![Page 1: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/1.jpg)
Radiation Therapy Radiation Therapy (RT)(RT)
![Page 2: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/2.jpg)
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
![Page 3: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/3.jpg)
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
![Page 4: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/4.jpg)
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 Ni=iVi
Number of clonogen cells after T is
TT
T
d
ieN2NTN iii
![Page 5: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/5.jpg)
Cancer treatment Cancer usually treated by:
Chemotherapy Surgery Radiation therapy
Treated also by Hyperthermia Hormone therapy Molecular targeted therapy
![Page 6: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/6.jpg)
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
![Page 7: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/7.jpg)
Dosimetry
Dose (actually absorbed dose) is defined as energy absorbed per unit massD=E/m
Biological effects not due to increased temperature Lethal dose increases temperature by
approximately 0.001 degree C
![Page 8: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/8.jpg)
Radiobiology
LQ survival curve Death from single
hit
Death from multiple
sublethal hits2DDi eS
![Page 9: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/9.jpg)
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 statisticsNeTCP
![Page 10: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/10.jpg)
Radiation therapy
Use of ionizing radiation to kill cancer cells, while delivering as low dose as possible to normal tissue
![Page 11: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/11.jpg)
How the systems look today…
![Page 12: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/12.jpg)
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)
![Page 13: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/13.jpg)
How we plan today…
Despite IMRT capabilities, uniform dose distribution is demanded
![Page 14: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/14.jpg)
How we will plan in the future…
Customized nonuniform dose distributions on a patient specific basis
![Page 15: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/15.jpg)
Planning and imaging
We may image Anatomy Functions or molecular processes
Molecular imaging maybe gives us an answer how to shape the dose
![Page 16: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/16.jpg)
Positron emission tomography
Nuclear medicine medical imaging technique
Produces a 3D image of molecular processes in the body
![Page 17: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/17.jpg)
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
![Page 18: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/18.jpg)
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
![Page 19: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/19.jpg)
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
![Page 20: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/20.jpg)
Spatial biology distribution
The only missing link in the BCRT chain Properties are phenomenologically
characterized by: Clonogen density Radiosensitivity
Redefined =’[1+’/’ D]; ’, ’ are LQ parameters
Proliferation rate
![Page 21: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/21.jpg)
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
Ti
ieS
Di
ieS
![Page 22: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/22.jpg)
Local tumor control probability
Taking into account growth and kill
Initial number of clonogen cells in
individual volume element is
Ni=iVi
Recalling equation for TCP from Poisson statistics final
iNi eTCP
TDi
iieS
![Page 23: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/23.jpg)
Local tumor control probability
Probability to eliminate all cells in i-th volume element
T in interval between RT fractions
TiDiii eV
i eTCP
![Page 24: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/24.jpg)
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
i
iTCPTCP
tii EDm
tiiii EDmTCPTCPTCPL ,...,...,1
![Page 25: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/25.jpg)
Solution of the optimization problem
We assume that all volume elements are equal We choose reference radiobiological
parameters ref, ref, ref and reference dose Dref that would give sensible TCP
ii
refref
iiref
iref
i
refT
i
TDiD
TCP
L
ln'
11
0
0
![Page 26: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/26.jpg)
Special cases Constant radiobiology parameters
implies uniform dose Not a surprise, just gives us confidence
that method may be correct Variable clonogen density
i
ref
iref
T DiD
ln'
10
Dose increases logarithmically with clonogen density.
![Page 27: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/27.jpg)
Another two special cases
Nonuniform radiosensitivity
Nonuniform proliferation rate
i
ref
iref
i
refT DiD
ln'
10
TDiD irefi
refT
1
0
Dose increases linearly with proliferation rate.
Dose is approximately inversely proportional to the radiosensitivity.
![Page 28: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/28.jpg)
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
![Page 29: Radiation Therapy (RT). What is cancer? Failure of the mechanisms that control growth and proliferation of the cells Uncontrolled (often rapid) growth](https://reader035.vdocument.in/reader035/viewer/2022062516/56649d485503460f94a24660/html5/thumbnails/29.jpg)
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.