| 1. |
- Jussila, Miro-Pekka, et al.
(författare)
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Late vertebral side effects in long-term survivors of irradiated childhood brain tumor
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Long-term side effects of the treatments are common in survivors of irradiated pediatric brain tumors. Ionizing radiation in combination with surgery and chemotherapy during childhood may reduce vertebral height and bone mineral density (BMD), and cause growth failure. The aim of this study was to evaluate the late consequences of tumor treatments on vertebrae in survivors of childhood brain tumors.Methods: 72 adult survivors (mean age 27.8 years, standard deviation 6.7) of irradiated childhood brain tumor were studied by spinal magnetic resonance imaging (MRI) for vertebral abnormalities from the national cohort of Finland. Patients were treated in five university hospitals in Finland between the years 1970 and 2008. Subject height and weight were measured and body mass index (BMI) was calculated. The morphology and height/ depth ratio of the vertebrae in the middle of the kyphotic thoracic curvature (Th8) and lumbar lordosis (L3) were examined. Vertebrae were analyzed by Genant's semiquantative (SQ) method and spinal deformity index (SDI) was calculated. BMD was measured by using dual X-ray absorptiometry.Results: 4.2% (3/72) of the patients had undiagnosed asymptomatic vertebral fracture and 5.6% (4/72) of patients had radiation- induced decreased vertebral body height. Male patients had flatter vertebrae compared with females. Patient age at the time of irradiation, BMI and irradiation area correlated to vertebral morphology differentially in males and females. BMD had no association with the vertebral shape. Patients who had received craniospinal irradiation were shorter than the general population.Conclusion: Childhood brain tumor survivors had a high number of vertebral abnormalities in young adulthood. Irradiation was associated with abnormal vertebral morphology and compromised final height. Male gender may predispose vertebrae to the side effects of irradiation.
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| 2. |
- Remes, Tiina Maria, et al.
(författare)
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Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors
- 2020
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press (OUP). - 2054-2577 .- 2054-2585. ; 7:4, s. 415-427
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy.MethodsSeventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files.ResultsForty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts.ConclusionsTreating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.
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| 3. |
- Remes, Tiina M., et al.
(författare)
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Radiation-Induced Meningiomas After Childhood Brain Tumor : A Magnetic Resonance Imaging Screening Study
- 2019
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Ingår i: Journal of Adolescent and Young Adult Oncology. - : Mary Ann Liebert. - 2156-5333 .- 2156-535X. ; 8:5, s. 593-601
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Childhood brain tumors (CBTs) and their treatment increase the risk of secondary neoplasms (SNs). We studied the incidence of secondary craniospinal tumors with magnetic resonance imaging (MRI) screening in a national cohort of survivors of CBT treated with radiotherapy, and we analyzed the Finnish Cancer Registry (FCR) data on SNs in survivors of CBT with radiotherapy registered as a part of the primary tumor treatment. Methods: A total of 73 survivors of CBT participated in the MRI study (mean follow-up of 19 +/- 6.2 years). The incidence of SNs in a cohort of CBT patients (N = 569) was retrieved from the FCR (mean follow-up of 11 +/- 12.9 years). Brain tumors were diagnosed at age <= 16 years between the years 1970 and 2008 in the clinical study and the years 1963 and 2010 in the FCR population. Results: Secondary brain tumors, meningiomas in all and schwannoma in one, were found in 6 of the 73 (8.2%) survivors with a mean of 23 +/- 4.3 years after the diagnosis of the primary tumor. The cumulative incidence was 10.2% (95% confidence interval [CI] 3.9-25.1) in 25 years of follow-up. In the FCR data, the 25-year cumulative incidence of SNs was 2.4% (95% CI 1.3-4.1); only two brain tumors, no meningiomas, were registered. Conclusion: Survivors of CBT treated with radiotherapy have a high incidence of meningiomas, which are rarely registered in the FCR.
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| 4. |
- Anttonen, Julia, et al.
(författare)
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Pre- and postdiagnosis growth failure, adult short stature, and untreated growth hormone deficiency in radiotherapy-treated long-term survivors of childhood brain tumor
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- PurposeGrowth failure is common in radiotherapy-treated long-term survivors of pediatric brain tumors, but studies on longitudinal growth in this patient group are lacking. Here, the aim was to assess the changes in growth patterns before and after brain tumor diagnosis, the adult height, and the risk factors for compromised growth. The incidence and treatment practices of growth hormone deficiency were analyzed.MethodsA cohort of 73 survivors of childhood brain tumor (median age 27.2 years, range 16.2 to 43.8 years) was studied after a median follow-up period of 20.4 years from diagnosis (IQR 14.9 to 22.9 years). Patients were treated in five university hospitals in Finland between 1970 and 2008. Growth curves, final height, and patient- and disease-related risk factors for compromised growth during different growth periods were analyzed. Laboratory analyses for IGF-1 and IGFBP-3 were performed at the follow-up.ResultsGrowth failure was evident at diagnosis, with a mean height decline of -0.6 SDS (standard deviation score) from birth (95% CI -1.15 to -0.05). Mean height SDS decline after the diagnosis was -1.09 SDS (95%CI -1.51 to -0.66). At follow-up, 37% of the study subjects (27/73) had true short stature (height < -2 SDS). The mean height deficit corrected for target height was -1.9 SDS (95% CI -1.45 to -2.40). Growth failure was associated with the age at diagnosis, corticosteroid dose, radiotherapy modality and mean dose of irradiation in the thalamic area. Low IGF-1 level (below -2.0 SDS) was found in 32% (23/72), and untreated growth hormone deficiency in 40% (29/72) of the subjects.ConclusionLongitudinal growth impairment was common in radiotherapy-treated survivors of childhood brain tumor, resulting in compromised adult height. Loss of growth potential was evident already at diagnosis and further accelerated by the treatments. At young adulthood, unrecognized growth hormone deficiency was common.
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| 5. |
- Remes, Tiina M., et al.
(författare)
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Bone mineral density is compromised in very long-term survivors of irradiated childhood brain tumor
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:5, s. 665-674
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The increase in the number of childhood brain tumor survivors warrants detailed research to increase our knowledge regarding the possible physical and psychosocial adverse outcomes of tumor and tumor therapy. The aim of this study was to evaluate the current bone health by measuring the bone mineral density (BMD) in irradiated, adult long-term survivors of childhood brain tumors.Material and methods: We studied a national cohort of 74 adult survivors of childhood brain tumors treated with irradiation in Finland between 1970 and 2008. Dual X-ray absorptiometry (DXA) was performed for the femoral necks, total hips, and lumbar spine. Laboratory tests were conducted for evaluating the pituitary, thyroid, and gonadal functions. The participants were interviewed, examined clinically, and the disease and treatment related data were retrieved from the patient files.Results: One fourth of the patients (23.6%) had sex- and age-normalized z-scores below the expected range for age (z-score -2.0). Mean BMD scores were decreased in all the DXA measurement sites. Male sex was associated with low BMD (p<.05), while body mass index (BMI) had a significant positive association with BMD (p<.01). Mode of irradiation (with or without spinal irradiation) or inclusion of chemotherapy in the treatment did not affect BMD significantly. However, patients with a ventriculoperitoneal shunt had lower BMD than those without a shunt (p<.05). Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were negatively associated with BMD in women (p<.05). However, a higher cumulative dose of glucocorticoids during treatment was not associated with lower BMD, while low BMD was significantly associated with previous fractures in long bones.Discussion: Low BMD should be taken in consideration in treatment of irradiated childhood brain tumor survivors especially in those with previous fractures in long bones.
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| 6. |
- Remes, Tiina M., et al.
(författare)
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Neurocognitive impairment, employment, and social status in radiotherapy-treated adult survivors of childhood brain tumors
- 2021
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:3, s. 266-277
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLittle is known of the cognitive functions, employment, and social status in adult survivors of childhood brain tumor (BT). We aimed to determine the long-term neurocognitive profile of radiotherapy-treated adult survivors of childhood BT and the relationship between cognitive functions and employment and social status.MethodsNeurocognitive profiles of survivors were assessed in a Finnish national cohort of 71 radiotherapy-treated survivors of childhood BT (median follow-up time: 21 years [range: 5-33 years]) using a cross-sectional design. Neurocognitive outcomes were compared to control (n = 45) and normative values. Tumor- and treatment-related data were collected from the patient files. Information on employment and social status was gathered.ResultsSurvivors’ (median age: 27 years [range: 16-43 years]) median verbal and performance intelligence quotient (IQ) was 90 (range: 49-121) and 87 (range: 43-119), respectively. The cognitive domains with the greatest impairment were executive functions (median z score, −3.5 SD [range: −25.0 to 1.3 SD]), and processing speed and attention (median z score, −2.5 SD [range: −24.9 to 0.5 SD]). Executive functions were associated with employment, educational level, living independently, having an intimate relationship, and having a driving license. Processing speed and attention were related to educational level, living independently, having an intimate relationship, and having a driving license. Performance IQ was associated with educational level and employment status. Working memory was associated with educational level and living independently.ConclusionsRadiotherapy-treated adult survivors of childhood BT experience significant neurocognitive impairment, which is associated with difficulties related to employment and social status.
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| 7. |
- Albertsen, Birgitte Klug, et al.
(författare)
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Asparaginase treatment in infants with acute lymphoblastic leukemia; pharmacokinetics and asparaginase hypersensitivity in Interfant-06
- 2019
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Ingår i: Leukemia and Lymphoma. - : TAYLOR & FRANCIS LTD. - 1042-8194 .- 1029-2403. ; 60:6, s. 1469-1475
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Tidskriftsartikel (refereegranskat)abstract
- Acute lymphoblastic leukemia (ALL) is a rare disease in infants. Asparaginase is an essential part of the treatment, and there Acute is a need to evaluate the efficiency and safety of this drug in this age group. We evaluated the pharmacokinetics of intramuscularly administered native E. coli asparaginase (Asparaginase Medac((R))) and PEG-asparaginase (Oncaspar((R))) as well as hypersensitivity reactions during treatment in Interfant-06 (www.clinicaltrials.gov: NCT01025804). All patients without hypersensitivity had sufficiently high enzyme activity levels during treatment with both preparations. Patients with hypersensitivity reactions during treatment, characterized by the presence of either or not of clinical symptoms and no measurable enzyme activity, received ineffective therapy. For optimization of the bad prognosis in infant ALL, therapeutic drug monitoring should be performed for identification of patients who should be switched to a different asparaginase preparation because of inactivation of the drug.
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| 8. |
- Banerjee, Joanna, et al.
(författare)
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The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia
- 2020
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 67:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with central nervous system (CNS) toxicity during therapy for acute lymphoblastic leukaemia (ALL) are at risk for treatment modifications, long-term sequelae and even higher mortality. A better understanding of CNS symptoms and their complications improves the potential to prevent and treat them.Methods: Patient files from 649 children treated with Nordic Society of Pediatric Hematology and Oncology ALL92 and ALL2000 protocols in Finland were reviewed retrospectively for any acute CNS symptom. Detailed data on symptoms, examinations and treatment of the underlying CNS complications were collected from the medical records. Disease-related and outcome data were retrieved from the Nordic leukaemia registry.Results: Altogether, 13% (86) of patients with ALL had acute CNS symptoms. Most symptoms (64%) occurred during the first 2 months of therapy. Posterior reversible encephalopathy syndrome was the most frequent complication (4.5%). Cerebrovascular events were diagnosed in 10 cases (1.6%), while methotrexate-related stroke-like syndrome (SLS) was observed in only one patient (0.2%). CNS symptoms due to systemic or unclear conditions, especially sepsis, were important for differential diagnosis. CNS leukaemia was associated with CNS symptoms (hazard ratio [HR] = 4.03; P = .003), and epilepsy was a common sequel of CNS complications (19%).Conclusions: Acute CNS symptoms are common during ALL therapy, occurring mainly during the first 2 months of treatment. Patients with CNS leukaemia at diagnosis are at a higher risk for CNS toxicity. Despite intensive CNS-directed methotrexate treatment, SLS was diagnosed extremely rarely in our series.
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| 9. |
- Kouhia, Virpi, et al.
(författare)
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Benchmark exercise on SBLOCA experiment of PWR PACTEL facility
- 2013
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 59, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- The PWR PACTEL benchmark exercise was organized in Lappeenranta, Finland by Lappeenranta University of Technology. The benchmark consisted of two phases, i.e. a blind and an open calculation task. Seven organizations from the Czech Republic, Germany, Italy, Sweden and Finland participated in the benchmark exercise, and four system codes were utilized in the benchmark simulation tasks. Two workshops were organized for launching and concluding the benchmark, the latter of which involved presentations of the calculation results as well as discussions on the related modeling issues. The chosen experiment for the benchmark was a small break loss of coolant accident experiment which was performed to study the natural circulation behavior over a continuous range of primary side coolant inventories. For the blind calculation task, the detailed facility descriptions, the measured pressure and heat losses as well as the results of a short characterizing transient were provided. For the open calculation task part, the experiment results were released. According to the simulation results, the benchmark experiment was quite challenging to model. Several improvements were found and utilized especially for the open calculation case. The issues concerned model construction, heat and pressure losses impact, interpreting measured and calculated data, non-condensable gas effect, testing several condensation and CCFL correlations, sensitivity studies, as well as break modeling. There is a clear need for user guidelines or for a collection of best practices in modeling for every code. The benchmark offered a unique opportunity to test the best practices and solutions in modeling and analyzing tasks as well as a possibility to increase knowledge about the interpretation of test results. The benchmark exercise served as a practical and rewarding forum to discuss the needs, problems and possibilities in the analysis and in producing useful data with an experiment facility. The workshops provided an advantageous site for interaction of the code users and the experimenters.
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| 10. |
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| 11. |
- Saarinen-Pihkala, Ulla M, et al.
(författare)
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RALLE Pilot: Response-guided Therapy for Marrow Relapse in Acute Lymphoblastic Leukemia in Children.
- 2012
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Ingår i: Journal of Pediatric Hematology/Oncology. - 1536-3678. ; 34:4, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.
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