Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Josephine Kersting; Andreas Ranft, PhD; Vivek Bhadri, MD, PhD; Bénédicte Brichard, MD; Stéphane Collaud, MD; Sona Cyprová, MD; Hans Eich, MD; Torben Ek, MD, PhD; Hans Gelderblom, MD, PhD; Jendrik Hardes, MD; Lianne Haveman, MD; Wolfgang Hartmann, MD; Peter Hauser, MD, PhD; Philip Heesen; Heribert Jürgens, MD; Jukka Kanerva, MD; Thomas Kühne, MD; Anna Raciborska, MD; Jelena Rascon, MD, PhD; Victor Rechl; Arne Streitbürger, MD; Beate Timmermann, MD; Yasmine Uhlenbruch, MD; Uta Dirksen, MD

Advances in Radiation Oncology (Jul 2023)

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Josephine Kersting,
Andreas Ranft, PhD,
Vivek Bhadri, MD, PhD,
Bénédicte Brichard, MD,
Stéphane Collaud, MD,
Sona Cyprová, MD,
Hans Eich, MD,
Torben Ek, MD, PhD,
Hans Gelderblom, MD, PhD,
Jendrik Hardes, MD,
Lianne Haveman, MD,
Wolfgang Hartmann, MD,
Peter Hauser, MD, PhD,
Philip Heesen,
Heribert Jürgens, MD,
Jukka Kanerva, MD,
Thomas Kühne, MD,
Anna Raciborska, MD,
Jelena Rascon, MD, PhD,
Victor Rechl,
Arne Streitbürger, MD,
Beate Timmermann, MD,
Yasmine Uhlenbruch, MD,
Uta Dirksen, MD

Affiliations

Josephine Kersting: Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium, Partnersite Essen, Essen, Germany; Corresponding authors: Josephine Kersting, XX; Andreas Ranft, PhD; and Uta Dirksen, MD;
Andreas Ranft, PhD: Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium, Partnersite Essen, Essen, Germany; Corresponding authors: Josephine Kersting, XX; Andreas Ranft, PhD; and Uta Dirksen, MD;
Vivek Bhadri, MD, PhD: Chris O´ Brien Lifehouse, Camperdown, Australia Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
Bénédicte Brichard, MD: Cliniques Universitaires Saint Luc, Department of Pediatric Haematology and Oncology, Université Catholique de Louvain, Brussels, Belgium
Stéphane Collaud, MD: Department of Thoracic Surgery, Lung Clinic, Cologne-Merheim City Hospital, University of Witten Herdecke, Cologne, Germany
Sona Cyprová, MD: Charles University, Motol Children´s Hospital, Prague, Czech Republic
Hans Eich, MD: Radiotherapy and Radiooncology, University Hospital Muenster, West German Cancer Center Network, Muenster, Germany
Torben Ek, MD, PhD: Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Hans Gelderblom, MD, PhD: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Jendrik Hardes, MD: German Cancer Consortium, Partnersite Essen, Essen, Germany; Clinic of Orthopedics, University Hospital Essen, West German Cancer Centre, Essen, Germany
Lianne Haveman, MD: Department of Solid Tumors, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Wolfgang Hartmann, MD: Gerhard Domagk Institute for Pathology, University Hospital Muenster, West German Cancer Center Network, Muenster, Germany
Peter Hauser, MD, PhD: Second Department of Pediatrics, Semmelweis University, Budapest, Hungary
Philip Heesen: Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Heribert Jürgens, MD: Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, West German Cancer Center Network, Münster, Germany
Jukka Kanerva, MD: HUS Helsinki University Hospital, New Children´s Hospital, Div. Hematology and Stem Cell Transplantation, Helsinki, Finland
Thomas Kühne, MD: Department of Oncology/Haematology, University Children´s Hospital Basel, Basel, Switzerland
Anna Raciborska, MD: Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, Warsaw, Poland
Jelena Rascon, MD, PhD: Center for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania
Victor Rechl: Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Arne Streitbürger, MD: German Cancer Consortium, Partnersite Essen, Essen, Germany; Clinic of Orthopedics, University Hospital Essen, West German Cancer Centre, Essen, Germany
Beate Timmermann, MD: German Cancer Consortium, Partnersite Essen, Essen, Germany; Clinic for Particle Therapy, West German Proton Beam Centre, University Hospital Essen, West German Cancer Centre, German Cancer Research Centre (DKTK), Essen, Germany
Yasmine Uhlenbruch, MD: St. Josef's Hospital Bochum, University Hospital, Bochum, Germany
Uta Dirksen, MD: Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium, Partnersite Essen, Essen, Germany; Corresponding authors: Josephine Kersting, XX; Andreas Ranft, PhD; and Uta Dirksen, MD;

Journal volume & issue: Vol. 8, no. 4
p. 101269

Abstract

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Purpose: Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS. Methods and Materials: The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response. Results: S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P = .42) and in the RT group 52.9%, 62.5%, and 70.3% (P = .63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, P = .96; histologic response, P = .07; tumor volume, P = .50; dose, P = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P = .15; age, P = .08; sex, P = .40). Conclusions: In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.

Published in Advances in Radiation Oncology

ISSN: 2452-1094 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General): Medical physics. Medical radiology. Nuclear medicine; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/advances-in-radiation-oncology/

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