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