VALIDATION AND ADAPTATION OF A NOMOGRAM
FOR PREDICTING SURVIVAL OF EXTREMITY STS
USING A 3 GRADE SYSTEM.
Mariani L, Miceli R, Kattan M, Brennan M,
Colecchia M, Fiore M, Casali PG and Gronchi A
Istituto Nazionale per lo studio e la cura dei Tumori Milano – Italy
Memorial Sloan Kettering Cancer Center New York – U.S.
Soft Tissue SarcomaINT 1980-2003
• N° pz. operated 2427
• Extremity 1615• Superficial Trunk 289• Retroperitoneum 275• Visceral 90• H&N 67• Others 91
• Primary 642
• Recurrences 269
911 STS extremity(INT 1980-2000)
Clinical outcome• Age
• Tumor size
• Histologic grade
• Histologic subtype
• Tumor depth
• Site
MSKCC nomogram
• Based on a Cox model.
• Non proportional hazard for grading.This implied stratifying for low and high grade (see nomogram)
• Internally validated.
Leiomiosarcoma 50 yrs.
high gradedeep thigh
> 10 cm.
70
30+
6+
60+
26+
192
UCLA MSKCC
INT STUDY AIMS
• Test the MSKCC nomogram
• Adapt the MSKCC nomogram to incorporate a different classification of histologic grade (FNCLCC)
MSKCC INT
642 (INT 1980-2000)
46%28%
26%
G I (180 pts.)G II (170 pts.)G III (292 pts.)
Grading
642 (INT 1980-2000)
• Median follow-up: 99 months (IQ range: 91-106)
• A small fraction of patients (4.5%) lost before the 10th year of follow-up
Statistical Methods• Nomogram testing:
– Check if the INT patients fare better or worse on average than predicted by the NSKCC nomogram.
– Test if the effects of covariates in INT series were stronger or weaker than predicted by the MSKCC nomogram.
• Nomogram revision:
The INT nomogram derived by incorporating histologic grade as GI-GIII in MSKCC nomogram.
RESULTS
• MSKCC nomogram predictions were quite accurate, within 10% of actual survival for all strata.
• Spread among predicted curves greater than that among actual curves, suggesting that predictions were somewhat overstated.
• The predictions may be improved by applying a shrinkage factor.
Nomogram testing
Time (months)
0 12 24 36 48 60 72 84 96 108 120
Dis
ea
se-S
pe
cific
Su
rviv
al
0.0
0.2
0.4
0.6
0.8
1.0
1st quartile
2nd quartile
3rd quartile
4th quartile
Solid lines: actual (Kaplan-Meier) curvesDashed lines: nomogram predicted curves
GII-GIII subgroup (“high grade”)
Nomogram testing
Nomogram revision
• In the revised model, the prognostic contribution of histologic grade highly significant (p<0.001).
• Prognostic trend from GI to GIII.
• Histologic grade the strongest covariate among the others (see corresponding axis in the nomogram)
Time (months)
0 12 24 36 48 60 72 84 96 108 120
Dis
ease
-Sp
eci
fic S
urv
iva
l
0.0
0.2
0.4
0.6
0.8
1.0
G I
G II
G III
MSKCC
Points 0 10 20 30 40 50 60 70 80 90 100
Size(cm)<= 5 > 10
5-10
DepthSuperficial
Deep
SiteUpper
Lower
HistologyFibro MFH Other MPNT
Lipo Leiomyo
Age(years)10 20 30 40 50 60 70 80 90
GradeI III
II
Total Points 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280
10-Year sarcoma-specific death0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
Synovial
INT
Leiomiosarcoma 50 yrs.
high gradedeep thigh
> 10 cm.
Points 0 10 20 30 40 50 60 70 80 90 100
Size(cm)<= 5 > 10
5-10
DepthSuperficial
Deep
SiteUpper
Lower
HistologyFibro MFH Other MPNT
Lipo Leiomyo
Age(years)10 20 30 40 50 60 70 80 90
GradeI III
II
Total Points 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280
10-Year sarcoma-specific death0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
Synovial
INT
40
16+
5+
35+
22+
100+
218
Conclusions• MSKCC nomogram is confirmed as a
valuable tool for individual prognostic assessment.
• The revised INT nomogram is proposed whenever the 3-grade system is applied in extremity STS.
Further considerations• Development of validated nomograms
in rare tumors, such as STS, is of major interest:– clinical decision making
– patients selections or stratifications in clinical trials
– adds to the evidence
Larger data sets may be obtained by
combining important series.
Subgroups analysis & studies
International collaboration for future studies among referral
centers
SARC
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