1. Total Lesion Glycolysis by 18 F-FDG PET/CT a Reliable Predictor of Prognosis in Soft Tissue Sarcoma Ilkyu Han Musculoskeletal Tumor Center, Seoul National University Cancer Hospital, Seoul, Korea - CTOS 2013 -

2. Total Lesion Glycolysis by 18 F-FDG PET/CT a Reliable Predictor of Prognosis in Soft Tissue Sarcoma Ilkyu Han Musculoskeletal Tumor Center, Seoul National University Cancer Hospital, Seoul, Korea - CTOS 2013 - Nothing to Disclose

3. Soft tissue sarcoma : Diverse subtypes and aggressiveness → Complicates the prediction of disease progression Further improvement of prognostication is warranted, besides conventional staging systems and nomograms Morphological imaging (MRI or CT) : Limited capacity for assessment of malignant capacity Prognosis in Soft Tissue Sarcoma

4. Functional imaging by evaluating tumor glucose metabolism Established role : Monitoring primary tumors, lymph nodes and metastases Potential role  Histological characteristics  Tumor response to treatment  Oncological outcomes 18 F-FDG PET/CT 18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

5. SUVmax Maximum standardized uptake value Represents only the most active spot of the tumor Soft tissue sarcoma Heterogeneity within the tumor Size of tumor SUVmax = 3.1 Size = 20cm SUVmax = 7.2 Size = 7cm

6. Volume-based Parameters Metabolic Tumor Volume (MTV) Volume of voxels with SUV > threshold value (cm 3 ) Total Lesion Glycolysis (TLG) MTV x SUVmean

7. Volume-based Parameters Metabolic Tumor Volume (MTV) Volume of voxels with SUV > threshold value (cm 3 ) Total Lesion Glycolysis (TLG) MTV x SUVmean SUVmax : 11.4

8. Volume-based Parameters SUVmax : 11.4 MTV 1) 56 cm 3 (Threshold SUV: 5.0) 2) 152 cm 3 (Threshold SUV: 2.5) Metabolic Tumor Volume (MTV) Volume of voxels with SUV > threshold value (cm 3 ) Total Lesion Glycolysis (TLG) MTV x SUVmean

9. Volume-based Parameters SUVmax : 11.4 MTV 1) 56 cm 3 (Threshold SUV: 5.0) 2) 152 cm 3 (Threshold SUV: 2.5) TLG 152 x 5.15 (SUVmean) = 782.8 Metabolic Tumor Volume (MTV) Volume of voxels with SUV > threshold value (cm 3 ) Total Lesion Glycolysis (TLG) MTV x SUVmean

10. Prognosis  MTV Ovarian, head and neck, non small cell lung cancer  TLG Colorectal, Breast, B cell lymphoma In soft tissue sarcoma  Monitoring tumor response: TLG < SUVmax  Few reports on volume based PET parameters Volume-based Parameters & Prognosis

11. Compare the volume-based parameters of TLG and MTV with SUVmax in predicting disease progression of STS Purpose

12. Review of 94 patients with FDG PET/CT before curative surgery of STS of extremities Exclusion Criteria Previous diagnosis of another malignancy (n=3) Diabetes (4) Less than 6 months follow-up (9) Well differentiated liposarcoma (12) 66 patients analyzed Patient Cohort

13. Demographics Patient Characteristics Tumor Treatment

14. PET/CT Scanners  Gemini, Philips Medical Systems, Milpitas, CA, USA  Biograph 40, Siemens Medical Solutions, Knoxville, TN, USA Measurement of SUVmax, MTV and TLG  Automated volume-contouring program (Synogo.via, Siemens) : Avoid interobserver and intraobserver bias  Two nuclear medicine physicians blinded to clinical information analyzed all images. PET-CT

15. Clinical endpoint: Progression-free survival  Distant metastases or local recurrence by 2 years  Histological or unequivocal clinical evidence Receiver operating characteristics  Accuracy of the parameters  Best discriminating cut-off values for parameters Prognostic Value of Parameters

16. Results

17. ROC Curve Analysis AUC: TLG 0.833 > SUVmax 0.771 > MTV 0.667 Cut-off values: TLG 20, SUVmax 6.0, MTV 40cm 3

18. Progression-free Survival TLG p=0.001 MTV p=0.031 SUVmax p=0.022 All 3 parameters were identified as significant prognostic factors for disease progression by log rank test.

19. Univariate Analysis Size, Stage, Margin, Initial Metastasis + SUVmax, TLG, MTV

20. Multivariate Analysis Stage, Initial Metastasis + TLG → TLG is an independent prognostic factor

21. Representative Case Myxoid Liposarcoma, Grade II, 20cm SUVmax: 3.07, TLG : 463 Metastases developed.

22. Summary This the first study to examine the prognostic roles of PET- based metabolic parameters of tumor burden, using MTV and TLG in STS.

23. Summary This the first study to examine the prognostic roles of PET- based metabolic parameters of tumor burden, using MTV and TLG in STS. TLG exhibited greater accuracy for predicting disease progression than SUVmax or MTV in ROC analysis.

24. Summary This the first study to examine the prognostic roles of PET- based metabolic parameters of tumor burden, using MTV and TLG in STS. TLG exhibited greater accuracy for predicting disease progression than SUVmax or MTV in ROC analysis. TLG was independent prognostic factor in multivariate analysis along with presence of metastasis at diagnosis.

25. Conclusion TLG, which combines metabolic and volumetric indices, may be a more accurate predictor of progression-free survival in STS than MTV or SUVmax.

26. Conclusion TLG, which combines metabolic and volumetric indices, may be a more accurate predictor of progression-free survival in STS than MTV or SUVmax. TLG enables preoperative assessment of disease progression with an accuracy comparable to those of conventional clinicopathological parameters.

27. Orthopaedic Surgery Eun-Seok Choi Han-Soo Kim Nuclear Medicine Jin Chul Paeng Seung-Gyun Ha

28. Thank you for your attention! Orthopaedic Surgery Eun-Seok Choi Han-Soo Kim Nuclear Medicine Jin Chul Paeng Seung-Gyun Ha