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
1982 - 2009
5641 pts
1987 - 2007
3607 pts
Localized 2863
Extremity 1962Retroperitoneum 394Trunk wall 262Head & Neck 75Visceral 133Other 37
1987 - 2007
3607 pts
Localized 2863
Extremity 1962Retroperitoneum 394Trunk wall 262Head & Neck 75Visceral 133Other 37
Excluded from the analysis:
DFSP
WD liposa
Desmoids
Local recurrences when first seen
Excluded from the analysis:
1987 - 2007
1094 pts
1987-1991 1921992-1997 2521998-2002 2742003-2007 376
Age & gender
Median size
Site of origin
Histological type
Quality of surgical margins
Prognostic factorsunchanging 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%)
Prognostic factorschanging over time
Amputationsdecreased from the 1st to the 4th period(9% 3% 1% 1%)
Concurrent chemo-radiation therapypreoperatively, confined to the 4th period(0 0 2% 12%)
Peri-operative chemotherapyincreased in the 4th period(23% 13% 22% 32%)
Treatment criteriachanging over time
Time (months)
0 12 24 36 48 60 72 84 96 108 120
CC
I
0.00
0.05
0.10
0.15
0.20
1987-19911992-19971998-20022003-2007
Gray test p<0.0001
Local recurrence
Period N pts
N LR
5-y CCI
95% CI 10-y CCI
95% CI
1987-1991 192 32 15.4% (10.9,21.7%) 17.9% (13.0,24.5%)
1992-1997 252 47 17.3% (13.2,22.7%) 18.6% (14.3,24.2%)
1998-2002 274 28 9.8% (6.8,14.1%) 11.0% (7.8,15.6%)
2003-2007 376 18 6.0% (3.6,9.8%) -- --
Factor HR 95% CI Wald test p Period
1987-1991 vs 2003-2007 2.85 (1.50,5.39) 0.0013 1992-1997 vs 2003-2007 3.19 (1.76,5.78) 1998-2002 vs 2003-200 1.86 (1.02,3.40)
Age 64 vs 36 1.79 (1.26,2.54) 0.0051
Size 10 vs 3 1.37 (0.86,2.16) 0.2608 Depth Deep vs Superficial 1.21 (0.68,2.15) 0.5164 Margins Positive vs Negative 2.58 (1.67,3.99) <0.0001 Histotype
Other vs MFH 0.45 (0.23,0.85) 0.0958Leiomyosarcoma vs MFH 0.53 (0.29,0.96) Dediff Liposarcoma vs MFH 0.61 (0.27,1.37)Myxoid/RC Liposarcoma vs MFH 0.52 (0.26,1.02) MPNST vs MFH 0.75 (0.38,1.48) Synovial sarcoma vs MFH 0.96 (0.51,1.80) Vascular sarcoma vs MFH 1.25 (0.44,3.58)
Grading
II vs I 1.61 (0.89,2.92) 0.1794III vs I 1.18 (0.63,2.21)
CT pre/post Y vs N 1.36 (0.83,2.23) 0.2226RT pre/post Y vs N 0.73 (0.49,1.09) 0.1258
Time (months)
Sur
viva
l Pro
babi
lity
0 12 24 36 48 60 72 84 96 108 120
0.0
0.2
0.4
0.6
0.8
1.0
1987-1991
1992-19971998-2002
2003-2007
Gray test p=0.0012
Log-rank test p=0.0003
Overall survival
Period N pts
N events
5-y prob
95% CI 10-y prob
95% CI
1987-1991
192 63 73.4% (67.0,80.3%) 64.2% (57.3,72.0%)
1992-1997
252 79 73.3% (67.9,79.2%) 68.4% (62.7%,74.6%)
1998-2002
274 73 77.1% (72.2,82.4%) 69.9% (63.9,76.5%)
2003-2007
376 32 88.8% (84.9,92.9%) -- --
Time (months)
0 12 24 36 48 60 72 84 96 108 120
CC
I
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
1987-19911992-19971998-20022003-2007
Gray test p=0.0012
Sarcoma-specific mortality
Period N pts
N deaths
5-y CCI
95% CI 10-y CCI
95% CI
1987-1991 192 53 22.5% (17.1,29.8%) 30.4% (24.1,38.3%)
1992-1997 252 60 20.8% (16.3,26.7%) 24.0% (19.1,30.1%)
1998-2002 274 59 19.4% (15.2,24.9%) 23.0% (18.3,29.0%)
2003-2007 376 27 9.2% (6.2,13.7%) -- --
Factor HR 95% CI Wald test p Period
1987-1991 vs 2003-2007 1.61 (0.95, 2.74) 0.0011 1992-1997 vs 2003-2007 2.16 (1.31, 3.57) 1998-2002 vs 2003-200 2.45 (1.53, 3.92)
Age 64 vs 36 1.18 (0.90, 1.55) 0.4994
Size 10 vs 3 2.62 (1.76, 3.91) <.0001 Depth Deep vs Superficial 1.85 (1.00, 3.44) 0.0504 Margins Positive vs Negative 1.58 (1.09, 2.29) 0.0159 Histotype
Other vs MFH 2.01 (1.15, 3.53) <0.0001 Leiomyosarcoma vs MFH 2.99 (1.77, 5.06) Dediff Liposarcoma vs MFH 1.82 (0.90, 3.67) Myxoid/RC Liposarcoma vs MFH 1.42 (0.72, 2.81) MPNST vs MFH 2.63 (1.43, 4.84) Synovial sarcoma vs MFH 3.83 (2.19, 6.69) Vascular sarcoma vs MFH 6.77 (2.84,16.14)
Grading
II vs I 3.53 (1.73, 7.19) <0.0001 III vs I 5.89 (2.91,11.95)
CT pre/post Y vs N 1.22 (0.87, 1.72) 0.2544 RT pre/post Y vs No 0.86 (0.63, 1.18) 0.3490
OS
local recurrences
deathdue to local disease
15%
26%
29%
34%
Gray test p=0.09
Sarcoma-specific mortality – G3
Metastasis-free survival
Time (months)
Sur
viva
l Pro
babi
lity
0 12 24 36 48 60 72 84 96 108
0.0
0.2
0.4
0.6
0.8
1.0
1987-19911992-1997
1998-2002
2003-2007
Time (months)
Sur
viva
l Pro
babi
lity
0 12 24 36 48 60 72 84 96 108
0.0
0.2
0.4
0.6
0.8
1.0
1987-2002
2003-2007
Post-metastasis survival
…….
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)
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