TY - JOUR
T1 - The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma
AU - Cameron, Alison L.
AU - Elze, Markus C.
AU - Casanova, Michela
AU - Geoerger, Birgit
AU - Gaze, Mark N.
AU - Minard-Colin, Veronique
AU - McHugh, Kieran
AU - van Rijn, Rick R.
AU - Kelsey, Anna
AU - Martelli, H. lène
AU - Mandeville, Henry
AU - Bisogno, Gianni
AU - Lowis, Stephen
AU - Ronghe, Milind
AU - Orbach, Daniel
AU - Guizani, Cecile
AU - Fürst-Recktenwald, Sabine
AU - Chisholm, Julia C.
AU - European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) and the European Innovative Therapies for Children with Cancer (ITCC) Consortium
AU - Merks, Johannes H. M.
N1 - Funding Information: This work was supported by F. Hoffmann-La Roche Ltd. Funding Information: Acknowledgments—The authors thank the patients, caregivers, and medical staff involved in this study from the recruiting countries. Dr M. N. Gaze is supported by the National Institute for Health Research Biomedical Research Centre of University College London Hospitals and by the Radiation Research Unit at the Cancer Research UK City of London Centre Award (C7893/A28990). Dr J. C. Chisholm and Dr H. C. Mandeville are supported by National Health Service funding to the National Institute for Health Research Biomedical Research Centre of the Royal Marsden Hospital. Dr J. C. Chisholm is also supported by the Royal Marsden Cancer Charity. Third-party medical writing assistance, under the direction of the authors, was provided by Abigail Robertson, PhD, medical writer, and Fiona Fernando, PhD, contract medical writer at Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. Funding Information: Disclosures: A.L.C. received nonfinancial support from Roche during the conduct of the study. M.C.E. is an employee of and owns shares in F. Hoffmann-La Roche Ltd. M.C. has received consultancy fees from F. Hoffmann-La Roche Ltd. R.RvR. has received consultancy fees from F. Hoffmann-La Roche Ltd. D.O. reports consultancy work for the French transparency committee and for F. Hoffmann-La Roche Ltd, and an independent translational research project partially supported by Bayer. C.G. is an employee of F. Hoffmann-La Roche Ltd. S.F.R. is an employee of F. Hoffmann-La Roche Ltd. J.C.C. has received consultancy fees from F. Hoffmann-La Roche Ltd relating to the BERNIE study, and advisory board and educational meeting speaker fees from Bayer. Publisher Copyright: © 2021 Elsevier Inc.
PY - 2021/11/15
Y1 - 2021/11/15
N2 - Purpose: There is limited evidence to define the role of radiation therapy in children with metastatic rhabdomyosarcoma (mRMS). In the international BERNIE study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with or without bevacizumab, with radiation therapy to all disease sites recommended after chemotherapy cycle 6. We retrospectively evaluated the impact of radiation therapy on survival in the mRMS cohort. Methods and Materials: Patients were grouped according to the radiation therapy they received: radical, partial, or none. Radical irradiation was defined as radiation therapy delivered to all disease sites, unless a site was completely surgically resected. Partial irradiation was defined as radiation therapy to ≥1, but not all, disease sites. Landmark analysis excluded patients with an event before day 221. Overall survival (OS) and event-free survival (EFS) were modeled using Cox proportional hazards models. Results: Of 102 patients with mRMS, 97 were included in the analysis for OS and 85 for EFS. Overall, 27 patients received radical irradiation, 46 partial irradiation, and 24 no irradiation. EFS was not significantly different among patient groups after adjustment for prognostic factors (hazard ratio [HR] = 0.520; P = .054 for any vs no irradiation). Radiation therapy was associated with improved OS compared with no radiation therapy (adjusted HR = 0.249; P = .00025), with OS being greater for radical versus partial irradiation (HR = 0.245; P = .039). The 3-year OS rate was 84%, 54%, and 23% for patients receiving radical, partial, and no irradiation, respectively. Radical treatment (surgery, irradiation, or both) of the primary site improved EFS and OS compared with no treatment. Conclusions: These findings demonstrate variability in the application of radiation therapy for mRMS and support the routine use of radical treatment to the primary site. Radical irradiation to metastatic sites may further improve OS. The burden of such treatment should be balanced against prognosis; further studies are needed.
AB - Purpose: There is limited evidence to define the role of radiation therapy in children with metastatic rhabdomyosarcoma (mRMS). In the international BERNIE study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with or without bevacizumab, with radiation therapy to all disease sites recommended after chemotherapy cycle 6. We retrospectively evaluated the impact of radiation therapy on survival in the mRMS cohort. Methods and Materials: Patients were grouped according to the radiation therapy they received: radical, partial, or none. Radical irradiation was defined as radiation therapy delivered to all disease sites, unless a site was completely surgically resected. Partial irradiation was defined as radiation therapy to ≥1, but not all, disease sites. Landmark analysis excluded patients with an event before day 221. Overall survival (OS) and event-free survival (EFS) were modeled using Cox proportional hazards models. Results: Of 102 patients with mRMS, 97 were included in the analysis for OS and 85 for EFS. Overall, 27 patients received radical irradiation, 46 partial irradiation, and 24 no irradiation. EFS was not significantly different among patient groups after adjustment for prognostic factors (hazard ratio [HR] = 0.520; P = .054 for any vs no irradiation). Radiation therapy was associated with improved OS compared with no radiation therapy (adjusted HR = 0.249; P = .00025), with OS being greater for radical versus partial irradiation (HR = 0.245; P = .039). The 3-year OS rate was 84%, 54%, and 23% for patients receiving radical, partial, and no irradiation, respectively. Radical treatment (surgery, irradiation, or both) of the primary site improved EFS and OS compared with no treatment. Conclusions: These findings demonstrate variability in the application of radiation therapy for mRMS and support the routine use of radical treatment to the primary site. Radical irradiation to metastatic sites may further improve OS. The burden of such treatment should be balanced against prognosis; further studies are needed.
UR - http://www.scopus.com/inward/record.url?scp=85111915580&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijrobp.2021.06.031
DO - https://doi.org/10.1016/j.ijrobp.2021.06.031
M3 - Article
C2 - 34217789
SN - 0360-3016
VL - 111
SP - 968
EP - 978
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 4
ER -