Deborah Fitzsimmons

Is late diagnosis of lung cancer inevitable? Interview study of patients' recollections of symptoms before diagnosis

Background: A study was undertaken to explore the pathway to diagnosis among a group of patients recently diagnosed with lung cancer. Methods: A directed interview study triangulating patients’ accounts with hospital and GP records was performed with 22 men and women recently diagnosed with lung cancer at two cancer centres in the south and north of England. The main outcome measures were the symptoms leading up to a diagnosis of lung cancer and patient and GP responses before diagnosis. Results: Patients recalled having new symptoms for many months, typically over the year before their diagnosis, irrespective of their disease stage once diagnosed. Chest symptoms (cough, breathing changes, and pain in the chest) were common, as were systemic symptoms (fatigue/lethargy, weight loss and eating changes). Although symptoms were reported as being marked changes in health, these were not in the main (with the exception of haemoptysis) interpreted as serious by patients at the time and not acted on. Once the trigger for action occurred (the event that took patients to their GP or elsewhere in the healthcare system), events were relatively speedy and were faster for patients who presented via their GP than via other routes. Patients’ beliefs about health changes that may indicate lung cancer appeared to have played a part in delay in diagnosis. Conclusion: Further investigation of the factors influencing the timing of diagnosis in lung cancer is warranted since it appears that patients did not readily attend GP surgeries with symptoms. Insight into patients’ perspectives on their experience before diagnosis may help medical carers to recognise patients with lung cancer more easily so that they can refer them for diagnosis and treatment. Encouragement to present early with signs of lung cancer should be considered alongside other efforts to speed up diagnosis and treatment.

The clinical effectiveness and cost-effectiveness of management strategies for sciatica: systematic review and economic model.

Background Sciatica is a symptom characterised by well-localised leg pain with a sharp, shooting or burning quality that radiates down the back of the leg and normally to the foot or ankle. It is often associated with numbness or altered sensation in the leg. Objectives To determine the clinical effectiveness and cost-effectiveness of different management strategies for sciatica. Data sources Major electronic databases (e.g. MEDLINE, EMBASE and NHS Economic Evaluation Database) and several internet sites including trial registries were searched up to December 2009. Review methods Systematic reviews were undertaken of the clinical effectiveness and cost-effectiveness of different treatment strategies for sciatica. Effectiveness data were synthesised using both conventional meta-analyses and mixed treatment comparison (MTC) methods. An economic model was then developed to estimate costs per quality-adjusted life-year gained for each treatment strategy. Results The searches identified 33,590 references, of which 270 studies met the inclusion criteria and 12 included a full economic evaluation. A further 42 ongoing studies and 93 publications that could not be translated were identified. The interventions were grouped into 18 treatment categories. A larger number of studies evaluated invasive interventions and non-opioids than other non-invasive interventions. The proportion of good-quality studies for each treatment category ranged from 0% to 50%. Compared with studies of less invasive interventions, studies of invasive treatments were more likely to confirm disc herniation by imaging, to limit patients included to those with acute sciatica (< 3 months’ duration) and to include patients who had received previous treatment. The MTC analyses gave an indication of relative therapeutic effect. The statistically significant odds ratios of global effect compared with inactive control were as follows: disc surgery 2.8, epidural injection 3.1, chemonucleolysis 2.0 and non-opioids 2.6. Disc surgery and epidural injections were associated with more adverse effects than the inactive control. There was some evidence for the effectiveness of biological agents and acupuncture. Opioid medication and activity restriction were found to be less effective than the comparator interventions and opioids were associated with more adverse effects than the inactive control. The full economic evaluations were of reasonable to good quality, but were not able to fully address our research question. Although individual studies raised a number of important issues, it was difficult to draw meaningful conclusions across studies because of their heterogeneity. The economic model demonstrated that stepped-care approaches to patient management were likely to be cost-effective, relative to strategies that involved direct referral to disc surgery. Limitations The limited number of studies for some comparisons, the high level of heterogeneity (within treatment comparisons) and the potential inconsistency (between treatment comparisons) weaken the interpretation of the MTC analyses. Conclusions These findings provide support for the effectiveness of currently used therapies for sciatica such as non-opioid medication, epidural corticosteroid injections and disc surgery, but also for chemonucleolysis, which is no longer used in the UK NHS. These findings do not provide support for the effectiveness of opioid analgesia, which is widely used in this patient group, or activity restriction. They also suggest that less frequently used treatments, such as acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be effective. Stepped-care approaches to treatment for patients with sciatica are cost-effective relative to direct referral for surgery. Future research should include randomised controlled trials with concurrent economic evaluation of biological agents and acupuncture compared with placebo or with currently used treatments. Development of alternative economic modelling approaches to assess relative cost-effectiveness of treatment regimes, based on the above trial data, would also be beneficial. Funding The National Institute for Health Research Health Technology Assessment programme.

Development of the European Organisation for Research and Treatment of Cancer quality of life questionnaire module for older people with cancer: The EORTC QLQ-ELD15

BACKGROUND AND AIM There is a lack of instruments that focus on the specific health-related quality of life (HRQOL) issues that affect older people with cancer. The aim of this study was to develop a HRQOL questionnaire module to supplement the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire, the EORTC QLQ-C30 for older (>70years) patients with cancer. METHODS Phases 1-3 were conducted in seven countries following modified EORTC Quality of Life Group guidelines for module development. Phase 1: potentially relevant issues were identified by a systematic literature review, a questionnaire survey of 17 multi-disciplinary health professionals and two rounds of qualitative interviews. The first round included 9 patients aged >70. The second round was a comparative series of interviews with 49 patients >70years with a range of cancer diagnoses and 40 patients aged 50-69years matched for gender and disease site. In Phase 2 the issues were formulated into a long provisional item list. This was administered in Phase 3 together with the QLQ-C30 to two further groups of cancer patients aged >70 (n=97) or 50-69years (n=85) to determine the importance, relevance and acceptability of each item. Redundant and duplicate items were removed; issues specific to the older group were selected for the final questionnaire. RESULTS In Phase 1, 75 issues were identified. These were reduced in Phase 2 to create a 45 item provisional list. Phase 3 testing of the provisional list led to the selection of 15 items with good range of response, high scores of importance and relevance in the older patients. This resulted in the EORTC QLQ-ELD15, containing five conceptually coherent scales (functional independence, relationships with family and friends, worries about the future, autonomy and burden of illness). CONCLUSION The EORTC QLQ-ELD15 in combination with the EORTC QLQ-C30 is ready for large-scale validation studies, and will assess HRQOL issues of most relevance and concern for older people with cancer across a wide range of cancer sites and treatment stages.

A systematic review of the use and validation of health-related quality of life instruments in older cancer patients

AIM The aim of this paper is to systematically review the use and validation of HRQOL instruments in older cancer patients. METHOD A systematic review of 5 databases and 3 research registers identified studies reporting the use and validation of HRQOL instruments in cancer patients aged over 65 years from 1995 to mid 2007. RESULTS Thirty-one studies reported the use of HRQOL measures in older people, using a range of generic and disease-specific instruments. Little work was reported in patients aged over 80 years. All studies exhibited methodological limitations. Fourteen studies were identified with variable evidence on the psychometric properties and clinical usefulness of identified instruments. CONCLUSION Our review identified that the development, validation and use of HRQOL instruments often ignore the specific needs of older people. This review highlights the need for a HRQOL instrument specifically designed to capture the issues and concerns most relevant to older cancer patients.

Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses

BACKGROUND There are numerous treatment approaches for sciatica. Previous systematic reviews have not compared all these strategies together. PURPOSE To compare the clinical effectiveness of different treatment strategies for sciatica simultaneously. STUDY DESIGN Systematic review and network meta-analysis. METHODS We searched 28 electronic databases and online trial registries, along with bibliographies of previous reviews for comparative studies evaluating any intervention to treat sciatica in adults, with outcome data on global effect or pain intensity. Network meta-analysis methods were used to simultaneously compare all treatment strategies and allow indirect comparisons of treatments between studies. The study was funded by the UK National Institute for Health Research Health Technology Assessment program; there are no potential conflict of interests. RESULTS We identified 122 relevant studies; 90 were randomized controlled trials (RCTs) or quasi-RCTs. Interventions were grouped into 21 treatment strategies. Internal and external validity of included studies was very low. For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, nonopioid analgesia, manipulation, and acupuncture. Traction, percutaneous discectomy, and exercise therapy were significantly inferior to epidural injections or surgery. For pain as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant. Biological agents were significantly better for pain reduction than bed rest, nonopioids, and opioids. Opioids, education/advice alone, bed rest, and percutaneous discectomy were inferior to most other treatment strategies; although these findings represented large effects, they were statistically equivocal. CONCLUSIONS For the first time, many different treatment strategies for sciatica have been compared in the same systematic review and meta-analysis. This approach has provided new data to assist shared decision-making. The findings support the effectiveness of nonopioid medication, epidural injections, and disc surgery. They also suggest that spinal manipulation, acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be considered. The findings do not provide support for the effectiveness of opioid analgesia, bed rest, exercise therapy, education/advice (when used alone), percutaneous discectomy, or traction. The issue of how best to estimate the effectiveness of treatment approaches according to their order within a sequential treatment pathway remains an important challenge.

Familial breast cancer: summary of updated NICE guidance

Familial breast cancer occurs in people with one or more family members affected by breast, ovarian, or a related cancer such as primary peritoneal cancer. About 5% of all breast cancers can be attributed to inherited mutations in specific high risk genes such as BRCA1, BRCA2, and TP53. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the classification and care of people at risk of familial breast cancer.1 The guideline updates previous NICE guidance on familial breast cancer, published in 2004 and 2006.2 3 It also provides new guidance on men and women with a newly or previously diagnosed breast cancer who have a family history of breast and ovarian cancer, as they were excluded from previous guidance.4 NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Information and support for patients ### Initial assessment in primary care for people without a personal history of breast cancer

Cost effectiveness of the NHS breast screening programme: life table model

Objective To assess the overall cost effectiveness of the NHS breast screening programme, based on findings of the Independent UK Panel on Breast Cancer Screening and taking into account the uncertainty of associated estimates of benefits, harms, and costs. Design A life table model comparing data from two cohorts. Setting United Kingdom’s health service. Participants and interventions 364 500 women aged 50 years—the population of 50 year old women in England and Wales who would be eligible for screening—were followed up for 35 years without screening, compared with a similar cohort who had regular mammographic screening between ages 50 and 70 years and were then followed for another 15 years. Main outcome measures Between the cohorts, we compared the number of breast cancer diagnoses, number of deaths from breast cancer, number of deaths from other causes, person years of survival adjusted for health quality, and person years of survival with breast cancer. We also calculated the costs of treating primary and end stage breast cancer, and the costs of screening. Probabilistic sensitivity analysis explored the effect of uncertainty in key input parameters on the model outputs. Results Under the base case scenario (using input parameters derived from the Independent Panel Review), there were 1521 fewer deaths from breast cancer and 2722 overdiagnosed breast cancers. Discounting future costs and benefits at a rate of 3.5% resulted in an additional 6907 person years of survival in the screened cohort, at a cost of 40 946 additional years of survival after a diagnosis of breast cancer. Screening was associated with 2040 additional quality adjusted life years (QALYs) at an additional cost of £42.5m (€49.8m;

Trends in stomach and pancreatic cancer incidence and mortality in England and Wales, 1951-2000

64.7m) in total or £20 800 per QALY gained. The gain in person time survival over 35 years was 9.2 days per person and 2.7 quality adjusted days per person screened. Probabilistic sensitivity analysis showed that this incremental cost effectiveness ratio varied widely across a range of plausible scenarios. Screening was cost effective at a threshold of £20 000 per QALY gained in 2260 (45%) scenarios, but in 588 (12%) scenarios, screening was associated with a reduction in QALYs. Conclusion The NHS breast screening programme is only moderately likely to be cost effective at a standard threshold. However, there is substantial uncertainty in the model parameter estimates, and further primary research will be needed for cost effectiveness studies to provide definitive data to inform policy.

A systematic review of health-related quality of life instruments in patients with cancer cachexia

The aim of this study was to describe period and cohort effects in incidence and mortality of stomach and pancreatic cancer in England and Wales.

International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer

PurposeAssessing the health-related quality of life (HRQOL) of cancer patients with cachexia is particularly important because treatments for cachexia are currently aimed at palliation and treatment efficacy must be measured in ways other than survival. The aim of this systematic review was to evaluate HRQOL assessment in cancer patients with cachexia.MethodsUsing guidance from the Centre for Reviews and Dissemination, relevant databases were searched from January 1980 to January 2012 with terms relating to cancer, cachexia and HRQOL for papers including adult cancer patients with cachexia or documented weight loss at baseline.ResultsWe found one cachexia-specific instrument, the Functional Assessment of Anorexia/Cachexia Therapy, but the tool has not been fully validated, does not cover all the relevant domains and the consensus-based standards for the selection of health status measurement instruments checklist highlighted a number of weaknesses in the methodological quality of the validation study. Sixty-seven studies assessed HRQOL in cachectic or weight-losing cancer patients. Most used generic cancer HRQOL instruments, limiting the amount of useful information they provide. A modified version of the Efficace minimum data checklist demonstrated that the quality of reporting on HRQOL tool use was inadequate in many of the studies. A negative relationship between HRQOL and weight loss was found in 23 of the 27 studies which directly examined this.ConclusionThere is a pressing need for a well-designed HRQOL tool for use with this patient group in both clinical trials and clinical practice.