Value of local treatment in extrapulmonary metastatic Ewing sarcoma

Value of local treatment in extrapulmonary metastatic

Ewing sarcomaUta Dirksen , Julia Häusler, Andreas Ranft, Tobias Bölling, Georg Gosheger, Volker Vieth, Heribert Jürgens

LONDON 2008

2

Ewing sarcoma require multimodal treatment concepts

Current paradigm:Ewing sarcoma cannot be cured by chemotherapy alone, but require additional local treatment 1,2,3,4,5,6,7,8.

What then is the impact of local treatment in the therapeutic concept in primary disseminated Ewing sarcoma with extrapulmonary metastases (EPMET)?

1) Jurgens H et al. Cancer 1988, 2) Paulussen M et al. J Clin Oncol 2001, 3) Burgert EO et al. J Clin Oncol 1990,4) Nesbit ME et al. J Clin Oncol 1990, 5) Craft AW et al. Eur J Cancer 1997, 6) Bacci G et al. Cancer 1998,

7) Rosito P et al. Cancer 1999, 8) Elomaa I et al. Eur J Cancer 2000

3

Patients

120 patientsEURO-E.W.I.N.G. 99 trial centre Münster (1999-2006)

age 16.2 y (4.2-54.1 y)median follow-up 1.38 y (0.3-8 y)sex 54 f (45%); 66 m

(55%)3-year EFS 0.24 [95% CI 0.16-

0.33]median tumour volume 493 ml

4

Patients` characteristics

Primary tumour

82 pts (68%) central axial (pelvis, spine, abdomen, chest, head, neck)

34 pts (28.5%) extremities (upper and lower extremities)

4 pts (3.5%) not defined

5

Patients` characteristics

Metastatic sites

97 pts (82.2%) bone1 met (11 pts; 11.7%), 2-5 met (30 pts; 31.9%), >5 met (53 pts; 56.4%)

49 pts (43.8%) (+) bone marrow

47 pts (39.5%) + lung

48 pts (40%) (+) other ln (26 pts; 22.8%), liver (11 pts; 9.4%), CNS (1 pt; 0.9%),other (10 pts; 9.3%)

6

Analyses of risk factors

Prognostic factors:- number of bone metastases- tumour volume- age

Treatment:- value of high dose chemotherapy- value of local therapy to primary tumour and /or metastases

7

Number of bone metastases

1 3y-EFS:0.61 (N=11) 2-5 3y-EFS:0.16 (N=30)

>5 3y-EFS:0.19 (N=53) p<.001

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

8

Tumour volume of the primary tumour

<200ml 3y-EFS: 0.33 (n=36) >200ml 3y-EFS: 0.23 (n=65)

p=.188

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

9

Age

<15y 3y-EFS: 0.30 (n=49) >15y 3y-EFS: 0.21 (n=71)

p=.114

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

10

EURO - E.W.I.N.G. 99

Treo-Mel

11

High dose chemotherapy

other HD 3y-EFS: 0.41 (n=15) Bu-Mel 3y-EFS: 0.26 (n=71)

no HD 3y-EFS: 0.13 (n=34) p<.001

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

12

Local therapy of primary tumour and/or metastases

LT of PT and MET 3y-EFS: 0.37 (n=49) LT of PT or MET 3y-EFS: 0.17 (n=41)

no LT 3y-EFS: 0.15 (n=30)

p<.001

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

13

Local treatment modalities of primary tumour

OP&RT 3y-EFS:0.47 (n=21) RT 3y-EFS:0.23 (n=40)

OP 3y-EFS:0.25 (n=26) no LT 3y-EFS:0.13 (n=33)

p<.001

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

14

Risk profile

Risk factor X comb. LT of PT (N=21)

Ø comb. LT of PT (N=99)

X1: TV >200 ml 68% 63%

X2: bone metastases 86% 81%

X3: >1 bone metastases 67% (of X2) 93% (of X2)

no significant difference in risk profile between patients with combined LT vs no combined LT.

comb. LT= combined local treatment (surgery and radiotherapy),PT= primary tumour, PT-Vol.= tumour volume of the primary tumour

15

Modalities of local treatment to extrapulmonary metastases

OP&RT 3y-EFS: 0.86 (n=7)

RT 3y-EFS: 0.27 (n=37) OP 3y-EFS: 0.25 (n=8)

no LT 3y-EFS: 0.17 (n=68) p=.002

Time from diagnosis (years)

Cum

ula

tive

Su

rviv

al

16

Risk profile

Risk factor comb. LT of EPM (N=7)

Ø comb. LT of EPM (N=113)

X1: PTV >200 ml 67% 64%

X2: bone metastases 86% 82%

X3: >1 bone metastases 67% (of X2) 90% (of X2)

comb. LT= combined local treatment (surgery and radiotherapy),EPM= extrapulmonary metastases, PTV = primary tumour volume

comparable risk profile between patients with combined LT vs no combined LT.

17

Multivariate analyses (N=101)

Variable Label Risk Ratio pLocal treatment

PT and EPM

1

(.002) PT or EPM 1.37 (0.73-2.57) .328

none 2.93 (1.60-5.35) .000

High dose chemotherapy

no 3.45 (1.94-6.16) .000

Age >15 y 1.11 (0.68-1.80) .672

Tumor volume >200 ml 1.66 (0.93-2.95) .085

Bone metastasis

no 1

(.153) 1 met 0.47 (0.15-1.46) .194

>1 met 1.31 (0.68-2.54) .417

18

Multivariate Analyses (N=101)

Bias:Patients showing progression within the first 6 monthsof treatment receive- no local treatment- no high dose chemotherapy

Exclusion of patients showing progressive disease within the first 6 months of therapy

19

Multivariate analyses (N=87)

Variable Label Risk ratio pLocal treatment

PT and EPM

1

(.066) PT or EPM 1.64 (0.85-3.16) .141

none 2.15 (1.07-4.33) .031

High dose chemotherapy

no 1.59 (0.73-3.44) .240

Age >15 y 1.04 (0.61-1.76) .899

Tumour volume

>200 ml 1.54 (0.83-2.84) .169

Bone metastases

no 1

(.186) 1 met 0.72 (0.22-2.32) .581

>1 met 1.64 (0.78-3.47) .194

20

Conclusion

Combined local treatment (OP&RT) of primary tumour and /or extrapulmonary metastases significantly improves the prognosis in pts with primary disseminated Ewing tumor.

Local treatment of primary tumour and /or extrapulmonary metastases significantly improves the prognosis in pts with primary disseminated Ewing tumor.

High dose chemotherapy must be compatible with local treatment.

21

Interdisciplinary care

22

THANKS to you

Regina Kloss

Gabriele Braun-Munzinger ewing@uni-muenster.de

Institutions for their support in completing the data set concerning local treatment of metastases.