1. How to integrate more effective systemic treatment into combined modality treatment?

2. T0 Pre-treatment Treatment T1T2TN … Anatomical Functional Time Information Combination of physics and biology for treatment optimization/adaptation

3. 10 patients PETFDG F-MISO CT MR TME (10) 5 patients PET FDG FLT CT MR TME (7) …….. Week 1 Week 2 Week 3Week 4Week 5 Surgery 1 2 3

4. 123 MR Delineation MR: manually

5. 1 2 3 CT FDG CT FLT

6. Signal to Background Daisne JF, Radioth Oncol, 2003 J. Lee, 2006 background tumor Watershed & Clustering FDG FMISO FLT Delineation FDG signal: SBR & WCA

7. Deformed FDG FMISO signal Delineation FLT/FMISO signal: WCA + ROI (FDG)

8. MeanSTDEVMeanSTDEVMeanSTDEV Before RT 27,1 (100%)  16,5 18,3 (100%)  12,4 15,5 (100%)  10,6 During RT 13,4 (47%)  10,2 11,4 (65%)  8,1 7,2 (46%)  6,7 After RT 6,7 (25%)  5,7 4,9 (25%)  4,3 2,5 (13%)  2,3 n=15 MR FDG (SBR)FDG (WCA)

9. FMISO (WCA) n=10 FDG (WCA)FLT (WCA) n=5 MeanSTDEVMeanSTDEV Before RT14,8  7,3 5,2  3,8 During RT7,3  7,6 1,6  1,5 MeanSTDEVMeanSTDEV Before RT14,5  6,0 9,2  3,3 During RT5,3  3,9 4,0  2,4

10. Multi-temporal image registration of FDG PET-CT images Rigid within tumor volume Biological Follow-up imaging during RT treatment before radiotherapy during therapy after therapy CT Image Registration CT PET

11. FDG volumeMismatch FDGMR volumeMR mismatch MeanBefore RT1647%2769% During RT753%1379% After RT268%785% rangeBefore RT4-4620%-100%11-7527%-100% During RT2-2712%-99%4-4260%-99% After RT0-735%-100%0,5-2044%-100% mismatch A-B = B-A/B (%) mismatch B-A = A-B/A (%) mismatch A-B = 0% Mismatch FDG-MR