Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

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

doi:10.1016/j.adro.2023.101269

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Adv Radiat Oncol. 2023 Jun 14;8(4):101269. doi: 10.1016/j.adro.2023.101269. eCollection 2023 Jul-Aug.

Authors

Josephine Kersting^{1

2}, Andreas Ranft^{1

2}, Vivek Bhadri³, Bénédicte Brichard⁴, Stéphane Collaud⁵, Sona Cyprová⁶, Hans Eich⁷, Torben Ek⁸, Hans Gelderblom⁹, Jendrik Hardes^{2

10}, Lianne Haveman¹¹, Wolfgang Hartmann¹², Peter Hauser¹³, Philip Heesen¹, Heribert Jürgens¹⁴, Jukka Kanerva¹⁵, Thomas Kühne¹⁶, Anna Raciborska¹⁷, Jelena Rascon¹⁸, Victor Rechl¹, Arne Streitbürger^{2

10}, Beate Timmermann^{2

19}, Yasmine Uhlenbruch²⁰, Uta Dirksen^{1

2}

Affiliations

¹ Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
² German Cancer Consortium, Partnersite Essen, Essen, Germany.
³ Chris O´ Brien Lifehouse, Camperdown, Australia Faculty of Medicine and Health, University of Sydney, Camperdown, Australia.
⁴ Cliniques Universitaires Saint Luc, Department of Pediatric Haematology and Oncology, Université Catholique de Louvain, Brussels, Belgium.
⁵ Department of Thoracic Surgery, Lung Clinic, Cologne-Merheim City Hospital, University of Witten Herdecke, Cologne, Germany.
⁶ Charles University, Motol Children´s Hospital, Prague, Czech Republic.
⁷ Radiotherapy and Radiooncology, University Hospital Muenster, West German Cancer Center Network, Muenster, Germany.
⁸ Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁹ Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁰ Clinic of Orthopedics, University Hospital Essen, West German Cancer Centre, Essen, Germany.
¹¹ Department of Solid Tumors, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
¹² Gerhard Domagk Institute for Pathology, University Hospital Muenster, West German Cancer Center Network, Muenster, Germany.
¹³ Second Department of Pediatrics, Semmelweis University, Budapest, Hungary.
¹⁴ Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, West German Cancer Center Network, Münster, Germany.
¹⁵ HUS Helsinki University Hospital, New Children´s Hospital, Div. Hematology and Stem Cell Transplantation, Helsinki, Finland.
¹⁶ Department of Oncology/Haematology, University Children´s Hospital Basel, Basel, Switzerland.
¹⁷ Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, Warsaw, Poland.
¹⁸ Center for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania.
¹⁹ Clinic for Particle Therapy, West German Proton Beam Centre, University Hospital Essen, West German Cancer Centre, German Cancer Research Centre (DKTK), Essen, Germany.
²⁰ St. Josef's Hospital Bochum, University Hospital, Bochum, Germany.

Abstract

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.