This contains some of the slides of the clinical radiobiology course conducted in Shimla

1. Glimpse of Clinical Radiobiology
Teaching Course
Prof Manoj Gupta
Indira Gandhi Medical College, Shimla

2. Ionizing Radiation
• Ionizing Radiation is capable of producing ion pairs
by interaction with matter.
• Two Types.
–Electromagnetic Radiation eg. X-rays and g-rays
–Particulate Radiation eg. Electron, Proton,
Neutron, charged Nuclei, a-particles.
• Important biologically since ionization is
the property which bring death to a cell.

3. Incidence Beam
Exit Beam
Radiation and Matter
•When Radiation passes through matter, the exit
beam has lower intensity than the incident beam.
Scattering
Absorption
Attenuation
Detector

4. Attenuation
• Depends upon:
– Thickness of the Material a T
– a Atomic Number of the material through
which it passes
– a Density of the material
– Inversely proportional to the energy of the
photons (1/E)
Attenuation is an EXPONENTIAL
function of the thickness of the matter.

5. 1 cm 1 cm 1 cm 1 cm
100 -10 = 90 rad 90-09=81rad 81-8.1=72.9rad 72.9-10%
Exponential Attenuation
Addition of the same thickness of the material will reduce the intensity by same
fraction and not by same number. This is called exponential relationship.
10% 10% 10% 10%
100 Rad

6. Excitation
Ionization
Excitation vs. Ionization

7. Photoelectric absorption
Occurs with bound electrons
Photon disappear completely and part of its
energy is utilized to dislodge the bound electron and
rest is given to dislodged electron as kinetic energy.
Photon Energy = Binding energy + KE
Eg. 100kv = 40 kv + 60kv
Bound Electron

8. Differential absorption in body
• a Z3
(Atomic Number)
• Bones are more likely to absorb radiation
– This is why they appear white on the film
• Soft tissue absorbs less than bone
– These structures will appear gray on the film
• Air-containing structures such as lungs absorbs least.
– These structures will appear black on the film
Diagnostic Radiology
a 1/E3
( Energy of the photon)
Low Energy X-rays are used in Diagnostic Radiology (KEV)

9. Therapeutic Radiology
• This interaction is unsuitable for radiotherapy as
differential absorption will results into more
radiation dose to bones as compare to other tissues
and bone exert a shielding effect which will results
into more osteo-necrosis and less dose to tumor
present behind the bone because of shielding
effect.

10. Pteris longifolia (fern spore)
– Raymond E. Zircle
Eccentric nucleus
Cytoplasm
Germination
Aluminum foil
Polonium α -particle
WITH SMALL DOSES OF
RADIATION TO THE NUCLEUS
•Inhibition of germination
•Chlorophyll development
•Cracking of spore coats
Journal of Cellular and Comparative Physiology
Volume 2, Issue 3, pages 251–274, December 1932
Aluminum Foil

11. Repair
How Radiation Injury is manifested
No effect
Lethal
Damage Cell Death
Few days
to wks
Few cells killed :
Organism will heal &
survives
More cells killed:
Organism may be
survived with
prolonged
symptoms
Large no. cells killed:
Organism will perish
Mis-Repair
Mutation
Somatic Cancer
Few Years
Germ cell Genetic defect
Generation

12. What is a cell survival curve?
• A cell survival curve is a graphical representation of
the fraction of cells surviving a given dose of
radiation
• This graph is obtained by plotting the dose along the
linear x-axis and the surviving fraction along the
logarithmic y-axis
Linear X-Axis
Logarithmic
Y-Axis

13. Steeper the slope, higher the
sensitivity and vice versa
Do
Remember:-
2. Slope of the curve represent the radiation sensitivity
.20
.70
.05
.30

14. D10 is the dose required to reduce the survival fraction to 10% = e-1
D0 is the dose required to reduce the survival fraction to 37% = e-1
2D0 is the dose required to reduce the survival fraction to two
exponential reduction i.e. 2D0 = e-2 (37% x 37%)
=(.37 x .37)
3D0 = e-3 (.37 x .37 x .37)
SF = e-D/D0
Total dose of Radiation
dose which reduces the
survival fraction to 37%
The D0 Dose

15. SF = e-D/D0
If D = D0
SF = e-D0/D0 = e-1
If D = 2D0
SF = e-2D0/D0 = e-2
If D = 3D0
SF = e-3D0/D0 = e-3
The D0 Dose
Total dose of Radiation
dose which reduces the
survival fraction to 37%

16. Dose
SF
1
.1
.01
.001
.0001
D
10
D
10 D
10
D
10
D
10
D
10
D
10
D
10
D
10
D
10
Graphical Representation showing SF is an exponential function of the Dose of Radiation
e-1
e-2
e-3
e-4
Remember
“If cell survival curve is a straight line
on semi-log graph, then it represent a
exponential relationship. A Curvy cell
survival curve reflects that it is not a
exponential relationship”

17. Dose
SF
B
Initial portion is
continuously bending
at low dose region till
it reaches at point B.
Mammalian Cell Survival Curve1
.1
.01
.001
.0001
At higher dose
region the curve
becomes a straight
line.
Not Exponential
Exponential

18. • Each cell contain more than one target (may be assumed n
number of target and n may be any number more than one)
• In order to bring cell death by radiation, all the target should
be deactivated.
• If n-1 targets are hit then cell survives.
• There are two type of cell killing taking place simultaneously
to inactivate n target resulting into cell death.
– Cell kill by single hit event (SHE)
– Cell kill by multiple hit event (MHE)
Low Dose Region
High Dose Region
Multi Target Model

19. SF
Dose
Multi Target Model
As dose increases the
probability of deactivation
of n target by MHE also
increases and MHE also
start contributing in total
cell kill.
The curve keeps bending
with increasing dose as
contribution in cell kill by
MHE keeps increasing
Low Dose High Dose

20. Dose(GY)
SF
1
.1
.01
.001
.0001
Single hit kill or Linear Cell kill or Alpha
cell kill seen in low dose region
Effect = aD
SF = e - aD
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Shoulder
Effect a D
This term represent the probability
of inactivating two strands of DNA
by single radiation event.
Linear Quadratic model (LQ Model)
Linear Kill

21. Less curvy or small shoulder or less repair capacity
More curvy or Broad shoulder or large repair capacity
Early
Reacting
Tissue or
Tumor
Late Reacting Tissue or Tumor
Cell Survival Curve of Early and Late Reacting Tissues
SF
Dose

22. • Fraction size (Dose per fraction)
• Turnover (proliferative status)
• Overall treatment time.
• Organization of functional subunit in the
organ.

23. Recovery from Radiation Injury in
Spinal Cord
• Spinal Cord remember the
irradiated dose.
• With time cord start forgetting
the irradiated dose.
How much dose is remembered, depends
upon the RT Dose delivered to spinal cord
during first treatment.
Time of Re-irradiation

24. Clinical Application of
BED

25. Concomitant boost:
30 x 1.8Gy in 6 weeks, 5 days
per week
Total dose = 54Gy
12 x 1.5 Gy in 2 and ½ week
Total dose = 18Gy
Total Dose to the tumor will be
54 + 18 = 72 Gy in 6 weeks.

26. Increase in cell cycle time
Less proliferation
Less repopulation

27. No difference
10% difference
Chemo-Radiation
Conventional RT
British Columbia Study
DHANCA Trial
10-12% difference
IAEA Trial
12% difference
12% difference
Hypothesis

28. Radiobiology of
SRS/SBRTNon Fractionated RT
20 Gy to 60 Gy given in single fraction or 2-5
fractions
Benign and Malignant Diseases

29. PTV
CTV
GTV
Normal Tissue
Red Shell
Serial critical
structures
Inner Red shell
Outer Red shell
Dip because of
careful
planning
bulge

30. New Biology of High dose RT
• Vascular/ Stromal damage at
high dose.
• Stem Cell death at high dose.

31. “Double Trouble”
Prescribed Dose to spinal cord
25 fractions of 2Gy = 50Gy
Hot spot: 110%
Physical dose: 55Gy
Dose per fx = 2.2 Gy
Biological dose: 60.5Gy

32. Factors affecting the cell survival
curves
• Fractionation
• Oxygen
• Cell Cycle
• Type of Radiation (high LET or Low LET)
• Type of cells
• Type of species

33. 100 cells
100 cells
100 cells
10 Colonies 12 Colonies 14 Colonies
200 cGy
100 cGy
100 cGy
66.6 cGy
66.6 cGy
66.6cGy
Total Dose = Same
Interval between
fraction = Same
No of fraction = different
As the no of fraction is increased the colony
counted also increases
Repair of sub-lethal damage takes place between
fractions
Had there been no repair of damage, the total
dose would have resulted into same cell kill
irrespective of fractions
Repair of sub lethal damages

34. Fractionated RT
Single Fx
Multiple Fx
Shallower
Less
Sensitivity
Radiation
less effective
SLDR

35. 10 Fx 20 Fx 30 Fx
Therapeutic Advantage
Low a/b (Spinal Cord)
Low a/b (Spinal Cord)
Low a/b (Spinal Cord)
High a/b (Tumor) High a/b (Tumor)
High a/b (Tumor)
As number of fraction increases, the gap between two curve also
increases.
So total dose of radiation will be more damaging to the tumor than
to the normal tissues
Fractionation is the most effective measures
to increase the therapeutic ratio.

36. Dose Rate Effect
SF
Dose
As No of Fraction Increases, Dose per Fc decreases
SHE(a) MHE(b)
SHE(a) increases MHE(b) decreases
All cell Kill SHE(a)
No contribution by MHE(b)

37. The effect of oxygen is seen more in
terminal portion of the curve and less in
shoulder region.
Or we can say that oxygen effect is
seen more in high dose region than low
dose region.
Effect of Oxygen on cell survival curve
SF
Dose
Oxic
hypoxic
Low Dose
Region
High Dose
Region
Why ??

38. Mechanism of Reoxygenation
1. Reduction in ratio of total tumor cells to the
surface area of blood vessels.
for example if there are 10 capillaries
supplying to 100 tumor cells the ratio
of tumor cells to capillary is 10 which
mean one capillary supplying 10 cells.
After RT, 80 cells survived then ratio
becomes 8 so now one capillary
supplying to 8 cells

39. Intrinsic Radiation Sensitivity
• Can be determined by SF2(survival fraction at
2 Gy).
• SF2 is defined as the probability of cells
surviving to single dose of 2 Gy, commonly
used fraction size in clinical practice.
• Typically for carcinoma the SF2 is 50% (0.5).

40. 4 Rs of Radiobiology
1. Re-oxygenation
2. Redistribution or Re-assortment
3. Repopulation Or Regeneration
4. Repair of Sub-lethal damage
5. Repair of Potential Lethal Damage
Therapeutic Gain = Outcome of treatment(Tumor cell Kill)
Toxicity of treatment
Forms the basis of fractionated radiotherapy

41. Therapeutic Ratio
Tumor Control Probability (TCP)
Normal Tissue Complication Probability (NTCP)

42. Question
• A patient has 1 cm3 tumor on his right tonsil.
How much dose of radiation in 2 Gy per
fraction is to be delivered to achieve a 90%
tumor control probability(TCP)?

43. Microscopic Disease in Nodes
• How much dose to be given to clinically
negative neck nodes in head and neck cancer
patients to achieve a 90% TCP in neck?

44. TCP for micros-metastasis in nodes
Common clinical Situation eg. Head and neck ca
100 patients of head and neck cancer with clinical
negative neck but high probability of microscopic
disease in neck nodes because of high risk featured
primary disease treated with radiation.
15% fails in neck.
Why??

45. 50 Gy
60 Gy
Radiation Dose to Different zones
Why?

46. Linear Energy Transfer (LET)
Relative-biological Effectiveness
(RBE)

47. Relative Biological Effectiveness (RBE)
• The National Bureau of Standards in 1954
defined relative biologic effectiveness (RBE)
as follows:
RBE D250
Dr
= Dose of X-rays
Dose of test radiation
Required to achieve the same biological effect

48. Relation between RBE and LET
RBE
5 10 100
LET(kev/mm)
Slow increase in RBE
This kind of
relationship can
be explained by
over kill effect.

49. Introduction of the course
• This course is divided into 5 modules.
• Specially designed for post graduate students
of Radiation Oncology and young radiation
oncologists.
• It is an one day (8 hours) program.
• All the important principles of radiobiology
with their clinical applications are covered

50. Introduction of the course
• “How a radiation oncologist looks at
radiobiology and how the principles can be
applied in day to day clinical practice” is
mainly emphasized.
• Lot of animations and special effects have
been created to make the subject simple.
• Some of the slides from different modules
have been uploaded to give the readers an
idea.

51. Introduction of the course
• All the five modules are taught by me only.
• Conduct this course once a year in my center.
• Also conducting at various other parts of the
country as and when invited.
• Address
– Dr Manoj Gupta, Professor, Radiation Oncology
Regional Cancer Center, Indira Gandhi Medical
College, Shimla 9HP)-171001 India
– Mob: +91-9418470607, 9816137344
– Email: mkgupta62@yahoo.co.in