Review question
We were looking for evidence on whether HDC plus AHCT improved event-free survival, overall survival, quality-adjusted survival, and progression-free survival better than conventional chemotherapy in children, adolescents, and young adults with their first recurrence of Ewing sarcoma. We were also looking for adverse effects that occurred because of these treatments.
Background
Ewing sarcoma is a tumour that occurs in the bone and soft tissue, especially in the long bones and pelvis, and mainly in children, adolescents and young adults. Since the introduction of chemotherapy following surgery, with or without radiation, the outcome of people with Ewing sarcoma has improved. However, even with improved chemotherapy, there are still too many people who eventually die of the disease, because it has progressed or come back. People with a first recurrence of Ewing sarcoma do not have a great prognosis: fewer than 3 out of 10 young people are still alive at 24 months, and fewer than 1 out of 10 are alive at 48 months. Improved therapy is essential for these people. High-dose chemotherapy (HDC), followed by autologous haematopoietic cell transplantation (AHCT; intravenous infusion of earlier collected stem cells to re-establish bone marrow ), is successfully used for young people with a variety of tumours. Theoretically, this seems to be a good option to treat the small number of remaining cancer cells, and to improve the survival rate after the first recurrence of Ewing sarcoma.
Key results
We conducted an extensive search of the medical literature, including related conference proceedings, and registers for ongoing trials, but we did not find any relevant studies. Therefore, we are unable to draw any conclusions as to whether HDC with AHCT improves event-free survival, overall survival, quality-adjusted survival, or progression-free survival better than conventional chemotherapy, or if it causes any side effects, in children, adolescents, and young adults with their first recurrence of Ewing sarcoma. Our results show that further research is needed.
How current is the evidence
The evidence is current to January 2020.
Since we did not identify any eligible studies, we are unable to draw any conclusions about the efficacy and toxicity of HDC with AHCT versus conventional chemotherapy in children, adolescents, and young adults with a first recurrence of Ewing sarcoma. Further high-quality research is urgently needed.
Ewing sarcoma is a solid tumour, which is the second most common primary bone malignancy in children, often occurring in the long bones and pelvis. An incidence rate of 4.5 per million a year is reported, with a peak incidence of 11 per million at the age of 12 years. Despite more intensive chemotherapy, 30% to 40% of young people with Ewing sarcoma will have recurrence of the disease. Less than 30% of young people with a recurrence of Ewing sarcoma are alive at 24 months, and less than 10% are alive at 48 months. High-dose chemotherapy (HDC), followed by autologous haematopoietic cell transplantation (AHCT), is used in a variety of paediatric groups with diverse solid tumours. The hypothesis is that HDC regimens may overcome resistance to standard polychemotherapy, and this way may eradicate minimal residual disease, leading to improved survival after a first recurrence of disease.
To assess the efficacy of HDC with AHCT versus conventional chemotherapy in improving event-free survival, overall survival, quality-adjusted survival, and progression-free survival in children, adolescents, and young adults with first recurrence of Ewing sarcoma, and to determine the toxicity of the treatment.
We searched CENTRAL, MEDLINE, Embase, conference proceedings from the SIOP, ASPHO, CTOS, ASBMT, EBMT, and EMSOS, and two trial registries in January 2020. We also searched reference lists of relevant articles and review articles.
We planned to include randomised controlled trials (RCTs) or (historical) controlled clinical trials (CCTs) comparing the effectiveness of HDC plus AHCT with conventional chemotherapy for children, adolescents, and young adults (up to 30 years old at the date of diagnostic biopsy) with a first recurrence of Ewing sarcoma.
We used standard methodological procedures expected by Cochrane.
We did not identify any eligible studies.