The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5192 ...children with cancer (age 0‐14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan–Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5‐year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in 2005‐2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1‐14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).
For many of childhood cancers, 5‐year survival improved in Japan and England. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries.
Pancreatic cancer (PC) represents a substantial public health burden. Pancreatic cancer patients have very low survival due to the difficulty of identifying cancers early when the tumour is localised ...to the site of origin and treatable. Recent progress has been made in identifying biomarkers for PC in the blood and urine, but these cannot be used for population-based screening as this would be prohibitively expensive and potentially harmful.
We conducted a case-control study using prospectively-collected electronic health records from primary care individually-linked to cancer registrations. Our cases were comprised of 1,139 patients, aged 15-99 years, diagnosed with pancreatic cancer between January 1, 2005 and June 30, 2009. Each case was age-, sex- and diagnosis time-matched to four non-pancreatic (cancer patient) controls. Disease and prescription codes for the 24 months prior to diagnosis were used to identify 57 individual symptoms. Using a machine learning approach, we trained a logistic regression model on 75% of the data to predict patients who later developed PC and tested the model's performance on the remaining 25%.
We were able to identify 41.3% of patients < = 60 years at 'high risk' of developing pancreatic cancer up to 20 months prior to diagnosis with 72.5% sensitivity, 59% specificity and, 66% AUC. 43.2% of patients >60 years were similarly identified at 17 months, with 65% sensitivity, 57% specificity and, 61% AUC. We estimate that combining our algorithm with currently available biomarker tests could result in 30 older and 400 younger patients per cancer being identified as 'potential patients', and the earlier diagnosis of around 60% of tumours.
After further work this approach could be applied in the primary care setting and has the potential to be used alongside a non-invasive biomarker test to increase earlier diagnosis. This would result in a greater number of patients surviving this devastating disease.
BACKGROUND
The lifetime risk of developing leukemia in the United States is 1.5%. There are challenges in the estimation of population‐based survival using registry data because treatments and ...prognosis vary greatly by subtype. The objective of the current study was to determine leukemia survival estimates in the United States from 1995 to 2009 according to subtype, sex, geographical area, and race.
METHODS
Five‐year net survival was estimated using data for 370,994 patients from 43 registries in 37 states and in 6 metropolitan areas, covering approximately 81% of the adult (15‐99 years) US population. Leukemia was categorized according to principal subtype (chronic lymphocytic leukemia, acute myeloid leukemia, and acute lymphocytic leukemia), and subcategorized in accordance with the HAEMACARE protocol. We analyzed age‐standardized 5‐year net survival by calendar period (1995‐1999, 2000‐2004, and 2005‐2009), leukemia subtype, sex, race, and US state.
RESULTS
The age‐standardized 5‐year net survival estimates increased from 45.0% for patients diagnosed during 1995‐1999 to 49.0% for those diagnosed during 2000‐2004 and 52.0% for those diagnosed during 2005‐2009. For patients diagnosed during 2005‐2009, 5‐year survival was 18.2% (95% confidence interval 95% CI, 17.8%‐18.6%) for acute myeloid leukemia, 44.0% (95% CI, 43.2%‐44.8%) for acute lymphocytic leukemia, and 77.3% (95% CI, 76.9%‐77.7%) for chronic lymphocytic leukemia. For nearly all leukemia subtypes, survival declined in successive age groups above 45 to 54 years. Men were found to have slightly lower survival than women; however, this discrepancy was noted to have fallen in successive calendar periods. Net survival was substantially higher in white than black patients in all calendar periods. There were large differences in survival noted between states and metropolitan areas.
CONCLUSIONS
Survival from leukemia in US adults improved during 1995‐2009. Some geographical differences in survival may be related to access to care. We found disparities in survival by sex and between black and white patients.
While survival from leukemia in adults in the United States has improved during 1995‐2009, disparities are found in survival by sex and between black and white patients.
Parental occupational exposures around conception (father) or during pregnancy (mother) have been hypothesized as potential predisposing factors for childhood leukaemia. We investigated parental ...exposure to several known occupational carcinogens and childhood leukaemia risk. We conducted a pooled analysis using case-control data from four European countries (3362 childhood leukemia cases and 6268 controls). Parental occupational exposures to polycyclic aromatic hydrocarbons (PAH), diesel engine exhaust (DEE), chromium, nickel, crystalline silica, and asbestos were assessed by a general population job-exposure matrix. We estimated odd ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models for all childhood leukaemia combined, by leukaemia type (ALL and AML) and by ALL subtype (B-lineage and T-lineage). We found an association between high paternal occupational exposure to crystalline silica and childhood ALL (OR 2.20, CI 1.60–3.01) with increasing trend from no exposure to high exposure (P = <0.001), and also for AML (OR 2.03, CI 1.04–3.97; P for trend = 0.008). ORs were similar for B- and T-lineage ALL. For ALL, ORs were also slightly elevated with wide confidence intervals for high paternal occupational exposure to chromium (OR 1.23, CI 0.77–1.96), and DEE (OR 1.21, CI 0.82–1.77). No associations were observed for paternal exposures to nickel, PAH and asbestos. For maternal occupational exposure we found several slightly elevated odds ratios but mostly with very wide confidence intervals due to low numbers of exposed mothers. This is a first study suggesting an association between fathers’ occupational exposure to crystalline silica and an increased risk of childhood leukaemia in their offspring. As this association was driven by certain occupations (field crop farmers and miners) where other potentially relevant exposures like pesticides and radon may also occur, more research is needed to confirm our findings of an association with crystalline silica, and if so, mechanistic studies to understand the pathways.
PurposeThe United Kingdom Childhood Cancer Study’s (UKCCS’s) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before ...15 years of age, comparing future healthcare patterns in 5-year cancer survivors to baseline activity seen in age- and sex-matched individuals from the general population.ParticipantsPredicated on a national childhood cancer case-control study conducted in the early 1990s (4430 cases, 9753 controls) in England, Scotland and Wales, the case population comprises 3125 cancer survivors (>5 years), and the control population 7156 age- and sex-matched individuals from the general population who did not have cancer as a child. Participants are now being followed up via linkage to national administrative healthcare databases (deaths, cancers and secondary care hospital activity).Findings to dateEnabling the creation of cohorts with minimal selection bias and loss to follow-up, the original case-control study registered all newly diagnosed cases of childhood cancer and their corresponding controls, regardless of their family’s participation. Early findings based on the registered case population found marked survival variations with age and sex across subtypes and differences with deprivation among acute lymphoblastic leukaemia (ALL) survivors. More recently, comparing the health-activity patterns of the case and control populations revealed that survivors of childhood ALL experienced excess outpatient and inpatient activity across their teenage/young adult years. Adding to increased risks of cancer and death and involving most clinical specialties, excesses were not related to routine follow-up monitoring and showed no signs of diminishing over time.Future plansWith annual linkage updates, the UKCCS’s maturing population-based matched cohorts provide the foundation for tracking the health of individuals through their lifetime. Comparing the experience of childhood cancer survivors to that of unaffected general-population counterparts, this will include examining subsequent morbidity and mortality, secondary care hospital activity and the impact of deprivation on longer term outcomes.
Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular ...lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005-2013.
Multivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables.
We included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40-1.73; FL: odds ratio 1.80, CI 1.45-2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities.
Underlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.
BACKGROUND
Robust comparisons of population‐based cancer survival estimates require tight adherence to the study protocol, standardized quality control, appropriate life tables of background ...mortality, and centralized analysis. The CONCORD program established worldwide surveillance of population‐based cancer survival in 2015, analyzing individual data on 26 million patients (including 10 million US patients) diagnosed between 1995 and 2009 with 1 of 10 common malignancies.
METHODS
In this Cancer supplement, we analyzed data from 37 state cancer registries that participated in the second cycle of the CONCORD program (CONCORD‐2), covering approximately 80% of the US population. Data quality checks were performed in 3 consecutive phases: protocol adherence, exclusions, and editorial checks. One‐, 3‐, and 5‐year age‐standardized net survival was estimated using the Pohar Perme estimator and state‐ and race‐specific life tables of all‐cause mortality for each year. The cohort approach was adopted for patients diagnosed between 2001 and 2003, and the complete approach for patients diagnosed between 2004 and 2009.
RESULTS
Articles in this supplement report population coverage, data quality indicators, and age‐standardized 5‐year net survival by state, race, and stage at diagnosis. Examples of tables, bar charts, and funnel plots are provided in this article.
CONCLUSIONS
Population‐based cancer survival is a key measure of the overall effectiveness of services in providing equitable health care. The high quality of US cancer registry data, 80% population coverage, and use of an unbiased net survival estimator ensure that the survival trends reported in this supplement are robustly comparable by race and state. The results can be used by policymakers to identify and address inequities in cancer survival in each state and for the United States nationally. Cancer 2017;123:4982‐93. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Population‐based cancer survival is a key measure of the overall effectiveness of health systems in managing the cancer burden. The high quality of US cancer registry data, 80% population coverage in the CONCORD‐2 study, and the use of an unbiased estimator of net survival ensure that the survival trends reported in this supplement are robustly comparable by race and state. These results can be used to plan and evaluate the cancer control strategy in each state and for the United States nationally.
ObjectivesTo examine morbidity and mortality among teenagers and young adults (TYAs) previously diagnosed with acute lymphoblastic leukaemia (ALL) in childhood, and compare to the general TYA ...population.DesignNational population-based sex-matched and age-matched case-control study converted into a matched cohort, with follow-up linkage to administrative healthcare databases.SettingThe study population comprised all children (0–14 years) registered for primary care with the National Health Service (NHS) in England 1992–1996.Participants1082 5-year survivors of ALL diagnosed<15 years of age (1992–1996) and 2018 unaffected individuals; followed up to 15 March 2020.Main outcome measuresAssociations with hospital activity, cancer and mortality were assessed using incidence rate ratios (IRR) and differences.ResultsMortality in the 5-year ALL survivor cohort was 20 times higher than in the comparison cohort (rate ratio 21.3, 95% CI 11.2 to 45.6), and cancer incidence 10 times higher (IRR 9.9 95% CI 4.1 to 29.1). Hospital activity was increased for many clinical specialties, the strongest associations being for endocrinology; outpatient IRR 36.7, 95% CI 17.3 to 93.4 and inpatient 19.7, 95% CI 7.9 to 63.2 for males, and 11.0, 95% CI 6.2 to 21.1 and 6.2 95% CI 3.1 to 13.5, respectively, for females. Notable excesses were also evident for cardiology, neurology, ophthalmology, respiratory medicine and general medicine. Males were also more likely to attend gastroenterology; ear, nose and throat; urology; and dermatology, while females were more likely to be seen in plastic surgery and less likely in midwifery.ConclusionsAdding to excess risks of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years, which is not related to routine follow-up monitoring. Involving most clinical specialties, associations are striking, showing no signs of diminishing over time. Recognising that all survivors are potentially at risk of late treatment-associated effects, our findings underscore the need to take prior ALL diagnosis into account when interpreting seemingly unrelated symptoms later in life.
We set out to estimate net survival trends for 10 common cancers in 279 cancer registry populations in 67 countries around the world, as part of the CONCORD-2 study. Net survival can be interpreted ...as the proportion of cancer patients who survive up to a given time, after eliminating the impact of mortality from other causes (background mortality). Background mortality varies widely between populations and over time. It was therefore necessary to construct robust life tables that accurately reflected the background mortality in each of the registry populations.
Life tables of all-cause mortality rates by single year of age and sex were constructed by calendar year for each population and, when possible, by racial or ethnic sub-groups. We used three different approaches, based on the type of mortality data available from each registry. With death and population counts, we adopted a flexible multivariable modelling approach. With unsmoothed mortality rates, we used the Ewbank relational method. Where no data were available from the registry or a national statistical office, we used the abridged UN Population Division life tables and interpolated these using the Elandt-Johnson method. We also investigated the impact of using state- and race-specific life tables versus national race-specific life tables on estimates of net survival from four adult cancers in the United States (US).
We constructed 6,514 life tables covering 327 populations. Wide variations in life expectancy at birth and mortality by age were observed, even within countries. During 1995-99, life expectancy was lowest in Nigeria and highest in Japan, ranging from 47 to 84 years among females and 46 to 78 years among males. During 2005-09, life expectancy was lowest in Lesotho and again highest in Japan, ranging from 45 to 86 years among females and 45 to 80 years among males. For the US, estimates of net survival differed by up to 4% if background mortality was fully controlled with state- and race-specific life tables, rather than with national race-specific life tables.
Background mortality varies worldwide. This emphasises the importance of using population-specific life tables for geographic and international comparisons of net survival.
Purpose
The early onset of childhood acute lymphoblastic leukemia (ALL) suggests that critical exposures occurring during pregnancy may increase risk. We investigated the effects of maternal coffee ...and tea consumption during pregnancy on ALL risk by pooling data from eight case–control studies participating in the Childhood Leukemia International Consortium.
Method
Data on maternal coffee intake were available for 2,552 cases and 4,876 controls, and data on tea intake were available for 2,982 cases and 5,367 controls. Coffee and tea intake was categorized into 0, > 0–1, > 1–2, and > 2 cups/day, and covariates were combined and harmonized. Data on genetic variants in
NAT2, CYP1A1
, and
NQO1
were also available in a subset. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression, and linear trends across categories were assessed.
Results
No association was seen with ‘any’ maternal coffee consumption during pregnancy, but there was evidence of a positive exposure–response; the pooled OR for > 2 cups/day versus none was 1.27 (95% CI 1.09–1.43),
p
trend = 0.005. No associations were observed with tea consumption. No interactions were seen between coffee or tea intake and age, maternal smoking or genotype, and there was little or no evidence that associations with coffee or tea differed among cases with and without chromosomal translocations.
Conclusions
Despite some limitations, our findings suggest that high coffee intake during pregnancy may increase risk of childhood ALL. Thus, current advice to limit caffeine intake during pregnancy to reduce risk of preterm birth may have additional benefits.
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