HISTOLOGY-SPECIFIC NOMOGRAM FOR PATIENTS AFFECTED BY PRIMARY RSTS Connective Tissue Oncology Society 15th Annual Meeting Miami, November 5-7th 2009 HISTOLOGY-SPECIFIC NOMOGRAM FOR PATIENTS AFFECTED BY PRIMARY RSTS Alessandro Gronchi alessandro.gronchi@istitutotumori.mi.it

Prognostication a duty for the clinician for taking decision on Complementary treatments Post-operative surveillance for informing the patient

Background

288 pts

122 pts

268 pts

268 pts

Methods

5641 pts, collected from 1982 to 2009 Institutional STS DB

INT 1985 - 2007 Localized STS 3085 Extremity 2043 Retroperitoneum 396 Trunk wall 273 Head & Neck 76 Visceral 112 Other 185 We selected the localized ones, located in the extremities

Local recurrence at presentation Pediatric histologies (pPNET…) We excluded… We excluded DFSP and patients presenting to our center having been operated elewhere and having already developed a local recurrence Local recurrence at presentation Pediatric histologies (pPNET…)

Parameters investigated Age Size Histotype Liposarcoma Leiomiosarcoma MPNST SFT Other Grade Completeness of surgical resection (Y/N) Gronchi et al Cancer 2004; 100: 2448-2455 Gronchi et al J Clin Oncol 2009; 27(1): 24-30

Statistical methods End point was OS at 5 and 10 yrs. Piecewise Regression Model (instead of the usual Cox Model). Age and size were modelled as continuous variables. Model performance evaluated through discriminating ability and calibration assessments.

Results

198 patients Gender Median age 55 (17-80) Median size 16 (4-75) Male 99 Female 93 Median age 55 (17-80) Median size 16 (4-75) Completeness of resection (y/n) 178/14 GIII GI GII

Survival at 5 and 10 years (+ 95% CI)

β SE HR 95% CI Age* 55 vs 43 years 66 vs 55 years 0.02 0.010 1.25 1.23 (0.99, 1.58) (0.99, 1.52) Tumour Size Linear Non linear 20 vs 10 cm 30 vs 20 cm 0.09 -0.12 0.041 0.053 1.78 1.02 (1.08, 3.11) (0.95, 1.04) Histological Subtype Leiomyiosarcoma vs Liposarcoma SFT vs Liposarcoma MPNST vs Liposarcoma Other vs Liposarcoma -0.46 -1.79 -0.22 0.45 0.374 1.029 0.467 0.406 0.63 0.17 0.80 1.58 (0.30, 1.30) (0.02, 1.24) (0.32, 1.99) (0.71, 3.49) Grading II vs I III vs I 1.20 2.05 0.391 0.377 3.32 7.74 (1.54, 7.14) (3.70, 16.2) Surgical Margins Macro (R2) vs Micro (R0/R1) 1.43 0.364 4.18 (2.05, 8.54)

…liposarcoma rarely get cured…

Log-Relative hazard of death for all causes according to tumour size from the piecewise regression model.

…our nomogram…

Model performance Predictive performance: adjusted C Index=0.73 (satisfactory accuracy) Calibration plots: predicted and observed survival probabilities in good agreement.

We do have now different tools… Which one should we choose ?

INT - Milan MDACC - Houston MSKCC - NY MSKCC - NY

10 yr OS 5 yr OS Liposarcoma 60 yr 25 cm GI 75% 85% 85% 80% GII 40% _ _ 40% GIII 10% 55% 46% 10% GI 65% _ 63% 60% GII 15% _ _ 15% GIII 0% _ 27% 0%

10 yr OS 5 yr OS Leiomyosarcoma 60 yr 25 cm GI 65% _ 52% _ GII 35% _ _ _ GIII 0% _ 16% _ GI 80% _ 80% _ GII 50% 45% _ _ GIII 15% _ 33% _

10 yr OS 5 yr OS MPNST 60 yr 25 cm GI 65% _ 28% _ GII 20% _ _ _ GIII 0% _ 3% _ GI 80% _ 64% _ GII 35% 45% _ _ GIII 0% _ 12% _

10 yr OS 5 yr OS SFT 60 yr 25 cm GI 90% _ 49% _ GI 95% _ 78% _ GII _ _ _ _ GIII 45% _ 13% _ GI 95% _ 78% _ GII _ 45% _ _ GIII 68% _ 30% _

Conclusions

Different nomograms for RSTS are available They seem to be quite consistent in the prediction of liposarcoma’s outcome (the commonest histology). Wy tried to improve the available nomograms by: using size as a continuous variable (and age…) introducing the histological subtype more frequently found at this site complementing histological subtype by histological grade of aggressiveness (a 3-tier grade according to FNCLCC)

…next step…

Cross-check comparisons INT - Milan MDACC - Houston

Call for somebody else in the game for external validation MDACC - Houston INT - Milan

Combine series to come out with a possibly better tool

alessandro.gronchi@istitutotumori.mi.it