1. Hit or Miss: Is there a role for CT/MRI fusion in Sarcoma radiotherapy planning? Paris-Ann Gfeller B.C. Cancer Agency, Vancouver, Canada Musculoskeletal Tumour Group C. Candish, K. Goddard, C. Grafton, L. Weir

2. Outline oBackground oStudy Design oResults oConclusions

3. Background Sarcoma Radiotherapy Planning oThe delineation of tumor from normal tissues is critical to the radiotherapy planning process oIn Sarcoma treatment planning, improper delineation of tumour can lead to: Over-treatment of normal tissues oSevere late effects of treatment (fibrosis, fracture, edema) Under-treatment of tumour oTumour recurrence

4. Background Sarcoma Radiotherapy Planning oAppropriate imaging is essential to properly delineate tumour volumes oMajority of current radiotherapy planning systems are CT based oWith CT images alone it can be difficult to differentiate between tumor and normal tissue oSarcomas are routinely imaged using MRI oMRI correlates with tumour extent and invasion into local structures oMRI shows peritumoral edema, which is included as part of target volume

5. Background CT vs. MRI CT MRI Tumour is better defined by MRI compared to CT

6. Background How Can We Combine CT and MRI? By co-registering (fusing) CT and MRI images, Radiation Oncologists can contour on CT and MRI simultaneously, using imaging information from both modalities CT MRI

7. Background How is Fusion Done? CTMRI-Fusion

8. Background CT/MRI Fusion for Sarcomas? There are no published studies describing the use of CT/MRI Fusion for sarcoma treatment oCT/MRI Fusion studies in other tumor sites have shown: oImproved tumor delineation with fusion oMore accurate representation of gross disease oDecreased interobserver, intraobserver variation with fusion oMore reproducible oIs there a benefit for CT/MRI fusion in sarcoma radiotherapy planning?

9. Study Questions? 1.Is CT-MRI Fusion useful in sarcoma planning? oDoes Fusion alter the tumour volumes? oDoes Fusion improve consistency between observers (interobserver variation)? oDoes Fusion improve consistency within observers (intraobserver variation)? 2.Is CT/MRI fusion felt to be valuable to the planning process? oRadiation Oncologists opinion oRadiation Therapists opinion

10. Study Design In 2004 a BCCA protocol was developed for fusion sarcoma patients oCoordination of planning CT and MRI on the same day, in treatment position, with an immobilization device o“Best” MRI image series selected in consult with radiology and fused with a planning CT

11. Study Design o19 patients were planned and treated from May 2004 to February 2005 at Vancouver Cancer Centre (BCCA) with the CT-MRI fusion protocol oIdentified all patients who had been treated according to protocol oExcluded patients who had received chemotherapy or surgery prior to radiation planning oExcluded tumours located in the thorax or head and neck o9 patients met study criteria o6 patients treated preoperatively, 3 patients had radiotherapy as definitive treatment o5 MFH, 3 Fibromatosis, 1 Liposarcoma

12. Study Design oOriginal non-contrast planning CT images and MRI images retrieved and then co-registered to produce CT/MRI fusion images o2 image sets for each patient created oCT image set oCT/MRI fusion image set

13. Study Design 3 Radiation Oncologists (RO’s) 9 CT Image Sets 9 Patient Summaries Contour tumour volumes Complete Survey 9 Fusion Image Sets, 9 Patient Summaries Contour tumour volumes Complete Survey 54 Image Sets Volumes Analyzed for: Difference in Mean Volumes Max/Min Ratio, X/Y/Z Observers repeated contours on CT and Fusion for Intraobserver Δ Minimum 2 week delay between contouring on image sets

14. RESULTS

15. Results Mean Contoured Tumour Volume By Patient CT volumes were 20% larger then fusion volumes

16. Results Contoured Tumour Volumes Oncologists included more NORMAL TISSUE if unsure of volume on CT vs. MRI oThis accounted for larger overall CT volumes CTFusion

17. Results Contoured Tumour Volumes CT contours not always inclusive of MRI signal changes oGROSS TUMOUR EXCLUDED CT Fusion

18. Interobserver Variation Maximum Variation Ratio Compare Max/Min Contoured Volume for each patient between observers o More Interobserver Variation with CT

19. oVolumes contoured with Fusion more consistent between observers CTFusion Interobserver Variation Maximum Variation Ratio

20. Intraobserver Variation Maximum Variation Ratio Compare Max/Min Contoured Volume for each patient within observers oMore Intraobserver Variation with CT

21. oContoured Tumour Volumes (GTV) oMean CT volumes by pt were larger then Fusion volumes oMean CT gross tumour volumes for each patient were 1.2 times larger (range 0.90-1.56) then CT/MRI fusion images op=0.04 oInterobserver Variation (Maximum Variation Ratio) oCT 3.72 (range 1.19- 9.0) oFusion 1.72 (range 1.16-3.07) oLess interobserver variation with fusion p=0.001 oIntraobserver Variation (Maximum Variation Ratio) oCT 1.41 (range 1.03-1.72) oFusion 1.10 (range 1.01-1.27) oLess intraobserver variation with fusion p=0.02 Results Contoured Tumour Volumes

22. Results Survey o10 question survey completed by Radiation Oncologists and Radiation Therapists involved in sarcoma planning after completing planning oRadiation Oncologists unanimously felt better able to delineate tumour from normal tissue with fusion oRadiation therapists felt fusion aided in their ability to prepare images (contour critical structures) in preparation for planning by Radiation Oncologists

23. Conclusions A Role for Fusion in Sarcoma Planning? oOne of first studies to formally evaluate use fusion for planning sarcomas oResults justify use of fusion oFusion allows Radiation Oncologists to define smaller more accurate volumes which may: odecrease dose to normal tissues oImprove tumour coverage oFusion increases consistency and reproducibility of treatment planning Results show the optimal modality for planning sarcoma is CT-MRI Fusion to ensure gross disease appropriately represented

24. Thank you oCTOS Abstract Review Committee oBCCA Musculoskeletal Tumour Group oDr. C. Candish oDr. K. Goddard oDr. C. Grafton oDr. L. Weir oDr. C. Keogh (Radiology) oC. Marlowe, K. Dahle, C. Mengerink (Radiation Therapy) oV. Morovan (Statistics) “Imaging Matters”

25. Questions?

26. Supplementary Slides

27. Results CT with Bowel Contrast CT with ContrastMRI

28. Results CT with IV Contrast CT with ContrastMRI

29. Results Imaging and Registration Registration Error Patient # MRI Typeavg error (cm)max error (cm) 1T2FS0.150.33 2STIR0.340.41 3T1FS0.280.61 4T2FS0.260.38 5T2FS0.310.63 6T2FS0.40.77 7T2FS0.570.79 8T2FS0.160.23 9T2FS0.280.45 0.3055560.511111 MRI slices 5mm

30. Results Contoured Tumour Volumes CT Fuse

31. Results Contoured Tumour Volumes PTV’s CT Fuse

32. Results Underestimate Tumour Extent

33. Results Contoured Tumour Volumes

34. Results Gross Tumour Volumes by Observer

35. Results Gross Tumour Volume By Patient

36. Results Mean Gross Tumour Volume By Patient oCT volumes 1.2 times larger then fusion, p=0.04

37. Results Mean PTV By Patient

38. Results Measuring Variation

39. Results MEAN X,Y,Z Variation CT Fusion avgSDavgSD med3.741.123.630.4 lat-4.441.63-4.280.4 ant4.930.74.30.4 post-3.911.4-3.780.6 sup7.431.86.570.8 inf-72.36-6.280.8 Standard Deviation smaller for fusion all directions All dimensions smaller for Fusion (sup/inf most significant)

40. Results Variation Superior to Inferior

41. Results Medial and Lateral Variation ct fuse medlat medlat 6-5.5 5-4 1-1.5 1-2 3-2.67 3-2 3.333-6.33 5.2-5 2-2.67 0-3.167 1.333-1.83 1.3-3 6-6 5.5-7.333 5-5.5 4.7-5 6-8 7-7 3.741-4.44 3.6-4.278

42. Results Completion Survey Survey completed for each image set at completion of contouring (N=88) Linear Analog Rating Scale Rate the general quality of this CT (fusion) image set? (1 – poor, 5-meets expectations, 10 – exceeds expectations) oCT score 4.9, Fusion 6.7 oBoth image sets were “acceptable” for contouring Rate the quality of this CT (fusion) image set for delineating: (1- can not delineate to 10 –exceeds expectations) a. Tumor volume oCT 4.0, Fusion 7.8 b. Critical Structures oCT 4.2, Fusion 7.4 Indicates Subjectively “Better" Delineation of Tumour and Critical Structures with Fusion

43. Results Radiation Oncologists Completion Survey Using a linear analog scale (poor to exceeds expectations) rate the quality of this CT (fusion) image set for delineating: Tumour Volumes oCT 4.0, Fusion 7.8 Fuse CT Fuse CT Normal Tissues  CT 4.2, Fusion 7.4 Improved Delineation of Tumour and Normal Structures with Fusion poor meets expectations exceeds

44. Results Radiation Therapists Opinions 8 question survey for Radiation therapists (n=4) involved in sarcoma fusions 1.Average time for fusion o35.5 minutes 2.Usefulness of Fusion for delineating normal structures oExtremely useful 3.Difficulty of Performing Fusions compared to other sites oSlightly more difficult, (extremities the most difficult) 4.Important factors in image fusion oTumour location, MRI quality, time available oIMMOBILIZATION and Position

45. Conclusions A Role for Fusion in Sarcoma Planning? oCT/MRI fusion is valuable to the planning process for sarcoma oContoured Tumour Volumes oMore normal tissue included in the target volumes with CT oDisease excluded on CT oVolume Variation oMore consistency in contours with Fusion oCompletion Survey oRadiation Oncologists and Therapists felt fusion was valuable