1. Janet Eary 1, Janet O'Sullivan 3, Finbarr O'Sullivan 3, E. U. Conrad 2 1. Nuclear Medicine/Radiology, University of Washington, Seattle, WA, United States. 2. Orthopedics, University of Washington, Seattle, WA, United States. 3. Statistics, University College Cork, Cork, Ireland STATISTICAL RISK ANLAYSIS FOR CLINICAL OUTCOMES USING MID- THERAPY FDG PET IN SARCOMA PATIENTS

2. UW Soft Tissue Sarcoma Treatment Protocol  Large Intermediate and High grade Tumors  pre-resection 4 chemotherapy cycles  Tumor resection  4 additional cycles of chemotherapy  3 FDG PET scans to monitor response

3. 18 FDG is the most important PET procedure 2-fluoro-2-deoxy-D-glucose  FDG reflects altered tissue metabolism More than just “grading” images.

4. Study Patients Variable Number of patients Age diagnosis Pediatric (10-20 years) 22 Adult (21-66 years)43 Variable Number of patients Tumor locations Upper Extremity8 Lower Extremity36 Pelvis14 Trunk7 Variable Number of Patients Tumor type Ewings’ sarcoma10 Osteosarcoma15 Fibrosarcoma1 Leiomyosarcoma7 Liposarcoma6 MPNST5 Sarcoma NOS13 Synovial sarcoma8

5. High Grade Sarcoma: Heterogeneous Response to Chemotherapy

6. : Study : Design : Analysis :  Aims: determine the value of the mid-therapy FDG PET scan for risk assessment for outcome  Hypothesis: the mid-therapy FDG PET scan will add predictive value to outcome prediction  Methods: Prospective study Univariate, and multivariate analyses with Cox proportional Hazards analysis, and models for variables for data reduction Creation of clinical risk scenarios for different sets of clinical variable combinations

7. Overall Survival (Univariate Models) VariableHazard RatioP-value Pre-therapy SUVmax 1.240.23 SUV diff 0.640.03 Tumor Size 1.510.01 Age 1.400.11 Gender 1.11.80 Tumor type (bone vs soft tissue 0.030.02 Tumor Grade 1.010.98 Tumor site (trunk vs extremity 2.630.02

8. Overall Survival (reduced model) VariableHazard RatioP-value Pre-therapy SUVmax1.460.04 SUVdiff0.560.01 Tumor site (trunk vs extremity) 2.370.04

9. Progression-free Survival (Reduced model) VariableHazard RatioP-value Pre-therapy SUVmax1.330.12 SUVdiff0.550.006 Tumor site (trunk vs extremity) 2.930.003

10. Local Progression-free Survival (reduced model) VariableHazard RatioP-value Pre-therapy SUVmax1.780.006 SUVdiff0.490.013 Tumor site (trunk vs extremity) 3.240.010

11. Survival

12. Survival (reduced model) Overall Survival Progression-free Survival Local Progression-free Survival

13. Survival Risk (multivariate model) Extremity tumors Truncal tumors

14. Local Progression-free Survival (Multivariate model) Extremity tumors Truncal tumors

15. FDG PET Risk Assessment in Sarcoma Conclusions:  The mid-therapy scan provides additional information for risk assessment based on FDG PET and clinical variables  In addition to overall and progression-free survival, local recurrence risk can be assessed  Reduced Hazards and multivariate models for risk assessments provide clinically useful data on an individual patient. Future Directions:  Comparison/inclusion of other risk assessment models into these analysis results  Descriptions of tumor subtype and specific responses to therapy types.  Use of tumor image regional analysis to assess areas at risk for local recurrence and metastases

16. Support your local Molecular Imaging Center ! (thanks.)

18. Progression-Free Survival (univariate models) VariableHazard RatioP-value Pre-therapy SUVmax1.080.65 SUVdiff0.630.01 Tumor Size1.460.02 Age1.280.17 Gender1.410.36 Tumor type (bone vs soft tissue) 0.270.004 Tumor Grade0.780.50 Tumor site (trunk vs extremity) 3.080.002

19. Local Progression-free Survival (Univariate models) VariableHazard RatioP-value Pre-therapy SUVmax1.470.04 SUVdiff0.660.08 Tumor size1.700.003 Age1.280.26 Gender1.050.92 Tumor type (bone vs soft tissue) 0.400.07 Tumor grade0.960.94 Tumor site (trunk vs extremity) 3.510.005

20. Progression-free Survival (Multivariate model) Extremity Tumors Truncal Tumors

21. Survival Risk Survival- extremity tumorsSurvival- truncal tumors