1. PRIMARY EXTREMITY STS: MULTIMODAL APPROACH MAY HAVE IMPROVED SURVIVAL
OVER TIME
Berselli M, Fiore M, Grosso F,
Bertulli B, Collini P, Lozza L,
Stacchiotti S, Pennacchioli E,
Casali PG & Gronchi A

3.
5641 pts

4.
3607 pts
Localized
Extremity
Retroperitoneum 394
Trunk wall
Head & Neck
Visceral
Other

5.
3607 pts
Localized
Extremity
Retroperitoneum 394
Trunk wall
Head & Neck
Visceral
Other

6. Excluded from the analysis:
DFSP
WD liposa
Desmoids
We excluded DFSP and patients presenting to our center having been operated elewhere and having already developed a local recurrence

7. Excluded from the analysis:
Local recurrences
when first seen
We excluded DFSP and patients presenting to our center having been operated elewhere and having already developed a local recurrence

8.
1094 pts

9. Prognostic factors unchanging over time
Age & gender
Median size
Site of origin
Histological type
Quality of surgical margins

10. Prognostic factors changing over time
Depth
more deep tumors in the 1st and 2nd period
(91%  91%  68%  63%)
Grade
more G3 tumors in the 1st period
(70%  47%  38%  50%)

11. Treatment criteria changing over time
Amputations
decreased from the 1st to the 4th period
(9%  3%  1%  1%)
Concurrent chemo-radiation therapy
preoperatively, confined to the 4th period
(0  0  2%  12%)
Peri-operative chemotherapy
increased in the 4th period
(23%  13%  22%  32%)

12. Local recurrence
Gray test p<0.0001
And local recurrence

13. Period N
pts LR
5-y
CCI
95% CI
10-y
192 32
15.4%
(10.9,21.7%)
17.9%
(13.0,24.5%)
252 47
17.3%
(13.2,22.7%)
18.6%
(14.3,24.2%)
274 28
9.8%
(6.8,14.1%)
11.0%
(7.8,15.6%)
376 18
6.0%
(3.6,9.8%) --

14. Factor HR 95% CI Wald test p
Period
vs (1.50,5.39)
vs (1.76,5.78)
vs (1.02,3.40)
Age vs (1.26,2.54)
Size vs (0.86,2.16)
Depth Deep vs Superficial (0.68,2.15)
Margins Positive vs Negative (1.67,3.99) <0.0001
Histotype
Other vs MFH (0.23,0.85)
Leiomyosarcoma vs MFH (0.29,0.96)
Dediff Liposarcoma vs MFH (0.27,1.37)
Myxoid/RC Liposarcoma vs MFH (0.26,1.02)
MPNST vs MFH (0.38,1.48)
Synovial sarcoma vs MFH (0.51,1.80)
Vascular sarcoma vs MFH (0.44,3.58)
Grading
II vs I (0.89,2.92)
III vs I (0.63,2.21)
CT pre/post Y vs N (0.83,2.23)
RT pre/post Y vs N (0.49,1.09)

18. Overall survival Gray test p=0.0012 Log-rank test p=0.0003
DSS at 10 years with a median FU of 85 months was comparable with all other reports
Gray test p=0.0012
Log-rank test p=0.0003

19. Period N
pts
events
5-y
prob
95% CI
10-y
192 63
73.4%
(67.0,80.3%)
64.2%
(57.3,72.0%)
252 79
73.3%
(67.9,79.2%)
68.4%
(62.7%,74.6%)
274 73
77.1%
(72.2,82.4%)
69.9%
(63.9,76.5%)
376 32
88.8%
(84.9,92.9%) --

20. Sarcoma-specific mortality
Gray test p=0.0012
DSS at 10 years with a median FU of 85 months was comparable with all other reports

21. Period N
pts
deaths
5-y
CCI
95% CI
10-y
192 53
22.5%
(17.1,29.8%)
30.4%
(24.1,38.3%)
252 60
20.8%
(16.3,26.7%)
24.0%
(19.1,30.1%)
274 59
19.4%
(15.2,24.9%)
23.0%
(18.3,29.0%)
376 27
9.2%
(6.2,13.7%) --

22. Factor HR 95% CI Wald test p
Period
vs (0.95, 2.74)
vs (1.31, 3.57)
vs (1.53, 3.92)
Age vs (0.90, 1.55)
Size vs (1.76, 3.91) <.0001
Depth Deep vs Superficial (1.00, 3.44)
Margins Positive vs Negative (1.09, 2.29)
Histotype
Other vs MFH (1.15, 3.53) <0.0001
Leiomyosarcoma vs MFH (1.77, 5.06)
Dediff Liposarcoma vs MFH (0.90, 3.67)
Myxoid/RC Liposarcoma vs MFH (0.72, 2.81)
MPNST vs MFH (1.43, 4.84)
Synovial sarcoma vs MFH (2.19, 6.69)
Vascular sarcoma vs MFH (2.84,16.14)
Grading
II vs I (1.73, 7.19) <0.0001
III vs I (2.91,11.95)
CT pre/post Y vs N (0.87, 1.72)
RT pre/post Y vs No (0.63, 1.18)

23. OS

24. death
due to local disease
local recurrences

25. Sarcoma-specific mortality – G3
Gray test p=0.09
34%
29%
26%
15%

26. Metastasis-free survival

27. Post-metastasis survival

28. …….

29. At INT, Milan, over the years…
Local control has definetely improved, while preoperative chemo-radiation therapy was the main change in treatment
Overall survival at 5 yrs has improved, while possibly less patients died of local relapse and distant metastases slightly lowered
Post-metastasis duration of survival has improved, while medical therapy became more histology-driven (and something which could be called ‘over-treatment’ in the advanced disease was on the rise)