(P 042) VALUE OF ADJUVANT RADIOTHERAPY IN PATIENTS WITH LOCALIZED EWING SARCOMA AT THE EXTREMITIES. REPORT FROM THE EWING 2008 TRIAL

Author(s)

Philip Heesen, BSc

Medical Student (MD)
University of Zurich
Zurich, Zurich, Switzerland

Co-Author(s)

AR

Andreas Ranft, N/A, PhD

University Hospital Essen, Pediatrics III, Essen, Germany
Essen, Nordrhein-Westfalen, Germany
Vivek A. Bhadri, MA MBBS PhD FRACP

Medical Oncologist
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
BB

Benedicte Brichard, MD

Cliniques Universitaires Saint Luc, Department of Pediatric Haematology and Oncology, Université Catholique de Louvain
Brussels, Brussels Hoofdstedelijk Gewest, Belgium
SC

Stephane Collaud, MD

Department of Thoracic Surgery, Ruhrlandklinik, University Hospital Essen, West German Cancer Center
Essen, Nordrhein-Westfalen, Germany
SC

Sona Cyprova, MD

Charles University, Motol Children´s Hospital
Prague, Hlavni mesto Praha, Czech Republic
HE

Hans Eich, MD

Radiotherapy and Radiooncology, University Hospital Muenster, West German Cancer Center Network,
Münster, Nordrhein-Westfalen, Germany
TE

Torben Ek, MD

Childhood Cancer Center Queen Silvia Children´s Hospital
Gotenburg, Vastra Gotaland, Sweden
Hans Gelderblom, MD, PhD

Professor medical oncology
Leiden University Medical Center, Leiden, Netherlands
Leiden, Zuid-Holland, Netherlands
JH

Jendrik Hardes, MD

Clinic of Orthopedics, University Hospital Essen, West German Cancer Centre, Germany
Essen, Nordrhein-Westfalen, Germany
LH

Lianne Haveman, N/A, n/a

Prinses Máxima Centrum voor Kinderoncologie, Pediatric Oncology, Utrecht, Netherlands
Utrecht, Utrecht, Netherlands
WH

Wolfgang Hartmann, N/A, n/a

University Hospital Muenster, West German Cancer Center Network, Gerhard Domagk Institute for Pathology, Münster, Germany
Münster, Nordrhein-Westfalen, Germany
PH

Peter Hauser, MD

Velkey László Child’s, Health Center, Borsod-Abaúj-Zemplén County University Teaching Hospital
Miskolc, Borsod-Abauj-Zemplen, Hungary
HJ

Heribert Jürgens, MD

Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster, West German Cancer Center Network
Münster, Nordrhein-Westfalen, Germany
Jukka Kanerva, MD

Consultant
Helsinki University Hospital
Helsinki, Uusimaa, Finland
Thomas Kühne, MD (he/him/his)

Acting Head of Division
University Children´s Hospital Basel, Department of Oncology/ Haematology, Basel, Switzerland
Basel, Basel-Stadt, Switzerland
AR

Anna Raciborska, MD

Mother and Child Institute, Department of Oncology and Surgical Oncology for Children and Youth
Warsaw, Mazowieckie, Poland
JR

Jelena Rascon, MD

Center for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius University
Vilnius, Vilniaus Apskritis, Lithuania
AS

Arne Streitbürger, MD

Clinic of Orthopedics, University Hospital Essen, West German Cancer Centre
Essen, Nordrhein-Westfalen, Germany
Beate Timmermann, MD (she/her/hers)

Director of the Clinic of Particle Therapy, Medical head of West German Proton Therapy Centre Essen (WPE)
Clinic for Particle Therapy, West German Proton Beam Centre, University Hospital Essen, West German Cancer Centre, German Cancer Research Centre (DKTK)
Essen, Nordrhein-Westfalen, Germany
YU

Yasmine Uhlenbruch, n/a

Patient representative, St. Josefs Hospital Bochum, University Hospital
Bochum, Nordrhein-Westfalen, Germany
UD

Uta Dirksen, N/A, MD

University Hospital Essen, Pediatrics III, Essen, Germany
Essen, Nordrhein-Westfalen, Germany

Objective: In patients with Ewing Sarcoma (EWS), adjuvant radiotherapy is often performed after surgery that could not obtain wide margins or after poor histological response to chemotherapy. However, the benefit of adjuvant radiotherapy is not fully clear. Therefore, we compared event-free survival (EFS) between surgery (SX) alone and SX combined with radiation therapy (RT), performed a subgroup analysis, identified independent prognostic factors and examined our results for robustness by including a propensity score weighted analysis.

Methods: The data from localized EWS patients with tumors at the extremities that were treated in the Ewing 2008 trial from 2009-2018 were included in this analysis. Patients received induction chemotherapy according to the protocol and then underwent local therapy. Patients receiving SX or adjuvant RT (combined SX/RT) were included in this analysis. Hazard ratios (HRs) (95% Confidence Intervals (CIs)) were calculated using Cox regression. Propensity-scores were calculated using prognostic variables mentioned in the Results as independent variables.

Results: 360 out of 863 patients (41.7%) presented with an EWS at the extremities with 81 tumors at the upper extremity, and 279 tumors at the lower extremity. Most patients were treated with surgery only (223, 61.94%), while 125 patients (34.72%) were treated with SX plus RT.
Adjuvant radiotherapy was conducted after a median time of 69 days (1st quartile, 3rd quartile; 54, 109).
Median EFS at 5-years for all patients was 0.74 (0.69, 0.80), 0.76 (0.70, 0.83) for patients after surgery only, and 0.73 (0.64, 0.83) after combined RT/SX.
After adjusting for sex, age, tumor volume, histological response and surgical margins, the HR for combined RT/SX vs SX alone was 0.69 (0.37, 1.26), p=0.22.
In patients with poor histological response to surgery (≥10% vital tumor cells) and with high tumor volume (≥ 200mL), additional radiotherapy did not decrease the hazards of any event, HR 0.72 (0.25, 2.06), p=0.54.
We identified high tumor volume, poor histological response to surgery as well as intralesional resection of the tumor as independent prognostic factors after adjusting for other known prognostic factors with HRs of 1.73 (1.04, 2.90), p=0.03; 2.79 (1.69, 4.62), p< 0.0001 and 215.9 (13.17, 3538.61), p=0.0002, respectively. Surgical complication was not a prognostic factor after adjusting for above mentioned variables, HR 0.85 (0.31, 2.34), p=0.75.
Including propensity score weights did not substantially change our results.

Conclusion: In our cohort, adjuvant radiotherapy was not superior compared to surgery alone in all patients with localized EWS at the extremities and neither in a subgroup of patients with high-risk factors.
Poor histological response, intralesional tumor resection as well as high tumor volume were identified as independent negative prognostic factors.
These results also held true after performing a propensity-score weighted analysis.