TY - JOUR
T1 - High-dose chemotherapy followed by autologous haematopoietic cell transplantation for children, adolescents, and young adults with primary metastatic Ewing sarcoma
AU - Haveman, Lianne M.
AU - van Ewijk, Roelof
AU - van Dalen, Elvira C.
AU - Breunis, Willemijn B.
AU - Kremer, Leontien Cm
AU - van den Berg, Henk
AU - Dirksen, Uta
AU - Merks, Johannes Hm
N1 - Funding Information: We would like to thank Stefan Burdach, MD, PhD, professor of Pediatrics and Pediatric Hematology/Oncology, Chair of the Department of Pediatrics Technische Universit?t M?nchen (TUM) who peer-reviewed this manuscript. We would like to thank professor Heribert Juergens, MD, PhD, of the Department of Pediatric Hematology and Oncology of the University Medical Centre M?nster for contribution to the development of the protocol. The Editorial Base of Cochrane Childhood Cancer has been funded by KiKa, and is located in the Prinsess M?xima Center for Pediatric Oncology, Utrecht, the Netherlands. We would like to thank Edith Leclercq, the late Cochrane Childhood Cancer Information Specialist, for designing the search strategies. Funding Information: The study was supported by FP7-EURO EWING Consortium; Association Enfants et Sante, Societe Française de Lutte Contre les Cancers et les Leucemies de l’Enfant et de l’Adolescent, Unicancer; Cancer Research UK (CRUK/02/ 014), National Institute for Health Research, University College London Hospitals, Biomedical Research Centre; Deutsche Krebshilfe (70-2551-Jue3 and 108128), and Bundesminis-terium fur Bildung und Forschung (BMBF 01GM0869; BMBF/Era-Net 01KT1310); National Cancer Institute, Bethesda, MD (U10CA098413, U10CA098543, U10CA180886, and U10CA180899); and The Swedish ChildhoodCancer Fund. Funding Information: The Editorial Base of Cochrane Childhood Cancer has been funded by KiKa, and is located in the Prinsess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. We would like to thank Edith Leclercq, the late Cochrane Childhood Cancer Information Specialist, for designing the search strategies. Publisher Copyright: Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PY - 2021/9/2
Y1 - 2021/9/2
N2 - BACKGROUND: Ewing sarcomas are solid tumours of the bone and soft tissue, that usually affect children, adolescents, and young adults. The incidence is about three cases per million a year, with a peak incidence at 12 years of age. Metastatic disease is detected in about 20 % to 30% of people, and is typically found in the lungs, bone, bone marrow, or a combination of these. Presence of metastatic disease at diagnosis (primary metastatic disease) is the most important adverse prognostic factor, and is associated with a five-year survival lower than 30%. High-dose chemotherapy (HDC) followed by autologous haematopoietic cell transplantation (AHCT) is used in various solid tumours with unfavourable prognoses in children, adolescents, and young adults. It has also been used as rescue after multifocal radiation of metastases. The hypothesis is that HDC regimens may overcome the resistance to standard multidrug chemotherapy and improve survival rates. OBJECTIVES: To assess the effects of high-dose chemotherapy with autologous haematopoietic cell transplantation compared with conventional chemotherapy in improving event-free survival, overall survival, quality-adjusted survival, and progression-free survival in children, adolescents, and young adults with primary metastatic Ewing sarcoma, and to determine the toxicity of the treatment. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings from major international cancer-related conferences, and ongoing trial registers until January 2020. We also searched reference lists of included articles and review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or (historical) controlled clinical trials (CCTs) comparing the effectiveness of HDC and AHCT with conventional chemotherapy for children, adolescents, and young adults (younger than 30 years at the date of diagnostic biopsy) with primary metastatic Ewing sarcoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified one RCT, which investigated the effects of HDC with AHCT versus conventional chemotherapy with whole lung irradiation (WLI) in people with Ewing sarcoma metastasised to the lungs only at diagnosis. Only a selection of the participants were eligible for our review (N = 267: HDC with AHCT group N = 134; control group N = 133). There may be no difference in event-free survival between the two treatment groups (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.59 to 1.17; low-certainty evidence). We downgraded one level each because of study limitations and imprecision. Overall survival and toxicity were not reported separately for the participants eligible for this review, while quality-adjusted survival and progression-free survival were not reported at all. We did not identify any studies that addressed children, adolescents, and young adults with Ewing sarcoma with metastases to other locations. AUTHORS' CONCLUSIONS: In people with Ewing sarcoma with primary metastases to locations other than the lungs, there is currently no evidence from RCTs or CCTs to determine the efficacy of HDC with AHCT compared to conventional chemotherapy. Based on low-certainty evidence from one study (267 participants), there may be no difference in event-free survival between children, adolescents, and young adults with primary pulmonary metastatic Ewing sarcoma who receive HDC with AHCT and those who receive conventional chemotherapy with WLI. Further high-quality research is needed. Results are anticipated for the EuroEwing 2008R3 study, in which the effects of HDC with treosulfan and melphalan followed by AHCT on survival, in people with Ewing sarcoma with metastatic disease to bone, other sites, or both were explored. Achieving high-quality studies in a selection of people with rare sarcoma requires long-term, multi-centre, international participant inclusion.
AB - BACKGROUND: Ewing sarcomas are solid tumours of the bone and soft tissue, that usually affect children, adolescents, and young adults. The incidence is about three cases per million a year, with a peak incidence at 12 years of age. Metastatic disease is detected in about 20 % to 30% of people, and is typically found in the lungs, bone, bone marrow, or a combination of these. Presence of metastatic disease at diagnosis (primary metastatic disease) is the most important adverse prognostic factor, and is associated with a five-year survival lower than 30%. High-dose chemotherapy (HDC) followed by autologous haematopoietic cell transplantation (AHCT) is used in various solid tumours with unfavourable prognoses in children, adolescents, and young adults. It has also been used as rescue after multifocal radiation of metastases. The hypothesis is that HDC regimens may overcome the resistance to standard multidrug chemotherapy and improve survival rates. OBJECTIVES: To assess the effects of high-dose chemotherapy with autologous haematopoietic cell transplantation compared with conventional chemotherapy in improving event-free survival, overall survival, quality-adjusted survival, and progression-free survival in children, adolescents, and young adults with primary metastatic Ewing sarcoma, and to determine the toxicity of the treatment. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings from major international cancer-related conferences, and ongoing trial registers until January 2020. We also searched reference lists of included articles and review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or (historical) controlled clinical trials (CCTs) comparing the effectiveness of HDC and AHCT with conventional chemotherapy for children, adolescents, and young adults (younger than 30 years at the date of diagnostic biopsy) with primary metastatic Ewing sarcoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified one RCT, which investigated the effects of HDC with AHCT versus conventional chemotherapy with whole lung irradiation (WLI) in people with Ewing sarcoma metastasised to the lungs only at diagnosis. Only a selection of the participants were eligible for our review (N = 267: HDC with AHCT group N = 134; control group N = 133). There may be no difference in event-free survival between the two treatment groups (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.59 to 1.17; low-certainty evidence). We downgraded one level each because of study limitations and imprecision. Overall survival and toxicity were not reported separately for the participants eligible for this review, while quality-adjusted survival and progression-free survival were not reported at all. We did not identify any studies that addressed children, adolescents, and young adults with Ewing sarcoma with metastases to other locations. AUTHORS' CONCLUSIONS: In people with Ewing sarcoma with primary metastases to locations other than the lungs, there is currently no evidence from RCTs or CCTs to determine the efficacy of HDC with AHCT compared to conventional chemotherapy. Based on low-certainty evidence from one study (267 participants), there may be no difference in event-free survival between children, adolescents, and young adults with primary pulmonary metastatic Ewing sarcoma who receive HDC with AHCT and those who receive conventional chemotherapy with WLI. Further high-quality research is needed. Results are anticipated for the EuroEwing 2008R3 study, in which the effects of HDC with treosulfan and melphalan followed by AHCT on survival, in people with Ewing sarcoma with metastatic disease to bone, other sites, or both were explored. Achieving high-quality studies in a selection of people with rare sarcoma requires long-term, multi-centre, international participant inclusion.
UR - http://www.scopus.com/inward/record.url?scp=85115286388&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/14651858.CD011405.pub2
DO - https://doi.org/10.1002/14651858.CD011405.pub2
M3 - Article
C2 - 34472082
SN - 1469-493X
VL - 2021
SP - CD011405
JO - Cochrane database of systematic reviews (Online)
JF - Cochrane database of systematic reviews (Online)
IS - 9
M1 - CD011405
ER -