Embed Size (px)
DESCRIPTION
Value of local treatment in extrapulmonary metastatic Ewing sarcoma. Uta Dirksen , Julia Häusler, Andreas Ranft, Tobias Bölling, Georg Gosheger, Volker Vieth, Heribert Jürgens. LONDON 2008. Ewing sarcoma require multimodal treatment concepts. Current paradigm: - PowerPoint PPT Presentation
Citation preview
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 [email protected]
Institutions for their support in completing the data set concerning local treatment of metastases.
