radiotherapy : past present future kmio 2015

Radiation Therapy

Rays of HopeThe Past , The Present & The Future

Lokesh Viswanath M.DProfessor & Head of Unit II , Radiation Oncology, Kidwai Memorial Institute of Oncology 2015

Radiotherapy

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.

visible

Infra Red Radio Waves

Microwaves Short Waves

T.V.Radio

Radar

IONIZINGRADIATION 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 MVHigh Energy - 18 Mv

6 Million Volts18 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 is a Double Edge Sword

↑ RT Dose

↓ RT Dose

↑ T – Control ↓↓ T – Control

↑↑ Normal Tissue Toxicitites

↓ Normal Tissue Toxicitites

Radiation therapy

Brachytherapy

Teletherapy

Tele Radiation Equipments

γ –Rays (Radioactive Source based) -

Radium BombTele

CesiumTelecobalt

Gamma Knife

X - RaysLinear Accelerato

r2D

Electrons3DCRT

SRS/SRTIMRTIGRT

Rapid ArcFFF

SBRT 4DRT – Target

tracking6D Couch

IORT

Tomotherapy

Cyber Knife

Particle Beam

ProtonsCarbon

Neutrons

Brachytherapy :

Radioactive source loading

Temporary

Pre Loaded After loading

Remote

LDR

HDR

Manual

Permanent

After PlanPre Plan

– Intracavitory / Luminal– Interstitial– Surface Mould

THE PAST1895- 1920s : Seeding - X - Ray & Radium1920 – 1930 : embryo Phase1930 -1950 : Quisent phase : World War I & II

•Artificial Radioactivity, •Development in Radar Technology

1950 – 1970 : Development Phase: Telecobalt & Linear Acclelrator –

1980 – 2000 : Infancy2000-2005 : Growth Phase2005 – 2010 : Maturation Phase2010 – 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 Therapy1938 Neutron therapy by John Lawrence and R.S. Stone

(Berkeley)1946 Robert Wilson suggests protons1948 Extensive studies at Berkeley confirm Wilson1954 Protons used on patients in Berkeley1957 Uppsala duplicates Berkeley results on patients1961 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 opens1972 Neutron therapy initiated at MD Anderson (Soon 6 places in

USA.)1974 Patient treated with pi meson beam at Los Alamos (Terminated in 1981) (Starts and stops also at PSI and TRIUMF)

(Cont)

1975 St. Petersburg proton therapy facility opens1975 Harvard team pioneers eye cancer treatment with protons1976 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 therapy1988 Proton therapy approved by FDA1989 Proton therapy at Clatterbridge1990 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

THE EVOLUTION OF RADIOTHERAPEUTIC 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.

IK/2007

IK/2007

IK/2007

IK/2007

IK/2007

THE EVOLUTION OF RADIOTHERAPEUTIC 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's Digital 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

THE EVOLUTION OF RADIOTHERAPEUTIC 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

Collimator Orientation

Multileaf CollimationMicroMLC

• 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

Tele Radiation Equipments

γ –Rays (Radioactive Source based) -

Radium BombTele

CesiumTelecobalt

Gamma Knife

X - RaysLinear Accelerato

r2D

Electrons3DCRT

SRS/SRTIMRTIGRT

Rapid ArcFFF

SBRT 4DRT – Target

tracking6D Couch

IORT

Tomotherapy

Cyber Knife

Particle Beam

ProtonsCarbon

Neutrons

Tomotherapy - 2003

Synchrony™

camera

Treatment couch

Linearaccelerator

Manipulator

Imagedetectors

X-ray sources

Targeting System

Robotic Delivery System

Cyber Knife – 2003+

IGRT - 2005

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

True Beam - 2010

Proton Beam therapy 2012

Brachytherapy :

Radioactive source loading

Temporary

Pre Loaded After loading

Remote

LDR

HDR

Manual

Permanent

After PlanPre Plan

– Intracavitory / Luminal– Interstitial– Surface Mould

125 I Seed Implant

Interstitial Brachytherapy

Prostate Brachytherapy

Prostate Brachytherapy

Iodine 125

t ½ = 60 days

Gamma emitter

Energy 35 kV

Treatment Planning

MLC

Control

Linac

Control

MLC

User Interface

CommonMemory

Linac MLC

ConsoleUser

Interface

Linac

LinacControl

MLCControl

MLC

Control

Linac

Control

MLCLinac

AddedGUI

Record/VerifyDB

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

Telecobalt 1970s

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

Linear Accelerator : 3DCRT / IMRT

HDR - Brachytherapy

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.

SCI

Radiation OncologyExpansion Plans

>2015Radiation Oncology Block

Fully Automated , Paperless environment

Sanctioned

Equipments Number

State of the ArtHigh energy Linear Accelerators

4 IMRT – Advanced rotationalIGRT4D / 6D Advanced tumor trackingFFFSRS/SRTWhole 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

Thank you

Cobalt- 60

Co 60 Radiosurgery – “Gamma Knife”

Linear Accelerator

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

Couch

CT Simulator

Treatment Planning

Beam Placement

Multileaf Collimator (MLC)

No more lead blocks!

Synchrony™

camera Linearaccelerator

Manipulator

Imagedetectors

X-ray sourcesTargeting System

Robotic Delivery System

Proton Therapy Center Czech

Photons Protons

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: 1941SCLC extensive disease

Name: B. H. DOB: 1941SCLC 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.