1. 14 th Annual Meeting of the Connective Tissue Oncology Society November 13-15, 2008, London, UK Oliver Zivanovic, Mario M. Leitao, Alexia Iasonos, Lindsay M. Jacks, Qin Zhou, Robert A. Soslow, Margrit M. Juretzka, Dennis S. Chi, Richard R. Barakat, Murray F. Brennan, Martee L. Hensley Memorial Sloan-Kettering Cancer Center New York, NY Stage Specific Outcomes of Patients with Uterine Leiomyosarcoma: A Comparison of FIGO and AJCC Staging Systems

2.  Uterine LMS: - annual incidence 0.64 per 100,000 women - poor prognosis - high local and distant failure rates (40-80%) - often without lymphatic spread at diagnosis Background

3.  no uterine LMS-specific staging system  staged using FIGO staging system for endometrial carcinoma  clinical course is difficult to predict  limited ability to identify appropriate patients for investigation of adjuvant treatment strategies Background Staging of uterine LMS

4. Background FIGO versus AJCC FIGOAJCC Organ-based staging - Compartment-based staging- Involvement of uterine cervix - Involvement of uterine serosa - Tumor size- Tumor grade- Lymph node/ pelvic metastasesStage IIIStage IV

5.  Commonly reported prognostic factors: - age - DNA ploidy - menopausal status - mitotic rate - hormone receptor status - LVSI  none are incorporated into the staging systems Background Prognostic factors

6. Objective  To determine and compare the predictive accuracy of the FIGO and AJCC staging systems  Hypothesis: neither staging system provides adequate prediction of PFS and OS in patients with uterine leiomyosarcoma

7. Methods  Patients with uterine LMS between 07/86 to 06/05 - Department of Surgery Sarcoma Database - Variables extracted: age, size, grade, staging criteria, treatment, outcome - Subset received prior treatment at outside institutions - Included only if initial pathology reviewed at MSK  Exclusion if insufficient information for staging

8. Methods  Patients staged based on FIGO and AJCC criteria - PFS and OS estimated using Kaplan-Meier method  Predictive accuracy estimated with concordance index: - Analyzing all possible pairs of patients - Determining concordance (1.0) or discordance (0.0) - Overall probability: sum of the values divided by total number of data pairs

9. Age (years), Median (range)51 (23-81) Tumor grade% High19489 Low2511 Tumor size ≤ 5cm3717 5-10cm9338 > 10 cm8342 Unknown63 Surgical resection performed20995 Primary treatment at MSKCC Yes13160 No8840 Lymph node sampling Performed5324 Not performed16676 Lymph node status Positive815 Negative4585 Patient status Alive without disease3717 Alive after recurrence2210 Dead of disease14968 Dead non disease related10 Dead of unknown cause105 Results Patient characteristics (N=219)

10. FIGO Stage AJCC StageIIIIIIIVTotal I1901020 II2013024 III8011140105 IV00214970 Total119123949219 Results Stage specific distribution by FIGO and AJCC

11. Results 5-year PFS and OS by stage and staging system

12. Results PFS by FIGO and AJCC N=119 N=12 N=39 N=49 N=20 N=24 N=105 N=70

13. Results OS by FIGO and AJCC N=119 N=12 N=39 N=49 N=20 N=24 N=105 N=70

14. EndpointStaging-Systemc-indexBootstrap 95% CI PFSFIGO0.600.566-0.641 AJCC0.600.560-0.639 OSFIGO0.620.586-0.660 AJCC0.630.594-0.678 Results Concordance indices (c-index)

15. Conclusion  Stage-specific PFS and OS altered substantially when comparing AJCC versus FIGO  Strength of AJCC: identifying patients with better prognosis  Strength of FIGO: identifying patients with worse prognosis  Overall predictive ability of AJCC not superior to FIGO

16. Implications of findings  Currently available staging systems fail to provide meaningful estimates of prognosis  Potential solution is a uterine LMS specific nomogram that combines the stage-specific variables with other established clinico-pathologic prognostic factors  The results of such individualized risk-prediction model have the potential to improve our management of women diagnosed with uterine LMS