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

Surgery vs Radiation Therapy inEwing’s Sarcoma the Extremities:Experience of a Single Institution

Surgery vs Radiation Therapy inEwing’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

N. Fabbri, G. Bacci, S. Ferrari, A. Longhi, D. Donati, M. Manfrini, E. Barbieri, M. Mercuri, F. Bertoni

Department of Musculoskeletal OncologyIstituto Ortopedico Rizzoli, Bologna, ItalyDepartment of Musculoskeletal OncologyIstituto 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 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


F, 17 - Ewing’s sarcoma: pre-chemotherapy


F, 17 - Ewing’s sarcoma: post-chemotherapy


3 yr FU

Disease-Free SurvivalDisease-Free Survival

72% (91-97)78% (91-97)

43% (83-87)43% (83-87)

Cum. SurvivalCum. Survival

MonthsMonths5050 100100 150150 200200 25025000

0.20.2

0.40.4

0.60.6

0.80.8

11

00



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 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


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


Materials and Methods

. Rizzoli series 1979-1999, 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



. 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


. Evaluation of Surgical MarginEnneking 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



. 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%)


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


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%)


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%


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


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


Results - Treatment Variables

. Response: GR 77% PR 38% p < .0001 GR: Grade II vs Grade III ns

. Cht: Adjuvant 57% Neoadjuvant 58% ns


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


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


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


Results - Multivariate Analysis

. Histologic Response p< .0001

. Local Management p< .01

. Surgical Margin p< .04

. Serum LDH p< .0001

. Tumor Volume p< .0004

. Age p< .003


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


Conclusions

. Reinforced importance for Surgical Margin

. Adequate Margin always needed

. Impact on Local Recurrence and Survival

2) Surgical margin, local control and survival


Conclusions

. No benefit from low-dose (45 Gy) postop Rxt

. Different strategy needed (60 Gy, IBRT, IORT?)

3) Postoperative Rxt after inadequate margin


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, ItalyNovember 2-4, 2006

Documents

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