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Surgery vs Radiation Therapy in Ewing’s Sarcoma the Extremities:

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.

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Surgery vs Radiation Therapy in Ewing’s Sarcoma the Extremities:

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  1. 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

  2. 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, biasRxt worse cases

  3. Surgery vs Radiation Therapy in Ewing’s Sarcoma Surgery vs Rxt: Literature .Pritchard et al., Cancer, 1975 - 229 pts, pre-Cht experience (1912-1968) - Extremity & Surgery in survivors > 5 yrs .Rosen et al., Cancer, 1978 - 20 pts, multimodal management since 1970 - 13 pts, T6 + T2 & Surgery +/- Rxt, 85% at 3 yrs .Bacci et al., JBJS-B, 1978 - 37 pts, multimodal management since 1972 - Surgery + Cht 90% vs Rxt + Cht 55% at 2 yrs

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

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

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

  7. 1 1 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0 0 Surgery vs Radiation Therapy in Ewing’s Sarcoma Disease-Free Survival Cum. Survival Cum. Survival 78% (91-97) 72% (91-97) 43% (83-87) 43% (83-87) 0 50 100 150 200 250 0 50 100 150 200 250 Months Months

  8. 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

  9. 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

  10. 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

  11. Surgery vs Radiation Therapy in Ewing’s Sarcoma Materials and Methods .Rizzoli series 1979-1999, retrospective .512 pts. with nonmetastatic ES of bone .4differentadjuvant (1) and neoadjuvant (3) studies .Surgery 196, Surgery+Rxt (45 Gy) 139: 335 pts .Full dose Rxt (61 Gy): 177 pts

  12. 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

  13. Surgery vs Radiation Therapy in Ewing’s Sarcoma Materials and Methods .Evaluation of Surgical Margin Enneking et al., Chir Organi Mov, 1990 .Assessment of Histologic Response Picci et al., J Clin Oncol, 1993 - Grade I macroscopic viable tumor PR - Grade II microscopic viable tumor - Grade III no viable tumor GR

  14. 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%)

  15. 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%) .Femur122, Tibia 80, Fibula 53, Humerus 44 .Pelvis-Sacrum109, Spine 20

  16. Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Population .LDH: normal 68%, elevated 32% (499 pts) .Volume: <150 ml 57%, >150 ml 43% (454 pts) .Cht: adjuvant 58 (11%), neoadjuv. 454 (89%)

  17. Surgery vs Radiation Therapy in Ewing’s Sarcoma Results - Overall Treatment .Surgery/+Rxt 335 (65%); Rxt 177 (35%) .Rxt 51% 1979-82 to 26% 1991-99 p < .0004 .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%

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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. Surgery vs Radiation Therapy in Ewing’s Sarcoma Results -Multivariate Analysis .Histologic Response p< .0001 .Local Managementp< .01 .Surgical Margin p< .04 .Serum LDH p< .0001 .Tumor Volume p< .0004 .Age p< .003

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

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

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

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

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

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