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Radiation Therapy (RT)

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Radiation Therapy (RT) What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth of the tissue ... – PowerPoint PPT presentation

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Title: Radiation Therapy (RT)


1
Radiation Therapy (RT)
2
What is cancer?
  • Failure of the mechanisms that control growth and
    proliferation of the cells
  • Uncontrolled (often rapid) growth of the tissue
  • Formation of the tumor
  • Metastasis spread to distant locations

3
Tumor biology
  • Tumors consist mainly from fully functional
    (mature) cells
  • Clonogenic (stem) cells are capable of infinite
    proliferation and therefore responsible for tumor
    growth
  • Dividing stem cells divides continuously and
    tumor is growing exponentially

4
Tumor biology
  • Growth rate described by doubling time Td
  • Potential doubling time (cell cycle period)
  • Real doubling time (cell loses up to 90)
  • Initial number of clonogen cells in individual
    volume element is NiriVi
  • Number of clonogen cells after DT is

5
Cancer treatment
  • Cancer usually treated by
  • Chemotherapy
  • Surgery
  • Radiation therapy
  • Treated also by
  • Hyperthermia
  • Hormone therapy
  • Molecular targeted therapy

6
Ionizing radiation effects
  • Standard physical effects take place first
  • Chemical reactions follows them
  • Biological consequences
  • Damage to the cell is mainly due to DNA damage
  • Cell is considered to survive if unlimited
    reproductive potential is preserved

7
Dosimetry
  • Dose (actually absorbed dose) is defined as
    energy absorbed per unit mass
  • DDE/Dm
  • Biological effects not due to increased
    temperature
  • Lethal dose increases temperature by
    approximately 0.001 degree C

8
Radiobiology
  • LQ survival curve
  • Death from single hit
  • Death from multiple sublethal hits

9
Number of clonogen cells
  • Survival curve predict average number N of
    survived cells after irradiation of the cells
  • One of the hypothesis says that
  • All clonogen cells has to be eliminated to cure
    the tumor
  • Cells follow Poisson statistics

10
Radiation therapy
  • Use of ionizing radiation to kill cancer cells,
    while delivering as low dose as possible to
    normal tissue

11
How the systems look today
12
How the systems work today
  • Conventional radiotherapy uses uniform beams that
    results uniform dose
  • Technique that uses
  • nonuniform beams
  • can produce arbitrary
  • dose distribution in
  • tumor (IMRT)

13
How we plan today
  • Despite IMRT capabilities, uniform dose
    distribution is demanded

14
How we will plan in the future
  • Customized nonuniform dose distributions on a
    patient specific basis

15
Planning and imaging
  • We may image
  • Anatomy
  • Functions or molecular processes
  • Molecular imaging maybe gives us an answer how to
    shape the dose

16
Positron emission tomography
  • Nuclear medicine medical imaging technique
  • Produces a 3D image of molecular processes in the
    body

17
How PET works
  • Production of radioisotope
  • Bounding of radioisotope to some bioactive
    compound
  • Injecting patient by that radiolabeled compound
  • Imaging of spatial distribution of that compound

18
PET usage
  • Delineation of the tumor volume and its stage
    (past and present use)
  • In the future, probably very important tool for
    the assessment of
  • tumor clonogen cells density distribution
  • oxygen status of the tumor
  • tumor response to the radiation treatment

19
BCRT
  • Planned dose distribution in target volume is not
    uniform, but tailored on patient specific basis
  • Integral tumor dose is constrained
  • Planned dose distribution should result highest
    probability to eliminate tumor
  • Planned dose conforms to the spatial tumor
    biology distribution

20
Spatial biology distribution
  • The only missing link in the BCRT chain
  • Properties are phenomenologically characterized
    by
  • Clonogen density r
  • Radiosensitivity a
  • Redefined aa1b/a D a, b are LQ
    parameters
  • Proliferation rate g

21
Local tumor kinetics
  • Parameters for one volume element!
  • Si is number of cells after something happens,
    relative to initial number
  • Growth of the cells with time
  • Killing the cells after irradiation

22
Local tumor control probability
  • Taking into account growth and kill
  • Initial number of clonogen cells in individual
    volume element is
  • NiriVi
  • Recalling equation for TCP from Poisson statistics

23
Local tumor control probability
  • Probability to eliminate all cells in i-th volume
    element
  • DT in interval between RT fractions

24
Global TCP maximization
  • TCP for whole tumor is product of TCPs for each
    voxel
  • Total dose to the tumor is constrained
  • To maximize TCP, we construct Lagrangian

25
Solution of the optimization problem
  • We assume that all volume elements are equal
  • We choose reference radiobiological parameters
    rref, aref, gref and reference dose Dref that
    would give sensible TCP

26
Special cases
  • Constant radiobiology parameters implies uniform
    dose
  • Not a surprise, just gives us confidence that
    method may be correct ?
  • Variable clonogen density r

Dose increases logarithmically with clonogen
density.
27
Another two special cases
  • Nonuniform radiosensitivity a
  • Nonuniform proliferation rate g

Dose is approximately inversely proportional to
the radiosensitivity.
Dose increases linearly with proliferation rate.
28
Conclusions
  • The formalism proposed here is questionable
    because is based on an LQ model
  • Not valid for high doses
  • Presumes uniform dose distribution
  • Formalism does not take into account
  • Redistribution of the cells through cell cycle
  • Reoxygenation of hypoxic cells
  • It presumes that spatial distribution of
    biological parameters is known

29
Conclusions
  • Formalism gives a rough overview how to optimally
    shape the dose distribution
  • Simplistic (beginners) approach to the patient
    specific radiation therapy, which is believed to
    be future of RT by many renowned researchers.
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