The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). ...Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960 - 1987. SMSTs were diagnosed in 1960-1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Since 1998, the staff of the International Monetary Fund has published a classification of countries' de facto exchange rate arrangements. Experience in operating this classification system has ...highlighted a need for changes. The present paper provides information on revisions to the system in early 2009. The changes are expected to allow for greater consistency and objectivity of classifications across countries, expedite the classification process, conserve resources, and improve transparency.
Purpose
To compare the earliest detection of progression in visual fields and monoscopic optic disc photographs at different stages of manifest glaucoma.
Methods
This study evaluated 306 eyes in 249 ...patients with manifest open‐angle glaucoma included in the Early Manifest Glaucoma Trial (EMGT). All patients in the trial were followed up regularly by standard automated perimetry and monoscopic optic disc photography, and the median follow‐up time was 8 years. Progression was assessed in series of optic disc photographs and in series of visual fields using glaucoma change probability maps and the predefined EMGT progression criterion. The proportion of progressions detected first in visual fields and the proportion detected first in optic disc photographs were compared at different stages of glaucoma severity defined by the perimetric mean deviation (MD) of the baseline visual field.
Results
Assessment of 210 eyes with early visual field loss, 83 eyes with moderate field loss, and 13 eyes with advanced field loss showed that, among the eyes exhibiting progression, the progression was detected first in the visual field in 80%, 79% and 100%, respectively. The predominance of visual field progressions at all stages was still apparent when using narrower (3‐dB) MD intervals for staging.
Conclusion
In the EMGT material on eyes with manifest open‐angle glaucoma, the initial progression was detected much more often in the visual field series than in the optic disc photographs at all stages of disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Aim of the study To analyse late morbidity and mortality in pre and post-menopausal breast cancer patients treated with postmastectomy radiotherapy, with emphasis on side-effects from the ...heart, cerebrovascular and respiratory systems. Methods Long term follow-up of two randomised, clinical trials with 1100 patients was carried out. Pre-menopausal women were allocated to radiotherapy (RT), RT + oral cyclophosphamide (RT + C) or cyclophosphamide only (C). Post-menopausal women were allocated to RT, RT + Tamoxifen for one year (RT + Tam) or tamoxifen only (Tam). Information on admission to hospital, mortality and causes of death was obtained from national registers. Results After 25 years, adding RT to cyclophosphamide in pre-menopausal women raised the mortality from heart disease from zero to 0.8% ( p = 0.04). In post-menopausal women, adding RT to Tam raised the mortality from heart disease from 10.5% to 18.4% ( p = 0.005). In post-menopausal women mortality due to cerebrovascular disease increased from 3.4% to 8.7% by adding RT to Tam ( p = 0.015). The differences were not evident until in the second decade of follow-up. In spite of differences in specific causes of death, there were no significant differences between the treatment arms concerning morbidity or overall mortality. Conclusion Postmastectomy radiotherapy to the chest wall and loco-regional lymph nodes including the parasternal lymph nodes as delivered in the end of the seventies did not reduce overall mortality, but gave a significantly increased risk of death from heart and cerebrovascular disease, which appeared during the second decade after radiotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
IMPORTANCE: Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve ...outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. OBJECTIVE: To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. INTERVENTIONS: Patients were randomized 1:1 either to 4 cycles of leukocyte nadir–based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was breast cancer recurrence–free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease–free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. RESULTS: Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median IQR age, 51 45-58 years; 80% with hormone receptor–positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0.63-0.99; P = .04; 5-year EFS, 86.7% vs 82.1%). The groups did not differ in OS (HR, 0.77; 95% CI, 0.57-1.05; P = .09; 5-year OS, 92.1% vs 90.2%) or DDFS (HR, 0.83; 95% CI, 0.64-1.08; P = .17; 5-year DDFS, 89.4% vs 86.7%). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (52.6%) in the tailored dose-dense group and 366 (36.6%) in the control group. CONCLUSIONS AND RELEVANCE: Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence–free survival. Nonhematologic toxic effects were more frequent in the tailored dose-dense group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665
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.
What's new?
The long‐term effects of cancer treatment in childhood cancer survivors can be serious, and more research is needed to fully investigate the relationship between treatment and chronic disease in aging survivors. This retrospective population‐based cohort study focused on cardiovascular late effects among childhood cancer survivors in the five Nordic countries. Survivors were found to be at significantly increased risk for cardiovascular disease throughout their lives. Relative risk was highest for heart failure, valvular dysfunction, and cerebrovascular diseases. Overall, survivors had a twofold increased lifetime risk for hospitalization for cardiovascular disease.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Conclusion: This study shows a persistent trend of an increase in the incidence of carcinoma of the tongue into the twenty-first century for both sexes and all age groups except for young ...males. Objectives: During the last decades increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been reported. We previously showed an increased incidence in SCC of the tongue in Scandinavia in 1960-1994, most pronounced in patients aged 20-39 years. The aim of this study was to investigate whether the trend of increased incidence of tongue cancer continued into the twenty-first century in a population-based study in the Nordic countries. Methods: Data for all reported SCCs of the tongue and base of tongue in patients aged 20-79 years during 1960-2008 were extracted from the NORDCAN registry, based on the National Cancer registries in the Nordic countries. Data from Sweden, Norway, Finland, Denmark, and Iceland were analyzed. The age groups 20-39, 40-64, and 65-79 years were studied separately as well as male and female figures. Results: In all, 12 280 cases were reported, of which 673 were diagnosed in patients aged 20-39 years. The trend of an increase persisted after 1994 in both sexes and all three age groups except in young males.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Many studies have focused on short term mortality after primary intracerebral haemorrhage (ICH) whereas long term prognosis and causes of death have been less studied. We therefore examined these ...issues in a population based cohort of 1 year ICH survivors.
ICH patients in a defined Swedish population (1.14 million inhabitants) were prospectively registered during 1996. Patients surviving 1 year after ICH onset were followed-up regarding survival status and cause of death until December 2009 using data from the National Census Office and the National Cause of Death Register. Patient prognosis was also compared with the general population using official Swedish mortality data. Clinical and radiological prognostic factors were evaluated.
Of 323 patients with ICH, 172 (53%) survived after 1 year, 127 (39%) after 5 years and 57 (18%) after 13 years. Mortality of the 172, 1 year survivors (mean age 67.7 years at ICH) persistently exceeded expected mortality; 13 years post ictus survival was only 34% compared with 61% in the general population. Of 115 deaths among the 172, 1 year survivors, 36% were from cerebrovascular disease and 19% from ischaemic heart disease. Independent risk factors for death among 1 year survivors were age (HR 1.08 per year; 95% CI 1.06 to 1.10; p<0.001), diabetes mellitus at baseline (HR 2.10; 95% CI 1.18 to 3.74; p=0.012) and anticoagulant therapy (HR 1.99; 95% CI 1.12 to 3.53; p=0.018) at ICH onset.
One year survivors after ICH had a substantial and persisting excess mortality compared with the general population. Major causes of death were stroke and ischaemic heart disease.
Abstract Aim An increased risk for diabetes mellitus (DM) adds significantly to the burden of late complications in childhood cancer survivors. Complications of DM may be prevented by using ...appropriate screening. It is, therefore, important to better characterise the reported increased risk for DM in a large population-based setting. Materials and methods From the national cancer registries of the five Nordic countries, a cohort of 32,903 1-year survivors of cancer diagnosed before the age of 20 between start of cancer registration in the 1940s and 1950s through 2008 was identified; 212,393 comparison subjects of the same age, gender and country were selected from national population registers. Study subjects were linked to the national hospital registers. Absolute excess risks (AERs) and standardised hospitalisation rate ratios (SHRRs) were calculated. Results DM was diagnosed in 496 childhood cancer survivors, yielding an overall SHRR of 1.6 (95% confidence interval (CI), 1.5–1.8) and an AER of 43 per 100,000 person-years, increasing from approximately 20 extra cases of DM in ages 0–19 to more than 100 extra cases per 100,000 person-years in ages ⩾50. The relative risks for DM were significantly increased after Wilms’ tumour (SHRR, 2.9), leukaemia (2.0), CNS neoplasms (1.8), germ-cell neoplasms (1.7), malignant bone tumours (1.7) and Hodgkin’s lymphoma (1.6). The risk for DM type 2 was slightly higher than that for type 1. Conclusion Childhood cancer survivors are at increased risk for DM, with absolute risks increasing throughout life. These findings underscore the need for preventive interventions and prolonged follow-up of childhood cancer survivors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy ...including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events.
Inclusion criteria were age 18–65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2–3 and WHO performance score 0–3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years.
A total of 156 eligible patients with a median age of 54 years (range 20–64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months.
The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis.
NCT01502982.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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