TY - JOUR
T1 - Metastatic Rhabdomyosarcoma
T2 - Results of the European Paediatric Soft Tissue Sarcoma Study Group MTS 2008 Study and Pooled Analysis With the Concurrent BERNIE Study
AU - Schoot, Reineke A.
AU - Chisholm, Julia C.
AU - Casanova, Michela
AU - Minard-Colin, Veronique
AU - Geoerger, Birgit
AU - Cameron, Alison L.
AU - Coppadoro, Beatrice
AU - Zanetti, Ilaria
AU - Orbach, Daniel
AU - Kelsey, Anna
AU - Rogers, Timothy
AU - Guizani, Cecile
AU - Elze, Markus
AU - Ben-Arush, Myriam
AU - McHugh, Kieran
AU - van Rijn, Rick R.
AU - Ferman, Sima
AU - Gallego, Soledad
AU - Ferrari, Andrea
AU - Jenney, Meriel
AU - Bisogno, Gianni
AU - Merks, Johannes H. M.
N1 - Funding Information: The authors thank the patients, caregivers, and medical staff involved in this study from the recruiting countries (United Kingdom, Ireland, France, Italy, the Netherlands, Spain, Israel, Argentina, Brazil, Belgium, Norway, and Slovakia). The overall organization of this study has been supported by Fondazione Città della Speranza. Funding Information: J.C.C. is supported by the Giant Pledge through the Royal Marsden Cancer Charity and this independent research (J.C.C.) is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. Publisher Copyright: © American Society of Clinical Oncology.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - PURPOSE: Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study. PATIENTS AND METHODS: In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible. RESULTS: MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% (P < .0001) and 3-year OS 60.0% versus 26.0% (P < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance. CONCLUSION: Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.
AB - PURPOSE: Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study. PATIENTS AND METHODS: In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible. RESULTS: MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% (P < .0001) and 3-year OS 60.0% versus 26.0% (P < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance. CONCLUSION: Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.
UR - http://www.scopus.com/inward/record.url?scp=85137864695&partnerID=8YFLogxK
U2 - https://doi.org/10.1200/JCO.21.02981
DO - https://doi.org/10.1200/JCO.21.02981
M3 - Article
C2 - 35709412
SN - 0732-183X
VL - 19
SP - 3730
EP - 3740
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 32
M1 - JCO.21.02981
ER -