Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population‐based cohort study of 32,308 one‐year survivors

The lifetime risk for cardiovascular disease in a large cohort of childhood cancer survivors has not been fully assessed. In a retrospective population‐based cohort study predicated on comprehensive national health registers, we identified a cohort of 32,308 one‐year survivors of cancer diagnosed before the age of 20 in the five Nordic countries between the start of cancer registration in the 1940s and 1950s to 2008; 211,489 population comparison subjects were selected from national population registers. Study subjects were linked to national hospital registers, and the observed numbers of first hospital admission for cardiovascular disease among survivors were compared with the expected numbers derived from the population comparison cohort. Cardiovascular disease was diagnosed in 2,632 childhood cancer survivors (8.1%), yielding a standardized hospitalization rate ratio (RR) of 2.1 (95% CI 2.0–2.2) and an overall absolute excess risk (AER) of 324 per 100,000 person‐years. At the end of follow‐up 12% of the survivors were ≥ 50 years of age and 4.5% ≥ 60 years of age. Risk estimates were significantly increased throughout life, with an AER of ～500–600 per 100,000 person‐years at age ≥ 40. The highest relative risks were seen for heart failure (RR, 5.2; 95% CI 4.5–5.9), valvular dysfunction (4.6; 3.8–5.5) and cerebrovascular diseases (3.7; 3.4–4.1). Survivors of hepatic tumor, Hodgkin lymphoma and leukemia had the highest overall risks for cardiovascular disease, although each main type of childhood cancer had increased risk with different risk profiles. Nordic childhood cancer survivors are at markedly increased risk for cardiovascular disorders throughout life. These findings indicate the need for preventive interventions and continuous follow‐up for this rapidly growing population.     

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Childhood cancer incidence and survival in Japan and England: A population‐based study (1993‐2010)

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).     

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population‐based cohort study of 32,839 one‐year survivors

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow‐up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1‐year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow‐up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub‐cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20‐year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment‐induced late liver complications.     

Inflammatory bowel disease,cancer and medication: Cancer risk in the Dutch population‐based IBDSL cohort

The management of inflammatory bowel disease (IBD) has changed since the mid‐1990s (e.g., use of thiopurines/anti‐TNFα agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal‐, extra‐intestinal‐ and overall cancer risk in the Dutch population‐based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender‐, phenotype‐, disease duration‐, diagnosis era‐ and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08–6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic‐ (2.41; 1.04–4.76), overall skin‐ (1.55; 1.06–2.19), skin squamous cell‐ (SCC; 3.83; 1.83–7.04) and overall cancer (1.28; 1.01–1.60), whereas UC patients had no increased risk for extra‐intestinal‐ and overall cancer. Finally, in a medication analysis on CD and UC together, long‐term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non‐Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long‐term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.     

Survivor profiles predict health behavior intent: the Childhood Cancer Survivor Study

Objectives: To determine whether unique groups of adult childhood cancer survivors could be defined on the basis of modifiable cognitive, affective, and motivation indicators. Secondary objectives were to examine to what extent group membership co‐varied with more static variables (e.g. demographics, disease, and treatment) and predicted intent for subsequent medical follow‐up. Methods: Using latent class analysis of data from 978 participants (ages, 18–52 years; mean, 31; and SD, 8) in the Childhood Cancer Survivor Study, we classified survivors according to their worries about health, perceived need for follow‐up care, health motivation, and background variables. Intent to participate in medical follow‐up, as a function of class membership, was tested using equality of proportions. Results: The best‐fitting model (BIC = 18 540.67, BLMRT = <0.001) was characterized by three distinctive survivor classes (worried, 19%; self‐controlling, 26%; and collaborative, 55%) and three significant class covariates (gender, perceptions of health, and severity of late effects). A smaller proportion of survivors in the self‐controlling group (81%) than in the worried (90%) (P = 0.015) and collaborative (88%) (P = 0.015) groups intended to obtain a routine medical checkup. A smaller proportion of survivors in the self‐controlling group (32%) than in the collaborative (65%) (P = <0.001) and worried (86%) (P = <0.001) groups planned a cancer‐related check‐up. A smaller proportion of survivors in the collaborative group (65%) than in the worried group (86%) (P = <0.001) were likely to obtain a cancer‐related check‐up. Conclusions: Childhood cancer survivors can be classified according to the modifiable indicators. The classification is distinctive, predicts intent for future medical follow‐up, and can inform tailored interventions. Copyright © 2011 John Wiley & Sons, Ltd.     

Cardiovascular morbidity in long‐term survivors of early‐onset cancer: A population‐based study

Improvements in cancer therapy have resulted in an expanding population of early‐onset cancer survivors. In contrast to childhood and adolescent cancer survivors, there is still a lack of data concerning late morbidities among young adult (YA) cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity among early‐onset cancer survivors with a special interest in YA cancer survivors. In a population‐based setting, we explored the risk of cardiovascular disease in early‐onset cancer survivors compared to healthy siblings. Patients diagnosed with cancer below 35 years of age since 1975 were identified from the Finnish Cancer Registry, and 5‐year survivors were included in our study (N = 13,860). Information on cardiovascular morbidity was collected from the national hospital discharge registry. Compared to siblings, cancer survivors aged 0–19 and 20–34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied outcomes: HR 13.5 (95% CI 8.9–20.4) and 3.6 (95% CI 2.8–4.6) for cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3–5.1) and 1.7 (95% CI 1.4–2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7–6.5) and 1.8 (95% CI 1.5–2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95% CI 1.2–2.6) and 1.4 (95% CI 1.2–1.7) for cardiac arrhythmia. In both groups, depending on the outcome, the HR for adverse events was highest among lymphoma, brain tumor, leukemia and testicular malignancy survivors. Our results regarding late effects of childhood cancer survivors confirmed previous findings. Additionally, our study provides novel information concerning the YA cancer survivor population. Hence, our data may help in planning the risk‐based long‐term follow‐up of early‐onset cancer survivors.     

Childhood cancer survival in Finland (1953–2010): A nation‐wide population‐based study

Population based survival studies are critical in monitoring changes in anticancer therapy, evaluating effectiveness of new treatments as well as identifying possibilities for further improvement. The previous report on cancer survival in Finland covered patients diagnosed in 1953–1995. Data on survival in the European and Nordic pediatric populations have been published with follow‐up ending in 2002. We describe population‐based survival of childhood cancer patients (n = 8270, age 0–14 years) in Finland overall and by disease category with follow‐up extending from 1953 to 2010 and focusing on the modern treatment era. Data were collected from the Finnish Cancer Registry. Age‐standardised observed survival proportions (rates) were calculated using the actuarial (or life‐table) method. Trends in observed survival rates were studied over six diagnostic periods: 1953–1960, 1961–1970, 1971–1980, 1981–1990, 1991–2000 and 2001–2010. The overall 5‐year survival reached 82.1% (95% CI 80.0–84.2) in the most recent period. In most diagnostic categories, the biggest leap in survival was seen between 1961–1970 and 1981–1990, after which slight improvements occurred between 1981–1990 and 1991–2000, with no significant increase thereafter. In analyses by diagnostic group, positive trends in survival over the last three decades were seen for leukemia (p = 0.000), non‐Hodgkin's lymphoma (p = 0.002) and CNS tumours (p = 0.02). Although survival of childhood cancer patients overall has significantly improved from 1953 to 2000, improvement thereafter has been marginal. Future treatment efforts should be directed at bone tumours, soft‐tissue sarcoma, neuroblastoma and malignant brain tumours as well as high‐risk leukemia.     

Smoking in pregnancy and risk of cancer among young children: A population‐based study

Smoking during pregnancy is a plausible risk factor for childhood cancer, yet previous studies have yielded conflicting results, and few prospective studies have been published. Data on maternal smoking were obtained from California birth certificates. We linked California birth certificates (births 2007–2011) with California Cancer Registry records for childhood cancer cases (diagnosed January 2007–September 2013) that were ages 5 or younger at diagnosis (N cases = 2,021). Controls (N = 40,356) were frequency‐matched by birth year and randomly selected from birth certificate records. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI) to assess the association between smoking during pregnancy and childhood cancer. We observed positive associations for gliomas (OR = 1.8, 95% CI: 1.0–3.4) and retinoblastoma (OR = 3.0, 95% CI: 1.4–6.6), particularly bilateral retinoblastoma (OR = 9.4, 95% CI 3.6–24.7) with maternal smoking in pregnancy. Maternal smoking during pregnancy may be a risk factor for retinoblastoma and certain types of childhood brain tumors.     

Coffee drinking and risk of endometrial cancer—A population‐based cohort study

Coffee drinking has been reported to have beneficial effects on insulin resistance, which has been directly associated with endometrial cancer. Although a relationship between coffee consumption and endometrial cancer risk is biologically plausible, this hypothesis has been previously explored in only 2 prospective studies, with a small number of cases. We used data from the Swedish Mammography Cohort, a population‐based prospective cohort study of 60,634 women. During 17.6 years of follow‐up, 677 participants were diagnosed with incident endometrial cancer (adenocarcinoma). We examined the association between self‐reported coffee consumption (at baseline 1987–90 and in 1997) and endometrial cancer risk using Cox proportional hazards models. Each additional cup (200 g) of coffee per day was associated with a rate ratio (RR) of 0.90 [95% confidence interval (CI), 0.83–0.97]. In women drinking 4 or more cups of coffee a day, the RR for the risk reduction of endometrial cancer was 0.75 (95% CI, 0.58–0.97) when compared with those who drank 1 cup or less. The association seemed largely confined to overweight and obese women, who showed a respective risk reduction of 12% (95% CI, 0–23%) and 20% (95% CI, 7–31%) for every cup of coffee, but was not observed among normal‐weight women. There was a statistically significant interaction between coffee consumption and body mass index (p_interaction < 0.001). These data indicate that coffee consumption may be associated with decreased risk of endometrial cancer, especially among women with excessive body weight. If confirmed by other prospective studies, these results are of major public health significance. © 2009 UICC     

Time from breast cancer diagnosis to therapeutic surgery and breast cancer prognosis: A population‐based cohort study

Theoretically, time from breast cancer diagnosis to therapeutic surgery should affect survival. However, it is unclear whether this holds true in a modern healthcare setting in which breast cancer surgery is carried out within weeks to months of diagnosis. This is a population‐ and register‐based study of all women diagnosed with invasive breast cancer in the Stockholm‐Gotland healthcare region in Sweden, 2001–2008, and who were initially operated. Follow‐up of vital status ended 2014. 7,017 women were included in analysis. Our main outcome was overall survival. Main analyses were carried out using Cox proportional hazards models. We adjusted for likely confounders and stratified on mode of detection, tumor size and lymph node metastasis. We found that a longer interval between date of morphological diagnosis and therapeutic surgery was associated with a poorer prognosis. Assuming a linear association, the hazard rate of death from all causes increased by 1.011 (95% CI 1.006–1.017) per day. Comparing, for example, surgery 6 weeks after diagnosis to surgery 3 weeks after diagnosis, thereby confers a 1.26‐fold increased hazard rate. The increase in hazard rate associated with surgical delay was strongest in women with largest tumors. Whilst there was a clear association between delays and survival in women without lymph node metastasis, the association may be attenuated in subgroups with increasing number of lymph node metastases. We found no evidence of an interaction between time to surgery and mode of detection. In conclusion, unwarranted delays to primary treatment of breast cancer should be avoided.