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New techniques-in-radiotherapy-1194294751859014-3


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New techniques-in-radiotherapy-1194294751859014-3

  1. 1. New Techniques inRadiation therapy Moderator: Dr S C Sharma Department of Radiotherapy PGIMER Chandigarh
  2. 2. Trends Number of Publications in Google Scholar2500200015001000 500 0 1990 1995 2000 2005 3 DCRT IMRT IGRT
  3. 3. Overview 3 DCRT IMRT Teletherapy IGRT DART Tomotherapy Gamma KnifeRadiation Stereotactic radiotherapy LINAC basedTherapy Cyberknife Image Assisted Brachytherpy Brachytherapy Electronic Brachytherapy
  4. 4. Solutions ? Electrons Protons Neutrons Use alternative radiation Develop technologies to circumvent limitations modalities π- Mesons Heavy Charged Nuclei Antiprotons
  5. 5. Development TimelineTakahashi discusses conformal RT 1950 1st MLCs invented (1959) Proimos develops gravity oriented 1960 blocking and conformal field shaping Tracking Cobalt unit invented 1970 at Royal Free Hospital 1st inverse planning algorithm Brahame conceptualized inverse planning 1980 developed by Webb (1989) & gives prototype algorithm for (1982-88) Boyer and Webb develop Carol demonstrates NOMOS MiMIC (1992) principle of static IMRT (1991) Tomotherapy developed in Wisconsin (1993) 1990 Stein develops optimal dMLC equations First discussion of Robotic (1994) IMRT (1999)
  6. 6. Modulation: Examples Block: Wedge: Binary Modulation Uniform ModulationCoarse spatial and Fine spatialCoarse intensity coarse intensity Fine Spatial and Fine Intensity modulation
  7. 7. Conformal Radiotherapy Conformal radiotherapy (CFRT) is a technique that aims to exploit the potential biological improvements consequent on better spatial localization of the high- dose irradiation volume - S. Webb in Intensity Modulated Radiotherapy IOP
  8. 8. Problems in conformation  Nature of the photon beam is the biggest impediment  Has an entrance dose.  Has an exit dose.  Follows the inverse square law.
  9. 9. Types of CFRT  Two broad subtypes :  Techniques aiming to employ geometric fieldshaping alone  Techniques to modulate the intensity of fluence across the geometrically- shaped field (IMRT)
  10. 10. Modulation : Intensity or Fluence? Intensity Modulation is a misnomer – The actual term is Fluence Fluence referes to the number of “particles” incident on an unit area (m-2)
  11. 11. How to modulate intensity Cast metal compensator Jaw defined static fields Multiple-static MLC-shaped fields Dynamic MLC techniques (DMLC) including modulated arc therapy (IMAT) Binary MLCs - NOMOS MIMiC and in tomotherapy Robot delivered IMRT Scanning attenuating bar Swept pencils of radiation (Race Track Microtron - Scanditronix)
  12. 12. Comparision
  13. 13. MLC based IMRT √
  14. 14. Step & Shoot IMRT  Since beam is interrupted between movements leakage radiation is less.  Easier to deliver and plan.  More time consumingIntesntiy Distance
  15. 15. Dynamic IMRT  Faster than Static IMRT  Smooth intensity modulation acheived  Beam remains on throughout – leakage radiation increased  More susceptible to tumor motion related errors.  Additional QA required for MLC motion accuracy.Intesntiy Distance
  16. 16. Caveats: Conformal Therapy Significantly increased expenditure:  Machine with treatment capability  Imaging equipment: Planning and Verification  Software and Computer hardware Extensive physics manpower and time required. Conformal nature – highly susceptible to motion and setup related errors – Achilles heel of CFRT Target delineation remains problematic. Treatment and Planning time both significantly increased Radiobiological disadvantage:  Decreased “dose-rate” to the tumor  Increased integral dose (Cyberknife > Tomotherapy > IMRT)
  17. 17. 3D ConformalRadiation Planning
  18. 18. How to Plan CFRT Patient positioning Volumetric Data Image Transfer and Immobilization acqusition to the TPS Target Volume DelineationTreatment QA Treatment Delivery Forward Planning Inverse Planning Dose distribution 3D Model Analysis generation
  19. 19. Positioning and Immobilization Two of the most important aspects of conformal radiation therapy. Basis for the precision in conformal RT Needs to be:  Comfortable  Reproducible  Minimal beam attenuating  Affordable Holds the Target in place while the beam is turned on
  20. 20. Types of Immobilization Invasive Frame based NoninvasiveImmoblization devices Frameless ➢Usually based on a combination of heat deformable “casts” of the part to be immobilized attached to a baseplate that can be reproducibly attached with the treatment couch. ➢The elegant term is “Indexing”
  21. 21. Cranial Immobilization BrainLab System TLC System Leksell Frame Gill Thomas Cosman System
  22. 22. Extracranial Immobilization Body Fix system Elekta Body Frame
  23. 23. Accuracy of systems System Techniqe Setup Accuracy Noninvasive Non invasive, 0.7– 0.8 mm (± 0.5–0.6 mm)Stereotactic frame mouthpiece Non invasive, x = 1.0 mm ± 0.7; y= 0.8 mm ± 0.8; z = 1.7 Latinen Frame nasion, earplugs mm ± 1.0 Non invasive, X = 0.35 mm ± 0.06; Y = 0.52 mm ± 0.09; GTC Frame mouthpiece Z= 0.34 mm ± 0.09Stereotactic Body Non invasive, X = 5 – 7 mm ,Y = 1 cm Z = 1.0 cm (mean) Frame vacccum based Non invasive,Heidelberg frame X = 5 mm,Y = 5 mm, Z = 10 mm (mean) vaccum based Non invasive, X = 0.4 ± 3.9 mm , Y = 0.1 ± 1.6 mm Z = 0.3 Body Fix Frame Vacccum based ± 3.6 mm. Rotation accuracy of 1.8 ± 1.6 with plastic foil degrees. With the precision of the body fix frame the target volume will be underdosed (< 90% of prescribed dose) 14% of the time!!!
  24. 24. CT simulator  70 – 85 cm bore  Scanning Field of View (SFOV) 48 cm – 60 cm – Allows wider separation to be imaged.  Multi slice capacity:  Speed up acquistion times  Reduce motion and breathing artifacts  Allow thinner slices to be taken – better DRR and CT resolution  Allows gating capabilities  Flat couch top – simulate treatment table
  25. 25. MRI Superior soft tissue resolution Ability to assess neural and marrow infiltration Ability to obtain images in any plane - coronal/saggital/axial Imaging of metabolic activity through MR Spectroscopy Imaging of tumor vasculature and blood supply using a new technique – dynamic contrast enhanced MRI No radiation exposure to patient or personnel
  26. 26. PET: Principle Unlike other imaging can biologically characterize a leison Relies on detection of photons liberated by annhilation reaction of positron with electron Photons are liberated at 180° angle and simultaneously – detection of this pair and subsequent mapping of the event of origin allows spatial localization The detectors are arranged in an circular array around the patient PET- CT scanners integrate both imaging modalities
  27. 27. PET-CT scanner PET scanner Flat couch top insert CT Scanner 60 cm  Allows hardware based registration as the patient is scanned in the treatment position  CT images can be used to provide attenuation correction factors for the PET scan image reducing scanning time by upto 40%
  28. 28. Markers for PET Scans  Metabolic marker  2- 18 Fluoro 2- Deoxy Glucose  Proliferation markers  Radiolabelled thymidine: 18 F Fluorothymidine  Radiolabelled amino acids: 11 C Methyl methionine, 11C Tyrosine  Hypoxia markers  Cu-diacetyl-bis(N-4- 60 methylthiosemicarbazone) (60Cu- ATSM)  Apoptosis markers  99 m Technicium Annexin V PET Fiducials
  29. 29. Image Registration Technique by which the coordinates of identical points in two imaging data sets are determined and a set of transformations determined to map the coordinates of one image to another Uses of Image registration:  Study Organ Motion (4 D CT)  Assess Tumor extent (PET / MRI fusion)  Assess Changes in organ and tumor volumes over time (Adaptive RT) Types of Transformations:  Rigid – Translations and Rotations  Deformable – For motion studies
  30. 30. Concept
  31. 31. Process: Image Registration The algorithm first measures the degree of mismatch between identical points in two images (metric). The algorithm then determines a set of transformations that minimize this metric. Optimization of this transformations with multiple iterations take place After the transformation the images are “fused” - a display which contains relevant information from both images.
  32. 32. Image Registration
  33. 33. Target Volume delineation The most important and most error prone step in radiotherapy. Also called Image Segmentation The target volume is of following types:  GTV (Gross Target Volume)  CTV (Clinical Target Volume)  ITV (Internal Target Volume)  PTV (Planning Target Volume) Other volumes:  Targeted Volume  Irradiated Volume  Biological Volume
  34. 34. Target Volumes GTV: Macroscopic extent of the tumor as defined by radiological and clinical investigations. CTV: The GTV together with the surrounding microscopic extension of the tumor constitutes the CTV. The CTV also includes the tumor bed of a R0 resection (no residual). ITV (ICRU 62): The ITV encompasses the GTV/CTV with an additional margin to account for physiological movement of the tumor or organs. It is defined with respect to a internal reference – most commonly rigid bony skeleton. PTV: A margin given to above to account for uncertainities in patient setup and beam adjustment.
  35. 35. Target Volumes
  36. 36. Definitions: ICRU 50/62 GTV CTV  Treated Volume: Volume of the tumor and surrounding normal ITV tissue that is included in the isodose surface representing the irradiation TV dose proposed for the treatment (V95)  Irradiated Volume: Volume included in an isodose surface with PTV IV a possible biological impact on the normal tissue encompassed in this volume. Choice of isodose depends on the biological end point in mind.
  37. 37. Example PTV CTV GTV
  38. 38. Organ at Risk (ICRU 62)  Normal critical structures whose radiation sensitivity may significantly influence treatment planning and/or prescribed dose.  A planning organ at risk volume (PORV) is added to the contoured organs at risk to account for the same uncertainities in patient setup and treatment as well as organ motion that are used in the delineation of the PTV.  Each organ is made up of a functional subunit (FSU)
  39. 39. Biological Target Volume  A target volume that incorporated data from molecular imaging techniques  Target volume drawn incorporates information regarding:  Cellular burden  Cellular metabolism  Tumor hypoxia  Tumor proliferation  Intrinsic Radioresistance or sensitivity
  40. 40. Biological Target Volumes Lung Cancer:  30 -60% of all GTVs and PTVs are changed with PET.  Increase in the volume can be seen in 20 -40%.  Decrease in the volume in 20 – 30%.  Several studies show significant improvement in nodal delineation. Head and Neck Cancer:  PET fused images lead to a change in GTV volume in 79%.  Can improve parotid sparing in 70% patients.
  41. 41. 3 D TPS Treatment planning systems are complex computer systems that help design radiation treatments and facilitate the calculation of patient doses. Several vendors with varying characteristics Provide tools for:  Image registration  Image segmentation: Manual and automated  Virtual Simualtion  Dose calculation  Plan Evaluation  Data Storage and transmission to console  Treatment verification
  42. 42. Planning workflow Total Dose Total Time of delivery of dose Define a dose objective Total number of fractions Choose Number of Beams Organ at risk dose levels Choose beam angles and couch angles Choose Planning Technique Forward Planning Inverse Planning
  43. 43. “Forward” Planning A technique where the planner will try a variety of combinations of beam angles, couch angles, beam weights and beam modifying devices (e.g. wedges) to find a optimum dose distribution. Iterations are done manually till the optimum solution is reached. Choice for some situations:  Small number of fields: 4 or less.  Convex dose distribution required.  Conventional dose distribution desired.  Conformity of high dose region is a less important concern.
  44. 44. Planning Beams Digital Composite Beams Eye View Radiograph Display Rooms Eye View
  45. 45. “Inverse” Planning Inverse Planning 1. Dose distribution specifiedForward Planning 3. Beam Fluence modulated to recreate 2. Intensity map created intensity map
  46. 46. Optimization Refers to the technique of finding the best physical and technically possible treatment plan to fulfill the specified physical and clinical criteria. A mathematical technique that aims to maximize (or minimize) a score under certain constraints. It is one of the most commonly used techniques for inverse planning. Variables that may be optimized:  Intensity maps  Number of beams  Number of intensity levels  Beam angles  Beam energy
  47. 47. Optimization
  48. 48. Optimization Criteria Refers to the constraints that need to be fulfilled during the planning process Types:  Physical Optimization Criteria: Based on physical dose coverage  Biological Optimization Criteria: Based on TCP and NTCP calculation A total objective function (score) is then derived from these criteria. Priorities are defined to tell the algorithm the relative importance of the different planning objectives (penalties) The algorithm attempts to maximize the score based on the criteria and penalties.
  49. 49. Multicriteria Optimization Intestine Sliders for adjusting EUDBladder DVH display Rectum PTV GTV
  50. 50. Plan Evaluation Differential DVH Cumulative DVH Colour Wash Display
  51. 51. Image GuidedRadiotherapy and4D planning
  52. 52. Why 4D Planning? Organ motion types:  Types of movement:  Interfraction motion  Translations:  Intrafraction motion  Craniocaudal Lateral Even intracranial structures  can move – 1.5 mm shift  Vertical when patient goes from  Rotations: sitting to supine!!  Roll  Pitch  Yaw  Shape:  Flattening  Balloning  Pulsation
  53. 53. Interfraction Motion Prostate:  Rectum:  Motion max in SI and AP  Diameter: 3 – 46 mm  SI 1.7 - 4.5 mm  Volumes: 20 – 40%  AP 1.5 – 4.1 mm  In many studies decrease in volume found  Lateral 0.7 – 1.9 mm  SV motion > Prostate  Bladder: Uterus:  Max transverse diameter mean 15 mm variation  SI: 7 mm  SI displacement 15 mm  AP : 4 mm  Volume variation 20% - Cervix: 50%  SI: 4 mm
  54. 54. Intrafraction Motion Liver:  Lung:  Normal Breathing: 10 – 25  Quiet breathing mm  AP 2.4 ± 1.3 mm  Deep breathing: 37 – 55 mm  Lateral 2.4 ± 1.4 mm Kidney:  SI 3.9 ± 2.6 mm  Normal breathing: 11 -18  2° to Cardiac motion: 9 ± 6 mm mm lateral motion  Deep Breathing: 14 -40 mm  Tumors located close to the chest wall and in upper lobe Pancreas: show reduced interfraction motion.  Average 10 -30 mm  Maximum motion is in tumors close to mediastinum
  55. 55. IGRT: Solutions Imaging techniques USG based Video based Planar X-ray CT MRI ●BAT ●AlignRT ●Sonoarray ●Photogrammetry ●I-Beam ●Real Time Video guided Fan Beam Cone Beam ●Resitu IMRT ●Video substraction ●Tomotherapy ●In room CT MV CT KV CT ●Siemens ●Mobile C arm KV X-ray OBI ●Varian OBI ●Elekta ●Siemens Inline Gantry Mounted Room Mounted MV X-ray●Varian OBI ●Cyberknife EPI ●●Elekta Synergy ●RTRT (Mitsubishi)●IRIS ●BrainLAB (Exectrac)
  56. 56. IGRT: Solution Comparision DOF = degrees of freedom – directions in which motion can be corrected – 3 translations and 3 rotations
  57. 57. EPI Uses of EPI:  Correction of individual interfraction errors  Estimation of poulation based setup errors  Verification of dose distribution (QA) Problems with EPI:  Poor image quality (MV xray)  Increased radiation dose to patient  Planar Xray – 3 dimensional body movement is not seen  Tumor is not tracked – surrogates like bony anatomy or implanted fiducials are tracked.
  58. 58. Types of EPID Liquid Matrix Ion Chamber* Camera based devices Amorphous silicon flat panel detectors Amorphous selenium flat panel detectors Electrode High voltage applied connected to high voltage “Output” Output read out Liquid 2,2,4 - ionized liquid electrode by the lower trimethylpentane electrodes
  59. 59. On board imaging Intensifier Gantry mounted OBIKV Xray Room Mounted OBI
  60. 60. 4 D CT acqusition Axial scans are acquired with the use of a RPM camera attached to couch.The “cine” mode of the scanner is used toacquire multiple axial scans atpredetermined phases of respiratory cyclefor each couch position
  61. 61. RPM SystemPatient imaged with the RPM system to ascertain baseline motion profile A periodicity filter algorithm checks the breathing periodicity Breathing comes to a rythm Breathing cycle is recorded
  62. 62. 4D CT Data set Normal
  63. 63. Problems with 4 D CT The image quality depends on the reproducibility of the respiratory motion. The volume of images produced is increased by a factor of 10. Specialized software needed to sort and visualize the 4D data. Dose delivered during the scans can increase 3-4 times. Image fusion with other modalities remains an unsolved problem
  64. 64. 4D Target delineation Target delineation can be done on all images acquired. Methods of contouring:  Manual  Automatic (Deformable Image Registration) Why automatic contouring?  Logistic Constraints: Time requirement for a single contouring can be increased by a factor of ~ 10.  Fundamental Constraints:  To calculate the cumulative dose delivered to the tumor during the treatment.  However the dose for each moving voxel needs to be integrated together for this to occur.  So an estimate of the individual voxel motion is needed.
  65. 65. 4D Manual Contouring The tumor is manually contoured in end expiration and end inspiration The two volumes are fused to generate at MIV – Maximum Intensity Volume The projection of this to a DRR is called MIP (Maximum Intensity Projection) End Inspiration MIV End Expiration
  66. 66. Automated Contouring Technique by which a single moving voxel is matched on CT slices that are taken in different phases of respiration The treatment is planned on a reference CT – usually the end expiration (for Lung) Matching the voxels allows the dose to be visualized at each phase of respiration Several algorithms under evaluation:  Finite element method  Optical flow technique  Large deformation diffeomorphic image registration  Splines thin plate and b
  67. 67. Automated Contouring Movement vectors
  68. 68. Automated Contouring Individaul Pixels + =Day 1 Image Day 2 Image Due to the changes in shape of the object the same pixel occupies a different coordinate in the 2nd image Deformable Image registration circumvents this problems
  69. 69. 4D Treatment Planning  A treatment plan is usually generated for a single phase of CT.  The automatic planning software then changes the field apertures to match for the PTV at each respiratory phase.  MLCs used should be aligned parallel to the long axis of the largest motion.
  70. 70. Limitations of 4D Planning Computing resource intensive – Parallel calculations require computer clusters at present No commercial TPS allows 4 D dose calculation Respiratory motion is unpredictable – calculated dose good for a certain pattern only Incorporating respiratory motion in dynamic IMRT means MLC motion parameters become important constraints Tumor tracking is needed for delivery if true potential is to be realized The time delay for dMLC response to a detected motion means that even with tracking gating is important
  71. 71. 4D Treatment delivery Options for 4D delivery Ignore motion Freeze the motion Follow the motion (Tracking) Patient breaths normally Breathing is controlled Respiratory Gating Breath holding (DIBH) Jet Ventilation Active Breathing control
  72. 72. Minimizing Organ Motion Abdominal Compression(Hof  Breath Hold technique: et al. 2003 – Lung tumors):  Patients instructed to hold  Cranio-caudal movement of breath in one phase tumor 5.1±2.4 mm.  Usually 10 -13 breath holding  Lateral movement 2.6±1.4 sessions tolerated (each 12 -16 sec)  Anterior-posterior movement 3.1±1.5 mm  Reduced lung density in irradiated area – reduced volume of lung exposed to high dose  Tumor motion restricted to 2-3 mm (Onishi et al 2003 – Lung tumors)
  73. 73. Minimizing Organ Motion Active Breathing Control  Consists of a spirometer to “actively” suspend the patients breathing at a predetermined postion in the respiratory cycle  A valve holds the respiratory cycle at a particular phase of respiration  Breath hold duration : 15 -30 sec  Usually immobilized at moderate DIBH (Deep Inspiration Breath Hold) – 75% of the max inspiratory capacity  Max experience: Breast  Intrafractional lung motion reduced  Mean reproducibility 1.6 mm
  74. 74. Tracking Target motion Also known as Real-time Postion Management respiratory tracking system (RPM) Various systems:  Video camera based tracking (external)  Radiological tracking:  Implanted fiducials  Direct tracking of tumor mass  Non radiographic tracking:  Implanted radiofrequncy coils (tracked magnetically)  Implanted wireless transponders (tracked using wireless signals)  3-D USG based tracking (earlier BAT system)
  75. 75. Results a = includes setup error
  76. 76. AdaptiveRadiotherapyPlanning
  77. 77. Adaptive Radiotherapy (ART) Adaptive radiotherapy is a technique by which a conformal radiation dose plan is modified to conform to a mobile and deformable target. Two components:  Adapt to tumor motion (IGRT)  Adapt to tumor / organ deformation and volume change. 4 ways to adapt radiation beam to tracked tumor motion:  Move couch electronically to adapt to the moving tumor  Move a charged particle beam electromagnetically  Move a robotic lightweight linear accelerator  Move aperture shaped by a dynamic MLC
  78. 78. ART: Concept 1. 2. 3. ●Offline ART●Conventional Rx ➢ Individual patient based ●Online ART ➢ Individual patient based➢ Sample Population based margins margins ➢ Frequent imaging of margins ➢ Daily imaging of patients➢ Accomadates variations of patients ➢ Daily error corrected setup for the populations ➢ Estimated systemic error➢ No or infrequent imaging corrected based on prior to the treatment ➢ Smallest margin➢ Largest margin repeated measurements ➢ A small margin kept for required ➢ Plans adapted to the random error ➢ Plans adapted to average changing anatomy daily! changes
  79. 79. ART: Why ? Due to a change in the contours (e.g. Weight Loss) the actual dose received by the organ can vary significantly from the planned dose despite accurate setup and lack of motion.
  80. 80. ART: Problem Real time adaptive RT is not possible “today”
  81. 81. ART: Steps..
  82. 82. ART: Steps
  83. 83. HelicalTomotherapy
  84. 84. Helical Tomotherapy  Gantry dia 85 cm  Integrated S Band LINAC  6 MV photon beam  No flattening filter – output increased to 8 Gy/min at center of bore  Independant Y - Jaws are provided (95% Tungsten)  Fan beam from the jaws can have thickness of 1 -5 cm along the Y axis
  85. 85. Helical Tomotherapy LINAC  Binary MLCs are provided – 2 positions – open or closed Cone Beam  Pneumatically driven 64 leaves Y jaw  Open close time of 20 msBinary MLC  Width 6.25 mm at isocenter  10 cm thickY jaw  Interleaf transmission – 0.5% in field and 0.25% out field  Maximum FOV = 40 cm Fan Beam  However Targets of 60 cm dia meter can be treated.
  86. 86. Helical Tomotherapy  Flat Couch provided allows automatic translations during treatment  Target Length long as 160 cm can be treated  “Cobra action” of the couch limits the length treatable  Manual lateral couch translations possible  Automatic longitudinal and vertical motions possible
  87. 87. Helical Tomotherapy  Integrated MV CT obtained by an integrated CT detector array.  MV beam produced with 3.5 MV photons  Allows accurate setup and image guidance  Allows higher image resolution than cone beam MV CT (3 cm dia with 3% contrast difference)  Tissue heterogenity calculations can be done reliably on the CT images as scatter is less (HU more reliable per pixel)  Not affected by High Z materials (implant)  Dose 0.3 – 3 Gy depending on slice thickness  Dose verification possible
  88. 88. Newer Techniquesin Radiation therapyTreatment Results (Clinical)
  89. 89. Prostate CancerLate rectal toxicity (Gr 2 or more) is seen in 20 – 30%; ED occurs in 50 -60%!!!
  90. 90. Prostate Cancer Zelefsky et al (2006, J. Urol) – 561 patients (1996 - 2000) All localized prostate cancer Risk group according to the NCCN guidelines Treated with IMRT ± NAAD Dose: 81 Gy in 1.8 Gy PTV dose homogenity ± 10% Rectal wall constraints:  53% vol = 46 Gy  36% vol = 75.6 Gy
  91. 91. Prostate Cancer  8 yr biochemical relapse free survival rates:  85% - Favourable  76% - Intermediate  72% - Unfavourable  CSS (8 yrs):  100% - Favourable  96% - Intermediate  84% - Unfavourable  NAAT: No significant difference in outcomes
  92. 92. Prostate Cancer Rectal Toxicity:  Grade 2: 7 patients (1.5%); Grade 3: 3 patients (less than 1%)  The 8-year actuarial likelihood of late grade 2 or greater rectal toxicity 1.6%. Urinary Toxicity:  Grade 2 chronic urethritis in 50 patients (9%); Urethral stricture requiring dilation (grade 3) developed in 18 patients (3%).  The 8-year actuarial likelihood of late grade 2 or greater urinary toxicities was 15%. 47% patient developed ED (43% IMRT alone; 57% ADT) No 2nd cancers!
  93. 93. Prostate Cancer  Arcangeli et al (2007) WP-IMRT 91% with Prostate boost 71%  N = 55; All had NAADT, Risk of 63% nodal mets > 15%  Dose:  55 – 59 Gy (Pelvis)  66 – 80 Gy (Prostate)  33 – 40 fractions  No Gr III toxicity  Late Gr II toxicity:  Rectum: 2 yr actuarial probablity 8%
  94. 94. Head and Neck Cancers Author Year N CCT Dose Result Huang 2003 41 (I) Yes 70/60/50 (2.18 68% Stage IV; 31% Gr III mucositis; (P,NR) Gy per #) 7% Gr IV mucositis; Gr II xerostomia 58.5%; 2 yr Locoregional control 89% ; 2 yr OS 89% Wendt 2006 39 (I) Yes 60-70 Gy / 48 Gr III mucositis 11%; 12% Gr III (P,NR) -54 Gy (I) xerostomia at 6 months; 2yr Crude LC 70%; 50 % recurrences outside high dose regionYao (P,NR) 2007 90 (I) Yes 70/60/54 Gy All N2/N3 disease; 71% Oropharynx; (SIB) 3 yr LC 96%; OS 67.5%; PET useful in patient selection for ND (10) Arruda 2006 50 (I) Yes 70 / 59.4 -54 Gy All oropharynx; 92% ≥ St III; 33% (P,NR) (76% - SIB) Gr II xerostomia (1 yr); Gr III mucositis 38%; 2 yr LRC 88%; OS 98% Table showing Results of IMRT in H&N Ca
  95. 95. Head and Neck CancersAuthor Year N CCT Dose Result Chao 2003 126 Yes 72 -68/ 64 -60 Gy 59% Post op IMRT; 67% St IV; 2 yr(P,NR) (I) (30%) (SIB) LRC 85% ; 89% (Post ND)Thorstad 2005 356 Yes 70/56 Gy – Def.; 63% Post op; 90% ≥ St III; 5 Yr LRC (P,NR) (I) (40%) 64/54 Gy – 76%; 14% of the failures were Postop marginal. All marginal failures in post op patients.Wolden 2005 79 (I) Yes 70 Gy (59 – All Npx; 80% ≥ Stage III; 3 yr(P,NR) Hyperfractionated actuarial LC 91%; OS 83%; Gr III ; 15 - SIB) hearing loss 15%; 32% Gr II xerostomia at 1 yr; distant mets dominant form of therapy Daly 2007 69 (I) Yes 66 Gy -Def (2.2 33% Post op; 2 yr LC and OS 92% and(P,NR) Gy per #); 60.2 – 74%(Def); 87% and 87% (Post op); Post op (2.15 per Mean xerstomia significantly improved #) than CRTSchwartz 2007 49 (I) Yes 60 / 50 Gy (25#) All Stage III/IV; Gr III mucositis 55%, (P,NR) - SIB Gr III dermatitis 8%; 2 yr LC 83% ; OS 80% Table showing results of IMRT in H& N Ca
  96. 96. Head and Neck CancersAuthor Year N CCT Dose Result Huang 2003 41 (I) Yes 70/60/50 68% Stage IV; 31% Gr III mucositis; 7% (P,NR) (2.18 Gy per Gr IV mucositis; Gr II xerostomia 58.5%; #) 2 yr Locoregional control 89% ; 2 yr OS 89% Jabbari 2004 30 (I), No 60-78 Gy (I); At 12 months, median XQ and HNQOL (P,NR) 10 (C) 63 -76.8 (C) scores were lower (better) in the IMRT compared with the standard RT patients by 19 and 20 points, respectivelyPow (P,R) 2006 24 No 68-70 / 66- All Stage II Npx; At 1 yr 83% had (I),21 68(I); 68 / 66 recovered 25% of the pre RT parotid flow (C) (C) in IMRT (9.5% in Conv RT arm). Subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group Braam 2006 30 (I), No I – 69/66/54 83% in I arm treated definitively (23% in (P,NR) 26 (C) (30#), C – 50 C arm);mean parotid flow ratio was 18% -70/46-50(25 (C) and 64% (I); parotid gland – 35#) complication rate was 81% (C) and 56% (I) (p = 0.04). Table showing Salivary sparing and QOL improvement with IMRT
  97. 97. Breast Cancer  Largest randomized trial Donovan et al (2007)  305 patients – 156(standard) and 150 (IMRT)  1997 – 2000  Aim:Impact of improved radiation dosimetry with IMRT in terms of external assessments of change in breast appearance and patient self-assessments of breast discomfort, breast hardness and quality of life.  Dose: 50 Gy / 25# with 10 Gy boost
  98. 98. Breast Cancer➢ The control arm had 1.7 times (95% CI 1.2–2.5) more likely to have had some change than the IMRT arm, p = 0.008.➢ Areas with dose > 105% have 1.9 times higher risk of any change in cosmesis
  99. 99. Breat Cancer Leonard et al 2007 – APBI 55 patients , Non randomized All patients stage I Dose: 34 Gy (n=7) / 38.5 (n = 48) BID over 5 days Median F/U – 1 yr Good to excellent cosmesis:  Patient assessed: 98% (54)  Physician assessed: 98% (54) Considered a reasonable option for patients who have large target volumes and/or target volumes that are in anatomic locations that are very difficult to cover.
  100. 100. Lung Cancer Author Year N CCT Dose ResultYom et al 2005 37 (I) Yes 63 Gy (median) 7% incidence of Gr III (R, NR) pneumonitisYorke et al 2005 78 No Dose escalation 22% incidence of Gr III (P, NR) (3D) (50.7 – 90 Gy); pneumonitis above doses of 70 Gy.Videtec (R, 2006 28 (I) No 50 Gy in 5 fraction 64% T1; 2.6% Gr II pneumonitis, NR) (SBRT) no Gr III reactions; LC and OS at 1 yr 96.4% and 93% respectivelyScarbrough 2006 17 (I) Yes 71.2 Gy (69–73.5 Mean age 70; 73% IIIB, FU 1 yr, (R, NR) Gy) No Gr III tox, 2 yr OS 66%Jensen (P, 2007 17 (I) Yes 66 Gy Patients no suited for CCRT. 1 Gr NR (citux) III esophagitis; 79% response (6 mo)Yom et al 2007 68 (I), Yes 63 Gy (median); 60% stage IIIB, FU = 8 mo (R, NR) 222 Dose > 60 Gy (median); Gr III pneumonitis 8% (3D) 84% (I), 63% (32% for 3D CRT); V20 35% (I) vs (3D) 38%(3D) (p = 0.001) Table showing results of IMRT in Lung Cancer
  101. 101. Brain Tumors Author Year N Dose ResultSultanem 2004 25 60 Gy (GTV); 40 All GBM,Post op volume < 110 cc; Gy (CTV); 20 # Majority RPA class 4/5; The 1-year overall survival rate is 40%, Median survial 9 mo. No late toxicity. Luchi 2006 25 48 – 68 Gy 2 AA patients; Median KPS 70; 2 yr PFS (GTV); 40 Gy 53.6%; 2 yr survival 55.6%; Pattern of (CTV1); 32 Gy death – CSF dissemination most (CTV2); 8 # common cause of death!Narayana 2006 58 60 Gy (PTV); 70% GBM; 1 yr OS 30% (2 yr 0%) for 30# GBM; No Gr III late toxicity; Pattern of failure – local Table showing results of IMRT in brain tumors
  102. 102. Cervical CancerAuthor Year N CCT Dose Result Mundt 2003 36 Y 45 Gy (1.8 80% stage I-II; PTV S3 to L4/5 (P,NR) (53%) Gy/#) interspace; Chronic GI toxicity 15% (n= 3; 1 Gr II, 2 Gr I); 50% incidence in Conventional Mundt 2002 40 Y 45 Gy (1.8 60% Acute Gr II toxicity (90% Gr II in (P,NR) Gy/#) Conv.); Less GU toxicity (10% vs 20%); Patients not requiring antidiarrheal halved! Chen 2007 33 Y 50.4 Gy / All Stage I -II; All Post Hysterectomy; 1 (P,NR) 28# yr LRC 93%; Acute GI toxicity 36% (Gr I- II); Acute Gu toxicity 30% (Gr I-II) Beriwal 2007 36 Y 45 Gy 2 Yr LC 80%; 2 yr OS 65%; 11 had (P,NR) (EFRT) + recurrences – 9 distant; Gr III toxicity – 10-15 Gy 10% boostKochanski 2005 62 Y 45 Gy (1.8 29% Post op; 20 Stage IIB-IIIB; 3 yr DFS (64%) Gy /#) 72.7%; 3 yr pelvic control 87.5%; 5% Gr II or higher late toxicity
  103. 103. Anal Canal Author Year N CCT Dose ResultSalama et 2006 40 (I) Yes 45 Gy WP + 9 Gy 12.5% Gr III GI toxicity, 0 Gr IIIal (R, NR) boost skin toxicity, 2 year colostomy- free, disease free, and overall survival 81%, 73%, and 86%Milano et al 2005 17 (I) Yes 45 Gy WP + 9 Gy 53% Gr II GI toxicity, No Gr III (P, NR) boost acute or late complications. 82% CR rate, the 2-year CFS, PFS, and overall survial are: 82%, 65%, and 91% Devisetty 2006 34 (I) Yes 45 Gy WP + 9 Gy 17% Acute GI toxicity; volume of (P,NR) boost bowel receiving 22 Gy (V22) was correlated with toxicity (31.8% acute GI toxicity for V22 > 563 cc vs. 0% for V22 ≤ 563 cc) Hwang 2006 12 (I) Yes 30.6 Gy WP + 42% Gr III dermal toxicity, 8% Gr (P,NR) 14.4 Gy Low III GI toxicity, 83% CR rate Pelvic + 9 Gy boost
  104. 104. New Techniques inStereotacticRadiation therapy
  105. 105. Stereotaxy Derived from the greek words Stereo = 3 dimensional space and Taxis = to arrange. A method which defines a point in the patient’s body by using an external three-dimensional coordinate system which is rigidly attached to the patient. Stereotactic radiotherapy uses this technique to position a target reference point, defined in the tumor, in the isocenter of the radiation machine (LINAC, gamma knife, etc.). Units used:  Gamma Knife  LINAC with special collimators or mico MLC  Cyberknife  Neutron beams
  106. 106. Stereotactic Radiation Rigid application of a  Two braod groups:stereotactic frame to the patient  Radiosurgery: Single treatment fraction3 D Volumetric imaging with the  Radiotherapy: Multiple frame attached fractions  Frameless stereotacticTarget delineation and Treatment radiation is possible in one planning system – cyberknife Postioning of patinet with the  Sites used: frame after verification  Cranial  Extracranial QA of treatment and delivery of therapy
  107. 107. Sterotactic Radiation The first machine used by Leksell in 1951 was a 250 KV Xray tube. In 1968 the Gamma knife was available LINAC based stereotactic radiation appeared in 1980 Other machines using protons (1958) and heavy ions – He (1978) were also used for stereotactic postioning of the Braggs Peak
  108. 108. Gamma Knife  Designed to provide an overall treatment accuracy of 0.3 mm  3 basic components  Spherical source housing  4 types of collimator helmets  Couch with electronic controls  201 Co60 sources (30 Ci)  Unit Center Point 40 cm  Dose Rate 300 cGy/min
  109. 109. LINAC Radiosurgery  Conventional LINAC aperture modified by a tertiary collimator.  Two commercial machines  Varian Trilogy  Novalis
  110. 110. Cyberknife Roof mounted KV X-ray Robotic arm with 6 degrees of 6 MV LINAC freedon Circular Collimator attached to headFrameless patient Floor mounted Amorphousimmobilization couch silicon detectors
  111. 111. Advantages of Cyberknife An image-guided, frameless radiosurgery system. Non-isocentric treatment allows for simultaneous irradiation of multiple lesions. The lack of a requirement for the use of a head-frame allows for staged treatment. Real time organ position and movement correction facility Potentially superior inverse optimization solutions available.
  112. 112. Cyberknife 185 published articles till date; 5000 patients treated. 73 worldwide installations Areas where clinically evaluated:  Intracranial tumors  Trigeminal neuralgia and AVMs  Paraspinal tumors – 1° and 2°  Juvenile Nasopharyngeal Angiofibroma  Perioptic tumors  Localized prostate cancer However till date maximum expirence with Intracranial or Peri-spinal Stereotactic RT
  113. 113. Results Tumor Year N Result Brain mets 2004 333 (164 Survival advantage for patients with single (Andrews et al) SRT / 164 brain mets (Median survival 6.5 – 4.9 mo); C) Better functional status at follow up – SRT with WBRT Rx in single brain mets (RTOG 9508) Benign brain 2003 285 95% tumor control (media F/U 10 yr); actuarial tumors tumor control rate at 15 years was 93.7%.( Kondziolka et al) Normal facial nerve function was maintained in 95% with aucostic neuromasMalignant Glioma UP 203 SRT + EBRT + BCNU did not result in significant (Souhami et al) survial advantage – 13.6 vs 13.5 mo (RTOG 9305)Malignant Glioma 2002 203 SRT + EBRT + BCNU did not result in significant (Souhami et al) improvement in Quality adjusted survival (RTOG 9305) The only randomized trial comparing stereotactic radiation therapy boosthas failed to reveal a significant survival benefit for patients with malignant gliomas. (RTOG 9305). However 18% of the patients in the stereotactic radiotherapy arm had significant protocol deviations.
  114. 114. New Techniques inBrachytherapy
  115. 115. Brachytherpy  An inherently conformal method of radiation delivery  Relies on the inverse square law for the conformity  Unlike traditional EBRT brachytherapy is both :  Physically conformal  Biologically conformal Rapid dose fall off from the radio-isotope  Recent advances haveDose focused on better method of target identification and radio-isotope placement. Distance
  116. 116. Brachytherapy: Whats New Image Based Brachytherapy Image Assisted Image Guided Brachytherapy Brachytherapy Robotic Brachytherapy‡ Electronic Brachytherapy* Image Based Brachytherapy: Technique where advanced imaging modalites are used to gain information about the volumetric dose delivery by brachytherapy Image Guided Brachytherapy: Technique where imaging is used to guide brachytherapy source placement as well give information regarding the volumetric dose distribution
  117. 117. Image Assisted Brachytherapy Principle: Cross sectional imaging utilized to plan and analyze a brachytherapy procedure Steps:  Image assisted provisional treatment planning  Image guided application  Image assisted definitive treatment planning  Image assisted quality control of dose delivery Provisional planning refers to the planning of the implant prior to the placement of the applicator in situ – important to realize the significant anatomical distrortions 2° to the applicator placement. Definitive planning refers to the definitve treatment planning with the applicator in situ.
  118. 118. Equipment: Overview
  119. 119. Equipment: Imaging Site 1st Choice 2nd ChoiceMobile Tongue MRI CTFloor of mouth MRI CT, USOropharynx MRI, ES CTNasopharynx ES, MRI CTCervix MRI CT, US (Endo)Endometrium MRI, ES CT, US (Endo)Vagina US (endo), MRI CTBreast Mammography, MRI CT, USBladder ES, MRI, CT USProstate MRI US (endo), CTAnorectal ES, MRI, US (endo) CTOesophagus ES, Oesophagogram (Barium) CT, MRI, US (endo)Bile duct Cholangiogram, ES CT, US, MRISoft tissue sarcoma MRI CTBronchus ES, CT, Chest X Ray MRIBrain MRI CT Table showing Imaging modality of choice in different anatomical areas
  120. 120. Equipment: Applicators
  121. 121. Image Acqusition Images should be acquired in 3 dimensions parallel and perpendicular to the axis of the applicator This minimizes reconstruction related artifacts The best modality in this respect is the MRI CE MRI can provide excellent soft tissue contrast too Para Sagittal Para Coronal Para Axial
  122. 122. Tumor Delineation  Tumor delineation requires a good clinical examination in brachytherapy:  Mucosal infiltration is usually picked up on visual inspection only.  The ideal imaging modality for soft tissue resolution : MRI  Tumors are usually contoured in the T2 weighted image  T1 images are better for detection of lymphadenopathy
  123. 123. Target Volumes The target volumes as defined by ICRU 58 are similiar to the ICRU 62 recommendations Modifications specific to brachytherapy:  PTV generally “approximates” CTV as applicators are considered to maintain positional accuracy.  If the patient is treated with EBRT / Sx prior to brachy the CTV is the initial tumor volume (GTV) prior to treatment.  The GTV for brachytherapy should be recorded seperately in such cases.  Due to high dose gradient organ delineation is meaningful if done in the vicinity of the applicator  For luminal structures wall delineation can give a better idea about the dose received as compared to the whole volume
  124. 124. Image based brachytherapyDose Distribution at level of 3 D view of the ovoids and tandem applicator geometry Bladder Rectum 3 D Dose distribution
  125. 125. Provisional PlanningB Mode USG with stepper PubicTemplate arch Prostate Urethra Rectum Saggital Image with template overlay Acquired sagittal image demonstrating bladder prostate interface
  126. 126. Provisional Planning Beaulieu et al reported on 35 cases (IJROBP 2002) Prostate contours were created in a preplan setting as well as in the operating room (OR).  In 63% of patients the volume of the prostate drawn had changed.  These changes in volume and shape resulted in a mean dose coverage loss of 5.7%.  In extreme cases, the V100 coverage loss was 20.9%. At present applied clinically for prostate cancer only. For both intraluminal and intracavitary significant changes of the anatomy on application preclude provisional planning.
  127. 127. Image Guided BrachytherapyRadiation Oncologist Contouring and dose acquiring sectional planning being done The finalized plan with USG images on the TPS the superimposed grid on the template indicated the point of placement of each needle
  128. 128. Image Guided Brachytherapy “Seed afterloader” with the needle containing the in postion. Needles being inserted into the prostate under direct USGA machine called the guidance seed loader can receive instructionsfrom the TPS directly
  129. 129. Image Guide Brachytherapy Final Seed placement View of the B Mode Stepped USG device with the template for insertion of the needles. Some needles have been placed already
  130. 130. Real Time dynamic IGBRT
  131. 131. Results Keasten et al (IJROBP 2006)  564 patients of prostate CA – IGRT or IGBRT (5 yr FU)  5-year BC rates were similar in both groups (78–82% for IGRT vs 80–84% for IGBRT)  IGRT higher chronic grade≥2 GI toxicity (22% vs 12% for EBRT+HDR)  EBRT+HDR higher chronic grade≥2 GU toxicity (30% vs 17% for IGRT) Nandalur et al (IJROBP 2006)  479 Prostate cancer patients IGRT vs IGBT  5 yr biochemical control rates > 90% (GR III toxicity ~ 4-6%!!)  C-IGBT patients experienced significantly less chronic grade 2 GI toxicity and sexual dysfunction.
  132. 132. Electronic Brachytherapy AXXENT Customized Ballon Applicator X ray Source Assembly KV Xray Tube
  133. 133. Conclusions Conformal radiation therapy requires a good imaging guidance and better machines for delivery – development expensive and time consuming Dosimetric results invariably show superiorty of conformal avoidance IMRT the best conformal EBRT technique can allow new methods of radiotherapy – bringing hypofractionation back into fashion Several unresolved questions – sparse but emerging clinical data Cancers of developing nations – stand maximum to gain from Conformal radiation therapy Approach – Cautious Embrace?
  134. 134. Thank YouRadiotherapy can treat 30% cancers while Chemo/Biotherapy 2% - But considered as the “sticking plaster” of oncology” S. Webb