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PURPOSE Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. METHODS Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. RESULTS The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION To our knowledge, we demonstrate—for the first time—that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.

Background Adolescent and young adult (AYA) cancer survivors face physical and psychological sequelae related to having cancer decades after treatment completion. It is unclear if AYA cancer survivors are at increased risk for late psychiatric disorders. Methods We used the Alberta AYA Cancer Survivor Study that includes 5-year survivors of cancer diagnosed at age 15-39 years during 1991 to 2013. The primary outcome was incidence of psychiatric disorder (composite outcome) including anxiety, depressive, trauma- and stressor-related, psychotic, and substance use disorders that were identified using coding algorithms for administrative health databases. A validated coding algorithm identified people who experienced a suicide attempt or event of self-harm. Secondary outcomes were incidences of diagnoses by type of psychiatric disorder. Results Among 12 116 AYA 5-year cancer survivors (n = 4634 [38%] males; n = 7482 [62%] females), 7426 (61%; n = 2406 [32%] males; n = 5020 [68%] females) were diagnosed with at least 1 of 5 psychiatric disorders occurring at least 3 years after cancer diagnosis. Survivors of all cancer types were most often diagnosed with anxiety (males: 39.0%, 95% confidence interval [CI] = 37.6% to 40.4%; females: 54.5%, 95% CI = 53.3% to 55.6%), depressive (males: 32.7%, 95% CI = 31.3% to 34.0%; females: 47.0%, 95% CI = 45.8% to 48.1%), and trauma- and stressor-related disorders (males: 13.5%, 95% CI =12.5% to 14.5%; females: 22.5%, 95% CI = 21.6% to 23.5%). Conclusions Anxiety, depressive, and trauma- and stressor-related disorders are common among 5-year survivors of AYA cancer. Primary, secondary, or tertiary preventive strategies for AYAs diagnosed with cancer, particularly at an early age, are needed to mitigate risk of potentially severe outcomes because of psychiatric disorders.

Fusion of the first metatarsophalangeal joint has been used by foot and ankle surgeons as a reproducible and useful means of treating end-stage arthritis of the great toe. However, the overall utility and successful outcomes of this procedure have led to its incorporation into the treatment of more significant bunion deformities, reconstruction forefoot, and salvage procedures. The authors review surgical fixation methods, offer insightful technical pearls for challenging cases and share examples of complex reconstructive and salvage procedures.

Purpose HRCT is the preferred imaging technique to evaluate Interstitial-Lung-Disease. Optimal Low-Dose-Computed-Tomography protocol for monitoring ILD with lowest radiation dose and optimal diagnostic accuracy and image quality unknown. Methods 28 Patients underwent HRCT. Image reconstructions with varying combinations of tube current (50mA, 20mA, 15 mA, 10mA) and image-thickness/increment (1/1mm, 2/2mm, 3/2.4mm, 5/4mm) were simulated from raw data. 448 CTs evaluated by 2 readers on image quality and ILD-specific features (ground glass opacification (ggo), honeycombing (hc), reticulation (ret)). Results Reduced dose settings with 20 mA did not show any significant difference to standard dose settings for all parameters in reader 1, while results were significantly altered in reader 2. Slice thickness did not significantly influence rating of typical ILD features like ggo, hc, ret or total disease extent. The correct differentiation between UIP and NSIP could be made on all dose settings and with all slice thickness. It was even found, that an increased slice thickness can compensate for the noise associated image quality degradation. Overall, for ggo detection a combination of 20 mA and 3 or 5 mm slice thickness was not different to the original evaluation. Conclusions Assessment of ILD specific CT features down to 20 mA and a slice thickness of 3 or 5 mm is feasible.

Computed tomography (CT) is gaining increased recognition in the assessment of body composition in lung transplant (LTx) candidates as a prognostic marker of post-transplant outcomes. This systematic review was conducted to describe the methodology of CT measures of body composition used in LTx patients and its association with post-transplant outcomes. Six databases were searched (inception-April 2020) for studies of adult LTx patients with thoracic or abdominal CT measures [muscle cross-sectional area (CSA) and/or adiposity]. Thirteen articles were included with 1911 LTx candidates, 58% males, mean age range (48-61 years) and body mass index of 21.0-26.1 kg/m2 . Several methods were utilized using thoracic or abdominal CT scans to assess skeletal muscle (n = 11) and adiposity (n = 4) at various anatomic locations (carina, thoracic, and lumbar vertebrae), differing muscle groups, and adipose tissue compartments. Low muscle mass was associated with adverse outcomes in 6/11 studies, including longer mechanical ventilation days (n = 2), intensive care (n = 2) and hospital stay (n = 2), and mortality (n = 4). Greater subcutaneous and mediastinal fat were associated with increased risk of primary graft dysfunction (n = 2), but implications of adiposity on survival were variable across four studies. Further standardization of CT body composition assessments is needed to assess the prognostic utility of these measures on LTx outcomes.

Summary Background Breast cancer has distinct causes, prognoses, and outcomes and effects in patients at premenopausal and postmenopausal ages. We sought to assess the global burden and trends in breast cancer by menopausal status. Methods We did a population-based analysis of global breast cancer incidence and mortality among premenopausal and postmenopausal women. Menopausal status was defined using age as a proxy, whereby breast cancer cases or deaths at age 50 years or older were regarded as postmenopausal. Age-standardised breast cancer incidence and mortality in 2018 were calculated using GLOBOCAN data. Incidence trends for 1998–2012 were assessed in 44 populations from 41 countries using the Cancer in Five Continents plus database, by calculating the annual average percent change. Findings Approximately 645 000 premenopausal and 1·4 million postmenopausal breast cancer cases were diagnosed worldwide in 2018, with more than 130 000 and 490 000 deaths occurring in each menopausal group, respectively. Proportionally, countries with a low UNDP human development index (HDI) faced a greater burden of premenopausal breast cancer for both new cases and deaths compared with higher income countries. Countries with a very high HDI had the highest premenopausal and postmenopausal breast cancer incidence (30·6 and 253·6 cases per 100 000, respectively), whereas countries with low and medium HDI had the highest premenopausal and postmenopausal mortality, respectively (8·5 and 53·3 deaths per 100 000, respectively). When examining breast cancer trends, we noted significantly increasing age-standardised incidence rates (ASIRs) for premenopausal breast cancer in 20 of 44 populations and significantly increasing ASIRs for postmenopausal breast cancer in 24 of 44 populations. The growth exclusively at premenopausal ages largely occurred in high-income countries, whereas the increasing postmenopausal breast cancer burden was most notable in countries under transition. Interpretation We provide evidence of a rising burden of both premenopausal and postmenopausal breast cancer worldwide. Although early diagnosis and access to treatment remain crucial in low-income and middle-income countries, primary prevention efforts seeking to decrease exposure to known breast cancer risk factors are warranted in all world regions to curb the future breast cancer burden. Funding None.

Background Although adolescent and young adult (AYA) cancers represent a unique spectrum of malignancies, epidemiological studies of cancer incidence often group AYAs together with younger or older populations, obscuring patterns specific to this population. Methods We examined AYA cancer incidence trends in 41 countries over a 15-year period using the CI5plus database. Truncated age-standardized incidence rates were calculated and the annual percentage change was assessed, with statistical significance corresponding to a 95% confidence interval that does not include zero. Results From 1998 to 2012, the 41 included countries contributed a total of 1 846 588 cancer cases and 3.1 billion person-years among AYAs. Although statistically significant increases in the overall cancer burden were observed in 23 countries, the magnitude varied considerably, with the greatest increase in incidence observed in South Korea (annual percentage change2002–2012 = 8.5%, 95% confidence interval = 7.6% to 9.4%) due to thyroid cancer. Notable trends included sharp increases in the incidence of obesity-related malignancies among AYAs; indeed, statistically significant increases were observed among AYAs for 10 of 11 and 9 of 11 obesity-related cancer sites in the US and UK, respectively, with at least five obesity-related cancers statistically significantly increasing in Canada, Japan, South Korea, Australia, and the Netherlands. Other striking trends were noted for thyroid and testicular cancer, with statistically significantly increasing rates observed in 33 and 22 countries, respectively, whereas statistically significant declines in incidence were observed for smoking-related cancers, cervical cancer, and Kaposi sarcoma in many countries. Conclusions Our results highlight the future health-care needs related to treatment as well as the urgency for public health initiatives that can mitigate the increasing burden of cancer in AYAs.

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5-year age group (ages 30-64) and 5-year calendar period (1993-2012) were extracted from Cancer Incidence in Five Continents. Female-to-male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age-specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female-to-male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45-49 year in the Netherlands increased from 0.7 (95% CI: 0.6-0.8) to 1.5 (95% CI: 1.4-1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.

Background Interstitial lung disease (ILD) comprises a heterogeneous group of inflammatory and fibrotic conditions, often resulting in progressive lung function decline and increased mortality. Connective tissue disease (CTD) should be considered in all patients with ILD, as distinguishing between CTD-ILD and other forms of fibrotic lung disease has important therapeutic and prognostic implications. The idiopathic inflammatory myopathies (IIM) represent a CTD subtype of growing interest to ILD experts. The expansion and availability of myositis-specific and myositis-associated antibody testing has allowed for improved disease detection and characterization. Content In this review, we highlight the relationship between myositis antibodies and ILD. Select forms of IIM, such as the antisynthetase syndrome and clinically amyopathic dermatomyositis can present with rapidly progressive ILD, warranting timely disease diagnosis and management. Disease phenotypes, prevalence, laboratory testing, prognosis, and management strategies are described according to select myositis antibodies. Summary Myositis antibodies provide valuable information for clinicians managing patients with ILD. This review aims to increase awareness of their role in disease detection, pathophysiology, and possibly therapeutics.

Rationale: Population-based analyses of hospitalization rates from countries with universal healthcare systems are lacking for patients with sarcoidosis. Objectives: To evaluate the long-term trend...

Consensus guidelines for the management of sarcoidosis recommend screening eye examinations for all patients, even in those without ocular symptoms. We aimed to determine the proportion of sarcoidosis patients that complete ophthalmologic evaluations and factors associated with their performance.We identified patients with sarcoidosis using population health services data from Ontario, Canada between 1991 and 2019. Sarcoidosis was defined by ≥ 2 physician visits for sarcoidosis within a two-year period. Ophthalmologic evaluations were based on an optometrist or ophthalmologist visit within the year prior or two years following the diagnosis. We estimated correlations between the number of eye care professionals and proportion of sarcoidosis patients completing ophthalmologic assessments within regional health units. We evaluated for associations between ophthalmologic screening and patient characteristics using multivariable logistic regression.We identified 21,679 patients with sarcoidosis in Ontario. An ophthalmologic evaluation was performed in 14,751 (68.0%), with a similar number of individuals seeing ophthalmologists and optometrists (43.7% vs. 42.2%). The percentage of sarcoidosis patients undergoing an ophthalmologic evaluation within corresponding regional health units was moderately correlated with the number of practicing ophthalmologists (r = 0.64, p = 0.01), but not the number of optometrists (r = 0.08, p = 0.77). Patients who were older [OR per year 1.02 (95% CI 1.01-1.02), p 0.001] and female [OR 1.54 (95% CI 1.44-1.63), p 0.001] were more likely to complete ophthalmologic evaluations. Immigrants to Canada were less likely to undergo ophthalmologic assessments [OR 0.66 (95% CI 0.60-0.73), p 0.001].Most patients with sarcoidosis complete ophthalmologic examinations, though a substantial proportion does not. Young adults, men and immigrants were less likely to complete ophthalmologic evaluations. Limited access to ophthalmologists may at least in part explain why some sarcoidosis patients fail to complete ophthalmologic screening.

We sought to understand the role of stage at diagnosis in observed age disparities in colon cancer survival among people aged 50 to 99 years using population-based cancer registry data from seven high-income countries: Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom. We used colon cancer incidence data for the period 2010 to 2014. We estimated the 3-year net survival, as well as the 3-year net survival conditional on surviving at least 6 months and 1 year after diagnosis, by country and stage at diagnosis (categorised as localised, regional or distant) using flexible parametric excess hazard regression models. In all countries, increasing age was associated with lower net survival. For example, 3-year net survival (95% confidence interval) was 81% (80-82) for 50 to 64 year olds and 58% (56-60) for 85 to 99 year olds in Australia, and 74% (73-74) and 39% (39-40) in the United Kingdom, respectively. Those with distant stage colon cancer had the largest difference in colon cancer survival between the youngest and the oldest patients. Excess mortality for the oldest patients with localised or regional cancers was observed during the first 6 months after diagnosis. Older patients diagnosed with localised (and in some countries regional) stage colon cancer who survived 6 months after diagnosis experienced the same survival as their younger counterparts. Further studies examining other prognostic clinical factors such as comorbidities and treatment, and socioeconomic factors are warranted to gain further understanding of the age disparities in colon cancer survival.

Background: Interstitial lung disease (ILD) is an established manifestation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Autoimmune serologic screening is recommended by international consensus guidelines during the evaluation of idiopathic ILD, but ANCA testing only on a case-by-case basis. Objective: We aimed to evaluate the role of ANCA screening in patients with idiopathic ILD. Methods: We performed a retrospective review of patients seen between September 2015 and April 2017 in the ILD clinic at Toronto General Hospital. Patients referred with confirmed or suspected connective tissue disease were excluded. Patient demographics, symptoms, chest imaging, and pulmonary function testing was collected. We performed descriptive statistics based on the presence of ANCAs and estimated operating characteristics for ANCA screening. Results: In total, 360 patients with idiopathic ILD were reviewed, 159 met study inclusion criteria and 4 (2.5%) tested positive for ANCAs. Two patients (1.2%) had elevated myeloperoxidase-ANCAs (MPO-ANCA) and 2 (1.2%) had elevated proteinase-3-ANCAs (PR3-ANCA). There were no significant associations between patient demographics and ANCAs. One patient (0.6%) with PR3-ANCAs was diagnosed with vasculitis following rheumatologic evaluation. Despite negative ANCA testing, 1 patient (0.6%) was diagnosed with vasculitis following rheumatologic evaluation. The sensitivity and specificity of ANCA screening for vasculitis in patients with ILD was calculated as 50% (95% CI, 1.3%-98.7%) and 98% (95%CI, 4.4-155.5) respectively. Negative and positive likelihood ratios were 0.5 (95%CI 0.1-2.0) and 26.2 (95%CI 4.4-155.5) respectively. Conclusion: ANCA screening in patients with idiopathic ILD rarely yields positive results. These results support an individualized approach to ANCA testing as opposed to widespread screening.

Background We previously reported that lung cancer incidence between Blacks and Whites younger than 40 years of age converged in women and approached convergence in men. Whether this pattern has continued in contemporary young birth cohorts is unclear. Methods We examined 5-year age-specific lung cancer incidence in Blacks and Whites younger than 55 years of age by sex and calculated the Black-to-White incidence rate ratios (IRRs) and smoking prevalence ratios by birth cohort using nationwide incidence data from 1997 to 2016 and smoking data from 1970 to 2016 from the National Health Interview Survey. Results Five-year age-specific incidence decreased in successive Black and White men born since circa 1947 and women born since circa 1957, with the declines steeper in Blacks than Whites. Consequently, the Black-to-White IRRs became unity in men born 1967-1972 and reversed in women born since circa 1967. For example, the Black-to-White IRRs in ages 40-44 years born between 1957 and 1972 declined from 1.92 (95% confidence interval [CI] = 1.82 to 2.03) to 1.03 (95% CI = 0.93 to 1.13) in men and from 1.32 (95% CI = 1.24 to 1.40) to 0.71 (95% CI = 0.64 to 0.78) in women. Similarly, the historically higher sex-specific smoking prevalence in Blacks than Whites disappeared in men and reversed in women born since circa 1965. The exception to these patterns is that the incidence became higher in Black men than White men born circa 1977-1982. Conclusions The historically higher lung cancer incidence in young Blacks than young Whites in the United States has disappeared in men and reversed in women, coinciding with smoking patterns, though incidence again became higher in Black men than White men born circa 1977-1982.

BackgroundSurvivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide.MethodsThe PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence.Results427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN—comparable to the risk among members of the general population with at least two first-degree relatives affected.ConclusionsColonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

Background It is unclear whether late-effect risks among childhood cancer survivors vary internationally. We compared late mortality in the North American Childhood Cancer Survivor Study (CCSS) and British Childhood Cancer Survivor Study (BCCSS). Methods Late mortality was assessed among 49 822 5-year survivors of childhood cancer diagnosed before 15 years of age from 1970 to 1999 (CCSS, n = 31 596; BCCSS, n = 18 226) using cumulative mortality probabilities (CM%) and adjusted ratios of the standardized mortality ratio. Results The all-cause CM% at 10 years from diagnosis was statistically significantly lower in the CCSS (4.7%, 95% confidence interval [CI] = 4.5% to 5.0%) compared with the BCCSS (6.9%, 95% CI = 6.5% to 7.2%), attributable to a lower probability of death from recurrence or progression of the primary cancer, with statistically significant differences observed in survivors of leukemia, lymphoma, central nervous system tumors, and sarcoma. However, at 40 years from diagnosis, the CCSS had a greater CM% (22.3% vs 19.3%), attributable to a twofold higher risk of mortality from subsequent malignant neoplasms, cardiac and respiratory diseases, and other health-related causes. Differences increased when assessed by follow-up interval, with the CCSS faring worse as time-since-diagnosis increased. Finally, the gap in all-cause mortality widened more recently, with CCSS survivors diagnosed in 1990-1999 experiencing one-half the excess deaths observed in the BCCSS (ratios of the standardized mortality ratio = 0.5, 95% CI = 0.5 to 0.6). Conclusions Our findings suggest that US survivors may have received more intensive regimens to achieve sustainable remission and cure, but the cost of this approach was a higher risk of death from late effects. Although the clinical impact of these differences is unclear, our results provide important evidence to aid the discussion of late effects management.

Cancer statistics for adolescents and young adults (AYAs) (aged 15-39 years) are often presented in aggregate, masking important heterogeneity. The authors analyzed population-based cancer incidence and mortality for AYAs in the United States by age group (ages 15-19, 20-29, and 30-39 years), sex, and race/ethnicity. In 2020, there will be approximately 89,500 new cancer cases and 9270 cancer deaths in AYAs. Overall cancer incidence increased in all AYA age groups during the most recent decade (2007-2016), largely driven by thyroid cancer, which rose by approximately 3% annually among those aged 20 to 39 years and 4% among those aged 15 to 19 years. Incidence also increased in most age groups for several cancers linked to obesity, including kidney (3% annually across all age groups), uterine corpus (3% in the group aged 20-39 years), and colorectum (0.9%-1.5% in the group aged 20-39 years). Rates declined dramatically for melanoma in the group aged 15 to 29 years (4%-6% annually) but remained stable among those aged 30 to 39 years. Overall cancer mortality declined during 2008 through 2017 by 1% annually across age and sex groups, except for women aged 30 to 39 years, among whom rates were stable because of a flattening of declines in female breast cancer. Rates increased for cancers of the colorectum and uterine corpus in the group aged 30 to 39 years, mirroring incidence trends. Five-year relative survival in AYAs is similar across age groups for all cancers combined (range, 83%-86%) but varies widely for some cancers, such as acute lymphocytic leukemia (74% in the group aged 15-19 years vs 51% in the group aged 30-39 years) and brain tumors (77% vs 66%), reflecting differences in histologic subtype distribution and treatment. Progress in reducing cancer morbidity and mortality among AYAs could be addressed through more equitable access to health care, increasing clinical trial enrollment, expanding research, and greater alertness among clinicians and patients for early symptoms and signs of cancer. Further progress could be accelerated with increased disaggregation by age in research on surveillance, etiology, basic biology, and survivorship.

Background Recent studies have identified increases in cancer incidence among younger adults for some cancers. This study examined incidence trends for 28 cancers in Canada by age and birth cohort from 1983 to 2012. Methods Canadian incidence data for 20 to 84 year-olds were obtained from the Cancer Incidence in Five Continents Plus database. Age-period-cohort modeling was used to estimate the average annual percentage changes (AAPCs) and incidence rate ratios (IRRs) for 10-year birth cohorts (reference cohort, 1943) for 28 cancer types. Results Incidence increased for 13 cancer sites among adults younger than 50 years (1983-2012), with the largest increase occurring for rectal cancer (AAPC20-24 , 5.62; 95% confidence interval [CI], 3.77-7.51) and colon cancer (AAPC20-24 , 4.08; 95% CI, 2.89-5.29). Compared with the 1943 birth cohort, persons born circa 1988 had approximately 5- and 2-fold greater risks of rectal cancer (IRR, 4.98; 95% CI, 2.87-8.63) and colon cancer (IRR, 2.31; 95% CI, 1.62-3.30), respectively. Incidence decreased among younger adults for 9 sites (1983-2012), with the largest decreases observed for lung cancer (AAPC25-29 ,-2.29; 95% CI, -3.57 to -0.98), cervical cancer (AAPC25-29 , -1.29; 95% CI, -1.67 to -0.90), and melanoma (AAPC25-29 , -0.61; 95% CI, -0.97 to -0.24). Decreased risks in recent birth cohorts were observed for all sites with decreasing trends in younger adults. For example, the risk of lung cancer was 60% lower in the 1988 birth cohort than the 1943 birth cohort (IRR, 0.42; 95% CI, 0.23-0.78). Conclusions Incidence among young adults is increasing for some cancers associated with obesity but decreasing for many cancers associated with infections or smoking. Although further studies are needed to replicate these findings and understand the etiology of early-onset cancers, measures to promote healthy behaviors in young adults warranted.

Objectives Fear of cancer recurrence (FCR) has not been widely explored in survivors of childhood cancer. Yet, childhood survivors are at risk of experiencing late effects and may be especially vulnerable. The aims of the current study were to conduct a retrospective chart review to determine the prevalence and persistence of FCR among survivors of childhood cancer and to examine factors that may be related to FCR. Methods Survivors of childhood cancer (n = 228, mean attained age = 14.5 years [range = 4.7-21 years]; mean diagnosis age = 4.4 years [range = 0-16.5 years]; mean time off treatment = 8.7 years [range = 2.8-19.3 years]) seen in a Long-Term Survivor Clinic (LTSC) completed questionnaires at each clinic visit detailing their current health. FCR was measured with a single item. Data from questionnaires from 2011 to 2018 were analyzed retrospectively. Descriptive statistics and a random effects model were used to address study aims. Results FCR was reported in 43% (n = 98) of survivors at least once across all clinic visits. Among survivors reporting FCR at least once, 66% were diagnosed with cancer under the age of 5, and 64% were 13 years or older at their most recent follow-up. Twenty-one percent of survivors (n = 48/224) reported FCR during at least 50% of their visits. Survivors with a higher number of depressive symptoms were more likely to report FCR (OR = 1.66, P = .03). Conclusions FCR is prevalent among survivors of childhood cancer and is related to other health concerns. Research is needed to understand who is at risk and how to.

Aims: This review examines the links between human development and cancer overall and for specific types of cancer, as well as cancer-related risk-factors and outcomes, such as disability and life expectancy. Methods: To assess human development, the Human Development Index was utilized continuously and according to four levels (low, medium, high, very high), where the low and very high categories include the least and most developed countries, respectively. All studies that assessed aspects of the global cancer burden using this measure were reviewed. Results: Although the present cancer incidence burden is greater in higher Human Development Index countries, a greater proportion of the global mortality burden is observed in less developed countries, with a higher mean fatality rate in the latter countries. Further, the future cancer burden is expected to disproportionally affect less developed regions; in particular, it has been estimated that low and medium Human Development Index countries will experience a 100% and 81% increase in cancer incidence from 2008 to 2030, respectively. Disparities were also observed in risk factors and average health outcomes, such as a greater number of years of life lost prematurely and fewer cancer-related gains in life expectancy observed in lower versus higher Human Development Index settings. Conclusions: From a global perspective, there remain clear disparities in the cancer burden according to national Human Development Index scores. International efforts are needed to aid countries in social and economic transition in order to efficiently plan, implement and evaluate cancer control initiatives as a means to reduce the widening gap in cancer occurrence and survival worldwide.

Background Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. Methods This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Results One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. Conclusions We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL.

BACKGROUND: Adverse effects from childhood leukemia treatment may persist or present years after cure from cancer. We provide a comprehensive evaluation of subsequent hospitalization in five-year survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). METHODS: In the Adult Life after Childhood Cancer in Scandinavia Study, we identified 4003 five-year survivors diagnosed with childhood leukemia 1970–2008 in Denmark, Sweden, Iceland, and Finland. Survivors and 129 828 population comparisons were followed for first-time nonpsychiatric hospitalizations for 120 disease categories in the hospital registries. Standardized hospitalization rate ratios and absolute excess rates were calculated. All statistical tests were two-sided. RESULTS: Survivors of ALL (n = 3391), AML (n = 389), and CML (n = 92) had an increased overall hospitalization rate compared with population comparisons. The rate ratio for any hospitalization was 1.95 (95% confidence interval [CI] = 1.83 to 2.07) in ALL, 3.09 (95% CI = 2.53 to 3.65) in AML, and 4.51 (95% CI = 3.03 to 6.00) in CML survivors and remained increased even 20 years from leukemia diagnosis. Corresponding absolute excess rates per 1000 person-years were 28.48 (95% CI = 24.96 to 32.00), 62.75 (95% CI = 46.00 to 79.50), and 105.31 (95% CI = 60.90 to 149.72). CONCLUSION: Leukemia survivors have an increased rate of hospitalization for medical conditions. We provide novel insight into the relative and absolute rate of hospitalization for 120 disease categories in survivors of ALL, AML, and CML, which are likely to be informative for both survivors and healthcare providers.

Background: Recent studies have identified significant increases in cancer incidence among younger adults for some cancers. We examined incidence trends of 27 cancer sites in Canada by age and birth cohort between 1983 and 2012. Methods: Canadian incidence data for 20-84 year-olds was obtained from the Cancer in Five Continents plus database. The average annual percentage change (AAPC) was calculated, and age-period-cohort modeling was used to estimate incidence rate ratios for 10-year birth cohorts. Results: Incidence significantly increased in 12 cancer sites among adults

Plantar fasciitis is one of the most common foot conditions affecting individuals both with a high level of activity and those with a high level of inactivity. While the diagnosis is frequently clear, the etiology has remained controversial. Up to 90–96% of plantar fasciitis cases resolve with nonoperative management including nonsteroidal anti-inflammatory drugs (NSAIDs), stretching, orthotics, oral/injectable steroid, physical therapy modalities, rest, night splints, and immobilization. When patients who present with the characteristic enthesopathy of plantar fasciitis develop neurogenic symptoms, other etiologies need to be investigated. A commonly overlooked source of inferomedial heel pain recalcitrant to nonoperative management is chronic plantar fasciitis associated with entrapment of the lateral plantar nerve and its first branch.

Ruptures of the tibialis anterior tendon are uncommon but will typically present after an acute injury or as either an acute or chronic foot drop. In the setting of an acute injury, the injury mechanism is typically blunt tendon trauma or laceration. Acute ruptures of a healthy tendon are rare. Atraumatic ruptures tend to occur in older individuals with underlying chronic tendinopathy. Those patients with diabetes mellitus, inflammatory arthropathy, or gout, or who are undergoing treatment with corticosteroids, are at higher risk for spontaneous ruptures. A minor traumatic event may involve an eccentric load applied to a plantar-flexed ankle.

Background: Breast cancer has distinct etiologies, prognoses, and patient impact at pre- and post-menopausal ages. We sought to assess the global burden and trends in breast cancer by menopausal status. Methods: Menopausal status was defined using age as a proxy, where breast cancer cases/deaths at >50 years were considered as post-menopausal. Age-standardized breast cancer incidence and mortality rates in 2018 were calculated using GLOBOCAN data. Incidence trends for 1998-2012 were assessed in 44 populations from 41 countries using CI5plus data by calculating the annual average percent change. Findings: Approximately 645,000 pre-menopausal and 1.4 million post-menopausal breast cancer cases were diagnosed in 2018, with approximately 130,000 and 490,000 deaths occurring in each menopausal group, respectively. Proportionally, Low Human Development Index (HDI) countries faced a greater burden of pre-menopausal breast cancer for both incidence and mortality compared to more developed countries. Very High HDI countries had the highest pre- and post-menopausal breast cancer incidence rates (30·6 and 253·6 per 100,000 respectively), while Low and Medium HDI countries had the highest pre-menopausal and post-menopausal mortality rates respectively (8·5 and 53·3 per 100,000 respectively). When examining incidence trends, we observed significantly increasing rates of pre-menopausal breast cancer in 20/44 populations, and significantly increasing rates of post-menopausal breast cancer in 24/44 populations. The increases exclusively at pre-menopausal ages largely occurred in the most developed countries, while the increasing post-menopausal breast cancer burden was most notable in countries under transition. Interpretation: We provide evidence of a rising burden of both pre- and post-menopausal breast cancer worldwide, and wide inequities in breast cancer care. Although early diagnosis and access to treatment remain crucial in developing countries, primary prevention efforts seeking to decrease obesity and alcohol consumption, and increase physical activity and breastfeeding, are warranted in all world regions to curb the future breast cancer burden. Funding Statement: This study was undertaken without any funding. Declaration of Interests: All authors declare no conflicts of interests. Ethics Approval Statement: Not required.

Socioeconomic factors are associated with cancer incidence through complex and variable pathways. We assessed cancer incidence for all cancers combined and 27 major types according to national human development levels. Using GLOBOCAN data for 184 countries, age-standardized incidence rates (ASRs) were assessed by four levels (low, medium, high, very high) of the Human Development Index (HDI), a composite index of life expectancy, education, and gross national income. A strong positive relationship between overall cancer incidence and HDI level was observed. When comparing the ASR in very high HDI regions with that in low HDI regions, we observed a positive association ranging from 2 to 14 and 2 to 11 times higher in males and females, respectively, depending on the cancer type. Positive dose–response relationships between the ASR and HDI level were observed in both sexes for the following cancer types: lung, pancreas, leukemia, gallbladder, colorectum, brain/nervous system, kidney, multiple myeloma, and thyroid. Positive associations were also observed for testicular, bladder, lip/oral cavity, and other pharyngeal cancers, Hodgkin lymphoma, and melanoma of the skin in males, and corpus uteri, breast, and ovarian cancers and non-Hodgkin lymphoma in females. A negative dose–response relationship was observed for cervical and other pharyngeal cancers and Kaposi sarcoma in females. Although the relationship between incidence and the HDI remained when assessed at the country-specific level, variations in risk within HDI levels were also observed. We highlight positive and negative associations between incidence and human development for most cancers, which will aid the planning of cancer control priorities among countries undergoing human development transitions.

Purpose Survivors of Wilms tumor (WT) are at risk for adverse health and social outcomes but risks beyond 30 years from diagnosis remain uncertain. We investigated the risks of adverse outcomes among 5-year survivors of WT, in particular, those between 30 and 50 years from diagnosis. Patients and Methods The British Childhood Cancer Survivor Study includes 1,441 5-year survivors of WT. We investigated cause-specific mortality, risk of subsequent primary neoplasms (SPNs), and, for those who completed a questionnaire, the extent of smoking and drinking, educational achievement, health status, and health service use compared with the general population. Results Cumulative risk of death from all causes, excluding recurrence, increased substantially from 5.4% to 22.7% at 30 years and 50 years, respectively, after WT diagnosis—75% of excess deaths beyond 30 years from diagnosis were attributable to SPNs (50%) and cardiac diseases (25%). Digestive cancer, most frequently bowel, accounted for 41% of excess cancers beyond 30 years. Conclusion Between 30 and 50 years from diagnosis, survivors of WT are at a substantially increased risk of premature mortality, and 75% of excess deaths were accounted for by SPNs and cardiac diseases. Radiotherapy exposure was a risk factor for both outcomes. The proportion of patients with WT who are exposed to radiotherapy has reduced substantially in recent decades because of initiatives such as the SIOP WT 2001 clinical trial, which sought to reduce late effects; however, the majority of current survivors, who are at least 30 years from diagnosis, received radiotherapy. Surveillance of this group should focus on SPNs, in particular, bowel and breast cancers, and cardiac conditions.

In the modern treatment of Charcot neuroarthropathy, beam screw fixation is an alternative to plate and screw fixation. Exposure is minimized for implantation, and this technique supports the longitudinal columns of the foot as a rigid load-sharing construct. A published data review identified a paucity of data regarding metatarsal intramedullary canal morphology relevant to beam screw fixation. The purpose of the present study was to describe metatarsal diaphyseal morphology qualitatively and quantitatively in an effort to provide data that can be used by surgeons when selecting axially based intramedullary fixation. Twenty fresh-frozen cadaveric below-the-knee specimens were obtained. The metatarsals were exposed, cleaned of soft tissue, and axially transected at the point of the narrowest external diameter. Next, a digital caliper was used to measure the size and shape of the diaphysis of the first through fourth metatarsals. The diaphyseal canal shape was categorized as round, oval, triangular, or pear. The widest distance between the endosteal cortical surfaces was measured. Triangular endosteal canals were only found in the first metatarsal, and the remainder of the metatarsal canals were largely round or oval. These data help to approximate the size of fixation needed to achieve maximal screw-endosteal purchase.

Universal Health Coverage (UHC) was implemented in Thailand in 2002. This study aims to compare cervical cancer incidence and survival before and after the implementation of UHC, including the national screening program, in the Chiang Mai population in Northern Thailand. Data of women diagnosed with in situ or malignant cervical cancer in Chiang Mai during 1998-2012 were used in our analysis. Annual age-standardized incidence rates (ASR) and age-adjusted relative survival (RS) were estimated for the following three diagnosis periods: period I: 1998-2002 (before UHC), period II: 2003-2007 (UHC implementation) and period III: 2008-2012 (after UHC). The ASR peaked in 2001 at 38 per 100,000, and then subsequently declined to 23 per 100,000 in 2012. The proportion of in situ and localized tumors increased in all age groups, while regional tumors declined. In all women (aged 15-89) with malignant cervical cancer or in situ, the 5-year RS in Period I, Period II and Period III was 73%, 74% and 77%, respectively; when only malignant cases were considered, the RS was 63%, 61% and 62%, respectively. In the screening target women (aged 30-59) with malignant or in situ tumors, the 5-year RS was 84%, 88% and 90%, respectively, in the three periods, while the RS was 71%, 74% and 75%, respectively, in only those with malignant cancers. The introduction of UHC including national cervical cancer screening program has likely reduced the magnitude and severity of cervical cancer and improved the survival of cervical cancer in the screening target age group.

Social inequalities in cancer are increasingly relevant to research, implementation science, and policy. In this brief perspective we provide an overview of global cancer inequalities by assessing different outcomes according to the Human Development Index (HDI) ; the HDI is a United Nations Development Programme composite indicator including the following measures: (i) access to education (based on mean and expected years of schooling), (ii) a long and healthy life (based on life expectancy), and (iii) a decent standard of living (based on gross national income per capita). We additionally touch upon the importance of prevention, access to oncological services, and the need to monitor progress in reducing and avoiding inequalities at subnational, national, world region, and global levels.

Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.

Background: Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer.Methods: We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated.Results: Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma.Conclusions: For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.

Introduction: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors.Methods: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided.Results: Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk.Conclusions: For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer.

Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case–control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.

List of ACCIS contributors = Monika Hackl, Anna Zborovskaya, Nadya Dimitrova, Zdravka Valerianova, Ladislav Dušek, Margit Mägi, Alain Monnereau, Jacqueline Clavel, Michel Velten, Anne-Valérie Guizard, Véronique Bouvier, Xavier Troussard, Anne-Sophie Woronoff, Emilie Marrer, Brigitte Trétarre, Marc Colonna, Olivier Ganry, Pascale Grosclaude, Berndt Holleczek, Zsuzsanna Jakab, Laufey Tryggvadóttir, Lucia Mangone, Franco Merletti, Stefano Ferretti, Bianca Caruso, Maria Michiara, Rosario Tumino, Fabio Falcini, Roberto Zanetti, Giovanna Tagliabue, Otto Visser, Giske Ursin, Ryszard Mężyk, Kamila Kepska, José Laranja Pontes, Maja Primic Žakelj, Rafael Fernández-Delgado, Marisa L Vicente Raneda, Enrique Almar Marqués, José Ramón Quirós Garcia, Arantza Lopez de Munain, Rafael Marcos-Gragera, Maria-Jose Sanchez-Perez, Maria Ramos Monserrat, Eva Ardanaz, Jaume Galceran, Staffan Khan, Claudia E Kuehni Christine Bouchardy, Fabio Levi, Isabelle Konzelmann, Sabine Rohrmann Sally Vernon, David H Brewster, Ceri White, Anastasia Dolya Background A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1∙3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings For the years 1991–2010, 53 registries in 19 countries contributed a total of 180335 unique cases. We excluded 15162 (8·4%) of 180335 cases due to differing practices of registration, and considered the quality indicators for the 165173 cases included to be satisfactory. The average annual age-standardised incidence was 137∙5 (95% CI 136∙7–138∙3) per million person-years and incidence increased significantly by 0∙54% (0∙44–0∙65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176∙2 (174∙4–178∙0) per million person-years based on all 35138 eligible cases and increased significantly by 0·96% (0∙73–1∙19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48458 cases in children was 46∙9 (46∙5–47∙3) per million person-years and increased significantly by 0∙66% (0∙48–0∙84) per year. The average overall incidence of leukaemia in adolescents was 23∙6 (22∙9–24∙3) per million person-years, based on 4702 cases, and the average annual change was 0∙93% (0∙49–1∙37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1∙17 [0∙82–1∙53]). Interpretation Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding Federal Ministry of Health of the Federal German Government, the European Union’s Seventh Framework Programme, and International Agency for Research on Cancer