Applications of Modern Radiotherapy Systems

Transcription

1 Applications of Modern Radiotherapy Systems Thomas Rockwell Mackie Professor University of Wisconsin Co-Founder and Chairman of the Board TomoTherapy Inc.

2 Financial Disclosure I am a founder and Chairman of TomoTherapy Inc. (Madison, WI) which is participating in the commercial development of helical tomotherapy.

3 Acknowledgements John Schreiner Jerry Battista Tim Holmes Gustavo Olivera Weiguo Lu Katja Langen Paul Keall David Shepard Cedric Yu Thomas Bortfeld An Liu Chet Ramsey

4 Outline Setup correction for interfraction motion Off-line adaptive techniques On-line adaptive strategies Modern Delivery methods Treatment Planning Issues Delivery time Novel clinical applications Clinical impact

5 Dose Sculpting and Painting 3-D Conformal Dose 2-D Planning Painting IMRT Courtesy of John Schreiner, Kingston Regional Cancer Centre, Ontario

6 Why 3D Image-Guided Radiotherapy (IGRT)? Eventually, most curative radiotherapy will be IMRT, even many palliative treatments, e.g., retreatments. All IMRT should be image-guided: IMRT is justified by sparing critical tissues (conformal avoidance) which produces higher dose gradients. IGRT enables higher gradients to be delivered safely and effectively. IGRT enables a smaller setup margins to be defined. In some radiotherapy sites, e.g., prostate, IGRT may be more important than IMRT. 2D imaging is inadequate to obtain volume information.

7 If you can t see it, you can t hit it If you can t hit it, you can t cure it From Jerry Battista

8 Radiotherapy Time Scales Intra-fractional time scale respiratory, cardiac motion digestive system motion bowel/ bladder filling Inter-fractional time scale random/ systematic setup errors tumor growth and shrinkage weight gain and loss time second minute hour day week

9 Is Daily Imaging Necessary? Translational Setup Error by Disease Site Rotational Setup Error by Disease Site 7.0 systematic random.4 systematic random 6.0 lateral longitudinal.2 roll vertical Error (mm) Error (degrees) Brain H&N Lung Prostate Brain H&N Lung Prostate Disease Site Disease Site Translational corrections smaller for brain and H&N than for lung and prostate treatments Rotational corrections greater for brain and H&N than for lung and prostate Shows that when we image, we do make shifts. Does this improve outcomes? Can we use this to image less?

10 Residual Errors For Imaging Protocols % Times Error Occurs Error As a Function of % Days Image Guidance Used Never Weekly % Image Guidance Every second day Every day Error > 3 mm Error > 5 mm Error > 0 mm Small residual uncertainty Head and Neck Adapted from Zeidan et al, Int. J. Radiat. Oncol. Biol. Phys. 2007; 67:

11 Off-line Adaptive Techniques Dose verification and replanning Dose reconstruction Deformable registration of contours and dose distributions Dose trending

12 3-D Imaging Off-Line Adaptive Optimized Planning Deformable Dose Registration Dose Reconstruction Radiotherapy Treatment Pre-Delivery Imaging Setup Adjustment

13 Quantitative Imaging for Adaptive Therapy Quantitative images are required for many Adaptive Therapy Processes: Delivery Verification. Dose Reconstruction. Deformable Dose Registration. Re-optimization. All of these can be achieved with tomotherapy s CT images.

14 Dose Verification Recomputing Dose Re-calculated plan with shifted target Patient courtesy of Tim Holmes, St. Agnes Cancer Center Baltimore, MD

15 Clinical Adaptive Planning Planed Dose to the PTV Delivered Dose to the PTV Per-fraction DVH Planned Max Cord Dose Max Cord Dose with Existing Plan Re-calculated plan with shifted target Patient courtesy of Tim Holmes St. Agnes Cancer Center Baltimore, MD

16 Replanning Planed Dose to the PTV Delivered Dose to the PTV Per-fraction DVH Planned Max Cord Dose Max Cord Dose with Existing Plan Max Cord Dose with Revised Plan Revised Plan DVH for remaining fractions Revised plan for remaining fractions Patient courtesy of Tim Holmes, St. Agnes Cancer Center Baltimore, MD

17 Original planning CT Reference CT Daily CT Daily CT mapped to Reference CT Original Planning CT

18 Original planning CT Reference CT Daily CT Daily CT mapped to Reference CT

19 Original planning CT Reference CT Daily CT Daily CT mapped to Reference CT

20 Accuracy of Automatic H+N MVCT contours Parotids: Visual inspection of automatic contours kvct contours: MVCT contours:

21 MVCT to kvct Deformable Image Registration kvct: PTV Cord MVCT: PTV Cord

22 Accuracy of Automatic H+N MVCT Contours Spinal Cord: Automatic vs. manual contours Compare dose-based end points: D max, D mean Dose (Gy).4.2 D max Dose (Gy) D mean Automatic Manual Treatment fraction 0.6 Automatic Manual Treatment fraction 3 patients: Dmax %difference: % Dmean %difference: % Langen et al., AAPM, 2006

23 st fraction Trending

24 Cont. to 35 fractions Trending

25 Re-plan at 20 fractions Trending

26 On-line Adaptive Techniques Detection of intrafraction motion Methods of motion management Gating Tracking Delivery modification

27 Lung Motion Dynamics Motion close to diaphragm Motion lower chest Motion mid lung Motion tumor at center The motion can be complex

28 Lung Motion Dynamics

29 Navotek RealTrack System Fine radioactive wire is implanted in the patient. Can see the wire on IGRT systems. Can track wire position in real time.

30 Calypso System Electromagnetic transponders are implanted in the patient. Can see the transponder on IGRT systems. Can track transponder position in real time.

31 Degradation of Alignment Quality after Initial Setup for Prostate Cancer 7 patients 55 Calypso sessions Mean: 32 tracks per patient Precentage of observations Percentage of displacements observed over time after initial alignment >3 mm >5 mm >7 mm >0 mm Time (minutes) Courtesy of Katja Langen, M.D. Anderson Cancer Center, Orlando, FL

32 MRI-Guided Systems for Real Time Imaging View Ray Utrecht Alberta

33 Motion Management Margin: Put an ITV on a CTV Breath holding: Either active or passive Gating: Not very efficient Tracking: Move the patient or move the beam Delivery Modification: Can also handle non-rigid motion

34 The Breathing Cycle Exhalation Gating Paradigm Assumes no motion in gated portion Loss of Efficiency Inhalation Inhalation

35 Motion Management (4D Planning and Delivery) Treating while the patient breathes is more accurate as compared to tracking, and saves time as compared to gating. Works in Progress

36 Nemo Demo Motion Surrogate Nemo Static Tank

37 Fish Represents a Moving Tumor

38 How Necessary is Motion Management? Magnitude of Motion < 5 mm > 5mm < cm > cm Not Needed Not Needed Not Needed Small Fraction, Including Margin, of OAR Volume Not Needed Perhaps Needed Likely Needed Medium Fraction of OAR Volume Tumor Size Not Needed Not Needed Perhaps Needed Large Fraction of OAR Volume

39 Why IMRT Is Needed 5 IMRT beams is more conformal than 5 conformally-shaped beams. If uniform fields were sufficient, the pencil beam weights for each beam would be identical

40 Multileaf Collimators (MLC s) Conventional Binary Siemens Varian NOMOS Conventional MLC s were designed for field shaping and have limitations when used for IMRT. Binary (off-on) MLC s are designed for IMRT and are the easiest to model and provide high modulation.

41 Segmental MLC IMRT Step and shoot. Deliver multiple MLC apertures within a field to apply the intensity in a paint-by-number fashion. May be a straightforward technique for forward optimization. Little change in paradigm involved in field boundary verification using portal imaging. May be relatively time consuming if field delivery is verified in exactly the same way. Only discrete intensity levels can be delivered.

42 Segmental MLC IMRT Conventional MLC s have been designed for field shaping not IMRT. A set of leaf sequences to deliver an intensity modulated field.

43 Dynamic MLC IMRT Pairs of MLC leaves are in continuous movement across the field with the intensity at a point equal to the total exposure time of the leaf pair above it. Most efficient delivery for modest modulation of intensities. High spatial variation of intensities are difficult. Continuous intensity levels. Difficult to verify with conventional techniques as anatomic details blend into the continuous intensity levels.

44 Dynamic MLC Leaf Motion From Paul Keall, Stanford University

45 Intensity Modulated Arc Therapy (IMAT) Collimator leaves move dynamically as the gantry rotates. Beams delivered from all coplanar directions. Requires multiple arc deliveries to achieve intensity modulation. Provided field length is not too long, no couch translations are necessary. Proposed by Cedric Yu and implemented by Wilfried DeNeve (Ghent, Belgium). Single arc IMAT is branded VMAT or RapidArc and also changes the dose rate during the rotation to achieve some limited modulation.

46 IMAT Field shape changes dynamically during rotation. Needs multiple rotations.

47 IMAT Intensity Levels Following Equation is from Cedric Yu: i= 2 n i is the number of non-zero intensity levels. n is the number of rotations. One Rotation IMAT Two Rotation IMAT Three Rotation IMAT n = n = 2 n = 3 i 3 7

48 Example of 3 IMAT Rotations 3 Separate Rotations with Different Intensities Per Rotation From David Shepard And Cedric Yu Yields 7 Unique Non- Zero Intensity Levels

49 Tomotherapy Tomotherapy is intensity modulated rotational therapy with a fan beam of radiation and is analogous to a CT scanner. It utilizes a binary collimator to provide the modulation. Serial tomotherapy was first form of IMRT In helical tomotherapy, the gantry and couch move simultaneously.

50 TomoTherapy HI-ART Unit Control Computer Gun Board Linac Shown Without Shielding Circulator Magnetron High Voltage Power Supply Beam Stop Detector Pulse Forming Network and Modulator Data Acquisition System

51 How the Intensity is Modulated with Tomotherapy One Rotation is Divided into Angular Segments Called a Projection Closed For Low Intensity A Leaf Is Open for a Short Time During The Projection Open For High Intensity A Leaf Is Open for a Long Time During The Projection Binary leaves were specifically designed for IMRT.

52 Sample Sinogram A delivery sinogram is a representation of the energy fluence delivered to the patient. The energy fluence distribution is the realization of the sinogram and takes into account photon attenuation. Angle Collimator Position

53 A Sinogram Specifies the Relation Between Collimators and Voxels Gantry Angle Collimator Index

54 Helical Delivery Sinogram The delivery sinogram specifies the intensity (or leaf opening time) as a function of gantry angle. Collimator Index Gantry Angle Darker Is Higher Intensity or Longer Opening Time Avoidance Of Normal Tissue Example with 3 Rotations

55 IMRT Requires Optimization Hard Constraints cannot be violated may not lead to a feasible solution Soft Constraints constraints may be violated find optimal intensity profile may lead to a local minimum

56 Beamlet-Based Optimized Planning Two-step approach to treatment planning:. Fluence map optimization Delivery constraints ignored 2. Leaf sequencing Accounts for delivery constraints Employed by nearly all vendors. Corvus (NOMOS) Eclipse (Varian) XiO (CMS) Pinnacle (Philips) Oncentra (Nucletron) Hi-Art (TomoTherapy)

57 Field Divided into a Grid of Beamlets From Cedric Yu, U. of Maryland

58 Optimized Fluence Map From Cedric Yu, U. of Maryland

59 Leaf Sequencing Optimized Fluence Map Deliverable Apertures From Cedric Yu, U. of Maryland

60 Beamlet IMRT Approach for Conventional MLC IMRT Clinical Objectives, Constraints Intensity Maps MLC Segments From Cedric Yu, U. of Maryland

61 Aperture-Based IMRT Clinical Objectives, Constraints Shepard, Earl, Li, Naqvi, Yu Direct aperture optimization Med. Phys. 29(6):007-08, 2002 MLC Segments From Cedric Yu, U. of Maryland

62 Delivery Type Dictates Ideal Optimization Type Delivery Type Ideal Optimization Type Beamlet Aperture SMLC (Step and Shoot) X IMAT X DMLC (Dynamic MLC) X Tomotherapy (Binary MLC) X

63 Inadequate spatial (pixel) resolution. Inadequate angular sampling Inadequate intensity sampling.

64 Spatial and Angular Resolution Angular sampling interval, Φ dominates image resolution at the periphery of an axial image. Pixel size, l dominates image resolution at the center. Φ l FOV

65 Angular Sampling Required for CT # Views / 360 o = π FOV l FOV is the field of view. l is the spatial resolution. Requirement Small FOV FOV = 20 cm l = 0. cm 630 views Large FOV FOV = 40 cm l = 0. cm 260 views

66 Angular Sampling Required for Radiotherapy # Views / 360 o = π FOV l FOV is the field of view (max field width) l is the spatial resolution (collimator resolution) Requirement Conv. IMRT FOV = 5 cm l = 0.5 cm 25 views Tomotherapy FOV = 40 cm l = 0.6 cm 5 views

67 Brahme s Classic 982 Paper on Rotational IMRT Rotating Source Phantom Dose Target OAR Fluence From Tomas Bortfeld

68 Sufficient Modulation and Beam Numbers Are Needed to Construct Dose Notice the High Degree of Modulation mm mm mm Beam 5 Beams Beams Required Even if Rotation is Used 7 Beams 25 Beams 5 Beams mm mm mm

69 Discretization Error Following Equation is from Imaging Theory: σ = 2 i N i is the number of non-zero intensity levels. N is the number of beam directions. Step and Shoot IMRT Single Arc VMAT Helical Tomotherapy i = 5 i = i = 00 N = 7 N = 80 N = 5 S.D. Error 2.2% 2.2% 0.04%

70 Conventional IMRT Delivery Time Analysis From Sha Chang, UNC Average Tomo

71 Tomo s Time In Room and Treatment Time Ave = 7 min Ave = 5 min Other studies have put the average beam on time at 7 minutes for tomotherapy Depends on the amount of modulation Shorter tumors like prostate have shorter beam on time Longer tumors like cranial spinal have longer beam on times Treatment Time = Beam on Time = Time for Treatment Irradiation

72 Re-Treatments Re-treatments, using tomotherapy for patients not eligible for conventional photon radiation therapy due to cord tolerance. Patients courtesy of UAB

73 Complex Abdominal/Pelvic Heidelberg University Clinic

74 Craniospinal Tomotherapy Traditional

75 Craniospinal Tomotherapy Traditional

76 Total Marrow Irradiation (TMI) Conformal Avoidance of: Brain Thyroid Lungs Liver Kidneys Small Bowel From Dr. An Liu, City of Hope, Duarte CA

77 Strategy for Conformal Avoidance Radiotherapy Use generous treatment volumes. Outline normal sensitive tissues and concentrate on avoiding them. Use image-guidance to assure that the normal tissues are being avoided. Conformal avoidance radiotherapy is the complement of conformal radiotherapy. If you can t see it you can t avoid it. If you can t avoid it you can t spare it.

78 With Better Avoidance of Normal Tissue is Hypofraction Possible? In prostate CA, the tumor may repair even better than the normal tissues. In lung CA, rapid proliferation reduces the treatment control probability as the treatment is extended in duration. Provided better avoidance of sensitive tissues is maintained, fewer fractions of higher dose/fraction will provide both better tumor control and be less expense to deliver. Carefulness can be cost effective.

79 Image-Guided Radiotherapy of the Future Image-based staging of the primary and regional field. Determine hypoxic and highly proliferative regions using bioimaging and paint in higher dose. Conformally avoid sensitive structures in the regional field. IMRT with 3-D image verification. Less fraction quantity greater fraction quality. Adaptive radiotherapy to provide patient-specific QA of the whole course of therapy.

80 Image-Guided Radiotherapy of the Future (Cont.) Image-based monitoring of outcome. e.g., PET scans for regional or metastatic development using a priori information. Aggressive treatment of recurrences or distant metastases using conformal avoidance to spare critical structures. Better QA of first treatment will allow safer retreatments. Weeding the garden with image-guided radiotherapy and prevent spread with chemotherapy and immunotherapy.

81 Oligometastases or Weeding the Garden Following definitive radiotherapy with local control we often have metastatic progression. Chemotherapy (analogous to pre-emergent herbicides) is known to be effective against 00 to 000 cell tumorlets. With PET it is possible to infer the presence of tumorlets with 00,000 to,000,000 labeled cells. Perform PET scan followups to catch the emergent tumorlets. Weed with conformal avoidance hypofractionated radiotherapy before they can seed more metastases. Keep careful track of the cumulative dose delivered so the process can be repeated several times if necessary.

82 Treating Multiple Metastases Determined From PET Scans Tomotherapy Treatment Plan PET-CT Scans Planned Using PET-CT Courtesy of Chet Ramsey, Thompson Cancer Survival Center

83 Visualization Gap Targeted Agents Effective Chemotherapy Effective Visualization Gap External Beam Radiotherapy Effective MR/CT Tumor Visualization PET Tumor Visualization Tumor Cell Density (cells/cm 3 ) 0 0

84 Implications of the Visualization Gap Systemic agents are effective for tiny tumorlets. Larger tumorlets may shrink so that they are not visible but they are likely to return. Systemic agents are more effective when no tumorlets are visible, i.e., used as a prophylaxis agent. Radiation therapy is effective for much larger tumors If imaging systems were sensitive for smaller tumors, radiation therapy could be used systemically. Systemic agents should aim for higher cell kill. If the tumor size range of systemic agents and radiation therapy could overlap, cancer could be made a chronic disease.

85 Conclusions Setup corrections can correct for translations and rotations. Adaptive therapy accounts for changes in the patient. Motion management can accommodate for breathing and organ filling. IMRT and rotational therapy will dominate curative treatments The type of optimization depends on the type of delivery. IMRT takes more time than conventional radiotherapy Treatments not possible with conventional radiotherapy are being done. Conformal avoidance enables hypofractionated treatments.