Mariani L, Miceli R, Kattan M, Brennan M, Colecchia M, Fiore M, Casali PG and Gronchi A

1. 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.

2. Soft Tissue SarcomaINT 1980-2003 • N° pz. operated 2427 • Extremity 1615 • Superficial Trunk 289 • Retroperitoneum 275 • Visceral 90 • H&N 67 • Others 91

3. 911 STS extremity(INT 1980-2000) • Primary 642 • Recurrences 269

4. Clinical outcome • Age • Tumor size • Histologic grade • Histologic subtype • Tumor depth • Site

6. MSKCC nomogram • Based on a Cox model. • Non proportional hazard for grading.This implied stratifying for low and high grade (see nomogram) • Internally validated.

8. Leiomiosarcoma 50 yrs.high gradedeep thigh > 10 cm.

9. 70 + 30 + 6 + 60 + 26 192

12. UCLA MSKCC

14. INT STUDY AIMS • Test the MSKCC nomogram • Adapt the MSKCC nomogram to incorporate a different classification of histologic grade (FNCLCC)

15. MSKCC INT

16. 642 (INT 1980-2000) Grading

17. 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

18. 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.

19. RESULTS

20. Nomogram testing • 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.

21. Nomogram testing 1st quartile 2nd quartile 3rd quartile 4th quartile Solid lines: actual (Kaplan-Meier) curves Dashed lines: nomogram predicted curves GII-GIII subgroup (“high grade”)

22. 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)

23. G I G II G III

24. MSKCC

25. Synovial INT

26. Leiomiosarcoma 50 yrs.high gradedeep thigh > 10 cm.

27. Synovial 40 + 16 + 5 + 35 + 22 + 100 218 INT

28. 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.

29. 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

30. Subgroups analysis & studies Larger data sets may be obtained by combining important series.

34. International collaboration for future studies among referral centers SARC