CTOS 12th Annual MeetingVenice, 2-4 November 2006

Myxoid/RC Liposarcoma: Prognostic Factors And Survival

Marco Fioremarco.fiore@istitutotumori.mi.it

Soft Tissue SarcomaINT 1980-2005

N° pz. operated 3026

Liposarcoma 685MFH/Pleomorphic sarcoma 389Leiomiosarcoma 372DFSP 260Aggressive Fibromatosis 240Synovial Sarcoma 224MPNST 222Sarcoma NOS 143 Others 491

23%

WD Liposarcoma 233

Dediff Liposarcoma 123

Myxoid Liposarcoma 202

Round cell Liposarcoma 66

Pleomorphic Liposarcoma 61

685 Liposarcoma INT 1980-2005

48%

FUS/TLS-CHOP t(12;16)(q13;p11) (95%)

FUS/TLS

EWS

CHOP/DDIT3

EWS-CHOP t(12;22)(q13;q12) (5%)

myxoid

round cell

pleomorphic

329 Myxoid/RC Liposarcoma INT 1980-2005

2 1%

15 5%

39 12%

273 83%

Head & Neck

Trunk

Retr./Intrapelvic

Extremities

75%

Median Age 49 yrsMale : Female 1 : 1Median Size 8.5 cmDeep Site 84%Grade (FNCLCC)

I 54%II 23%III 22%

329 Myxoid/RC Liposarcoma INT 1980-2005

Primary Recurrent

Total 214 65% 115 35%

MLPS 132 62% 70 61%

RCLPS 44 21% 22 19%

PLPS 38 18% 23 20%

RTNot Done 130 61% 71 62%

Done 84 39% 44 38%

CTNot Done 175 82% 93 81%

Done 39 18% 22 19%

Primary Recurrent

Total 214 65% 115 35%

Site**Extremities 190 89% 83 72%

Intrabd/RP 16 7% 23 20%

Surgical ProcedureLimb Sparing 177 83% 75 65%

Amputation 5 2% 6 5%

NA (trunk, H&N, RP) 32 15% 34 30%

Surgical Margins**Negative 186 87% 75 65%

Positive 28 13% 40 35%

Prognosis depends on…

•the tumor

Hazard Ratio 95% C. I.

Presentation: Recurrence ( Primary ) 2.781** 1.659 4.661

Depth: Deep ( Superficial ) 1.632** 0.556 4.794

Size : >5 cm ( 5 cm ) 2.161** 0.911 5.124

Site: Extremity ( Other ) 0.580** 0.317 1.062

Grade: II ( I ) 2.356** 1.107 5.013

Grade: III ( I ) 1.853** 0.701 4.899

Histology: PLPS (MLPS ) 0.908** 0.369 2.232

Multivariate Analysis - DSS

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1 STS high gradeDFS

Suit HD. J Clin Oncol 1988; 6: 854

<2,5 2,5-5 5-10 10-15 15-20 >20 cm

Size…

Site…

0

0.2

0.4

0.6

0.8

1

0 1 2 3 4 5 6 7 aa

grade 1

grade 2

grade 3

OS

Grading…

Round cell component…

Antonescu CR, Clin Cancer Res 2001;7:3977

RC >5%

Primary: Disease-Specific Survival

Years

0 1 2 3 4 5 6 7 8 9 10

Pro

babi

lity

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

MLPSRCLPSPLPS

0.2217P

214 Primary Myxoid/RC LPS - DSS INT 1980-2005

5-yrs 10-yrs

Overall 90% 87%

MLPS 93% 90%

RCLPS 87% 81%

PLPS 82% 82%

Primary: Crude Cumulative Incidence of Local-Regional Relapse

Years

0 1 2 3 4 5 6 7 8 9 10

Pro

bab

ility

0.0

0.1

0.2

0.3

0.4

0.5

0.6MLPSRCLPSPLPS

0.8907P

214 Primary Myxoid/RC LPS - LR INT 1980-2005

5-yrs 10-yrs

Overall 13% 18%

MLPS 12% 18%

RCLPS 10% 15%

PLPS 19% 19%

Primary: Crude Cumulative Incidence of Distant Metastasis

Years

0 1 2 3 4 5 6 7 8 9 10

Pro

ba

bilit

y

0.0

0.1

0.2

0.3

0.4

0.5

0.6MLPSRCLPSPLPS

0.0018P

214 Primary Myxoid/RC LPS - DM INT 1980-2005

5-yrs 10-yrs

Overall 10% 11%

MLPS 4% 5%

RCLPS 23% 23%

PLPS 20% 20%

p=.0018

Pattern of Distant Mets

41% extra-pulmonary mets

26% lung mets

33% both

• 74% of metastatic patients had at least one extra-pulmonary mets

Extra-pulmonary metastatic pattern according to histological subtype.

MLPS RCLPS PLPS Overall

Intrabdominal 6 4/2 5 3/2 - - 11 7/4

Bone/Spine 6 2/4 3 2/1 - - 9 4/5

Paraspinal 3 0/3 5 2/3 - - 8 2/6

Extremities 4 2/2 3 2/1 1 1/0 8 5/3

Soft tissues 1 0/1 4 3/1 - - 5 3/2

Thoracic wall 3 2/1 2 0/2 - - 5 2/3

Retroperitoneum 3 1/2 1 0/1 - - 4 1/3

Liver 1 1/0 1 0/1 2 2/0 4 3/1

Heart/Pericardium 2 1/1 1 0/1 1 1/0 4 2/2

Mediastinum 2 1/1 2 2/0 - - 4 3/1

Brain - - 1 0/1 1 1/0 2 1/1

Regional nodes 1 0/1 1 0/1 - - 2 0/2

Abdominal wall 1 0/1 - - - - 1 0/1

Overall 33 14/19 29 14/15 5 5/0 67 33/34

Multiple extra-pulmonary sites 8 4/4 6 5/1 - - 14 9/5

* Number of localization at single sites (primary/recurrent cases) in 43 patients with extrapulmonary metastases.

49% 43%

33%

Local Relapse

Distant Mets

MLPS 5 – 9636

8 – 7215

RCLPS 8 – 6612

6 – 5420

PLPS 4 – 3012

6 – 4818

Time to Event (mos)

Local Relapse

Point Estimate 95% CI

MLPS >266 143 - >266

RCLPS 103 46 - >158

PLPS >97 90 - >277

Post-Event Median Survival (mos)

Lung Mets Extra-Lung Mets

Point Estimate 95% CI Point

Estimate 95% CI

MLPS 23 7 - 39 14 4 - >52

RCLPS >12 . - . >19 5 - >19

PLPS 13 6 - 98 >42 >42 - >42

Post-Event Median Survival (mos)

•the surgeon

Intralesional 100%

Marginal 60-80%

Wide 10-30%

Radical < 5%

LR

Enzinger and Weiss’s SOFT TISSUE TUMORS - 2001

Margins status: +/- 2.161** 1.2333.78

7 0.0071

Hazard Ratio 95% C. I. P

Multivariate Analysis - DSS

Local recurrence has an independent effect on

prognosis

Recurrent: Disease-Specific Survival

Years

0 1 2 3 4 5 6 7 8 9 10

Pro

babi

lity

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

MLPSRCLPSPLPS

0.1512P

115 Recurrent Myxoid/RC LPS - DSS INT 1980-2005

5-yrs 10-yrs

Overall 72% 56%

MLPS 79% 62%

RCLPS 58% 43%

PLPS 64% 53%

Recurrent: Crude Cumulative Incidence of Local-Regional Relapse

Years

0 1 2 3 4 5 6 7 8 9 10

Pro

babi

lity

0.0

0.1

0.2

0.3

0.4

0.5

0.6

MLPSRCLPSPLPS

0.2837P

115 Recurrent Myxoid/RC LPS - LR INT 1980-2005

5-yrs 10-yrs

Overall 37% 39%

MLPS 35% 37%

RCLPS 31% 31%

PLPS 48% 52%

Recurrent: Crude Cumulative Incidence of Distant Metastasis

Years

0 1 2 3 4 5 6 7 8 9 10

Pro

ba

bilit

y

0.0

0.1

0.2

0.3

0.4

0.5

0.6MLPSRCLPSPLPS

0.0164P

115 Recurrent Myxoid/RC LPS - DM INT 1980-2005

5-yrs 10-yrs

Overall 22% 23%

MLPS 19% 19%

RCLPS 44% 44%

PLPS 13% 17%

… in conclusion

Prognosis of myxoid/round cell liposarcoma is relatively good, if compared with other STS

Cut-off of 5% of RC component single out a group tumor with 81% 10-yrs DSS, which is actually in the range of intermediate grade STS

As expected, phase at presentation, tumor size and grade, and surgical margins are independent prognostic factors for survival

Pattern of metastases can affect survival

… marco.fiore@istitutotumori.mi.it