Radiotherapy Dose Escalation in Unresectable Ewing's Sarcoma: Final Results of a Phase III Randomized Controlled Trial
Mené entre 2005 et 2015 sur 95 patients atteints d'un sarcome d'Ewing non métastatique et non résécable (âge médian : 17 ans ; durée médiane de suivi : 67 mois ; 59 % d'hommes), cet essai randomisé de phase III évalue l'intérêt, du point de vue du contrôle local, d'augmenter la dose de radiothérapie
PURPOSE/OBJECTIVE: Assess the impact of Radiation Therapy (RT) dose escalation on outcomes in surgically unresectable Ewing's sarcoma (ES)/ Primitive Neuroectodermal Tumor (PNET). MATERIALS/METHODS: Patients with non-metastatic unresectable ES/PNET (excluding intracranial/chest wall) receiving VAC/IE chemotherapy, planned for definitive RT were accrued in this single institute open label Phase III Randomized Controlled Trial. Randomization was between standard dose RT (SDRT: 55.8Gy/31 fractions/ 5 days a week) vs. escalated dose RT (EDRT: 70.2Gy/39 fractions/ 5 days a week) with a primary objective of improving Local Control (LC) by 17% (65% to 82%). Secondary outcomes included Disease Free Survival (DFS), Overall Survival (OS) and functional outcomes by Musculoskeletal Tumor Society (MSTS) score. RESULTS: Between April 2005 to December 2015, 95 patients (SDRT: 47 and EDRT: 48) with a median age of 17 years (IQR 13-23 years) were accrued. Majority of patients were males (59%). Pelvis was the commonest site of primary disease {60 (63%)}. The median largest tumor dimension (9.7cm) and the median SUVmax (8.2) on the pre-treatment FDG PET-CT were similar. At a median follow-up of 67 months, the 5 year LC, DFS and OS for the entire cohort was 62.4%, 41.3% and 51.9% respectively. The 5 year LC was significantly better in EDRT as compared to SDRT (76.4% vs 49.4%, p=0.02). The differences in DFS and OS at 5 year (for EDRT vs SDRT) did not achieve statistical significance {(DFS- 46.7% vs. 31.8%, p=0.22) and (OS - 58.8% vs. 45.4%, p=0.08)}. There was a higher incidence of RTOG >Grade 2 skin toxicity (acute) in the EDRT arm (10.4% vs. 2.1%, p=0.08) with excellent functional outcomes (Median MSTS-29) in both arms. CONCLUSIONS: EDRT results in improved LC with good functional outcomes without a significant increase in toxicities. Radiation dose escalation should be considered for surgically unresectable non-metastatic ES/ PNET.
International Journal of Radiation Oncology, Biology, Physics 2022