Stéphanie Foulon1, Bernadette Brennan2, Nathalie Gaspar3, Uta Dirksen4, Lee Jeys5, Anna Cassoni6, Line Claude7, Beatrice Seddon8, Perrine Marec-Berard9, Jeremy Whelan6, Michael Paulussen10, Arne Streitbuerger11, Odile Oberlin3, Heribert Juergens4, Robert Grimer5, Marie-Cécile Le Deley12. 1. Biostatistics Unit, Gustave Roussy, Villejuif, France; CESP Centre for Research in Epidemiology and Population Health, INSERM U1018, Team-2, Paris-Sud University, Villejuif, France. 2. Paediatric Oncology Department, Royal Manchester Children's Hospital, Manchester, United Kingdom. 3. Department of Childhood and Adolescent Oncology, Gustave Roussy, Villejuif, France. 4. Department of Paediatric Oncology, University Hospital Münster, Münster, Germany. 5. Orthopedic Department, Royal Orthopaedic Hospital, Birmingham, United Kingdom. 6. National Institute for Health Research University College London Hospitals Biomedical Research Centre and Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, United Kingdom. 7. Radiotherapy Department, Léon-Bérard Center, Lyon, France. 8. Radiotherapy Department, University College London Hospital National Health Service Foundation Trust, London, United Kingdom. 9. Institute for Paediatric Haematology and Oncology, Léon-Bérard Center, Lyon, France. 10. Paediatric Department, Vestische Kinder-und Jugendklinik, Datteln, Germany; Witten/Herdecke University, Datteln, Germany. 11. Orthopedic Surgery, University Hospital Münster, Münster, Germany. 12. Biostatistics Unit, Gustave Roussy, Villejuif, France; CESP Centre for Research in Epidemiology and Population Health, INSERM U1018, Team-2, Paris-Sud University, Villejuif, France. Electronic address: marie-cecile.LEDELEY@gustaveroussy.fr.
Abstract
BACKGROUND: The role of postoperative radiotherapy (PORT) in Ewing sarcoma (ES) is unclear. We assessed the impact of PORT on local control in patients with localised ES and good histological response to chemotherapy (<10% cells). PATIENTS AND METHODS: All randomised patients in the EE99-R1 trial (comparing two consolidation chemotherapy regimens) undergoing surgery after induction chemotherapy were included. Local relapse (LR) cumulative incidence was estimated using a competing risk approach. Impact of PORT was assessed in multivariable models, adjusted for country, age, tumour site and volume, quality of resection and histological response. We also evaluated the heterogeneity of PORT effect by patient and tumour characteristics. RESULTS:One hundred forty-two (24%) of the 599 patients included from 1999 to 2009 received PORT (median dose: 45 Grays). With median follow-up of 6.2 years, 67 patients had an LR (with concomitant metastases in 28), leading to an 8-year LR-incidence = 11.9% (standard error [se] = 1.4%). Overall survival (OS) = 21% (se = 5%) 3 years after LR (31% in isolated LR). Controlling for possible confounders, we observed a statistically significant reduction of LR in patients treated by surgery + PORT compared to surgery alone (subdistribution-hazard ratio = 0.43, 95% confidence interval, 0.21-0.88, p = 0.02). The benefit of PORT was particularly marked for tumours larger than 200 ml at diagnosis and 100% necrosis. We observed a non-significant trend for benefit associated with PORT for disease-free, event-free and OS. CONCLUSION:Radiotherapy appears to improve local control. We now recommend PORT in case of incomplete removal of the tissues involved by the pre-chemotherapy tumour volume. Further studies are required to assess the balance between benefit and risks.
RCT Entities:
BACKGROUND: The role of postoperative radiotherapy (PORT) in Ewing sarcoma (ES) is unclear. We assessed the impact of PORT on local control in patients with localised ES and good histological response to chemotherapy (<10% cells). PATIENTS AND METHODS: All randomised patients in the EE99-R1 trial (comparing two consolidation chemotherapy regimens) undergoing surgery after induction chemotherapy were included. Local relapse (LR) cumulative incidence was estimated using a competing risk approach. Impact of PORT was assessed in multivariable models, adjusted for country, age, tumour site and volume, quality of resection and histological response. We also evaluated the heterogeneity of PORT effect by patient and tumour characteristics. RESULTS: One hundred forty-two (24%) of the 599 patients included from 1999 to 2009 received PORT (median dose: 45 Grays). With median follow-up of 6.2 years, 67 patients had an LR (with concomitant metastases in 28), leading to an 8-year LR-incidence = 11.9% (standard error [se] = 1.4%). Overall survival (OS) = 21% (se = 5%) 3 years after LR (31% in isolated LR). Controlling for possible confounders, we observed a statistically significant reduction of LR in patients treated by surgery + PORT compared to surgery alone (subdistribution-hazard ratio = 0.43, 95% confidence interval, 0.21-0.88, p = 0.02). The benefit of PORT was particularly marked for tumours larger than 200 ml at diagnosis and 100% necrosis. We observed a non-significant trend for benefit associated with PORT for disease-free, event-free and OS. CONCLUSION: Radiotherapy appears to improve local control. We now recommend PORT in case of incomplete removal of the tissues involved by the pre-chemotherapy tumour volume. Further studies are required to assess the balance between benefit and risks.
Authors: Simone de Campos Vieira Abib; Chan Hon Chui; Sharon Cox; Abdelhafeez H Abdelhafeez; Israel Fernandez-Pineda; Ahmed Elgendy; Jonathan Karpelowsky; Pablo Lobos; Marc Wijnen; Jörg Fuchs; Andrea Hayes; Justin T Gerstle Journal: Ecancermedicalscience Date: 2022-02-17
Authors: Safia K Ahmed; R Lor Randall; Steven G DuBois; William S Harmsen; Mark Krailo; Karen J Marcus; Katherine A Janeway; David S Geller; Joel I Sorger; Richard B Womer; Linda Granowetter; Holcombe E Grier; Richard G Gorlick; Nadia N I Laack Journal: Int J Radiat Oncol Biol Phys Date: 2017-08-24 Impact factor: 7.038
Authors: Ricardo G Becker; Lauro J Gregianin; Carlos R Galia; Reynaldo Jesus-Garcia Filho; Eduardo A Toller; Gerardo Badell; Suely A Nakagawa; Alexandre David; André M Baptista; Eduardo S Yonamime; Osvaldo A Serafini; Valter Penna; Julie Francine C Santos; Algemir L Brunetto Journal: BMC Cancer Date: 2017-06-15 Impact factor: 4.430
Authors: Dimosthenis Andreou; Andreas Ranft; Georg Gosheger; Beate Timmermann; Ruth Ladenstein; Wolfgang Hartmann; Sebastian Bauer; Daniel Baumhoer; Henk van den Berg; P D Sander Dijkstra; Hans Roland Dürr; Hans Gelderblom; Jendrik Hardes; Lars Hjorth; Justus Kreyer; Jarmila Kruseova; Andreas Leithner; Sergiu Scobioala; Arne Streitbürger; Per-Ulf Tunn; Eva Wardelmann; Reinhard Windhager; Heribert Jürgens; Uta Dirksen Journal: Clin Orthop Relat Res Date: 2020-02 Impact factor: 4.755
Authors: Jeremy Whelan; Allan Hackshaw; Anne McTiernan; Robert Grimer; David Spooner; Jessica Bate; Andreas Ranft; Michael Paulussen; Herbert Juergens; Alan Craft; Ian Lewis Journal: Clin Sarcoma Res Date: 2018-03-30