Helen A. Powell

Early mortality after surgical resection for lung cancer: an analysis of the English National Lung cancer audit

Introduction For appropriately staged non-small cell lung cancer (NSCLC) surgical resection can dramatically improve survival, but some may not be offered this treatment because of concerns about perioperative mortality. Methods We used data from the National Lung Cancer Audit (NLCA) to determine the proportions of English patients who died within 30 and 90 days after surgery for NSCLC. We quantified the predictors of early postoperative death and using these results devised a score to predict risk of death within 90 days of surgery. Results We analysed data on 10 991 patients operated on between 2004 and 2010. Three per cent (334) of patients died within 30 days of their procedure and 5.9% (647) within 90 days. Age was strongly associated with early postoperative death (adjusted OR within 90 days for 80–84 years vs 70–74 years: 1.46, 95% CI 1.07 to 1.98); significant associations were also observed with performance status (PS) (adjusted OR within 90 days for PS 2 vs PS 0: 2.40, 95% CI 1.68 to 3.41), as well as lung function, stage and procedure type. Conclusions Our results show that age is the most important predictor of death within both of these early postoperative periods. We used the data in the NLCA to develop a predictive score, based on an English population and specific to lung cancer surgery, which estimates risk of death within 90 days; this score should be tested in future cohorts.

Chronic Obstructive Pulmonary Disease and Risk of Lung Cancer: The Importance of Smoking and Timing of Diagnosis

Introduction: The majority of cases of both lung cancer and chronic obstructive pulmonary disease (COPD) are attributable to cigarette smoking, but whether COPD is an independent risk factor for lung cancer remains unclear. Methods: We used The Health Improvement Network, a U.K. general practice database, to identify incident cases of lung cancer and controls matched on age, sex, and practice. Using conditional logistic regression, we assessed the effects of timing of first diagnoses of COPD, pneumonia, and asthma on the odds of lung cancer, adjusting for smoking habit. Results: Of 11,888 incident cases of lung cancer, 23% had a prior diagnosis of COPD compared with only 6% of the 37,605 controls. The odds of lung cancer in patients who had COPD diagnosed within 6 months of their cancer diagnosis were 11-fold those of patients without COPD (odds ratio 11.47, 95% confidence interval 9.38–14.02). However, when restricted to earlier COPD diagnoses, with adjustment for smoking, the effect markedly diminished (for COPD diagnoses >10 years before lung cancer diagnosis, odds ratio: 2.18, 95% confidence interval: 1.87–2.54). The pattern was similar for pneumonia. The effect of COPD on lung cancer remained after excluding patients who had a codiagnosis of asthma. Conclusion: A diagnosis of COPD is strongly associated with a diagnosis of lung cancer, however, this association is largely explained by smoking habit, strongly dependent on the timing of COPD diagnosis, and not specific to COPD. It seems unlikely, therefore, that COPD is an independent risk factor for lung cancer.

What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK

Background The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. Methods All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. Results Of 20 142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65–69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. Conclusions Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment.

The Association Between Smoking Quantity and Lung Cancer in Men and Women

BACKGROUND Studies have shown that for the same quantity of cigarettes smoked, women are more likely to develop heart disease than men, but studies in lung cancer have produced conflicting results. We studied the association between smoking quantity and lung cancer in men and women. METHODS Using data from The Health Improvement Network (a UK medical research database), we generated a data set comprising 12,121 incident cases of lung cancer and 48,216 age-, sex-, and general practice-matched control subjects. We used conditional logistic regression to calculate ORs for lung cancer according to highest-ever-quantity smoked in men and women separately. RESULTS The odds of lung cancer in women who had ever smoked heavily compared with those who had never smoked were increased 19-fold (OR, 19.10; 95% CI, 16.98-21.49), which was more than for men smoking the same quantity (OR, 12.81; 95% CI, 11.52-14.24). There was strong evidence of a difference in effect of quantity smoked on lung cancer between men and women (interaction P < .0001), which remained after adjusting for height (a proxy marker for lung volume). CONCLUSIONS Moderate and heavy smoking carry a higher risk of lung cancer in women than in men, and this difference does not seem to be explained by lung volume. The findings suggest that extrapolating risk estimates for lung cancer in men to women will underestimate the adverse impact of smoking in women.

Risk Factors for Cardiovascular Disease in People With Idiopathic Pulmonary Fibrosis: A Population-Based Study

OBJECTIVE People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors. METHODS We used data from a large, UK primary care database to identify incident cases of IPF and matched general-population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects. RESULTS We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors. CONCLUSIONS Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients.

Lung cancer survival in England: trends in non-small-cell lung cancer survival over the duration of the National Lung Cancer Audit.

Background:In comparison with other European and North American countries, England has poor survival figures for lung cancer. Our aim was to evaluate the changes in survival since the introduction of the National Lung Cancer Audit (NLCA).Methods:We used data from the NLCA to identify people with non-small-cell lung cancer (NSCLC) and stratified people according to their performance status (PS) and clinical stage. Using Cox regression, we calculated hazard ratios (HRs) for death according to the year of diagnosis from 2004/2005 to 2010; adjusted for patient features including age, sex and co-morbidity. We also assessed whether any changes in survival were explained by the changes in surgical resection rates or histological subtype.Results:In this cohort of 120 745 patients, the overall median survival did not change; but there was a 1% annual improvement in survival over the study period (adjusted HR 0.99, 95% confidence interval (CI) 0.98–0.99). Survival improvement was only seen in patients with good PS and early stage (adjusted HR 0.97, 95% CI 0.95–0.99) and this was partly accounted for by changes in resection rates.Conclusion:Survival has only improved for a limited group of people with NSCLC and increasing surgical resection rates appeared to explain some of this improvement.

The impact of the ‘hub and spoke’ model of care for lung cancer and equitable access to surgery

Objectives To determine the influence of where a patient is first seen (either surgical or non-surgical centre) and patient features on having surgery for non-small cell lung cancer (NSCLC). Design Cross-sectional study from individual patients, between 1January 2008 and 31March 2012. Setting Linked National Lung Cancer Audit and Hospital Episode Statistics datasets. Participants 95 818 English patients with a diagnosis of NSCLC, of whom 12 759 (13%) underwent surgical resection. Main outcome measure Odds of having surgery based on the empirical catchment population of the 30 thoracic surgical centres in England and whether the patient is first seen in a surgical centre or a non-surgical centre. Results Patients were more likely to be operated on if they were first seen at a surgical centre (OR 1.37; 95% CI 1.29 to 1.45). This was most marked for surgical centres with the largest catchment populations. In these surgical centres with large catchment populations, the resection rate for local patients was 18% and for patients first seen in a non-surgical centre within catchment was 12%. Conclusions Surgical centres that serve the largest catchment populations have high resection rates for patients first seen in their own centre but, in contrast, low resection rates for patients first seen at the surrounding centres they serve. Our findings demonstrate the importance of going further than relating resection rates to hospital volume or surgeon number, and show that there is a pressing need to design lung cancer services which enable all patients, including those first seen at non-surgical centres, to have equal access to lung cancer surgery.

Small-Cell Lung Cancer in England: Trends in Survival and Chemotherapy Using the National Lung Cancer Audit

Background The purpose of this study was to identify trends in survival and chemotherapy use for individuals with small-cell lung cancer (SCLC) in England using the National Lung Cancer Audit (NLCA). Methods We used data from the NLCA database to identify people with histologically proven SCLC from 2004–2011. We calculated the median survival by stage and assessed whether patient characteristics changed over time. We also assessed whether the proportion of patients with records of chemotherapy and/or radiotherapy changed over time. Results 18,513 patients were diagnosed with SCLC in our cohort. The median survival was 6 months for all patients, 1 year for those with limited stage and 4 months for extensive stage. 69% received chemotherapy and this proportion changed very slightly over time (test for trends p = 0.055). Age and performance status of patients remained stable over the study period, but the proportion of patients staged increased (p-value<0.001), mainly because of improved data completeness. There has been an increase in the proportion of patients that had a record of receiving both chemotherapy and radiotherapy each year (from 19% to 40% in limited and from 9% to 21% in extensive stage from 2004 to 2011). Patients who received chemotherapy with radiotherapy had better survival compared with any other treatment (HR 0.24, 95% CI 0.23–0.25). Conclusion Since 2004, when the NLCA was established, the proportion of patients with SCLC having chemotherapy has remained static. We have found an upward trend in the proportion of patients receiving both chemotherapy and radiotherapy which corresponded to a better survival in this group, but as it only applied for a small proportion of patients, it was not enough to change the overall survival.

The pathological confirmation rate of lung cancer in England using the NLCA database

BACKGROUND The National Lung Cancer Audit (NLCA) recommends that trusts obtain pathology (histology or cytology) for 75% of their lung cancer patients, however this figure was arbitrarily chosen and the optimal pathological confirmation rate is unknown, and many countries report somewhat higher rates. The aims of this study were to provide a simple means of benchmarking appropriate pathological confirmation rates by stratifying patients into groups, and whether obtaining pathology based on those groups is associated with a survival benefit. METHODS We calculated the proportion of patients with non-small cell or small cell lung cancer in the NLCA database, first seen between 1st January 2004 and 31st December 2010, who had pathological confirmation of their diagnosis. Using logistic we assessed the independent influence of patient factors on the likelihood of having histology or cytology, and the overall effect on survival. We also used bivariate analysis to identify the features which were most strongly associated with having pathology and performed Cox regression to identify any survival advantage. FINDINGS We analysed data on 136,993 individuals. Age and performance status (PS) were the strongest predictors of pathological confirmation: age ≥ 85 odds ratio (OR) 0.20 (95% confidence interval (CI) 0.19-0.22) compared with age<55; PS 4 OR 0.11 (95%CI 0.10-0.12) compared with PS 0. Pathological confirmation of diagnosis was associated with a small early survival advantage for groups 1 & 2 which represented younger patients with good PS, even after adjusting for other patient features: hazard ratio (HR) 0.93 & 0.89 respectively. CONCLUSION Stratifying patients by age and performance status is useful and appropriate when benchmarking standards for pathological confirmation of the diagnosis of lung cancer. We have shown better survival at six months and one year for younger patients with better PS, even after adjusting for confounders. Much of the survival advantage was accounted for by adjusting for the use of chemotherapy.

Venous thromboembolism in people with idiopathic pulmonary fibrosis: a population-based study

To the Editor: Laboratory studies and animal models have suggested that the activation of the clotting cascade may be important in the pathogenesis of idiopathic pulmonary fibrosis (IPF) [1–3]. Epidemiological studies have also suggested a strong association between IPF and venous thromboembolism (VTE) [4–6]. We estimated the incidence of pulmonary embolus and deep vein thrombosis (DVT) in people with IPF and the general population, and compared these with the prevalence of a warfarin prescription. We used data from THIN (The Health Improvement Network; www.thin-uk.com), a UK longitudinal database of electronic primary care records containing information recorded in routine clinical care, from face-to-face consultations, and following communication from secondary care. Medical and diagnostic data are entered using medical Read codes, a comprehensive list of medical terms …