development. The work should gain the views of key stakeholders and be iterative, with registration of studies at the outset to develop international collaboration and avoid unnecessary duplication of work. The work presented in the four papers should be considered alongside ongoing research in this field with the aim of working toward a global consensus about core outcomes that are most relevant to patients and health care professionals (9,10).

Reporting outcomes of definitive radiation-based treatment for esophageal cancer: a review of the literature.

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer.

Protocol for the systematic review of the reporting of transoral robotic surgery

Introduction Transoral robotic surgery (TORS) has been adopted in some parts of the world as an innovative approach to the resection of oropharyngeal tumours. The development, details and outcomes of early-to-later phase evaluation of this technique and the quality of evidence to support its adoption into practice have hitherto not been summarised. The aim of this review is to identify and summarise the early and later phase studies of, and evidence for, TORS and to understand how early phase studies report intervention development, governance procedures and selection and reporting of outcomes to optimise methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice. The protocol has been written in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. Methods and analysis Electronic searches in OVID SP versions of Medline and EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from the start of indexing to 30 April 2017 will identify studies reporting TORS. At least two independent researchers will identify studies for inclusion. Two researchers will extract data from each paper. Studies will be categorised into IDEAL stages of study design from ‘pre-IDEAL’ to randomised controlled trials (stage 3). Data will be collected about the (1) novel intervention and criteria for modification, (2) governance arrangements and patient information provision, (3) outcome domains selected and reported and (4) quality of study design, conduct and reporting. Descriptive statistics and a narrative synthesis will be presented. Ethics and dissemination The results of this systematic review will be presented at relevant conferences. The methods will be used to inform future reviews exploring other novel surgical innovations. The findings will be published in a peer-reviewed journal. This study does not require ethical approval.

Informed Consent and the Reasonable-Patient Standard

In Reply Dr Bhupathiraju and colleagues suggest that our findings are biased because of differences in follow-up time between cohorts and not adequately addressing confounding by restricting the analyses to never smokers younger than 70 years, without chronic disease at baseline, and excluding the first 5 years of follow-up. We were aware of these potential pitfalls, and several sensitivity analyses in the article addressed such issues. First, the findings could not be attributed to differences in follow-up time, as shown in Figure 3 and eFigure 4 in the article. Second, an analysis restricted to never smokers without baseline disease still placed the BMI associated with the lowest mortality in the overweight range (26.1) for the most recent cohort (2003-2013) (eFigure 2 in the article). However, these sensitivity analyses have limited statistical power and further restriction would not provide usable results (eg, the additional suggested restrictions would reduce the sample size to 14 453 individuals [15% of original] and 63 deaths [1% of original] in the 2003-2013 cohort). Furthermore, we specifically wished to investigate the reported association between BMI and mortality in the general population and not in subgroups only. Also, the use of restrictions is not without pitfalls and has controversies of its own.1-3 Bhupathiraju and colleagues also mention that larger pooled studies have shown that the BMI associated with lowest mortality is less than 25. Even though the pooled studies may be larger, they may be lacking in some aspects of data quality compared with our study. For example, we sampled 3 cohorts from the same population; data collection was carried out in a similar fashion across all 3 cohorts; precise measurements of height and weight were available; and follow-up was 100% complete because in Denmark all deaths are registered. Thus, our study is less affected by errors in ascertainment of follow-up time and death, BMI, and sample heterogeneity than pooled studies. Dr Wang suggests additional analyses restricted by using a fixed follow-up time. We now have carried out analyses wherein follow-up was defined so that those with follow-up less than 8 years were excluded and follow-up was stopped at the end of the eighth year. The estimate for the BMI associated with the lowest mortality was 24.2 (12074 individuals, 248 deaths) in the 1976-1978 cohort and 27.2 (27036 individuals, 421 deaths) in the 2003-2013 cohort. The power was too low to derive meaningful confidence intervals or further restrict the analysis based on age. We agree that our study on BMI and mortality should not stand alone in informing weight guidelines, and that the relationship of body weight with incidence of chronic diseases should also be considered. That said, despite numerous sensitivity analyses our data seem robust, demonstrating that the BMI associated with the lowest mortality has increased in the past 30 to 40 years in Denmark.

Reporting outcomes of definitive radiation-based treatment for esophageal cancer

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer.

Reporting outcomes of definitive radiation-based treatment for esophageal cancer: a review of the literature: Outcome reporting in esophageal cancer trials

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer.

Patient perceptions regarding the likelihood of cure after surgical resection of lung and colorectal cancer: Communication of survival benefit

death is superior with FIT than with gFOBT. A recent study from Italy demonstrated a reduction in CRC mortality in regions in which screening with FIT was adopted compared with others, which is consistent with the results we obtained. Collectively, it is highly anticipated that FIT can achieve a greater effectiveness compared with gFOBT if the coverage rate is enhanced and the cohort is followed for an equivalent long period of time. With regard to the higher detection of CRC in men compared with women, this finding is the result of different disease prevalence rates in the target population, which is consistent with the findings from other programs and also comparable to the well-established evidence that males have a higher incidence rate than females. Finally, we agree that attention should be paid to every step of the screening program. In the Taiwanese program, we have monitored the entire screening process with a central screening database through various indicators and linkage to the national death and cancer registry so as to evaluate the long-term outcome. Last but not least, we should identify any barriers for public participation such that we can maximize the effectiveness of this population-based, organized service screening program.