1. IGRT Robotica G.Beltramo Centro Diagnostico Italiano Varese 13 Giugno 2009

2. Image-Guided Radiation Therapy “Any use of imaging within the radiation treatment room, to improve the precision of radiation-therapy delivery” “Use of any planar imaging, volumetric imaging, or volumetric ciné imaging, marker localization, marker tracking, patient surface imaging, patient surface tracking to improve the precision of radiation therapy delivery.” “ IGRT is the process of in-room imaging that guides the radiation delivery.”

3. Focus: Image guided RT Intervention Three essential steps: Acquire an image Acquire the positional information of the target, target surrogates, or avoidance structures Obtain “target” registration error Image registration Deviations from the original plan Perform an intervention Correction strategies – Inter fraction/intra fraction, online/offline etc.

5. Advances in radiation technology

7. Stereotactic Radiosurgery System CyberKnife® In 1991 Jonh Adler, an american neurosurgeon, develop a delivering stereotactic radiosurgery system without the need for rigid immobilization

8. CyberKnife® Robotic Radiosurgery Non-coplanar treatment delivery Total of more than 1500 different beams Delivery of 150 to 200 uniquely angled beams per fraction Image courtesy of Georgetown University Hospital

9. Need X ray vision! The target volume is located on X rays (orthogonal or stereoscopic) with fiducial markers or without them (if the target volume can be seen on X rays) The images are to be fused and registered with the pretreatment DRR’s The required shifts are calculated using customized software. Shifts are made

10. Dx X-Ray Sources Amorphous Silicon Detectors Cyberknife (CK) therapy. CK (Accuray, Inc., Sunnyvale, California) is an image guided, frameless, radiotherapy device with a compact linear accelerator installed on an industrial-derived robotic arm, The intelligent arm has the capability of rotating around 6 axes with millimetric accuracy allowing a stereotactic radiosurgery (SRS) with high radiation doses to relatively small lesions. The treatment unit can verify target position with a real-time tracking during radiation delivery using two kV X-ray sources mounted on the ceiling and two amorphous- silicon image detectors mounted on the floor on either side of the patient in an orthogonal geometry to detect bony landmarks or fiducial markers within or near the target. The targeting system continuously acquires radiographs that are compared with the digitally reconstructed radiographs (DRR) derived from the treatment planning CT scans to update the changes in target position which are compensated by adjusting the aim of the robotic arm [ ]. Stereotactic Radiosurgery System CyberKnife®

11. Flowchart of the patient set up and delivery process in Cyberknife treatment Cyberknife data acquisition Image guidance Stereographic X-ray images are compared with DRRs or fiducial positions Robot corrects after each stereographic X-ray image acquisition Robot can correct: ± 10 mm all components ± 1º roll ± 1º pitch ± 3º yaw

12. Planar X Rays (2D+) Advantages – Fast image acquisition (single or fluoroscopic modes) – High temporal resolution – Tracking – Beam by beam correction – Motion management Disadvantages – Use of target surrogates (in most situations) – Obstructions in image viewing angles (anatomies or couch support in the beam path) – Not easy to reconstruct 3D dose distributions “On-line Correction” Analysis of images and/or related data for potential corrections of the delivery of the current fraction (i.e. analysis performed while the patient is still on the treatment couch). Y X-ray source B Pit ch Image A Image B X-ray source A Cam era A Cam era B

13. Verification of treatment accuracy Skull may be good surrogate for brain

14. Bone or marker??? spine bone poor surrogate for extracranial cancer Verification of treatment accuracy

15. Accuracy of radiotherapy delivery depends on the visualisation of implanted gold fiducials at the time of treatment and comparison with references images obteined during treatment planning,. The advantage of Cyberknife tracking sistem is to verify in every step of treatment the real position of neoplstic target and the possibility to adjust the aim of robotic arm if the target position change during radiotherapy treatment

16.  Total error in patient pose is dependent on the number of fiducials being tracked  3 fiducials significant improvement in targeting accuracy  > 6 fiducials adds little more improvement  Error in translations unaffected by spacing  Error in rotation is  50% by doubling the distance between fiducials Accuracy of fiducial targetting

17. Rigid body constraint Distances between like fiducials compared

18. Histogram of prostate volume as a function of time duration and shift

19. Accuracy of fiducial targetting Percentage of data set of having a movement as a function of time Rigid body error curve of three fiducials for four rappresentative patients

20. Inter-fractional motion of the prostate during hypofractionated radiotherapy CDI Cyberknife experience

21. Real Time Imaging Imaging with a temporal resolution that’s sufficient to capture the trajectory of a moving or changing subject. Real time IGRT correction refers to frequent imaging while the treatment is being delivered, with repositioning based on that imaging. real-time monitoring of any parameter must be fast enough to modify the treatment in order to account for the impact of that parameter on treatment.

22. State of the art in room techniques for respiratory motion management Technologies available Optical MV/EPI kV X ray kV/MV/Optical 4D CBCT/CT Electromagnetic Ultrasound MRI

23. Respiratory Guided Radiation Therapy moving the treatment beam as the target moves Infrared LED-camera system records the respiration cycle Real time

24. Motion management methods

25. CyberKnife® Robotic Radiosurgery Accuracy – Total targeting accuracy Targets not affected by respiration: 0.5 millimeter** Targets that move with respiration: 0.7 millimeter*** – Targeting accuracy sustained throughout the treatment ** Muacevic, A., Staehler, M., Drexler, C., Wowra, B., Reiser, M. and Tonn, J. Technical description, phantom accuracy and clinical feasibility for fiducial-free frameless real-time image-guided spinal radiosurgery. J Neurosurgery Spine. Xsight accuracy specification of.95 mm. *** Dieterich S, Taylor D, Chuang C, Wong K, Tang J, Kilby W, Main W. The CyberKnife Synchrony Respiratory Tracking System: Evaluation of Systematic Targeting Uncertainty. Synchrony clinical accuracy specification of 1.5 mm for moving targets *Kuka KR240-2 Specification 04.2004.05

26. Individually fitted vacuum pillow Device for diaphragm compression (breathing tumor movements >10 mm at fluoroscopy) Laser system for tattoos Patient fixation - Stereotactic Elekta ® Body Frame

27. Methods to avoid geographic miss - ITV (abd compression), breath hold (ABC), gating, and tracking

28. Cyberknife Radiosurgery : clinical rationale

29. Take Home Messages (Target Delineation) With robotic IGRT, treatment precision may be improved: More accurate contours are REQUIRED Inaccurate contours could introduce unexpected target miss or increased toxicities

30. Day 0: fiducial insertion Day 7: treatment planning TC. fiducial migration Day 10: missing Use For Tracking  Cannot be extracted  Migration  Obscured

31. Inaccurate target delineation

32. IMAGE FUSION TC-RM Clinical use of this tecnique for treatment planning has resulted in improvements in localization of treatment volumes and critical structures in the brain Kessler M.L.1991 Lattanzi J.P.1997 Use CT for geometric accuracy Use RM for target delineation

33. Image guidance facilitates targetting TC-MRI image Fusion

34. MRI for Target Delineation Advantages Superior soft tissue image quality For some tumors - greater sensitivity Greater accuracy - delineation of some normal tissues Functional information – normal tissues Biological information – TME, blood flow, hypoxia No radiation dose Disadvantages Lack of specificity for tumor vs. other pathological states Multiple effects that can lead to image distortion Does not provide relative radiation attenuation Requires fusion of grayscale images with CT dataset Motion artifact Cost

35. 3D CRT and IMRT aim to achieve better locoregional control and improve survival by radiation dose escalation, but such techniques demand more accurate localization of tumor and surrounding normal tissues

36. Imaging in Target Delineation Use of PET imaging to reduce interobserver variations in contouring STEENBAKKERS et al., IJROBP, Vol64, pp435, 2006 PET in Target Definition Do SUVs mean anything?

37. Uncertainties in Manual Volume Alignment Differences in Image Interpretation Inter-observer variation Contours may not be drawn perfectly One person’s alignment may not agree with another person’s judgment Impact of organ deformation Imperfect alignment

38. SBRT theoretical basis

39. Operable lung cancer patients  Extent of resection impacts local control (e.g., wedge vs. lobectomy – LCSG trial)  Local control impacts survival Goal with SBRT in inoperable patients should be very high local control until proven otherwise At treatment After 3 monthsAfter 12 months

40. Large Japanese Study (Onishi, 2007) SBRT for early stage lung carcinoma Indiana phase I trial

42. SBRT toxicity

43. Respect Normal Tissue Constraints

45. Organ at risk dose coinstrain

47. 12 months post SBRT 3 months post SBRT 6 months post SBRT Respect Normal Tissue Constraints GRADE II GRADE III GRADE IV

49. Local Therapy and Image-Guidance Radiation therapy is a proven local therapy. Increased precision in therapy offers: – Reduce severity and risk of therapy-induced complications. – Increase both quality and probability of success. Further potential: – Broaden application of proven therapies. – Permit new therapies that are intolerant to geometric imprecision. Addressing geometric uncertainties may expose other factors determining outcome.

50. Not a single IGRT solution can correct all sources of uncertainties Systematic Random Inter-fractional Intra-fraction Shape Variations Time Trends

51. The living patient and the dynamic treatment problem What could possibly go wrong and how could that happen? Inadequate implementation of IGRT technology for the treatment site What effects would such a failure produce?  Suboptimal treatment  Failure to control cancer  Increased toxicities  Waste of resources

52. Clinical benefit of image guided robotic radiotherapy Stereotactic body radiotherapy (SBRT) is the Latest Generation of “Targeted “ therapies for radiation