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Image guided adaptive radiotherapy

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This seminar is presented in weekly journal club and seminar held in Apollo Hospital, Kolkata Department of Radiation Oncology.

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Image guided adaptive radiotherapy

  1. 1. IMAGE GUIDED-ADAPTIVE RADIOTHERAPY ….Have We Really Understood ? Where do we stand now? Presented by: Dr. Vijay Kumar K Moderator: Dr. Tanweer
  2. 2. LINE OF PRESENTATION • What exactly is Adaptive Radiotherapy • Rationale • Concept Of ART • Types or Components • Site Specific
  3. 3. NATURE ADAPTS • From Latin “adaptare” means “to fit”
  4. 4. IGRT…! what exactly it is ? • “External beam radiation therapy with positional verification using imaging prior to each treatment fraction” • “Any use of imaging to aid in decisions in the radiotherapy process” • “A procedure that refines the delivery of therapeutic radiation by applying image-based target re-localization to allow proper patient repositioning for the purpose of ensuring accurate treatment and minimizing the volume of normal tissue exposed to ionizing radiation” – ASTRO • “The use of imaging for detection and diagnosis, delineation of target and organs at risk (OAR), determining biological attributes, dose distribution design, dose delivery assurance, and deciphering treatment response,” a so-called six-dimensional definition
  5. 5. • Although both IGRT and Adaptive Radiotherapy exists from long back, With time… with improving technology… • Radiation techniques improved and so, THE OUTCOMES. • Adaptive Radiotherapy never an individual entity without IGRT..!!
  6. 6. EVOLUTION OVER DECADES
  7. 7. • A radiation treatment process where the treatment plan can be modified using a systematic feedback of measurements is named ‘Adaptive radiation therapy’ (ART). • The importance of using an adaptive process in radiation therapy is that the treatment plan, especially the margin and treatment dose, can eventually be customized to the individual patient. • Adaptive radiation therapy has been introduced to incorporate the position variation of the individual patient into the treatment optimization process during the course of radiotherapy.
  8. 8. • The concept of ART can also be applied to compensate for other treatment variations such as radiation sensitivity and density of clonogenic cells when they become measurable during the treatment course.
  9. 9. 15/07/2016
  10. 10. DEFINITION OF ART • Adaptive radiotherapy can be defined as, Temporally changing the treatment plan delivered to a patient based on observed anatomic changes caused by tumor shrinkage, weight loss, or internal motion – Leibel Philips. “The ability to measure changes in location, morphology and physiology (like breathing, tumor response, weight loss) and adapt the course of treatment will lead to adaptive treatment, also called 4D adaptive treatment” – ICRU 83
  11. 11. FACTORS CAUSING ANATOMIC CHANGES TO TUMOR AND NORMAL TISSUES • Anatomic motion (PHYSIOLOGICAL) caused by the musculoskeletal, respiratory, cardiac, gastrointestinal, and genitourinary systems. • Treatment-induced changes such as cell death and tumor shrinkage, tumor growth resulting from accelerated repopulation, weight loss or gain because of changes in appetite caused by radiation, concomitant chemotherapy or hormone therapy, fibrosis of normal tissue, and so on
  12. 12. RATIONALE • Changing anatomy  of both tumor and normal tissue— It naturally follows that the delivery of radiotherapy should be temporally changing to match the observed anatomic changes In other terms, If the PTV and normal anatomy are changing with time, we are obligated to adapt our treatment delivery where possible.
  13. 13. DIFFERENT WAYS TO ADAPT TYPES OF ART Examples Motion adaptive Beaumont’s ART process, ‘Plan of the day’ IMRT Biological adaptive Theragnostic planning Response adaptive Mid-treatment response evaluation, shrinkage of GTV & OAR Time adaptive Mid-course CT and planning
  14. 14. PROCESS INVOLVED IN ART
  15. 15. COMPONENTS • Adapt to tumor motion • Adapt to tumor / organ deformation and volume change
  16. 16. ADAPTING TO TUMOR MOTION • Move couch electronically to adapt to the moving tumor • Exac trac 6D Robotic couch • Move a charged particle beam electromagnetically • RPM system • Move a robotic lightweight linear accelerator • Cyber knife • Move aperture shaped by a dynamic MLC • Calypso system
  17. 17. CONCEPT OF ART • Adaptive radiotherapy can occur at three different timescales: Offline - between treatments, Online - immediately prior to a treatment, and in Real time - during a treatment
  18. 18. IMAGE REGISTRATION • Registration : means to align two imaging data sets in a common coordinate space by transforming one image set while keeping the other one fixed. • Voxel to voxel matching b/n 2 image sets. • Fixed image to floating image • A transformation matrix created • It is an optimization process- success achieved after iterative comparisons.
  19. 19. IMAGE REGISTRATION • According to the nature of transformation- • It is of 2 types- Rigid registration and Deformable registration. • Rigid fusion- • Direct intensity match or point match • No compensation for motion or patient position • 6 degrees of freedom
  20. 20. • Deformable image registration – • Complicated • Consists of a matrix with huge number of unknowns. • Multimodality images can be fused • Allows dose and contour information to be transferred between images, substantially reducing workload. • As the timescales for adaptation decrease, the computation time of deformable image registration must correspondingly decrease.
  21. 21. APPLICATIONS (1) Better Target Definition (2) Image Enhancement (3) Propagation Of Organ Contours From One Image Set To Another (4) Calculation Of Accumulated Dose In Organs Experiencing Inter- Or Intra- fraction Organ Deformation For 4-D Or Adaptive Therapy Planning (5) 4-D Image Reconstruction
  22. 22. ISSUES: • Definition of registration metric function • Algorithm Registration can be broadly divided into • Manual, landmark-based, surface-based, intensity-based, and mutual information–based registrations. Depending on the mechanism or method used to model the deformation, registration can usually be categorized into • Elastic model, viscous fluid model, optical flow model, finite element model, radial-basis function model such as basis spline model, and thin-plate spline model.
  23. 23. • Basis spline model- most commonly used • Selection algorithm- depend on metric function • Most of algorithms depend on intensity matching but ignore tissue features – can be countered by physiologic and anatomic knowledge • Eg- Bone wrapping • Cost function- Similarity measure • Penalty function- discourages undesirable transformations.
  24. 24. Deformable Transformation Fixed Image Moving ImageFixed Image Courtesy Dr Prahlad
  25. 25. Deformable Transformation Courtesy Dr Prahlad
  26. 26. Deformable Transformation y x Courtesy Dr Prahlad
  27. 27. FIXED IMAGE Courtesy Dr Prahlad
  28. 28. MOVING IMAGE Courtesy Dr Prahlad
  29. 29. REGISTERED IMAGE Courtesy Dr Prahlad
  30. 30. REGISTERED IMAGE Courtesy Dr Prahlad
  31. 31. REGISTRATION BEYOND DEFORMATION MODEL • pCT vs pCT- easy but pCT vs CBCT-- ? • d/t poor quality or gross anatomic changes Eg- 1. variation in rectal contents, bowel gas, feacal matter- direct intensity matching cannot be done. 2. motion of lung, liver 3. weight loss or gain ( algorithms reliable only for a volume change of 3% - time span b/n consequent imaging to be reasonable)
  32. 32. TRANSFER OF CONTOURS • Accuracy of registration matters- influenced by image content distant from ROI. • Surface mapping techniques: efficient for pCT to CBCT contour transfer • ROI contour extended surface • Hybrid – deformable and surface model  best method • Narrow shell around ROI extended 1-2cm on pCT  merged with CBCT
  33. 33. CBCT • Large variation of HU for same material under different scanning conditions. • In the absence of organ motion– Accuracy is acceptable for dose verification but not for treatment planning. • With organ motion– 5-8% discrepancy can be seen. • Electron density matching– may be a solution. • Where it stand in ART  ?
  34. 34. OFFLINE ADAPTATION • The imaging system used : Conventional CT scanner or an in-room CT scanner. • The adaptation can be triggered by : • As a protocol (for example after 20 and 40Gy delivered dose), • Clinical observations of masks not fitting, weight loss, or other surface changes, or by changes observed on an in-room imaging system
  35. 35. • The rationale - substantial shrinkage of the tumor/weight loss throughout the course of therapy, between the anatomy at the time of the original CT scan and the cone beam CT scans acquired during treatment. Planning CT After 16# After 25#
  36. 36. ONLINE ART • Online Adaptation is typically referred to Imaging Just prior to each treatment and the plans were adapted to changing anatomy daily.
  37. 37. ONLINE ART • This can be done either by correcting the errors or by modifying the contours. • Daily re-planning ??
  38. 38. • Although it may be trivial to occasionally re-plan a limited number of patients offline, frequent re-plannings of many patients are labour and time intensive, especially if online re-planning is necessary.
  39. 39. GRAPHICS PROCESSING UNIT (GPU) • Researchers at the University of California–San Diego have explored the potential to perform online re-planning utilizing the vast computational capability of the graphics card technology. • It is possible to dramatically improve the computational efficiency of the traditionally computationally intense tasks in RT such as dose calculations, inverse planning re-optimizations, CT reconstructions,and deformable image registrations for fast contour mapping.
  40. 40. • Gu et al. have shown that a full 3D-dose calculation based on finite-size pencil beam algorithm achieved a speed up of 200 to 400 times, taking less than 1 second for typical IMRT plans. • Men et al. found that, for a typical nine-field prostate IMRT plan with 5-by-5 mm2 beam-let size and 2.5-by-2.5-by-2.5 mm3 voxel size, re-optimization would only take 2.8 seconds. • Park et al. found that for a filtered back-projection reconstruction of a typical 3D CBCT, volume can be done in a real-time fashion (i.e., as soon as the scan is done)
  41. 41. CLOUD COMPUTING • Pioneered by Meng et al. And Wang et al. at stanford university. • It’s a form of SUPERCOMPUTING technology. • The task is divided up and handled in a parallel computing manner, automatically. • This system does not require the computers to be physically located near the user, and they can be accessed from anywhere with an internet connection, • The larger the number of nodes used, the faster the computations.
  42. 42. WORK-FLOW
  43. 43. LIMITATIONS • The technology is new and research in RT is in its infancy; but the potential benefits remain to be seen. • How often should new plans be generated? Once? Weekly? Daily? • Whether altering the target volume would adversely impact tumor control ?
  44. 44. REAL-TIME IMAGE-GUIDED ADAPTIVE RADIOTHERAPY • Imaging session and treatment session are intertwined • Time separation is shown to be on the order of seconds or less. • Rationale - significant drift in the mean position of a tumor during radiotherapy treatment. • The concept of intra-fraction motion management arises…here !
  45. 45. MOTION MANAGEMENT • Respiration induced • Organ motion
  46. 46. METHODS TO CONTROL / COMPENSATE FOR LUNG MOTION DURING RESPIRATION • Free breathing methods: Internal Target Volume (ITV)-based treatment Gating Tracking • Breath-hold methods: Active Breathing Coordinator (ABC) - DIBH
  47. 47. GATING • Treatment delivery is done in the phase of respiration where the tumor motion & resulting treatment volume is minimum, by coupling the beam delivery with the phase of respiration • It can be invasive or non-invasive.
  48. 48. REAL TIME TUMOR TRACKING • Imaging is used to track the actual tumour motion during treatment delivery and to move the treatment beam accordingly based on the varying position of the tumour. • Usually requires an internal fiducial, implanted within the tumour. • Can also be done non-invasively in some cases.
  49. 49. SIMULATION • Patients for gating/ tracking/ITV- based treatment undergo plain 4DCT scan for planning (3mm slices), using Mayo belt/ Anzai belt/ RPM system to correlate the respiratory phases and corresponding CT images. • Ten data sets are thereby generated.
  50. 50. VOLUME DELINEATION • Tumor delineation is done on the end-expiratory data set. This is because, in this phase, lung motion is minimum. • No CTV margin is given for stereotactic body radiotherapy for early inoperable lung cancers. • For locally advanced disease, CTV margins between 0.6-0.8 cm are usually applied. • Setup margins of 0.5 cm are normally applied (to the GTV/ CTV/ITV, as appropriate) to arrive at the PTV
  51. 51. Gating can be internal or external • Internal – Uses tumor motion surrogates such as implanted fiducial markers or marker-less imaging of internal anatomy. • Eg: RTRT system • External – uses external respiratory surrogates such as markers placed on the surface of the patient’s abdomen, a compression belt, or spirometer signals. • Eg: RPM system, Exac trac
  52. 52. RPM SYSTEM (VARIAN) • Lightweight plastic block with two or six passive infrared reflective markers • Monitored by video camera mounted on the treatment room wall. • The surrogate signal is the abdominal surface motion. • Both amplitude and phase gating are allowed. • disables the beam when the waveform becomes irregular, such as with patient motion or coughing, and re enables the beam after establishing breathing is again regular.
  53. 53. EXAC-TRAC GATING/NOVALIS GATING • This device uses external markers for gating. • it uses x-ray imaging to determine the internal anatomy position and to verify its reproducibility during treatment. • By updating the correlation between the internal and external signals in a reasonable frequency, x-ray exposure to the patient is minimized, while the external gating signal accuracy is maintained.
  54. 54. • Oblique image pairs are taken by Exac-Trac system’s stereoscopic X ray imagers. • The system builds a correlation model between the end-positions and the respiratory phase (accuracy of correlation 3mm). • The treatment beam is then turned on and is configured to treat ONLY in the gating window
  55. 55. R T -TRACKING • Most ideal—and most technologically intense—strategy, • Real-time tumor localization, fast processing and relay of information, and corresponding repositioning of the beam all need to be dynamically seamlessly integrated. Available Systems: • ExacTrac system (VERO) • Cyberknife • Calypso System
  56. 56. PRINCIPLE OF TRACKING
  57. 57. REQUISITES OF CORRELATION MODEL • Accuracy • Speed • Imaging dose required should be minimum
  58. 58. CYBER KNIFE: RTT MODES Non-invasive: Xsight lung • Possible if: • Tumour >1.5 cm, surrounded by air • Tumour visible by imaging system Invasive (with implanted fiducial): Synchrony • 3-5 fiducial markers need to be inserted in close proximity to the lesion. • They have to be well- separated (>2cm) and non overlapping on projections from the in room x-ray images
  59. 59. VERO (BRAIN LAB-MITSUBISHI)
  60. 60. • Has 6MV C-band LA mounted on O- ring gantry • Gantry is mounted on gimbals • Capable of Pan & Tilt motions • Maximum motion allowed=2.5 cm in isocentre plane or 2.5 degrees in each direction • Also has 2 kV X ray imagers, mounted at 45 degree angle with the MV beam axis • Has facility for Cone Beam CT & Real Time Tumor Tracking (based on Infrared & stereoscopic X rays) . • 6 degrees of freedom • Patient repositioning not required as the system can move itself • Image verification possible at any position during treatment.
  61. 61. ELECTROMAGNETIC TRACKING SYSTEMS (CALYPSO) • Make use of electromagnetic transponders (beacons) • Embedded within the tumor • Motion of these beacons may be tracked in real time using a detector array system. • Beacons need to be placed through a minimally invasive procedure, their presence may introduce artifacts in mr images, and there are limitations to the patient size. • Calypso has a geometric accuracy of <2 mm, but its use at present is limited to prostate radiotherapy.
  62. 62. BIOLOGY GUIDED ART
  63. 63. RATIONALE FOR NON UNIFORM DOSE ESCALATION • Local recurrences arise from micro environmental niches that are relatively resistant at the radiation dose level that can safely be delivered using a uniform dose distribution • molecular and functional imaging will allow spatiotemporal mapping of these regions of relative radio-resistance • advances in radiation therapy planning and delivery technologies facilitate the delivery of a graded boost to such regions, which, in turn, should lead to improved local tumor control with acceptable side effects
  64. 64. CHASING THE FAILURE PATTERNS
  65. 65. COMPARISON OF VARIOUS IMAGING MODALITIES
  66. 66. • Biology-based objective functions can be introduced to the radiation treatment planning process by co-registration • Dose painting -Subvolume boosting-imaging defined discrete volume is given an additional boost - Dose painting by numbers- in which a dose is prescribed at the voxel level and it is left for the dose plan optimizer to arrive at a physically deliverable dose distribution
  67. 67. DOSE PAINTING BY NUMBERS Gregoire et al., Lancet Oncol 2012
  68. 68. DOSE ESCALATION VS TOLERANCE
  69. 69. SITE SPECIFIC ADAPTIVE RADIOTHERAPY
  70. 70. HEAD AND NECK • We usually adapt to changes in morphology of tumor and OAR’s. • Provoking factors: weight loss, tumor response, progression of disease Hansen et al. • evaluated the impact of replanning in a cohort of 13 HNC patients with either significant weight loss or tumor response during IMRT. • Compared to replanning, not replanning significantly decreased dose to the target volume and increased doses to normal tissues (spinal cord and brainstem). The doses to 95% of the PTV-GTV and the PTV-CTV decreased by up to 6.3 Gy and 7.4 Gy, respectively.
  71. 71. Adaptive radiotherapy of head and neck cancer Pierre Castadot, MD, John A. Lee, Eng, Phd, Xavier Geets, MD, Phd, And Vincent Grégoire, MD, Phd, FRCR • Positioning errors and their causes and strategies that could be adopted to counteract setup uncertainties. • Anatomical modifications
  72. 72. Anatomical Modifications Of Target Volumes And Organs At Risk During Radiation Therapy • These include the shrinkage of the primary tumor and nodal volumes, resolving postoperative changes or edema, and weight loss.
  73. 73. Dosimetric Impact Of Anatomical Modifications • Alteration in patient anatomy during treatment  modifications of both target volumes and OARs,  the dose distribution that is actually delivered to the patient might significantly differ from what was planned.
  74. 74. • 51 papers were reviewed. • Adaptive radiotherapy (ART) could be applied to reduce dose to OARs and eventually to improve quality of life. • It is unlikely that every patient will benefit from ART. • Selection of patients is most important. • There are no guidelines to when and what time schedules adaptation should be done.
  75. 75. • Anatomic and dosimetric changes are more pronounced in Parotid gland. • The average volume decrease of the PG’s during radiotherapy was 26 ± 11%. (Mostly during first half of treatment). • The most common reported anatomic changes were volume loss and medial shifts of the PG’s. • On average, the PG mean dose increased with 2.2 ± 2.6 Gy as compared to the dose calculated on the planning CT at baseline. (Site specific- may go up to 10Gy)
  76. 76. • It was directly associated with higher grade 2 or more xerostomia in those patients. • Weight loss >5% and/or decrease of neck diameter >10% was associated with higher xerostomia. • Chen et al. - In less than 20% of all head and neck patients replanning was needed because of target underdosage or OAR overdosage, usually during the first three weeks of treatment
  77. 77. • 36 patients • 54-Gy dose to both high-risk and low-risk target volumes in Phase I. • Phase II (adaptive) plans for 16 Gy to high-risk planning target volume. RESULTS: • Median reductions in gross primary and nodal disease volumes on mid-treatment scans were 34% and 43.2%, respectively. Four patients developed local recurrences, all within the RT field. Median DFS and OS were 17.5 and 23.5 months, respectively. ADVANCES IN KNOWLEDGE: • This study supports the need for adaptive replanning for minimizing normal tissue toxicity without compromising local control and adds to the existing body of literature.
  78. 78. ART IN PROSTATE CANCER • Major concern is to reduce the treatment margins to reduce normal tissue toxicity • To incorporate generic set up errors and application of predetermined set up margins. • Individualized setup adjustments to reduce the magnitude of setup error IGRT forms the basis for adaptation
  79. 79. DISTENDED RECTUM ON PLANNING CT LEADS TO INFERIOR CONTROL RATES
  80. 80. BEAUMONT’S ART PROCESS CL-PTV can be constructed within the first week of treatment using feedback of imaging measurements Single plan modification during second week can lead to dose escalation
  81. 81. Divided into three groups based on PTV patient specific dose- 70.2-72.0, 72.0-75.6 ,75.6-79.2 (based on bladder and rectal dose constraints) Patients-280 180 patients (65%) were treated to a prostate field only and 99 patients (35%) to prostate and seminal vesicles Toxicity at the high dose level was not different from toxicity at the intermediate or lower dose levels
  82. 82. DEVELOPING CL PATIENT SPECIFIC PTV Brabbins et al, IJROBP 2007
  83. 83. IMPACT ON TUMOR CONTROL (N-3062) Brabbins et al IJROBP 2008
  84. 84. ‘PLAN OF THE DAY’ • Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). CONCLUSIONS: • Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.
  85. 85. N-54 3DCRT technique 4 plans generated by 10# CBCT daily on 1st week and then every 5# (post RT also) Without further bladder filling control or imaging, a CTV to PTV margin of 7 mm is insufficient
  86. 86. N- 113 N-87 (77%) N- 1274
  87. 87. No strong correlations were found between V95%(total-dose) reduction and initial seroma volume or between V95%(total-dose) reduction and seroma volume decrease
  88. 88. -28 patients -Repeat CT scans were taken daily during 1st week f/b once weekly -Substantial systematic and random shape variation demanded for a PTV margin up to 2.4 cm at the upper- anterior part of the CTV. Plan adaptation after fraction 4 resulted in a maximum 0.7 cm margin reduction and a significant PTV reduction from 1185 to 1023 cc
  89. 89. CT -planning CT -4 Conclusions: With adaptive radiotherapy, maximum required PTV margins can be reduced from 2.4 to 1.7 cm, resulting in significantly less dose to the bowel area

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