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IMRT and 3D CRT in cervical Cancers
 

IMRT and 3D CRT in cervical Cancers

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IMRT and 3 DCRT in cervical Cancers - Principles, Uses, Methods and Planning. A short summary of results of contemporary series are also provided.

IMRT and 3 DCRT in cervical Cancers - Principles, Uses, Methods and Planning. A short summary of results of contemporary series are also provided.

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IMRT and 3D CRT in cervical Cancers IMRT and 3D CRT in cervical Cancers Presentation Transcript

  • 3D CRT and IMRT in Cervical Cancers Department of Radiotherapy PGIMER Chandigarh
  • 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
  • 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.
  • 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)‏
  • 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 ) ‏
  • 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) ‏
  • Comparision
  • MLC based IMRT
  • Step & Shoot IMRT
    • Since beam is interrupted between movements leakage radiation is less.
    • Easier to deliver and plan.
    • More time consuming
    Intesntiy Distance
  • 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
  • Potential of Conformal RT
    • For Whole Pelvic Treatments :
        • Reduction in acute small bowel morbidity.
        • Reduction in acute hematological toxicity with bone marrow sparing.
        • Prevention of late term anorectal/ GI and GU dysfunction.
        • Escalation of dose to the pelvic lymphnodes.
        • Better matching of dose profiles in simultaneous treatments.
        • For simultaneous extended field irradiation (± CCT).
        • Better target coverage with modern day improvements in conjunction with image based brachytherapy
    • As an alternative to brachytherapy:
        • In distorted anatomy to circumvent limitations of brachytherapy.
        • To give higher dose to pelvic nodes present at time of brachyRx.
        • In postoperative patients with residual central disease instead of intersitial brachytherapy.
  • 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.
    • Radiobiological disadvantage:
      • Decreased “dose-rate” to the tumor
      • Increased integral dose (Cyberknife > Tomotherapy > IMRT) ‏
  • Conformal Radiation Planning
  • Initial Steps
    • Clinical Examination to note down tumor extent:
      • Vaginal mucosal extension is best appreciated on clinical examination
    • Preplanning steps:
      • Oral Contrast
      • Rectal Contrast
      • Cervical markers
  • Patient Preperation
  • 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
    • Several types of immobilization options available for cervical cancers
  • Types of Immobilization Immoblization devices Frame based Frameless Invasive Noninvasive
    • 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 ”
  • Thermoplastics
  • Immobilization options
    • Thermoplastics form the basis for immobilzation in head and neck
    • In the pelvis these are difficult to be used as:
      • Lack of bony points for fixation for rigid devices.
      • Continuing abdominal movements with respiration
      • Presence of fat pads and folds
    • Therefore other techniques needed for immobilization.
    • In PGI we use simple supine positioning with skin markings:
      • Cheap
      • Reproducible
      • Ease of use and comfortable for patient.
  • Patient Positioning
  • Our Method
  • Immobilization: Other methods Elekta Body Frame Body Fix system
  • Accuracy of systems With the precision of the body fix frame the target volume will be underdosed (< 90% of prescribed dose) 14% of the time!!!
  • 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
  • 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
  • Importance of MRI Dimopoulos JC, Schard G, Berger D, Lang S, Goldner G, Helbich T, et al. Systematic evaluation of MRI findings in different stages of treatment of cervical cancer: Potential of MRI on delineation of target, pathoanatomic structures, and organs at risk. International Journal of Radiation Oncology*Biology*Physics. 2006 Apr 1;64(5):1380-1388.
  • 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
  • PET-CT scanner Flat couch top insert CT Scanner PET 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%
  • 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, 11 C Tyrosine
    • Hypoxia markers
      • 60 Cu-diacetyl-bis(N-4-methylthiosemicarbazone) ( 60 Cu-ATSM)‏
    • Apoptosis markers
      • 99 m Technicium Annexin V
    PET Fiducials
  • 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
  • Concept
  • 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.
  • Image Registration
  • 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 Tumor Volume) ‏
      • CTV (Clinical Target Volume) ‏
      • ITV (Internal Target Volume) ‏
      • PTV (Planning Target Volume) ‏
    • Other volumes:
      • Targeted Volume
      • Irradiated Volume
      • Biological Volume
  • 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.
  • Definitions: ICRU 50/62
    • Treated Volume : Volume of the tumor and surrounding normal tissue that is included in the isodose surface representing the irradiation dose proposed for the treatment (V 95 ).
    • Irradiated Volume : Volume included in an isodose surface with a possible biological impact on the normal tissue encompassed in this volume. Choice of isodose depends on the biological end point in mind.
    GTV CTV ITV PTV TV IV
  • 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 )‏
  • CTV Delineation
    • The CTV to be delineated for cervical cancers consists of three components (if patient is treated with RT ± CT alone) ‏
      • Low Risk CTV : Consists volume at risk of potential microscopic disease spread at the time of diagnosis. Typically treated to a dose of 45 -50 Gy.
      • Intermediate Risk CTV : Major risk of local recurrence in areas that correspond to initial macroscopic extent of disease. The intent is to deliver a total radiation dose appropriate to cure significant microscopic disease in cervix cancer, which corresponds to a dose of at least 60 Gy.
      • High Risk CTV : Major risk of local recurrence because of residual macroscopic disease. The intent is to deliver a total dose as high as possible (85 - 90 Gy) and appropriate to eradicate all residual macroscopic tumour.
  • CTV Parametrium
    • Ventral: Bladder
    • Dorsal: Perirectal fascia
    • Medial: Tumor/cervical rim,
    • Lateral: Pelvic wall (PW)‏
    • At the PW, the space that contains vessels and lymph nodes is particularly important.
  • Nodal Anatomy Superficial common iliac – 24% Deep Common iliac – 20% Internal Iliac – 12% External Ilac – 24% Superficial Obturator – 92% Deep Obturator – 8% Presacral - 8%
  • Delineation of Nodal Volume Common Iliac Nodes : 7 mm margin around vessels. Extend posterior and lateral borders to psoas and vertebral body Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550.
  • Delineation of Nodal Volume External iliac Nodes : 7 mm margin around vessels. Extend anterior border by a further 10 mm anterolaterally along the iliopsoas muscle to include the lateral external iliac nodes Internal iliac Nodes : 7 mm margin around vessels. Extend lateral borders to pelvic side wall Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550.
  • Delineation of Nodal Volume Presacral Nodes : Subaortic: 10 mm strip over anterior sacrum; Mesorectal: cover entire mesorectal space Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550.
  • Delineation of Nodal Volume Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550.
  • Delineation of Nodal Volume Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550. Obturator Nodes : Join external and internal iliac regions with a 17 mm wide strip along the pelvic side wall
  • Delineation of Nodal Volume Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550.
  • Extent of Nodes Covered
  • PTV Delineation
    • The exact PTV depends on:
      • Setup inaccuracies
      • Organ motion
    • The extent of setup inaccuracies will differ from institution to instituiton
    • In PGI we use the following margins:
      • 1 cm cranio-caudal direction
      • 0.7 cm lateral
      • 0.7 cm antero posterior
  • Interfraction Motion: ITV
    • Uterus :
      • SI: 7 mm
      • AP : 4 mm
    • Cervix :
      • SI: 4 mm
    • Rectum :
      • Diameter: 3 – 46 mm
      • Volumes: 20 – 40%
      • In many studies decrease in volume found during treatment
    • Bladder :
      • Max transverse diameter mean 15 mm variation
      • SI displacement 15 mm
      • Volume variation 20% - 50%
  • Planning workflow Define a dose objective Total Dose Total Time of delivery of dose Total number of fractions Choose Number of Beams Choose beam angles and couch angles Organ at risk dose levels Choose Planning Technique Forward Planning Inverse Planning
  • “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.
  • Planning Beam orientation Beams Eye View Display Room's Eye View Digital Composite Radiograph
  • Beam Arrangement
  • “Inverse” Planning 1. Dose distribution specified Forward Planning 2. Intensity map created 3. Beam Fluence modulated to recreate intensity map Inverse Planning
  • 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
  • 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.
  • Normal Organ Constraints
    • As per data given by Perez et al:
      • Gr III rectosigmoid complications:
        • 1-4% with dose < 80 Gy
        • 9% with dose ≥ 80 Gy
      • Moderate Urinary sequale:
        • 2% < 70 Gy
        • 5% ≥ 75 Gy
      • Grade III small bowel sequale:
        • 1% ≤ 50 Gy
        • 2% to 4% > 60 Gy
    Rectum Bladder
  • Normal Organ Constraints Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies . International Journal of Radiation Oncology*Biology*Physics. 2002 Apr 1;52(5):1330-1337.
  • Small Intestine: DVH correlates
    • Acute GI toxicity correlates with small bowel dose
      • % volume of small intestine receiving doses in the range of 75 -100% of prescribed dose significant predictor.
    • In a study of 50 patients Volume of small bowel receiving 100% of prescribed dose retained significance in multivariate analysis.
  • Colorectum: DVH Correlates
    • Anal Canal Dysfunction:
      • Correlated with radiation doses in the range from 50 to 60 Gy.
    • Rectal Dysfunction:
      • Risk of late rectal bleeding significantly high when the rectum is enclosed by the 50 -60 Gy isodose curve for more than 1 cm length
  • Bone Marrow: DVH correlates
    • Significant correlation of volume of bone marrow receiving doses of >10 Gy
  • Optimization
  • Plan Evaluation: Cumulative DVH
    • Cumulative DVHs give a quick overview of the 3D Dose distribution.
    • Analysis of a absolute volume vs absolute dose histogram is more intuitive.
    • Always look for the absolute volume incorporated in the dose limit.
    • Also look for the tail of the curve and look what is the dose there.
  • Plan Evaluation: Differntial DVH
    • Differential DVH allow a visual representation of the dose homogenity in the target volume.
    • Ideally the DVH should have a sharp peak in the differential DVH
    • The peak of the curve gives a good representation of the modal dose being received by the volume in question.
  • Plan Evaluation: Color Wash
    • The color wash and it's counterpart the isodose views allow quick visual verification of the dose distribution.
    • Coverage of the PTV should be assessed with the color wash or isodose curve display on each slice
    • Oragan doses should also be evaluated for the clinically relevant dose limit set.
  • Verification
    • Both absolute and relative dosimetric verification is essential for each IMRT plan.
    • Absolute dose variations should be ≤ ±3%.
    • Should be measured in a region of low dose gradient.
    • Relative dose variation ≤ ±5% is acceptable.
  • Clinical Results
  • Dosimetric Comparisions
    • Selvaraj et al compared IMRT and conventional 3D CRT plans for cervical cancer patients using 7 field IMRT.
  • WPIMRT: Clinical Results
  • WPIMRT: Chronic Toxicity
    • Mundt et al reported a detailed comparision of IMRT vs 3DCRT
    • WPIMRT reduced chronic GI toxicity to 11% from 50% in conventional 3D CRT.
    • Significant difference on multivariate analysis
    • Majority of patients of WPIMRT who had GI toxicity had grade I toxicity only.
  • IMRT: Extended Pelvic Radiation
    • RTOG 92-10:
      • 31% acute Grade 3 - 4 nonhematologic toxicity
      • 76% acute Grade 3 - 4 chemotherapy related toxicity
      • 31% of patients did not complete radiotherapy
    • Salama et al (University of Illinois):
      • 13 patients with various pelvic malignancies (11 mo followup) ‏
      • Only 2 / 13 patients had Grade III acute toxicity
      • Late Gr III toxicity:
        • Small bowel obstruction:1
        • Lymphedema: 1
  • IMRT: Extended Pelvic RT
    • Beriwal et al (University of Pittsburg):
      • 36 patients with Stage IB2–IVA cervical cancer
      • Para-aortic nodes to the superior border of L1 treated
      • Weekly Cisplatin CCT
      • Gr III late toxicity: 10%
      • 2yr LRC: 80%
      • 2yr DFS: 51%
  • Bone Marrow Sparing
    • Dosimetric comparision of bone marrow sparing IMRT (Lujan et al):
      • Found that between a dose level of 18 – 20 Gy a significant reduction in volume of bone marrow irradiated was obtained with IMRT.
    • Brixey and Colleagues specifically compared hematological toxicity of WP-IMRT vs WPRT in the setting of concurrent CCT
  • Conclusions
    • Both 3D CRT and IMRT are still investigational tools.
    • However unless dose escalation is done no significant improvement in the control rates should be expected.
    • Chronic and acute toxicity amelioration are the more relevant endpoints.
    • Also may allow tighter integration of brachy therapy/ chemotherpay / biological therapy
    • Biologically optimized radiotherapy is an exciting new development
    • Real impact can only be realised with meticulous care in planning and execution.
  • Thank You