1. Overskrift her Navn på oplægsholder Navn på KU- enhed For at ændre ”Enhedens navn” og ”Sted og dato”: Klik i menulinjen, vælg ”Indsæt” > ”Sidehoved / Sidefod”. Indføj ”Sted og dato” i feltet for dato og ”Enhedens navn” i Sidefod Volume-based 18 F-FDG PET/CT imaging markers provide prognostic information beyond histologic grading – a retrospective study of 92 patients with high-grade bone or soft tissue sarcoma Kim Francis Andersen 1, Hanna Maria Fuglø 2, Sine Hvid Rasmussen 1, Michael Mørk Petersen 2 & Annika Loft 1 Department of Clinical Physiology, Nuclear Medicine & PET 1 Department of Orthopedic Surgery 2 Rigshospitalet, University of Copenhagen Denmark

2. Overskrift her Navn på oplægsholder Navn på KU- enhed For at ændre ”Enhedens navn” og ”Sted og dato”: Klik i menulinjen, vælg ”Indsæt” > ”Sidehoved / Sidefod”. Indføj ”Sted og dato” i feltet for dato og ”Enhedens navn” i Sidefod Volume-based 18 F-FDG PET/CT imaging markers provide prognostic information beyond histologic grading – a retrospective study of 92 patients with high-grade bone or soft tissue sarcoma Kim Francis Andersen 1, Hanna Maria Fuglø 2, Sine Hvid Rasmussen 1, Michael Mørk Petersen 2 & Annika Loft 1 Department of Clinical Physiology, Nuclear Medicine & PET 1 Department of Orthopedic Surgery 2 Rigshospitalet, University of Copenhagen Denmark No disclosures

3. Background Potential benefits of 18 F-FDG PET: -Staging -Treatment response evaluation -Oncological outcomes Difficult to standardize the implementation of this imaging modality in the diagnostic work-up and follow-up of patients with sarcoma Clinical evidence suffers to the low incidence of tumors as well as high intra- and inter-tumoral heterogeneity Pre-treatment estimation of SUV max of the primary tumor in sarcoma patients has been suggested being a significant prognostic factor for overall and progression-free survival

4. Background SUV max purely represents the maximum value of a single voxel in the acquired imaging data - it does not reflect important prognostic tumor properties such as: a) Tumor heterogeneity b) Tumor size and burden

5. Background SUV max purely represents the maximum value of a single voxel in the acquired imaging data - it does not reflect important prognostic tumor properties such as: a) Tumor heterogeneity b) Tumor size and burden Volume-based 18 F-FDG PET imaging markers: a) Metabolic tumor volume (MTV) b) Total lesion glycolysis (TLG): - MTV x (SUV mean of the MTV)

6. Background In sarcoma patients: a)Clinical evidence is minimal and conflicting -TLG: predictor of progression-free survival in STS 1 -Volume-based 18 F-FDG PET imaging markers (MTV & TLG) may not provide additional prognostic information in STS 2 b)Prognostic value of MTV and TLG in terms of overall survival in patients with BS? 1 Choi et al. Eur J Nucl Med Mol Imaging 2013;40(12):1836-1842 2 Hong et al. Skeletal Radiol 2014;43(5):641-8

7. Background In sarcoma patients: a)Clinical evidence is minimal and conflicting -TLG: predictor of progression-free survival in STS 1 -Volume-based 18 F-FDG PET imaging markers (MTV & TLG) may not provide additional prognostic information in STS 2 b)Prognostic value of MTV and TLG in terms of overall survival in patients with BS? 1 Choi et al. Eur J Nucl Med Mol Imaging 2013;40(12):1836-1842 2 Hong et al. Skeletal Radiol 2014;43(5):641-8 ‘…to compare the prognostic value of volume-based semi-quantitative calculations of primary tumor metabolic activity using 18 F-FDG PET/CT in the initial assessment of patients with high-grade bone or soft-tissue sarcoma…’

8. Materials & methods Single-site study Retrospective design Inclusion period: July 1 st 2002 – December 31 st 2012 Inclusion criteria: a) Histologically verified high-grade BS or STS b) No previous history of malignancy c) On-site pre-treatment 18 F-FDG PET/CT scan d) Follow-up period >12 months for survived patients

9. Materials & methods N=92 (37 BS; 55 STS) 47 male; 45 female Median age 49.8y Median follow-up 2.8y

10. Materials & methods Pre-treatment 18 F-FDG PET/CT scan VOI of primary tumor Metabolic tumor volume (MTV 40% ) Total lesion glycolysis (TLG) Clinical data acquired Clinical endpoint: overall survival

11. Clinical characteristics

12. ROC curve analysis

13. Kaplan-Meier survival estimates

14. Cox proportional hazards regression analysis All other variables included in the multivariate regression analysis failed to demonstrate independent prognostic properties in terms of overall survival: Gender Tumor size Metastasis at diagnosis MTV 40%

15. Conclusion & future perspectives In patients with high-grade sarcoma: Estimation of pre-treatment total lesion glycolysis can be recognized as an independent prognostic marker for overall survival Further studies are needed to demonstrate the clinical utility of volume-based 18 F-FDG PET imaging markers, especially TLG

16. Conclusion & future perspectives In patients with high-grade sarcoma: Estimation of pre-treatment total lesion glycolysis can be recognized as an independent prognostic marker for overall survival Further studies are needed to demonstrate the clinical utility of volume-based 18 F-FDG PET imaging markers, especially TLG Tumor heterogenity? Asphericity? PET/MRI? Hyperpolarization? Tumor-specific tracers?

17. Thank you for your attention!

18. SUV max vs. total lesion glycolysis (TLG) TLG: High-significant, slightly larger AUC Increased sensitivity Unchanged specificity High-significant differences in average survival; hazard ratios higher Contrary to SUV max, TLG remained an independent prognostic factor for overall survival during subgroup analysis