Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Routes to diagnosis for hepatocellular carcinoma patients: predictors and associations with treatment and mortality.

BACKGROUND: Hepatocellular carcinoma (HCC) incidence has increased rapidly, and prognosis remains poor. We aimed to explore predictors of routes to diagnosis (RtD), and outcomes, in HCC cases. METHODS: HCC cases diagnosed 2006-2017 were identified from the National Cancer Registration Dataset and linked to Hospital Episode Statistics and the RtD metric. Multivariable logistic regression was used to explore associations between RtD, diagnosis year, 365-day mortality and receipt of potentially curative treatment. RESULTS: 23,555 HCC cases were identified; 36.1% via emergency presentation (EP), 30.2% GP referral (GP), 17.1% outpatient referral, 11.0% two-week wait and 4.6% other/unknown routes. Odds of 365-day mortality was >70% lower via GP or OP routes than EP, and odds of curative treatment 3-4 times higher. Further adjustment for cancer/cirrhosis stage attenuated the associations with curative treatment. People who were older, female, had alcohol-related liver disease, or were more deprived, were at increased risk of an EP. Over time, diagnoses via EP decreased, and via GP increased. CONCLUSIONS: HCC RtD is an important predictor of outcomes. Continuing to reduce EP and increase GP and OP presentations, for example by identifying and regularly monitoring patients at higher risk of HCC, may improve stage at diagnosis and survival.

COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes. METHODS: Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described. RESULTS: Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes. CONCLUSIONS: During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.

The incidence of Kawasaki disease using hospital admissions data for England 2006-2021.

OBJECTIVE: To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. METHODS: We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. RESULTS: We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged <5 years was 8.9 (95% CI: 8.6, 9.2)/100 000 person-years; in children aged 5-9, 2.4 (95% CI: 2.3, 2.6)/100 000 person-years; and in children aged 10-15, 0.6 (95% CI: 0.6, 0.7). Male : female ratio was 1.5 : 1. Incidence was higher among non-White than White ethnicities [adjusted IRR 2.1 (2.0-2.2) for Asian, 3.0 (2.8-3.3) for Black and 4.5 (4.2-4.8) for other ethnicities]. The incidence increased with socioeconomic deprivation; the adjusted IRR of the least deprived IMD quintile compared with the most deprived quintile was 0.81 (0.77-0.84). CONCLUSIONS: Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Morbidity and measures of the diagnostic process in primary care for patients subsequently diagnosed with cancer.

BACKGROUND: There is uncertainty regarding how pre-existing conditions (morbidities) may influence the primary care investigation and management of individuals subsequently diagnosed with cancer. METHODS: We identified morbidities using information from both primary and secondary care records among 11,716 patients included in the English National Cancer Diagnosis Audit (NCDA) 2014. We examined variation in 5 measures of the diagnostic process (the primary care interval, diagnostic interval, number of pre-referral consultations, use of primary care-led investigations, and referral type) by both primary care- and hospital records-derived measures of morbidity. RESULTS: Morbidity prevalence recorded before cancer diagnosis was almost threefold greater using the primary care (75%) vs secondary care-derived measure (28%). After adjustment, there was limited variation in the primary care interval and the number of pre-referral consultations by either definition of morbidity. Patients with more severe morbidities were less likely to have had a primary care-led investigation before cancer diagnosis compared with those without any morbidity (adjusted odds ratio, OR [95% confidence interval]: 0.72 [0.60-0.86] for Charlson score 3+ vs 0; joint P < 0.001). Patients with multiple primary care-recorded conditions or a Charlson score of 3+ were more likely to have diagnostic intervals exceeding 60 days (aOR: 1.26 [1.10-1.45] and 1.19 [>1.00-1.41], respectively), and more likely to receive an emergency referral (aOR: 1.60 [1.26-2.02] and 1.61 [1.26-2.06], respectively). CONCLUSION: Among cancer cases with up to 2 morbidities, there was no evidence of differences in diagnostic processes and intervals in primary care but higher morbidity burden was associated with longer time to diagnosis and higher likelihood of emergency referral.

Individuals with pre-existing long-term conditions (morbidities) may have a different pathways leading to their cancer diagnosis compared with those without such conditions but detailed evidence is limited. We aimed to investigate how morbidities were associated with a range of measures of the diagnostic process in primary care. We examined morbidity in 2 ways, using information from a primary care audit and hospital records. We found that three-quarters of patients were living with 1 or more conditions according to primary care-based information, while the prevalence was almost threefold lower when estimated using hospital records. There was little difference in the time from first primary care appointment to specialist referral and the number of appointments before specialist referral by morbidity, particularly when comparing patients with 1 or 2 conditions vs those without. However, patients with multiple conditions or more serious diseases experienced lower likelihood of investigation, greater likelihood of being sent to the hospital as an emergency, and longer time to diagnosis. We did not find evidence of substantial differences in primary care-based diagnostic processes by morbidity. However, once an initial referral has been made, multiple or more severe conditions appear to influence the time taken to reach a diagnosis.

Palliative chemotherapy for breast cancer: A population-based cohort study of emergency hospital admissions and place of death.

OBJECTIVE: Patients with incurable breast cancer may be treated with chemotherapy to improve cancer-related symptoms, quality of life and survival. We examined the association between use of palliative chemotherapy towards the end of life in breast cancer patients and outcomes including unplanned hospital admission and place of death. METHODS: A total of 10,966 women, treated with palliative chemotherapy for breast cancer (diagnosed 1995-2017 in England) within the 2 years prior to death (death between 2014 and 2017), were analysed. Logistic regression (outcome = emergency hospital admission in last 90 days of life yes/no; outcome = place of death hospital/other) was performed, adjusting for line of palliative chemotherapy in the last 90 days of life and patient demographics. RESULTS: The odds of hospital admission reduced with increasing line of chemotherapy received (1st line odds ratio [OR] = 2.7, 2nd line OR = 2.1, 3rd line OR = 1.9, 4th+ line OR = 1.7; baseline chemotherapy) in last 90 days of life. A similar relationship was observed for hospital death (1st line OR = 2.4, 2nd line OR = 2.1, 3rd line OR = 1.7, 4th+ line OR = 1.5). CONCLUSION: This study finds palliative chemotherapy towards the end of life to be associated with increased odds of unplanned hospital admissions and hospital death. These findings can be used to inform discussions between patients and healthcare professionals towards the end of life.

Presenting symptoms of cancer and stage at diagnosis: evidence from a cross-sectional, population-based study.

BACKGROUND: Early diagnosis interventions such as symptom awareness campaigns increasingly form part of global cancer control strategies. However, these strategies will have little impact in improving cancer outcomes if the targeted symptoms represent advanced stage of disease. Therefore, we aimed to examine associations between common presenting symptoms of cancer and stage at diagnosis. METHODS: In this cross-sectional study, we analysed population-level data from the English National Cancer Diagnosis Audit 2014 for patients aged 25 years and older with one of 12 types of solid tumours (bladder, breast, colon, endometrial, laryngeal, lung, melanoma, oral or oropharyngeal, ovarian, prostate, rectal, and renal cancer). We considered 20 common presenting symptoms and examined their associations with stage at diagnosis (TNM stage IV vs stage I-III) using logistic regression. For each symptom, we estimated these associations when reported as a single presenting symptom and when reported together with other symptoms. FINDINGS: We analysed data for 7997 patients. The proportion of patients diagnosed with stage IV cancer varied substantially by presenting symptom, from 1% (95% CI 1-3; eight of 584 patients) for abnormal mole to 80% (71-87; 84 of 105 patients) for neck lump. Three of the examined symptoms (neck lump, chest pain, and back pain) were consistently associated with increased odds of stage IV cancer, whether reported alone or with other symptoms, whereas the opposite was true for abnormal mole, breast lump, postmenopausal bleeding, and rectal bleeding. For 13 of the 20 symptoms (abnormal mole, breast lump, post-menopausal bleeding, rectal bleeding, lower urinary tract symptoms, haematuria, change in bowel habit, hoarseness, fatigue, abdominal pain, lower abdominal pain, weight loss, and the "any other symptom" category), more than 50% of patients were diagnosed at stages other than stage IV; for 19 of the 20 studied symptoms (all except for neck lump), more than a third of patients were diagnosed at stages other than stage IV. INTERPRETATION: Despite specific presenting symptoms being more strongly associated with advanced stage at diagnosis than others, for most symptoms, large proportions of patients are diagnosed at stages other than stage IV. These findings provide support for early diagnosis interventions targeting common cancer symptoms, countering concerns that they might be simply expediting the detection of advanced stage disease. FUNDING: UK Department of Health's Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis; and Cancer Research UK.

Geographical access to GPs and modes of cancer diagnosis in England: a cross-sectional study.

BACKGROUND: Poor geographical access to health services and routes to a cancer diagnosis such as emergency presentations have previously been associated with worse cancer outcomes. However, the extent to which access to GPs determines the route that patients take to obtain a cancer diagnosis is unknown. METHODS: We used a linked dataset of cancer registry and hospital records of patients with a cancer diagnosis between 2006 and 2010 across eight different cancer sites. Primary outcomes were defined as 'desirable routes to diagnosis' [screen-detected and 2-week wait (TWW) referrals] and 'less desirable routes' [emergency presentations and death certificate only (DCO)]. All other routes (GP referral, inpatient elective and other outpatient) were specified as the reference category. Geographical access was measured as travel time in minutes from patients to their GP, and multinomial logistic regression was used to estimate relative risk ratios (RRR). RESULTS: Longer travel was associated with increased risk of diagnosis via emergency and DCO, but decreased risk of diagnosis via screening and TWW. Patients travelling over 30 minutes had the highest risk of a DCO diagnosis, which was statistically significant for breast, colorectal, lung, prostate, stomach and ovarian cancers (compared with patients with travel times ≤10 minutes: RRR 5.89, 7.02, 2.30, 4.75, 10.41; P < 0.01 and 3.51, P < 0.05). DISCUSSION: Poor access to GPs may discourage early engagement with health services, decreasing the likelihood of screening uptake and increasing the likelihood of emergency presentations. Extra effort is needed to promote early diagnosis in more distant patients.

Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological study.

BACKGROUND: Large variation in measures of diagnostic activity has been described previously between English general practices, but related predictors remain understudied. OBJECTIVE: To examine associations between general practice population and characteristics, with the use of urgent referrals for suspected cancer, and use of endoscopy. METHODS: Cross-sectional observational study of English general practices. We examined practice-level use (/1000 patients/year) of urgent referrals for suspected cancer, gastroscopy, flexible sigmoidoscopy and colonoscopy. We used mixed-effects Poisson regression to examine associations with the sociodemographic profile of practice populations and other practice attributes, including the average age, sex and country of qualification of practice doctors. RESULTS: The sociodemographic characteristics of registered patients explained much of the between-practice variance in use of urgent referrals (32%) and endoscopic investigations (18-25%), all being higher in practices with older and more socioeconomically deprived patients. Practice-level attributes explained a substantial amount of between-practice variance in urgent referral (19%) but little of the variance in endoscopy (3%-4%). Adjusted urgent referral rates were higher in training practices and those with younger GPs. Practices with mean doctor ages of 41 and 57 years (at the 10th/90th centiles of the national distribution) would have urgent referral rates of 24.1 and 19.1/1000 registered patients, P < 0.001. CONCLUSION: Most between-practice variation in use of urgent referrals and endoscopies seems to reflect health need. Some practice characteristics, such as the mean age of GPs, are associated with appreciable variation in use of urgent referrals, though these associations do not seem strong enough to justify targeted interventions.

Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013-2014.

BACKGROUND: Sociodemographic inequalities in cancer treatment have been generally described, but there is little evidence regarding patients with advanced cancer. Understanding variation in the management of these patients may provide insights into likely mechanisms leading to inequalities in survival. METHODS: We identified 50,232 patients with stage IV lung, oesophageal, pancreatic and stomach cancer from the English national cancer registry. A generalised linear model with a Poisson error structure was used to explore variation in radiotherapy and chemotherapy within 6 months from diagnosis by age, sex, deprivation, ethnicity, cancer site, comorbidity and, additionally, performance status. RESULTS: There was substantial variation by cancer site, large gradients by age, and non-trivial associations with comorbidity and deprivation. After full adjustment, more deprived patients were consistently least likely to be treated with chemotherapy alone or chemotherapy and radiotherapy combined compared with less deprived patients with equally advanced disease stage (treatment rate ratio: 0.82 95% CI (0.78, 0.87) for CT, 0.78 95% CI (0.71, 0.85) for CTRT p < 0.0001). CONCLUSIONS: There was marked variation in the management of patients with stage IV cancer. Routinely collected data could be used for surveillance across all cancers to help reduce treatment variation and optimise outcomes among patients with advanced cancer.

The nature and frequency of abdominal symptoms in cancer patients and their associations with time to help-seeking: evidence from a national audit of cancer diagnosis.

Background: Raising awareness of possible cancer symptoms is important for timely help-seeking; recent campaigns have focused on symptom groups (such as abdominal symptoms) rather than individual alarm symptoms associated with particular cancer sites. The evidence base supporting such initiatives is still emerging however; understanding the frequency and nature of presenting abdominal symptoms among cancer patients could inform the design and evaluation of public health awareness campaigns. Methods: We examined eight presenting abdominal symptoms (abdominal pain, change in bowel habit, bloating/distension, dyspepsia, rectal bleeding, dysphagia, reflux and nausea/vomiting) among 15 956 patients subsequently diagnosed with cancer in England. We investigated the cancer site case-mix and variation in the patient interval (symptom-onset-to-presentation) by abdominal symptom. Results: Almost a quarter (23%) of cancer patients presented with abdominal symptoms before being diagnosed with one of 27 common and rarer cancers. The patient interval varied substantially by abdominal symptom: median (IQR) intervals ranged from 7 (0-28) days for abdominal pain to 30 (4-73) days for dysphagia. This variation persisted after adjusting for age, sex and ethnicity (P < 0.001). Conclusions: Abdominal symptoms are common at presentation among cancer patients, while time to presentation varies by symptom. The need for awareness campaigns may be greater for symptoms associated with longer intervals to help-seeking.

30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study.

BACKGROUND: 30-day mortality might be a useful indicator of avoidable harm to patients from systemic anticancer treatments, but data for this indicator are limited. The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England allows the assessment of factors affecting 30-day mortality in a national patient population. The aim of this first study based on the SACT dataset was to establish national 30-day mortality benchmarks for breast and lung cancer patients receiving SACT in England, and to start to identify where patient care could be improved. METHODS: In this population-based study, we included all women with breast cancer and all men and women with lung cancer residing in England, who were 24 years or older and who started a cycle of SACT in 2014 irrespective of the number of previous treatment cycles or programmes, and irrespective of their position within the disease trajectory. We calculated 30-day mortality after the most recent cycle of SACT for those patients. We did logistic regression analyses, adjusting for relevant factors, to examine whether patient, tumour, or treatment-related factors were associated with the risk of 30-day mortality. For each cancer type and intent, we calculated 30-day mortality rates and patient volume at the hospital trust level, and contrasted these in a funnel plot. FINDINGS: Between Jan 1, and Dec, 31, 2014, we included 23 228 patients with breast cancer and 9634 patients with non-small cell lung cancer (NSCLC) in our regression and trust-level analyses. 30-day mortality increased with age for both patients with breast cancer and patients with NSCLC treated with curative intent, and decreased with age for patients receiving palliative SACT (breast curative: odds ratio [OR] 1·085, 99% CI 1·040-1·132; p<0·0001; NSCLC curative: 1·045, 1·013-1·079; p=0·00033; breast palliative: 0·987, 0·977-0·996; p=0·00034; NSCLC palliative: 0·987, 0·976-0·998; p=0·0015). 30-day mortality was also significantly higher for patients receiving their first reported curative or palliative SACT versus those who received SACT previously (breast palliative: OR 2·326 99% CI 1·634-3·312; p<0·0001; NSCLC curative: 3·371, 1·554-7·316; p<0·0001; NSCLC palliative: 2·667, 2·109-3·373; p<0·0001), and for patients with worse general wellbeing (performance status 2-4) versus those who were generally well (breast curative: 6·057, 1·333-27·513; p=0·0021; breast palliative: 6·241, 4·180-9·319; p<0·0001; NSCLC palliative: 3·384, 2·276-5·032; p<0·0001). We identified trusts with mortality rates in excess of the 95% control limits; this included seven for curative breast cancer, four for palliative breast cancer, five for curative NSCLC, and seven for palliative NSCLC. INTERPRETATION: Our findings show that several factors affect the risk of early mortality of breast and lung cancer patients in England and that some groups are at a substantially increased risk of 30-day mortality. The identification of hospitals with significantly higher 30-day mortality rates should promote review of clinical decision making in these hospitals. Furthermore, our results highlight the importance of collecting routine data beyond clinical trials to better understand the factors placing patients at higher risk of 30-day mortality, and ultimately improve clinical decision making. Our insights into the factors affecting risk of 30-day mortality will help treating clinicians and their patients predict the balance of harms and benefits associated with SACT. FUNDING: Public Health England.

Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: evidence from a National Audit of Cancer Diagnosis in Primary Care.

Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the 'patient interval'). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009-2010). Proportions of patients with 'prompt'/'non-prompt' presentation (0-14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0-38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p < 0.001). Prompt presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p <.001). Using lung cancer as reference, the adjusted odds ratios of non-prompt presentation were 2.26 (95% confidence interval 1.57-3.25) and 0.42 (0.34-0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer.

Routes to Diagnosis in Danish Lung Cancer Patients: Emergency Presentation, Age and Smoking History-A Population-Based Cohort Study.

BACKGROUND: The fast-track cancer pathway aims to expedite diagnosis of lung cancer and treatment and is the preferred route to diagnosis. Diagnosis following an unplanned admission (unplanned route) has been associated with poor outcomes. OBJECTIVE: This study explores factors associated with lung cancer diagnosis following unplanned admissions, focusing on the elderly population. METHODS: A retrospective cohort study using population-based data from Danish registries. Factors such as age, comorbidity, performance status, smoking history, socioeconomic parameters and treatment modality were analyzed in relation to route to diagnosis and prognosis. RESULTS: Among 17,835 patients, 16% were elderly (≥ 80 years). The unplanned route constituted 28% of diagnostic routes, with higher proportion among the elderly (33%). Poor performance status and advanced disease stage were associated with the unplanned route. Married patients were less likely to undergo an unplanned route to diagnosis. Smoking did not significantly influence diagnostic route. The adjusted odds ratio for curative treatment and dying 12 months after diagnosis, following unplanned route to diagnosis were 0.68 (95% CI, 0.61-0.76) and 1.48 (95% CI, 1.36-1.61), respectively. CONCLUSION: Frailty (poor performance status and high burden of comorbidity) in addition to unfavorable socioeconomic factors, which all were more prevalent among elderly patients, were associated with undergoing an unplanned route to diagnosis. However, age itself was not. Diagnosis following unplanned admission correlated with reduced likelihood of curative treatment and poorer prognosis. Expanding screening initiatives to include frail elderly individuals living alone, along with alertness by primary care clinicians, is warranted to improve outcomes for these patients.

Lung cancer among the Elderly in Denmark - A comprehensive population-based cohort study.

OBJECTIVE: Lung cancer primarily occurs in the elderly with a median age at diagnosis in Denmark of 73 years. However, elderly patients are under-represented in clinical trials as well as in screening studies. In this study, we aim to characterize elderly patients with lung cancer and explore the diagnostic intensity, treatment patterns, and survival. METHOD: Patients diagnosed with lung cancer between 2014 and 2017 according to the Danish Cancer Registry, and with clinical information in the Danish Lung Cancer Registry were included. Patient information was linked by the unique social identification number to information from Statistics Denmark. RESULTS: We included n = 17,835 patients in this study, of whom 2,871 (16.1 %) were 80 years or older. Fewer elderly patients had lung biopsies (47 % vs 53 %) or mediastinal procedures (34 % vs 26 %), compared to the younger patients (p < 0.001). Fewer elderly patients had treatment registration (60 % vs 85 %), and fewer received treatment with curative intent (23 % vs 42 %) compared to patients younger than 80 years (p < 0.001). The elderly patients had 2.1 (CI 95 % 1.9 - 2.2) times higher odds of dying within 12 months after diagnosis than younger patients. CONCLUSION: The diagnostic intensity among lung cancer patients aged eighty years or above is lower compared to younger patients. Being elderly is associated with not undergoing surgical treatment or treatment with curative intent. Across all treatment groups, being older than eighty years of age was associated with an adverse prognosis.

Pre-Referral Primary Care Blood Tests and Symptom Presentation before Cancer Diagnosis: National Cancer Diagnosis Audit Data.

BACKGROUND: Blood tests can support the diagnostic process in primary care. Understanding how symptomatic presentations are associated with blood test use in patients subsequently diagnosed with cancer can help to benchmark current practices and guide interventions. METHODS: English National Cancer Diagnosis Audit data on 39,751 patients with incident cancer in 2018 were analysed. The frequency of four generic (full blood count, urea and electrolytes, liver function tests, and inflammatory markers) and five organ-specific (cancer biomarkers (PSA or CA125), serum protein electrophoresis, ferritin, bone profile, and amylase) blood tests was described for a total of 83 presenting symptoms. The adjusted analysis explored variation in blood test use by the symptom-positive predictive value (PPV) group. RESULTS: There was a large variation in generic blood test use by presenting symptoms, being higher in patients subsequently diagnosed with cancer who presented with nonspecific symptoms (e.g., fatigue 81% or loss of appetite 79%), and lower in those who presented with alarm symptoms (e.g., breast lump 3% or skin lesion 1%). Serum protein electrophoresis (reflecting suspicion of multiple myeloma) was most frequently used in cancer patients who presented with back pain (18%), and amylase measurement (reflecting suspicion of pancreatic cancer) was used in those who presented with upper abdominal pain (14%). Prostate-specific antigen (PSA) use was greatest in men with cancer who presented with lower urinary tract symptoms (88%), and CA125 in women with cancer who presented with abdominal distention (53%). Symptoms with PPV values between 2.00-2.99% were associated with greater test use (64%) compared with 52% and 51% in symptoms with PPVs in the 0.01-0.99 or 1.00-1.99% range and compared with 42% and 31% in symptoms with PPVs in either the 3.00-4.99 or ≥5% range (p < 0.001). CONCLUSIONS: Generic blood test use reflects the PPV of presenting symptoms, and the use of organ-specific tests is greater in patients with symptomatic presentations with known associations with certain cancer sites. There are opportunities for greater blood test use in patients presenting with symptoms that do not meet referral thresholds (i.e., <3% PPV for cancer) where information gain to support referral decisions is likely greatest. The findings benchmark blood test use in cancer patients, highlighting opportunities for increasing use.