Surgery vs Radiation Therapy in Ewing’s Sarcoma the Extremities: Experience of a Single Institution Surgery vs Radiation Therapy in Ewing’s Sarcoma the.

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Surgery vs Radiation Therapy in Ewing’s Sarcoma the Extremities: Experience of a Single Institution Surgery vs Radiation Therapy in Ewing’s Sarcoma the Extremities: Experience of a Single Institution N. Fabbri, G. Bacci, S. Ferrari, A. Longhi, D. Donati, M. Manfrini, E. Barbieri, M. Mercuri, F. Bertoni Department of Musculoskeletal Oncology Istituto Ortopedico Rizzoli, Bologna, Italy Department of Musculoskeletal Oncology Istituto Ortopedico Rizzoli, Bologna, Italy

Surgery vs Radiation Therapy in Ewing’s Sarcoma Ewing’s Sarcoma in 21st Century. Outcome considerably improved from 70’s. Multiagent chemotherapy fundamental. Improved LC and survival with surgery. Retrospective data, bias Rxt worse cases

Surgery vs Radiation Therapy in Ewing’s Sarcoma Surgery vs Rxt: Literature. Pritchard et al., Cancer, pts, pre-Cht experience ( ) - Extremity & Surgery in survivors > 5 yrs. Rosen et al., Cancer, pts, multimodal management since pts, T6 + T2 & Surgery +/- Rxt, 85% at 3 yrs. Bacci et al., JBJS-B, pts, multimodal management since Surgery + Cht 90% vs Rxt + Cht 55% at 2 yrs

Surgery vs Radiation Therapy in Ewing’s Sarcoma F, 17 - Ewing’s sarcoma: pre-chemotherapy

Surgery vs Radiation Therapy in Ewing’s Sarcoma F, 17 - Ewing’s sarcoma: post-chemotherapy

Surgery vs Radiation Therapy in Ewing’s Sarcoma 3 yr FU

Disease-Free Survival 72% (91-97) 78% (91-97) 43% (83-87) Cum. Survival Months Surgery vs Radiation Therapy in Ewing’s Sarcoma

Surgery vs Rxt: Multicentric Studies. Jurgens et al., Cancer, 1988 (CESS). Burgert et al., J Clin Oncol, 1990 (IESS). Oberlin et al., J Clin Oncol, 1992 (FSPO). Craft et al., Eur J Cancer, 1997 (UKCCSG). Grier et al., N Eng J Med, 2003 (CCG-POG) More surgery, trend towards better survival

Surgery vs Radiation Therapy in Ewing’s Sarcoma Surgery vs Rxt: Monocentric Studies. Wilkins et al., Cancer, 1986 (Mayo Clinic). Ozaki et al., Cancer, 1996 (Munster). Bacci et al., J Clin Oncol, 2000 (Rizzoli). Sluga et al., CORR, 2001 (Vienna). Bacci et al., JBJS-B, 2003 (Rizzoli) Surgery better survival, statistical evidence

Surgery vs Radiation Therapy in Ewing’s Sarcoma Controversies in Local Management 1) Surgery vs Rxt to survival 2) Margin and local control to survival 3) Postoperative Rxt after inadequate margin 4) Histol. response and margin to local control

Surgery vs Radiation Therapy in Ewing’s Sarcoma Materials and Methods. Rizzoli series , retrospective. 512 pts. with nonmetastatic ES of bone. 4 different adjuvant (1) and neoadjuvant (3) studies. Surgery 196, Surgery+Rxt (45 Gy) 139: 335 pts. Full dose Rxt (61 Gy): 177 pts

Surgery vs Radiation Therapy in Ewing’s Sarcoma Materials and Methods. Evolving strategies for local control. Surgery initially only if no reconstruction needed. Postop Rxt individual basis (no risk, inad. margin). Full dose Rxt: nonoperable, refuse amputation. Initial target: 5 cm axial and 2 cm radial margins 45 Gy target volume + 16 Gy central boost

Surgery vs Radiation Therapy in Ewing’s Sarcoma. Evaluation of Surgical Margin Enneking et al., Chir Organi Mov, Assessment of Histologic Response Picci et al., J Clin Oncol, Grade I macroscopic viable tumor PR - Grade II microscopic viable tumor - Grade III no viable tumor Materials and Methods GR

Surgery vs Radiation Therapy in Ewing’s Sarcoma Materials and Methods. Pts traced from diagnosis to relapse or last FU. Local management and margin to EFS and LC. Cumulative EFS and LC by Kaplan-Meier. Statistics by chi-square test with Fisher’s correction. Cox regression multiv. analysis in factors significant at univ. analysis in neoadj. pts (90%)

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Population. M 328 (64%), F 184 (36%); median age 17. Extremities 326 (64%), Axial 186 (36%). Femur 122, Tibia 80, Fibula 53, Humerus 44. Pelvis-Sacrum 109, Spine 20

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Population. LDH: normal 68%, elevated 32% (499 pts). Volume: 150 ml 43% (454 pts). Cht: adjuvant 58 (11%), neoadjuv. 454 (89%)

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Overall Treatment. Surgery/+Rxt 335 (65%); Rxt 177 (35%). Rxt 51% to 26% p < FU 5-22 years, median FU 12 years. EFS 271 pts (53%), Relapse 231 (45%) - 10 pts (2%) died of tmx complic. or 2nd tumor. 5 yr EFS 58%, 5 yr OS 66%

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Patient / Tumor Variables. Gender: M 54% F 66% p <.005. Age: 14 yrs 56% p <.002. Site: Extremity 62% Axial 51% p <.02. Serum LDH: N 68% E 37% p <.001. Volume: 150 ml 54% p <.01

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Treatment Variables. Local Tmx: Surgery 68% Rxt 47% p <.0003 Surgery + Rxt 58% ns. Surgery vs Rxt: Extremity p <.03 Axial ns. Margin: Adeq. 69% Inad. 47% p <.0003 Inadequate Surgery + Rxt ns

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Treatment Variables. Response: GR 77% PR 38% p <.0001 GR: Grade II vs Grade III ns. Cht: Adjuvant 57% Neoadjuvant 58% ns

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Treatment and LR. LR: Surgery 9% Rxt 19% p<.04. Surgery vs Rxt: Extremity p<.06 Axial ns. LR rate: Extremity 9% Axial 19% p<.003

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Margin, LR and Response. LR rate: Adeq. 7% Inadeq. 19% p<.001 Inadequate Surgery + Rxt ns. Ad. Margin: Extremity 88% Axial 36% p<.001. GR (II+III): Adeq 79% Inadeq 67% p<.001. LR rate: GR 6% PR 21% p<.0002

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Margin, LR and Response. LR, Margin and Response: - Adequate + G I 14% - Adequate + G II / III 5% - Inadequate + G I 22% - Inadequate + G II / III 13% p<.005

Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Multivariate Analysis. Histologic Response p< Local Management p<.01. Surgical Margin p<.04. Serum LDH p< Tumor Volume p< Age p<.003

Surgery vs Radiation Therapy in Ewing’s Sarcoma Conclusions. Overall better results with Surgery than Rxt. Significant in extremities, ns in axial. Reinforced role for Surgery in local management 1) Surgery vs Radiation Therapy to survival

Surgery vs Radiation Therapy in Ewing’s Sarcoma Conclusions. Reinforced importance for Surgical Margin. Adequate Margin always needed. Impact on Local Recurrence and Survival 2) Surgical margin, local control and survival

Surgery vs Radiation Therapy in Ewing’s Sarcoma Conclusions. No benefit from low-dose (45 Gy) postop Rxt. Different strategy needed (60 Gy, IBRT, IORT?) 3) Postoperative Rxt after inadequate margin

Surgery vs Radiation Therapy in Ewing’s Sarcoma Conclusions. Correlates with Local Recurrence and Survival. Good Response does not protect from LR. Always aiming for Adequate Margin 4) Histologic response and optimal margin

CTOS 2006, Venice, Italy November 2-4, 2006