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- Bielack, Stefan S, et al.
(författare)
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Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:20, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.
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- Budde, Axel, et al.
(författare)
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Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma
- 2022
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 170, s. 209-235
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The available questionnaires for quality-of-life (QoL) assessments are age-group specific, limiting comparability and impeding longitudinal analyses. The comparability of measurements, however, is a necessary condition for gaining scientific evidence. To overcome this problem, we assessed the viability of harmonising data from paediatric and adult patient-reported outcome (PRO) measures. Method: To this end, we linked physical functioning scores from the Paediatric Quality of Life Inventory (PedsQL) and the Paediatric Quality of Life Questionnaire (PEDQOL) to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) for adults. Samples from the EURAMOS-1 QoL sub-study of 75 (PedsQL) and 112 (PEDQOL) adolescent osteosarcoma patients were concurrently administered both paediatric and adult questionnaires on 98 (PedsQL) and 156 (PEDQOL) occasions. We identified corresponding scores using the single-group equipercentile linking method. Results: Linked physical functioning scores showed sufficient concordance to the EORTC QLQ-C30: Lin's ρ = 0.74 (PedsQL) and Lin's ρ = 0.64 (PEDQOL). Conclusion: Score linking provides clinicians and researchers with a common metric for assessing QoL with PRO measures across the entire lifespan of patients.
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- Calaminus, Gabriele, et al.
(författare)
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Quality of life of patients with osteosarcoma in the european american osteosarcoma study-1 (EURAMOS-1) : Development and implementation of a questionnaire substudy
- 2019
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Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The quality of life (QoL) of patients with osteosarcoma (OS) may be adversely affected by the disease or its treatment. Therefore, it is important to understand the QoL of patients undergoing treatment for OS to improve the QoL. We report on the first prospective international QoL study that was embedded within a large randomized clinical trial from 4 national study groups. Objective: This paper aimed to describe the QoL study development, methodology, accrual details, and characteristics of the QoL cohort. Methods: A total of 2260 patients registered in the EURopean AMerican Osteosarcoma Study-1 (EURAMOS-1), of whom 97.92% (2213/2260) were eligible for the optional QoL assessment and could participate in terms of questionnaire availability. Overall, 61.86% (1369/2213) of patients and/or proxies completed the QoL evaluation at the first assessment time point (E1) after the start of preoperative treatment. The QoL measures used (self- and/or proxy reports) depending on the patient’s age and national study group. Participants and nonparticipants in the ancillary QoL study were compared regarding relevant demographic and disease-related characteristics at registration in the trial. Results: The participation rate at time point E1 did not differ with regard to age, gender, the occurrence of pathological fracture, or the presence of any metastases at diagnosis. No differences were found regarding the primary tumor site. Only the national study group affiliation had an influence on participation. Participation decreased linearly with trial progress up to 20% at the final time point of QoL assessment. Conclusions: This study demonstrates the feasibility of international cooperation for the purpose of assessing and understanding the QoL of pediatric and adolescent/young adult patients with cancer. Future outcomes of this QoL substudy will help to adapt interventions to improve QoL.
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5. |
- Câmara-Costa, Hugo, et al.
(författare)
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Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy.
- 2015
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 92:5, s. 978-85
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Tidskriftsartikel (refereegranskat)abstract
- In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms.
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- Jankovic, Momcilo, et al.
(författare)
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Long-term survivors of childhood cancer : cure and care—the Erice Statement (2006) revised after 10 years (2016)
- 2018
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 12:5, s. 647-650
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The number of persons who have successfully completed treatment for a cancer diagnosed during childhood and who have entered adulthood is increasing over time, and former patients will become aging citizens. Methods: Ten years ago, an expert panel met in Erice, Italy, to produce a set of principles concerning the cure and care of survivors of childhood and adolescent cancer. The result was the Erice Statement (Haupt et al. Eur J Cancer 43(12):1778–80, 2007) that was translated into nine languages. Ten years on, it was timely to review, and possibly revise, the Erice Statement in view of the changes in paediatric oncology and the number and results of international follow-up studies conducted during the intervening years. Results: The long-term goal of the cure and care of a child with cancer is that he/she becomes a resilient and autonomous adult with optimal health-related quality of life, accepted in society at the same level as his/her age peers. “Cure” refers to cure from the original cancer, regardless of any potential for, or presence of, remaining disabilities or side effects of treatment. The care of a child with cancer should include complete and honest information for parents and the child. Conclusions and implication for cancer survivors: Some members of the previous expert panel, as well as new invited experts, met again in Erice to review the Erice Statement, producing a revised version including update and integration of each of the ten points. In addition, a declaration has been prepared, by the Childhood Cancer International Survivors Network in Dublin on October 2016 (see Annex 1).
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8. |
- Marina, Neyssa M., et al.
(författare)
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Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1) : an open-label, international, randomised controlled trial
- 2016
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Ingår i: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
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Tidskriftsartikel (refereegranskat)abstract
- Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.
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9. |
- Pritchard-Jones, Kathy, et al.
(författare)
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Sustaining innovation and improvement in the treatment of childhood cancer: lessons from high-income countries
- 2013
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Ingår i: The Lancet Oncology. - 1474-5488. ; 14:3, s. 95-103
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Tidskriftsartikel (refereegranskat)abstract
- Cancer in children and adolescents is rare and biologically very different from cancer in adults. It accounts for 1.4% of all cancers worldwide, although this proportion ranges from 0.5% in Europe to 4.8% in Africa, largely because of differences in age composition and life expectancy. In high-income countries, survival from childhood cancer has reached 80% through a continuous focus on the integration of clinical research into front-line care for nearly all children affected by malignant disease. However, further improvement must entail new biology-driven approaches, since optimisation of conventional treatments has in many cases reached its limits. In many instances, such approaches can only be achieved through international collaborative research, since rare cancers are being subdivided into increasingly smaller subgroups on the basis of their molecular characteristics. The long-term effect of anticancer treatment on quality of life must also be taken into account because more than one in 1000 adults in high-income countries are thought to be survivors of cancer in childhood or adolescence. The introduction of drugs that are less toxic and more targeted than those currently used necessitates a partnership between clinical and translational researchers, the pharmaceutical industry, drug regulators, and patients and their families. This therapeutic alliance will ensure that efforts are focused on the unmet clinical needs of young people with cancer. Most children with cancer live in low-income and middle-income countries, and these countries account for 94% of all deaths from cancer in people aged 0-14 years. The immediate priority for these children is to improve access to an affordable, best standard of care in each country. Every country should have a national cancer plan that recognises the unique demographic characteristics and care needs of young people with cancer. Centralisation of the complex components of treatment of these rare diseases is essential to improve survival, accelerate research, and train the future specialist workforce. Referral routes and care pathways must take account of the large geographical distances between many patients' homes and treatment centres, and the economic, cultural, and linguistic diversity of the populations served.
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