Radiotherapy : Past Present Future KMIO 2015

Radiation Therapy
Rays of Hope
The Past , The Present & The Future
Lokesh Viswanath M.D
Professor & Head of Unit II , Radiation Oncology,
Kidwai Memorial Institute of Oncology
2015

Definition of Radiation Oncology
• discipline of human medicine concerned with the
generation, conservation, and dissemination of
knowledge concerning the causes, prevention, and
treatment of cancer and other diseases involving
special expertise in the therapeutic applications of
ionizing radiation.
• radiation oncology is concerned with the investigation
of the fundamental principles of cancer biology, the
biologic interaction of radiation with normal and
malignant tissue, and the physical basis of therapeutic
radiation.
• As a learned profession, radiation oncology is
concerned with clinical care, scientific research, and
the education of professionals within the discipline.

Radiation Oncology
Principle & Practice
of Oncology
Radiation therapy &
Technology
Radiation Physics
Radiation Safety &
Protection
Quality assurance
Regulations
Radiation Biology
Clinical -Basic
Science / Cellular /
Genetic

The aim of radiation therapy
• to deliver a precisely measured dose of
radiation to a defined tumor volume with as
minimal damage as possible to surrounding
healthy tissue, resulting in eradication of the
tumor, a high quality of life, and prolongation
of survival at competitive cost.

• under our care we take full and exclusive responsibility,
exactly as does the surgeon who takes care of a patient
with cancer.
• This means that we examine the patient personally, review
the microscopic material, perform examinations and take a
biopsy if necessary.
• On the basis of this thorough clinical investigation we
consider the plan of treatment and suggest it to the
referring physician and to the patient.
• We reserve for ourselves the right to an independent
opinion regarding diagnosis and advisable therapy and if
necessary, the right of disagreement with the referring
physician.
• During the course of treatment, we ourselves direct any
additional medication that may be necessary and are ready
to be called in an emergency at any time.

Radiation Oncology Team
• Physician : Radiation Oncologist
• Radiation Physicist
• Dosimetrist
• RT Technologist (RTTs) – Radiotherapist
• RT Nurses

Radiation Therapy :
Fundamentals

ELECTROMAGNETIC RADIATIONS
Photon E = h(energy = Planck’s const x frequency)
= hc/ (c = speed of light,  = wave length)
10-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 10-1 1 10 102 103 104
 rays
X-rays U.V.
v
i
s
i
b
l
e
Infra Red Radio Waves
Microwaves Short Waves
T.V.
Radio
Radar
IONIZING
RADIATION NON-IONIZING RADIATION
 (cms)
E (eV) 1.24x107 1.24x102 1.24x10-13

Incandescent Light
Bulbs
Diagnostic
X Ray tube
Voltage of a Lightning Bolt
110-240 Volts 80-140Kilo Volts 3 to 120 million volts
Telecobalt Machine Linear Accelerator
1.1 Mv (Mega =
Million Volts)
Low Energy - 4-6 MV
High Energy - 18 Mv
6 Million Volts
18 Million Volts

Introduction
• Basics of Radiation Therapy
– High energy Ionizing Radiation – X / γ Rays
– Interaction of Radiation with matter
Transmission Attenuation
Scatter Absorption
Rad / Gray / cGy

Cancer Cell & Ionizing Radiation
• Cancer cell multiply faster than normal cell
• DNA is primary target
• Double Strand breaks
>>> Reproductive Cell Death

• Injury to DNA is the primary mechanism by which
ionizing radiation kills cells .
– Most DNA damage is repaired
– Lethal double-strand breaks -persist (locally multiply
damaged sites (300) of about 15 to 20 nucleotides in size)
– Micronuclei formation
– Chromosome aberrations
– Cell death through loss of the reproductive integrity of the
cell's genome.
• Many biologic factors affect the relationship between
the amount of physical energy deposited, the extent of
DNA damage that is caused, the number of cells that
are killed, and the severity of the tissue response

• Radiation therapy is the art of using high
energy ionizing radiation to destroy malignant
tumors while being able to minimize damage
to normal tissue.
• To be practiced like a Religion
• SOPs

↑ RT Dose ↓ RT Dose
↑ T – Control ↓↓ T – Control
↑↑ Normal Tissue
Toxicitites
↓ Normal Tissue
Toxicitites

Radiation therapy
BrachytherapyTeletherapy

Tele Radiation Equipments
γ –Rays
(Radioactive
Source based) -
Radium Bomb
Tele Cesium
Telecobalt
Gamma Knife
X - Rays
Linear Accelerator
2D
Electrons
3DCRT
SRS/SRT
IMRT
IGRT
Rapid Arc
FFF
SBRT
4DRT – Target
tracking
6D Couch
IORT
Tomotherapy
Cyber Knife
Particle
Beam
Protons
Carbon
Neutrons

Brachytherapy :
Radioactive source loading
Temporary
Pre Loaded After loading
Remote
LDR HDR
Manual
Permanent
After Plan
Pre Plan
– Intracavitory / Luminal
– Interstitial
– Surface Mould

THE PAST
1895- 1920s : Seeding - X - Ray & Radium
1920 – 1930 : embryo Phase
1930 -1950 : Quisent phase : World War I & II
•Artificial Radioactivity,
•Development in Radar Technology
1950 – 1970 : Development Phase: Telecobalt & Linear
Acclelrator –
1980 – 2000 : Infancy
2000-2005 : Growth Phase
2005 – 2010 : Maturation Phase
2010 – 2015 : Flower
> 2015 : Fruits

Marie Curie (1867 – 1934)
Born in Poland
University of Paris age 24
Discovered Radium 1898
t1/2 = 1602 years

Irene Joliot-Curie and Frederic Joliot Curie
• Artificial radioactivity

Emil Grubbe (1875-1960)
: the World’s first Radiation Oncologist.
• medical student in Chicago
• convinced his professor to
allow him to irradiate a
cancer patient, a woman
named Rose Lee
• Ms. Lee benefited greatly
from Grubbe’s intervention,
demonstrating the potential
value of x-ray treatments.

Claude Regaud (1870-1940) : Paris
• recognized that treatment may be better tolerated
and more effective if delivered more slowly with
modest doses per day over several weeks.

Henri Coutard (1876-1950) Paris
• pioneered the use of fractionated
Radiotherapy in a wide variety of
tumors.
• Note, he reported impressive
results using this approach in
patients with locally advanced
laryngeal cancers. His seminal
1934 report of the outcome of
these patients is still quoted
today.

Ralston Patterson (1897-1981) : England
• Holt Radium Hospital - center for radiation
treatment and research

Gilbert Fletcher
• MD Anderson Cancer Center
• established optimal
treatment regimens in a
wide variety of tumor sites
including head and neck
cancers and cervical cancer.

Brief History of Radiation Therapy
Chronologic Milestones:
• 1895 W.K.Rontgen discovered X-Rays.
• The first patient was treated with radiation in 1896,
two months after the discovery of the X-ray.
• 1896 Becquerel reported natural radioactivity in
Uranium compounds.
• 1898 Marie and Pierre Curie isolated radium from
pitchblende.
• 1900 Villard reported that radium emitted alpha,
beta and gamma radiations.
• 1934 Frederic and Irene Joliot (Curie’s daughter)
discovered artificial radioactivity.

FIRST CURE OF CANCER BY X-RAYS
1899 - BASAL CELL CARCINOMA
X-rays were used to cure cancer very soon after their discovery

Natural radioactivity was discovered by Becquerel, who was awarded the Nobel Prize
in Physics in 1903 along with Marie and Pierre Curie "in recognition of the
extraordinary services they have rendered by their joint researches on the radiation
phenomena"
“One wraps a Lumiere photographic plate with a bromide emulsion in two sheets of very thick black paper, such that the plate does not become clouded upon
being exposed to the sun for a day. One places on the sheet of paper, on the outside, a slab of the phosphorescent substance, and one exposes the whole to
the sun for several hours. When one then develops the photographic plate, one recognizes that the silhouette of the phosphorescent substance appears in
black on the negative. If one places between the phosphorescent substance and the paper a piece of money or a metal screen pierced with a cut-out design,
one sees the image of these objects appear on the negative. One must conclude from these experiments that the phosphorescent substance in question emits
rays which pass through the opaque paper and reduces silver salts.” Paris 1896
Maltese crossHenri Becquerel Marie Curie

Radioisotopes also were soon being used
to treat and cure cancer.
Radium applicators were used for many
other conditions!
Radioactive plaques
and implants are still
in common use, for
example in prostate
implant seeds.
cure of cancer
by radium
plaque - 1922

• 1898 Becquerel’s vest-pocket skin erythema and reports
of x-ray ‘burns’.
• 1903 Bergonie and Tribondeau described radiosenstivity
of proliferating cells.
• 1930 Coutard proposed treatment fractionation.
• 1950 Paterson’s definition of Therapeutic Ratio: Normal
Tissue Tolerance/ Tumor Control Dose.
Chronologic Milestones

THE EVOLUTION OF RADIOTHERAPEUTIC
TECHNIQUES :EARLY CHALLENGES
• Detection of Ionizing Radiation
• Defining the Quality of Radiation
• Defining the Quantity of Radiation
• Understanding the Mechanism of Action of
Radiation
• Optimizing Radiation Delivery Equipments

THE EVOLUTION: Measuring Radiation Dose:
• Skin Erythema Dose.
• 1902 Holzknecht in Vienna developed the Chromoradiometer -
An apparatus once used for estimating radiation exposure by
means of the color changes produced in slides placed next to
the skin.
• 1904 Sabouraud and Noire in France modified Holzknecht’s
method to Pastille-dose technique using pastilles of barium
platinocyanide.
• 1913 Ionization current measurement developed in Paris, and
adopted in 1928 at the ICR as the standard unit “r”: x or gamma
radiation producing 1 e.s.u in 1 cc of air.
• 1953 at the ICR the ‘rad’ was introduced as the unit of absorbed
dose: equal to 100 ergs per gram.
• 1970 the rad was redefined in a metric system: the Gray: joules
absorbed per kg. 1 Gray = 100 rads.

THE EVOLUTION : Quality of Radiation
 1913 Coolidge in the USA engineered the first successful X-ray
tube using hot-filament and Tungsten target.
 1920 higher voltages X ray units with more powerful
transformers and rectifiers:
 Contact therapy @ 50 KV,
 Superficial @ 100-150 KV
 Deep X-rays @ 200-400 KV.
 Effect of added filtration.
 Quality measured by HVL.
 1933-1950 the evolution Megavolt era:
 Van de Graaff electrostatic,
 the Betatron,
 the Cobalt units and
 the Linear accelerator.

History of Particle Beam Therapy
1938 Neutron therapy by John Lawrence and R.S. Stone
(Berkeley)
1946 Robert Wilson suggests protons
1948 Extensive studies at Berkeley confirm Wilson
1954 Protons used on patients in Berkeley
1957 Uppsala duplicates Berkeley results on patients
1961 First treatment at Harvard (By the time the facility closed
in 2002, 9,111patients had been treated.)
1968 Dubna proton facility opens
1969 Moscow proton facility opens
1972 Neutron therapy initiated at MD Anderson (Soon 6 places in
USA.)
1974 Patient treated with pi meson beam at Los Alamos (Terminate
in 1981) (Starts and stops also at PSI and TRIUMF)

(Cont)
1975 St. Petersburg proton therapy facility opens
1975 Harvard team pioneers eye cancer treatment with protons
1976 Neutron therapy initiated at Fermilab. (By the time the
facility closed in 2003, 3,100 patients had been treated)
1977 Bevalac starts ion treatment of patients. (By the time the
facility closed in 1992, 223 patients had been treated.)
1979 Chiba opens with proton therapy
1988 Proton therapy approved by FDA
1989 Proton therapy at Clatterbridge
1990 Medicare covers proton therapy and Particle Therapy
Cooperative Group (PTCOG) is formed:
1990 First hospital-based facility at Loma Linda (California)

Hammersmith Hospital, London, 1905

KMIO: 100 Kv : Orthovoltage / Superficial X Ray
Unit

Telecesium
• At KMIO Decomissioned few years back

Selectron
• Remote controlled
after loading
brachytherapy unit
• Pneumatic driven

1951 – First Cobalt machine
• Saskatoon, Saskatchewan
• London, Ontario
• Co 60
– t ½ = 5.26 years
– Gamma emitter
– Energy 1.25 MV

1956, Henry Kaplan, MD
• The first patient to
receive radiation
therapy from the
medical linear
accelerator
• Stanford
• 2-year-old boy
with
retinoblastoma

History of Radiation Delivery
• Linear Accelerators: 1950 to present
– Traveling wave systems
– Standing wave systems
– Microtron
– Reflexotron

TECHNIQUES 1970 & 80s
Treatment Planning:
 Central Axis % Depth Dose.
 Plotting Isodose Curves.
 Multiple Fields Cross-Fire.
 Manual Patient Contouring and Manual Isodose
Curve Summation.
 Computer Treatment Planning Central Axis and Off-
Axis.
 Image Based 3-D Dose Distribution.

TECHNIQUES
Understanding the biology of Cancer:
The natural history of different tumors based
on cell types.
The importance of cancer staging.
Retrospective outcome studies and
prospective Clinical Trials.
Identifying Dose Response expectations.

• 1970's Computed Tomography (CT)
Ultrasound (US)
• 1980's Magnetic Resonance Imaging (MRI)
Digital Subtraction Angiography (DSA)
Computed Radiography (CR)
• 2000'sDigital Radiography (DR)

• >1985 – CT scan for RT Planning , Involved Manual
Digitization of Contours only
• > 1990 – CT Scan Data was used for Target localization
& Contouring
– 3 D Rendering of Body contours and Tumour and normal
tissue Grids
– Beams Eye view
• > 1995
– 3D Planning
– 3D Conformal Bocks
• CD Scan data of Tissue Density used for RT calculation
• > 1998 - 3 D Conformal RT
• 2000 : Evolution of IMRT (Conceptualized in 1960s)

• Early 2000 IGRT – Cyber knife , non-isocentric
mount , Celing mounted KV Imaging and
advanced verification and repositioning
• 2005 IMRT as a routine
• With IGRT – Adaptive Radiotherpay need for
advanced Imaging
• CT on Rails or Onboard Mv/Kv Cones CT
imaging,
• Integration of ceiling mounted KV imaging

TECHNIQUES
Impact of Modern Technology:
Impact of Computer technology.
New Imaging technology.
Advances in Molecular biology.
The multidisciplinary approach to Cancer
treatment.

MODERN RADIOTHERAPEUTIC
TECHNIQUES
Image based treatment planning.
3-d conformal treatment planning.
Intensity Modulated Radiation Treatment
(IMRT).
Image Guided Radiation Treatment and
Adaptive Radiation Treatment.
Investigational: Proton and Particle Therapy.

Key Mile stone
• Use of CT Scan DICOM image for RT Planning
• 3 D rendering
• BEV

MLC Multileaf collimator
Advanced
computerization and
Hardware control
and processing.
Advanced radiation
safety devices

Lateral Isocenter Verification
Portal Imaging

Multileaf Collimation
MicroMLC
• Maximum field size: 72 x 63 mm
•Number of leaves: 40 per side
•Leaf thickness: 1 mm
•Material: tungsten
• Maximum field size: 100 x 100
mm
•Number of leaves: 26 per side
•Leaf thickness: 5.5, 4.5, 3 mm
•Material: tungsten

• Electronic portal imaging
• Motion management
Image Guidance Technology

Advanced Image Guidance
Elekta Synergy
Varian Trilogy

Solid state imaging panel
Kilovoltage X-ray source
90cm
Clearance
Image Guidance - Components

Synchrony™
camera
Treatment couch
Linear
accelerator
Manipulator
Image
detectors
X-ray sources
Targeting System
Robotic Delivery System
Cyber Knife – 2003+

True beam - All in One FFF SBRT / 4DRT
–

Prostate Brachytherapy
Iodine 125
t ½ = 60 days
Gamma emitter
Energy 35 kV

Treatment Planning
MLC
Control
Linac
Control
MLC
User
Interface
Common
Memory
Linac MLC
Console
User
Interface
Linac
Linac
Control
MLC
Control
MLC
Control
Linac
Control
MLCLinac
Added
GUI
Record/Verify
DB
User
Interface
Electronics
Hardware
Control of Radiation Delivery

Present : KMIO RO
Teletherapy
• Orthovoltage – 1 (not
working)
• Telecobalt – 3 (1 due for
decomissioning)
• Linear Accelerator
– Low energy : Simple – 1
– High – Dual energy : 3DCR
/IMRT/Electorns - 1
Brachytherapy
• HDR – 1
– ICBT - 2
– ISBT – due for
decomissioning
– ILBT - 1
• LDR – 2 sets

Linear Accelerator
• 3DCRT > 1998+
• IMRT > 2000+

Linear Accelerator : 3DCRT / IMRT

Future : KMIO RO
• KMIO has been granted a status of State
cancer Institute : Apex Institution in the State
of Karnataka to forsee cancer related activities
in the region.

Radiation Oncology
Expansion Plans

>2015
Radiation
Oncology Block
Fully Automated ,
Paperless
environment
Sanctione
d
Equipments Number
State of the Art
High energy Linear Accelerators
4 IMRT – Advanced rotational
IGRT
4D / 6D
Advanced tumor tracking
FFF
SRS/SRT
Whole body SBRT
HDR Brachytherapy 2 IR / Cobalt
Virtual Widebore CT Simulators 2
Permanent Implant Brachytherapy
suit with advanced planning system
1 Capable of handling Iodine seed –
BARC / Imported
Intra operative Electronic
Brachytherapy / Electorns suit
1
Advanced Doismetry equipments Set

Future - Research
• Cell biology - understand effects of ionizing radiation on cells,
tumors, and normal tissues.
• molecular cancer biology - clinical decision-making in oncology
• development of novel biology-driven strategies in the
multidisciplinary clinical environment.
– Molecular pathology of tumors - basis for improved
treatment stratification in oncology .
– Molecular pathophysiology - manifestation of radiation
sequelae in normal tissues .
– Molecular imaging - staging , biologic characterization of
tumors, and for determination of target volumes in
radiation oncology, including new approaches such as dose
painting.
– Molecular targeting in radiotherapy - enhancing the
therapeutic gain of the treatment.

Proton Therapy vs. IMRTProton Beam

Co 60 Radiosurgery – “Gamma Knife”

Linac Radiosurgery – “X Knife”
• High energy beam
• 1 moving source
• 5mm – 4cm target

Linac Radiosurgery – “X Knife”
Advantages
• Allows multiple fractions
• More widely available
• Linac has other uses

Treatment Planning
Beam
Placement

Multileaf Collimator (MLC)
No more
lead blocks!

Synchrony™
camera
Linear
accelerator
Manipulator
Image
detectors
X-ray sources
Targeting System
Robotic Delivery System

rapid dose fall-off
unecessary
radiation in
normal tissues
beam exit beam exit

Physical and technical principles
Leksell gamma knife

Exposure to the gel dosimeters by Leksell
Gamma Knife of varying diameter collimator
4 mm 18 mm14 mm8 mm

Name: B. H. DOB: 1941
SCLC extensive disease

Grenz Rays
Megavoltage
Orthovoltage
Superficial Therapy
Contact Therapy
20 KeV
50 KeV
150 KeV
500 KeV
1-25 MeV Major improvements in RT
during the mid-1900s came
from improved penumbra
and decreased skin dose
associated with higher
energy x-rays, cobalt, and
high energy photons.
More recently conformal
RT, IMRT, IGRT,
Gammaknife, Cyberknife,
tomotherapy, SRS, SRT,
protons, heavy ions, etc.
have added considerable
variety to the choices for
physical radiation delivery
and present radiobiological
challenges.

Radiotherapy : Past Present Future KMIO 2015

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Radiotherapy : Past Present Future KMIO 2015