| 1. |
- Van Dorp, Wendy, et al.
(författare)
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Recommendations for premature ovarian insufficiency surveillance for female survivors of childhood, adolescent, and young adult cancer : A report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup consortium
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 34:28, s. 3440-3450
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were treated with alkylating agents and/or radiation, with potential exposure of the ovaries, have an increased risk of premature ovarian insufficiency (POI). Clinical practice guidelines can facilitate these survivors' access to optimal treatment of late effects that may improve health and quality of survival; however, surveillance recommendations vary among the existing long-term follow-up guidelines, which impedes the implementation of screening. Patients and Methods: The present guideline was developed by using an evidence-based approach and summarizes harmonized POI surveillance recommendations for female survivors of CAYA cancer who were diagnosed at age < 25 years. The recommendations were formulated by an international multidisciplinary panel and graded according to the strength of the evidence and the potential benefit gained from early detection and intervention. The harmonized POI surveillance recommendations were developed by using a transparent process and are intended to facilitate care for survivors of CAYA cancer. Results and Conclusion: The harmonized set of POI surveillance recommendations is intended to be scientifically rigorous, to positively influence health outcomes, and to facilitate the care for female survivors of CAYA cancer.
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| 2. |
- Mulder, Renée L., et al.
(författare)
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Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer : recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
- 2021
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:2, s. 68-80
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Forskningsöversikt (refereegranskat)abstract
- Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.
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| 3. |
- van der Kamp, Ananda, et al.
(författare)
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Automated Deep Learning-Based Classification of Wilms Tumor Histopathology
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Wilms tumor (WT) is the most frequent pediatric tumor in children and shows highly variable histology, leading to variation in classification. Artificial intelligence-based automatic recognition holds the promise that this may be done in a more consistent way than human observers can. We have therefore studied digital microscopic slides, stained with standard hematoxylin and eosin, of 72 WT patients and used a deep learning (DL) system for the recognition of 15 different normal and tumor components. We show that such DL system can do this task with high accuracy, as exemplified by a Dice score of 0.85 for the 15 components. This approach may allow future automated WT classification.(1) Background: Histopathological assessment of Wilms tumors (WT) is crucial for risk group classification to guide postoperative stratification in chemotherapy pre-treated WT cases. However, due to the heterogeneous nature of the tumor, significant interobserver variation between pathologists in WT diagnosis has been observed, potentially leading to misclassification and suboptimal treatment. We investigated whether artificial intelligence (AI) can contribute to accurate and reproducible histopathological assessment of WT through recognition of individual histopathological tumor components. (2) Methods: We assessed the performance of a deep learning-based AI system in quantifying WT components in hematoxylin and eosin-stained slides by calculating the Sorensen-Dice coefficient for fifteen predefined renal tissue components, including six tumor-related components. We trained the AI system using multiclass annotations from 72 whole-slide images of patients diagnosed with WT. (3) Results: The overall Dice coefficient for all fifteen tissue components was 0.85 and for the six tumor-related components was 0.79. Tumor segmentation worked best to reliably identify necrosis (Dice coefficient 0.98) and blastema (Dice coefficient 0.82). (4) Conclusions: Accurate histopathological classification of WT may be feasible using a digital pathology-based AI system in a national cohort of WT patients.
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| 4. |
- van der Kamp, Ananda, et al.
(författare)
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Artificial Intelligence in Pediatric Pathology: The Extinction of a Medical Profession or the Key to a Bright Future?
- 2022
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Ingår i: Pediatric and Developmental Pathology. - : SAGE PUBLICATIONS INC. - 1093-5266 .- 1615-5742. ; 25:4, s. 380-387
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Forskningsöversikt (refereegranskat)abstract
- Artificial Intelligence (AI) has become of increasing interest over the past decade. While digital image analysis (DIA) is already being used in radiology, it is still in its infancy in pathology. One of the reasons is that large-scale digitization of glass slides has only recently become available. With the advent of digital slide scanners, that digitize glass slides into whole slide images, many labs are now in a transition phase towards digital pathology. However, only few departments worldwide are currently fully digital. Digital pathology provides the ability to annotate large datasets and train computers to develop and validate robust algorithms, similar to radiology. In this opinionated overview, we will give a brief introduction into AI in pathology, discuss the potential positive and negative implications and speculate about the future role of AI in the field of pediatric pathology.
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| 5. |
- van Santen, Selveta S, et al.
(författare)
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Bariatric Surgery for Hypothalamic Obesity in Craniopharyngioma Patients: A Retrospective, Matched Case-Control Study.
- 2021
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:11
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Tidskriftsartikel (refereegranskat)abstract
- Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (~98%) and hypothalamic obesity (~50%).To determine the efficacy regarding long-term weight loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction.Retrospective case control study.Multicenter international study.Obese craniopharyngioma patients (N = 16; of which 12 women) with a history of bariatric surgery [12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age of 21 years (range 15-52), median follow-up 5.2 years (range 2.0-11.3)] and age/sex/surgery/BMI-matched obese controls (N = 155).Weight loss and obesity-related comorbidities up to 5 years after bariatric surgery were compared and changes in hormonal replacement therapy evaluated.Mean weight loss at 5-year follow-up was 22.0% (95% CI 16.1, 27.8) in patients versus 29.5% (28.0, 30.9) in controls (P = 0.02), which was less after Roux-en-Y gastric bypass (22.7% [16.9, 28.5] vs. 32.0% [30.4, 33.6]; P = 0.003) but at a similar level after sleeve gastrectomy (21.7% [-1.8, 45.2] vs. 21.8% [18.2, 25.5]; P = 0.96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems.Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5-year follow-up after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after Roux-en-Y gastric bypass. Bariatric surgery appears effective and relatively safe in the treatment of obese craniopharyngioma patients.
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| 6. |
- van Santen, Selveta S, et al.
(författare)
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Body composition and bone mineral density in craniopharyngioma patients: a longitudinal study over 10 years.
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:12
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Tidskriftsartikel (refereegranskat)abstract
- Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD).To describe body composition and BMD (change).Retrospective longitudinal study.Two Dutch/Swedish referral centers.Patients with craniopharyngioma (n=112) with a DXA-scan available [two DXA-scans, n=86; median Δtime 9.6 years (range 0.4-23.3)] at age ≥18 years [58 (52%) male, 50 (44%) childhood-onset].Longitudinal changes of body composition and BMD, and associated factors of ΔZ-score (sex and age standardized).BMI (from 28.8±4.9 to 31.2±5.2kg/m 2, P<0.001), fat mass index (FMI) (from 10.5±3.6 to 11.9±3.8kg/m 2, P=0.001) and fat free mass index (FFMI) (from 18.3±3.2 to 19.1±3.2kg/m 2, P<0.001) were high at baseline and increased. Fat percentage and Z-scores of body composition did not increase, except for FFMI Z-scores (from 0.26±1.62 to 1.06±2.22, P<0.001). Z-scores of total body, L2-L4, femur neck increased (mean difference 0.66±1.00, P<0.001; 0.78±1.63, P<0.001; 0.51±1.85, P=0.02). Linear regression models for ΔZ-score were positively associated with growth hormone replacement therapy (GHRT) [femur neck: beta 1.45 (95% CI 0.51-2.39)]; and negatively with radiotherapy [femur neck: beta -0.79 (-1.49--0.09)], glucocorticoid dose [total body: beta -0.06 (-0.09--0.02)]) and medication to improve BMD [L2-L4: beta -1.06 (-1.84--0.28)]).Z-scores of BMI, fat percentage and FMI remained stable in patients with craniopharyngioma over time, while Z-scores of FFMI and BMD increased. Higher glucocorticoid dose and radiotherapy were associated with BMD loss and GHRT with increase.
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| 7. |
- van Santen, Selveta Sanne, et al.
(författare)
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Diagnosing Metabolic Syndrome in Craniopharyngioma Patients: Body Composition versus BMI.
- 2019
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Ingår i: European journal of endocrinology. - 1479-683X. ; 181:2, s. 173-183
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Tidskriftsartikel (refereegranskat)abstract
- Craniopharyngioma patients often have poor metabolic profiles due to hypothalamic-pituitary damage. Previously, using body mass index (BMI) as obesity marker, the occurrence of the metabolic syndrome in these patients was estimated at 46%. Our aim was to determine if Dual X-ray Absorptiometry (DXA-) scan in evaluation of obesity and metabolic syndrome would be superior.Retrospective study of craniopharyngioma patients for whom DXA-scan results were available.BMI, fat percentage and fat mass index were used to evaluate obesity and as components for obesity in metabolic syndrome.Ninety-five craniopharyngioma patients were included (51% female, 49% childhood-onset disease). Metabolic syndrome occurred in 34-53 (45-51%) subjects (depending on the definition of obesity, although all definitions occurred in higher frequency than in the general population). Metabolic syndrome frequency was higher if obesity was defined by fat percentage (52% vs. 42%) or fat mass index (51% vs. 43%) compared to BMI. Misclassification appeared in 9% (fat percentage vs. BMI) and 7% (fat mass index vs. BMI) for metabolic syndrome and 29% and 13% for obesity itself, respectively. For metabolic syndrome, almost perfect agreement was found for BMI compared with fat percentage or fat mass index. For obesity, agreement was fair to moderate (BMI vs. fat percentage).Using BMI to evaluate obesity underestimates the true prevalence of metabolic syndrome in patients with craniopharyngioma. Furthermore, fat percentage contributes to a better evaluation of obesity than BMI. The contribution of DXA-scan might be limited for identification of the metabolic syndrome.
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| 8. |
- Winther, Jeanete F., et al.
(författare)
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Childhood cancer survivor cohorts in Europe
- 2015
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Ingår i: Acta Oncologica. - 1651-226X. ; 54:5, s. 655-668
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Forskningsöversikt (refereegranskat)abstract
- With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.
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| 9. |
- Chagtai, Tasnim, et al.
(författare)
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Gain of 1q as a prognostic biomarker in Wilms Tumors (WTs) treated with preoperative chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 trial : A SIOP renal tumours biology consortium study
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 34:26, s. 3195-3203
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods: WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results: One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P < .001; hazard ratio, 2.33) and OS (P = .01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion: Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.
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| 10. |
- Pritchard-Jones, Kathy, et al.
(författare)
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Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001) : an open-label, non-inferiority, randomised controlled trial
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9999, s. 64-1156
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation.METHODS: For this international, multicentre, open-label, non-inferiority, phase 3, randomised SIOP WT 2001 trial, we recruited children aged 6 months to 18 years at the time of diagnosis of a primary renal tumour from 251 hospitals in 26 countries who had received 4 weeks of preoperative chemotherapy with vincristine and actinomycin D. Children with stage II-III intermediate-risk Wilms' tumours assessed after delayed nephrectomy were randomly assigned (1:1) by a minimisation technique to receive vincristine 1·5 mg/m(2) at weeks 1-8, 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27, plus actinomycin D 45 μg/kg every 3 weeks from week 2, either with five doses of doxorubicin 50 mg/m(2) given every 6 weeks from week 2 (standard treatment) or without doxorubicin (experimental treatment). The primary endpoint was non-inferiority of event-free survival at 2 years, analysed by intention to treat and a margin of 10%. Assessment of safety and adverse events included systematic monitoring of hepatic toxicity and cardiotoxicity. This trial is registered with EudraCT, number 2007-004591-39, and is closed to new participants.FINDINGS: Between Nov 1, 2001, and Dec 16, 2009, we recruited 583 patients, 341 with stage II and 242 with stage III tumours, and randomly assigned 291 children to treatment including doxorubicin, and 292 children to treatment excluding doxorubicin. Median follow-up was 60·8 months (IQR 40·8-79·8). 2 year event-free survival was 92·6% (95% CI 89·6-95·7) for treatment including doxorubicin and 88·2% (84·5-92·1) for treatment excluding doxorubicin, a difference of 4·4% (95% CI 0·4-9·3) that did not exceed the predefined 10% margin. 5 year overall survival was 96·5% (94·3-98·8) for treatment including doxorubicin and 95·8% (93·3-98·4) for treatment excluding doxorubicin. Four children died from a treatment-related toxic effect; one (<1%) of 291 receiving treatment including doxorubicin died of sepsis, three (1%) of 292 receiving treatment excluding doxorubicin died of varicella, metabolic seizure, and sepsis during treatment for relapse. 17 patients (3%) had hepatic veno-occlusive disease. Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin. 12 children receiving treatment including doxorubicin, and ten children receiving treatment excluding doxorubicin, died, with the remaining deaths from tumour recurrence.INTERPRETATION: Doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification.FUNDING: See Acknowledgments for funders.
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| 11. |
- Skinner, Roderick, et al.
(författare)
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Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors : a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium
- 2017
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:2, s. 75-90
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Forskningsöversikt (refereegranskat)abstract
- Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.
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| 12. |
- van Atteveld, Jenneke E., et al.
(författare)
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Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors : evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
- 2021
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:9, s. 622-637
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Tidskriftsartikel (refereegranskat)abstract
- Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dualenergy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > -1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.
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| 13. |
- van der Beek, Justine N., et al.
(författare)
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MRI Characteristics of Pediatric Renal Tumors : A SIOP-RTSG Radiology Panel Delphi Study
- 2022
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 55:2, s. 543-552
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Tidskriftsartikel (refereegranskat)abstract
- Background: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics. Purpose: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors. Study Type: Consensus process using a Delphi method. Population: Not applicable. Field Strength/Sequence: Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T. Assessment: Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions. Statistical Tests: The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale. Results: Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors. Data Conclusion: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts. Level of Evidence: 3. Technical Efficacy Stage: 3.
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| 14. |
- Wijnen, Mark, et al.
(författare)
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Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study.
- 2018
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Ingår i: European journal of endocrinology. - 1479-683X. ; 178:1, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma.Hospital-based retrospective cohort study conducted between 1987 and 2014.We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups.Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8-6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1-8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0-3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1-4.5) and respiratory (SMR: 6.0, 95% CI: 2.5-14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality.Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.
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| 15. |
- Wijnen, Mark, et al.
(författare)
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The metabolic syndrome and its components in 178 patients treated for craniopharyngioma after 16 years of follow-up.
- 2018
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Ingår i: European journal of endocrinology. - 1479-683X. ; 178:1, s. 11-22
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Tidskriftsartikel (refereegranskat)abstract
- Patients with craniopharyngioma are at an increased risk for cardio- and cerebrovascular mortality. The metabolic syndrome (MetS) is an important cardiometabolic risk factor, but barely studied in patients with craniopharyngioma. We aimed to investigate the prevalence of and risk factors for the MetS and its components in patients with craniopharyngioma.Cross-sectional study with retrospective data.We studied the prevalence of and risk factors for the MetS and its components in 110 Dutch (median age 47 years, range 18-92) and 68 Swedish (median age 50 years, range 20-81) patients with craniopharyngioma with ≥3 years of follow-up (90 females (51%); 83 patients with childhood-onset craniopharyngioma (47%); median follow-up after craniopharyngioma diagnosis 16 years (range 3-62)). In Dutch patients aged 30-70 years and Swedish patients aged 45-69 years, we examined the prevalence of the MetS and its components relative to the general population.Sixty-nine (46%) of 149 patients with complete data demonstrated the MetS. Prevalence of the MetS was significantly higher in patients with craniopharyngioma compared with the general population (40% vs 26% (P<0.05) for Dutch patients; 52% vs 15% (P<0.05) for Swedish patients). Multivariable logistic regression analysis identified visual impairment as a borderline significant predictor of the MetS (OR 2.54, 95% CI 0.95-6.81; P=0.06) after adjustment for glucocorticoid replacement therapy and follow-up duration. Age, female sex, tumor location, radiological hypothalamic damage, 90Yttrium brachytherapy, glucocorticoid replacement therapy and follow-up duration significantly predicted components of the MetS.Patients with craniopharyngioma are at an increased risk for the MetS, especially patients with visual impairment.
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| 16. |
- Williams, Richard D, et al.
(författare)
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Multiple mechanisms of MYCN dysregulation in Wilms tumour.
- 2015
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Ingår i: Oncotarget. - 1949-2553. ; 6:9, s. 7232-7243
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Tidskriftsartikel (refereegranskat)abstract
- Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation.
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| 17. |
- Balgobind, Brian V, et al.
(författare)
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Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia : results of an international retrospective study.
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 114:12, s. 2489-2496
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Tidskriftsartikel (refereegranskat)abstract
- Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.
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| 18. |
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| 19. |
- Blink, Marjolein, et al.
(författare)
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Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome : a retrospective, international study
- 2014
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 99:2, s. 299-307
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.
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| 20. |
- Buitenkamp, Trudy D., et al.
(författare)
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Acute lymphoblastic leukemia in children with Down syndrome : a retrospective analysis from the Ponte di Legno study group
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:1, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- < 1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 x 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups.
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| 21. |
- Coenen, Eva A, et al.
(författare)
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Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients : results of an international study
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 117:26, s. 7102-7111
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Tidskriftsartikel (refereegranskat)abstract
- We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P < .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.
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| 22. |
- Hasle, Henrik, et al.
(författare)
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Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia : an international retrospective study.
- 2007
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Ingår i: Blood. - 0006-4971. ; 109:11, s. 4641-7
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Tidskriftsartikel (refereegranskat)abstract
- Monosomy 7 (-7) and deletion 7q \del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and -7 or del(7q) with or without other cytogenetic aberrations \+/- other]. Karyotypes included -7 (n = 90), -7 other (n = 82), del(7q) (n = 21), and del(7q) other (n = 65). Complete remission (CR) was achieved in fewer patients with -7 +/- other compared with del(7q) +/- other (61% versus 89%, P < .001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) +/- other compared with -7 +/- other (51% versus 30%, P < .01). Cytogenetic aberrations considered favorable in AML \t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P = .03). Patients with -7 and inv(3),-5/del(5q), or + 21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratification.
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| 23. |
- Noort, Sanne, et al.
(författare)
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Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group.
- 2018
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 132:15, s. 1584-1592
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Tidskriftsartikel (refereegranskat)abstract
- To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n = 23) had significantly lower median white blood cell count (12.5 × 109/L, P = .03) compared with the reference cohort. FUS-ERG rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P = .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE = 8%, P = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in FUS-ERG, 0% (SE = 0%) in RUNX1-CBFA2T3, compared with 32% (SE = 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.
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| 24. |
- Perotti, Daniela, et al.
(författare)
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Hallmark discoveries in the biology of Wilms tumour
- 2023
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Ingår i: Nature Reviews Urology. - 1759-4812.
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Forskningsöversikt (refereegranskat)abstract
- The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the ‘two-hit’ model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics — from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.
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| 25. |
- Sandahl, Julie Damgaard, et al.
(författare)
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t(6;9)(p22; q34)/DEK-NUP214-rearranged pediatric myeloid leukemia : an international study of 62 patients
- 2014
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 99:5, s. 865-872
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia with t(6; 9)(p22; q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6; 9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6; 9)/DEKNUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6; 9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6; 9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.
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| 26. |
- Tonorezos, Emily S., et al.
(författare)
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Models of care for survivors of childhood cancer from across the globe : Advancing survivorship care in the next decade
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:21, s. 2223-2230
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Forskningsöversikt (refereegranskat)abstract
- With improvements in cancer treatment and supportive care, a growing population of survivors of childhood cancer at risk for significant and potentially life-threatening late effects has been identified. To provide a current snapshot of the models of care from countries with varying levels of resources and health care systems, stakeholders in childhood cancer survivorship clinical care and research were identified from 18 countries across five continents. Stakeholders responded to a survey and provided a brief narrative regarding the current state of survivorship care. Findings indicate that among pediatric-age survivors of childhood cancer (allowing for differences in age cutoffs across countries), resources are generally available, and a large proportion of survivors are seen by a physician familiar with late effects in most countries. After survivors transition to adulthood, only a minority are seen by a physician familiar with late effects. Despite the need to improve communication between pediatric oncology and primary care, only a few countries have existing national efforts to educate primary care physicians, although many more reported that educational programs are in development. These data highlight common challenges and potential solutions for the lifelong care of survivors of childhood cancer. Combining risk-based and patient-oriented solutions for this population is likely to benefit both providers and patients.
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