Pronostic des sarcomes des tissus mous

Transcription

Prognosis of soft tissue sarcomas
• Local recurrence : 20 - 30 %
• Metastasis : 30 - 50 %
• Overall survival : 40 - 60 %
Soft tissue sarcomas - GSF data base (1 437 patients)
1
0,9
0,8
0,7
Metastasis-free survival
0,6
0,5
0,4
Overall survival
0,3
0,2
0,1
1
2
3
4
5
Years
6
7
8
9
10
• Local recurrence : surgical margins
• Metastasis and overall survival :
histologic grade
Tanabe et al – Cancer 1994, 73, 1652-9
Soft tissue sarcomas
Gross examination
• Macroscopic information
• Surgical margins
• Sampling for histopathology
Macroscopic information
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•
•
•
•
Tumor size
Location (superf., muscle, …)
Periphery
Necrosis
Involvement of tissues
Histologic evaluation of surgical
margins
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•
•
•
Whole resected sample, uncut
Surgeon collaboration
Staining with ink
Sampling
Histologic evaluation of surgical
margins: results
• Positive : tumor tissue on margins
• Negative : > 1cm or fascia
• Marginal : close to tumor tissue
Evaluation : macro + histo
T
Classification :
- R0 : complete resection
- R1 : histologic tumor
- R2 : macroscopic tumor
histologic grade
Grade and prediction of metastasis
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•
•
•
•
•
•
•
•
•
Markhede - 1982
Heise - 1986
Bell - 1989
Mandard - 1989
Alvegard - 1990
Gaynor - 1992
Ravaud - 1992
Pisters - 1996
Coindre - 1996
……...
WHO classification of soft tissue
tumors (2002)
Histologic grading
• French system (FNCLCC)
• American system (NCI)
French Grading System
A 3-grade system with 3 parameters
• Differentiation (1,2,3)
• Mitotic index (1,2,3)
• Necrosis (0,1,2)
Total
• 2-3 : grade 1
• 4-5 : grade 2
• 6-7-8 : grade 3
French grading System
Differentiation
• Histologic type/subtype ± true differentiation
• Scores :
1. Sarcomas closely resembling normal adult tissue
2. Sarcomas for which histologic typing is certain
3. Embryonal and poorly differentiated sarcomas,
synovial sarcoma, PNET, osteosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic
liposarcoma, round cell liposarcoma
Differentiation
• Scores :
Differentiation
• Scores :
Differentiation
• Scores :
Mitotic index
• In 10 successive HPF (.1734 mm²), in most
mitotic areas
• Scores :
1. 0 to 9/10 HPF
2. 10 to 19/10 HPF
3. More than 19/10 HPF
Rules for counting mitoses
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•
•
•
•
early and adequate fixation of tumor
good macroscopic sampling
sections of good quality
adequate sampling at the microscopic level
take your time
Necrosis
• Extension of tumor necrosis at histologic,
macroscopic, (and radiologic ?) levels
• Scores :
0 : no necrosis
1 : < 50 % of T. necrosis
2 : > 50 % of T. necrosis
A 3-grade system with 3 parameters
• Differentiation (1,2,3)
• Mitotic index (1,2,3)
• Necrosis (0,1,2)
Total
• 2-3 : grade 1
• 4-5 : grade 2
• 6-7-8 : grade 3
SOFT TISSUE SARCOMAS (N = 694)
(French Sarcoma Group)
1
M
E
T
A
S
T
A
S
I
S
F
R
E
E
S
U
R
V
I
V
A
L
0.9
GRADE 1
0.8
N = 83
P = .0002
0.7
GRADE 2
0.6
N = 296
0.5
P < .0001
0.4
GRADE 3
0.3
N = 315
0.2
0.1
fb 08-94
0
0
1
2
3
4
5
6
7
8
9
10
YEARS
Reproducibility
• 25 cases - 15 pathologists
• Grade :
- differentiation
- mitotic index
- necrosis
• Histologic type
75 %
74 %
73 %
81 %
61 %
WHO classification of soft tissue
tumors (2002)
Histologic grading
• French system (FNCLCC)
• American system (NCI)
Soft-tissue sarcomas
(n = 410)
overall survival
1
.9
.8
n = 73
n = 64
grade 1
n = 189
n = 241
grade 2
n = 148
n = 105
grade 3
.7
.6
.5
.4
.3
.2
FNCLCC system
.1
p=
NCI system
5x10-13
p = 6,2x10-9
0
0
12
24
36
48
60
72
84
96
108
120 months
(n = 410)
overall survival
1
.9
.8
n = 73
n = 64
grade 1
n = 189
n = 241
grade 2
n = 148
n = 105
grade 3
.7
.6
.5
.4
.3
.2
FNCLCC system
.1
p=
NCI system
5x10-13
p = 6,2x10-9
0
0
12
24
36
48
60
72
84
96
108
120 months
(n = 410)
overall survival
1
.9
.8
n = 73
n = 64
grade 1
n = 189
n = 241
grade 2
n = 148
n = 105
grade 3
.7
.6
.5
.4
.3
.2
FNCLCC system
.1
p=
NCI system
5x10-13
p = 6,2x10-9
0
0
12
24
36
48
60
72
84
96
108
120 months
French and NCI Grading Systems
Multivariate analysis - 410 patients
Metastasis-free survival
Parameters
Relative-risk
p value
French - G3
Size > 10 cm
Deep tumor
French -G2
7.70
2.10
2.61
2.81
2.14 x 10-7
2.45 x 10-4
3.73 x 10-3
8.48 x 10-3
Histologic grading
Conditions of use and limitations
• Grading is not a substitute for typing
• Not applicable to every sarcoma
• Representative sampling of good quality
• Value of grade according to histologic types
• Importance of clinical factors
Sarcomas and Grade
• Soft tissue sarcomas
• Adult
• Untreated tumors
Histologic grading
Core needle biopsy and grading
• Studies with a good concordance (84-88%)
Heslin et al Ann Surg Oncol 1997 (163 patients)
Welker et al Cancer 2001 (155 patients)
Hoeber et al Ann Surg Oncol 2001 (179 patients)
• Problem of sampling error
• Underestimation of grade
Histologic grading
• French Sarcoma Data Base
• 1980 - 1994 :
1240 adult STS
non metastatic
first tumoral event
5 % lost to follow-up
median FU : 88 months
Histologic types of STS and prediction of
metastases
Multivariate analysis (n = 1240)
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MFH (n = 349)
Unclassified sarcomas (n = 140)
Synovial sarcomas (n = 125)
Miscellaneous sarcomas (n = 158)
Liposarcomas (n = 188)
Leiomyosarcomas (n = 148)
MPNST (n = 72)
Rhabdomyosarcomas (n = 60)
Grade
Grade
Grade, T3
Grade
Size, Grade, Subtype
T3, Grade, Size
-
SOFT TISSUE SARCOMAS : Synovial sarcomas and Grade (n = 125)
1
M
E
T
A
S
T
A
S
I
S
F
R
E
E
S
U
R
V
I
V
A
L
0,9
0,8
grade 2 (n=56)
0,7
0,6
0,5
0,4
grade 3 (n=69)
0,3
0,2
p = 1.9x10-5
0,1
1
2
3
4
5
6
7
8
9
10
11
12
13
years
SOFT TISSUE SARCOMAS : Myxoid Liposarcomas and Grade (n = 66)
1
grade 1 (n=43)
0,9
M
E
T
A
S
T
A
S
I
S
F
R
E
E
S
U
R
V
I
V
A
L
0,8
0,7
grade 2 (n=23)
0,6
0,5
0,4
0,3
0,2
p = .02
0,1
1
2
3
4
5
6
7
8
9
10
years
Which sarcomas should not be graded ?
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Tumors of intermediate malignancy
MPNST
Alveolar soft part sarcoma
Clear cell sarcoma
Extraskelettal myxoid chondrosarcoma
Dedifferentiated liposarcoma
Histologic grading
Cox multivariate analysis - 1199 patients
Parameters
Grade 3
Tumor size > 10 cm
T3
Deep tumor
Relative-risk
p value
7.81
2.02
1.50
1.47
1.1 x 10-14
1.2 x 10-5
.0003
.048
SOFT TISSUE SARCOMAS (N = 692)
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1
M
E
T
A
S
T
A
S
I
S
F
R
E
E
S
U
R
V
I
V
A
L
(French Sarcoma Group)
GRADE 1 + Superficial GRADE 2
0.9
N = 146
0.8
0.7
0.6
Deep GRADE 2 + GRADE 3
0.5
N = 546
0.4
0.3
0.2
P < .0001
0.1
fb 08-94
0
0
1
2
3
4
5
6
7
8
9
10
YEARS
histologic grade
• Importance of cooperation with the surgeon
• Importance of histo type and clinical factors

Pronostic des sarcomes des tissus mous

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