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YL Presentation RT Evolution Ohrid18.Pdf

YL Presentation RT Evolution Ohrid18.Pdf

International Medical Physics & Biomedical Engineering Workshop in Ohrid Congress Centre, 25-28 July 2018

Yves Lemoigne IFMP, Ambilly, France & TERA Foundation @ CERN Geneva, Ch

From the beginning to now Following alternatively the « X-rays » line (in green) and the particle line (in red)

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Two parallel lines: X-Rays & particle

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch First « decade » of radiotherapy

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch First « decade » of radiotherapy

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch First « decade » of radiotherapy

Henri

Marie Sklodowska (7/11/1867-4/7/1934) was a French-Polish physicist and chemist. She was the first person honored with two Nobel Prizes – in physics an chemistry. She was the first female professor at the University of Paris, and in 1995 became the first woman to be entombed on her own merits in the Pantheon in Paris. developed methods for separation of radium from radioactives residues in sufficient quantities to allow for its characterization and the careful study of its properties, therapeutic properties in particular.

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch First « decade » of radiotherapy

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch First « decade » of radiotherapy

Red line = Particle Green line = X-Rays

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Second Decade of Radiotherapy

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

1911 : Almost by chance, Claudius Regaud discovers the interest of fractionation

Why Fractionation works ? We ‘ll see later with the cell’s cycle and

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

 High Technology !

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

Birth of scientific dosimetry for Radiation

Why only is honored ?

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

1913: Hot Cathode Tube

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

Treatment in the Kitchen or Dining Room of the patient ?

• A pré-history stage… In the dining room ?

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

Machine built by !

Slow Progresses in the skin depth…

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch A new 20 years period

==> This announces the future Megavoltage machines ?

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch After 40 years : Maturity Period ?

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch After 40 years : Maturity Period ?

This machine anticipates the next generation of Megavolts devices

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch The Decade 1929 - 1939

Henri Coutard summarizes what is understood and defines:

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch The Decade 1929 - 1939

Note the modesty of the speech .... 26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch The Decade 1929 - 1939

Opens the door to future Teletherapy machines….

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch The Decade 1929 - 1939

• Important fact at the beginning of the decade:

A new era can open... But during the next decade, scientists were busy with less peacefull activities…

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Ernest Lawrence and Cyclotrons • E.Lawrence has built cyclotrons of increasing size: • In 1929 a 11-Inch ( 26 cm) diameter accelerating Protons to 1 MeV • In 1932 a 27-Inch (65 cm) with a magnet of 80 tons • In 1937 a 37-Inch (89 cm) • In 1939 a 60-Inch (144 cm)See picture below. Lawrence thought only of increasing the power of cyclotrons. Otherwise he could have discovered artificial radioactivity by noticing that his cyclotrons continued to radiate after the swith-off. This new radioactivity was discovered in 1935 by Irene Curie and Frédérick Joliot with less costly equipment. .

E.L.

E.L. 27 inch Cyclotron (1932) 60 inch Cyclotron (1939)

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch W W II and Post War period

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Synchrotrons

• A synchrotron is a particular type of cyclic particle accelerator, descended from the cyclotron, in which the accelerating particle beam travels around a fixed closed- loop path. The magnetic field which bends the particle beam into its closed path increases with time during the accelerating process, being synchronized to the increasing kinetic of the particles, hence the name. One of the early large synchrotrons, now retired, is the Bevatron, constructed in 1950 at the Lawrence Berkeley Laboratory. The name of this proton accelerator comes from its power, in the range of 6.3 GeV.

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Robert Rathbun Wilson

Robert R. Wilson: Shaping Matter Robert Wilson’s seminal contribution to proton was made manifest in a paper he published In 1946. Titled “Radiological Use of Fast Protons” (Radiology 1946:47:487-91), the article’s established the fundamental tenets and techniques that are being followed today at about all proton therapy facilities around the world. He was a serious sculptor of international renown, whose works are displayed at many universities and institutions, like Fermilab and he championed unceasingly the peaceful use of atomic energy he helped to unleash.. Despite …. 26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Teletherapy and the “cobalt bomb”

• In 1951, University of Saskatchewan medical physicist Dr. Harold Johns and his graduate students became the first researchers in the world to successfully treat a cancer patient using cobalt-60 radiation therapy. •This innovative technology—dubbed the “cobalt bomb” by the media - revolutionized cancer treatment and saved the lives of millions of cancer patients around the world. With this new teletherapy technique: •This radiation machine bombarded cancers deep • The cure rate for cervical cancer soon climbed from in the body where previous therapies had been 25 per cent to 75 per cent. ineffective. In effect, it dropped a «bomb» on • In the '40s, only one in five patients survived for five cancer. years after getting such cancer (Cf Coutard Paper) • It is cheaper than the other techniques • The cobalt bomb is the grandfather of all radiation (Linacs, Proton and Ion therapy…) therapy units in modern cancer facilities today.

. 26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch The Betatron

6 MeV Betatron 1942

• A Betatron is a type of cyclic particle accelerator. • It is essentially a transformer with a torus-shaped vacuum tube as its secondary coil. An alternating current in the primary coils accelerates electrons in the vacuum around a circular path. • The betatron was the first machine capable of producing electron beams at higher than could be achieved with a simple electron gun •The maximum energy that a betatron can impart is limited by the strength of the magnetic field due to the saturation of iron and by practical size of the magnet core. The next generation of accelerators, the Synchrotrons overcame these limitations.

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch In the Fifties: Louis Harold & Theo Puck

Louis H Gray (1905-1965) an English physicist who worked on the effects of Radiation on Biological systems. He was an early contributor to the field of . • Amongst many other achievements, he defined a unit of radiation dosage which was later named after him as an SI unit, the gray. • The concept of RBE (Relative Biological Effectiveness) of doses of (1940) • Research into cells in hypoxic tumors and hyperbaric oxygen

Theodore Puck (1916 –2005) was an American geneticist born in Chicago, Illinois. • Puck was an early pioneer of "somatic cell genetics" and single-cell plating ( i.e. "cloning".) This work allowed the genetics of human and other mammalian cells to be studied in detail. • Puck's key work ultimately made modern genetics, such as the human genome and other mammalian genome projects, possible. • Puck made many basic discoveries in several areas. His team found that humans had 46 chromosomes rather than 48 which had earlier been believed.

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch And the linacs come on the scene…

Gordon Isaac and the Linac

Gordon's right eye was removed on January 11, 1956 because cancer had spread there. His left eye, however, had only a localized tumor that prompted Kaplan to treat it with the electron beam.

Cancer Linac-based radiation therapy began in treatment of the first patient in at Hammersmith Hospital, with an 8 MV machine • Medical grade linacs accelerate electrons using a tuned-cavity waveguide • Some linacs have short, vertically mounted waveguides, while higher energy machines have a horizontal, longer waveguide and a bending magnet to turn the beam verticallytowards the patient. • Medical linacs use monoenergetic electron beams between 4 and 25 MeV, giving an X-ray output with a spectrum of energiesup to and including the electron energy when the electrons are directed at a high-density (such as tungsten) target. • The LINAC produces a reliable, flexible and accurate radiation beam.The versatility of LINAC is a potential advantage over cobalt therapy as a treatment tool. In addition, the device can simply be powered off when not in use; there is no source requiring heavy shielding –

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch More recent Period

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch In the seventies and later

Modern imaging technologies, x-ray-computed tomography (CT) and magnetic resonance imaging (MRI) provide a fully 3D model of the anatomy of the patient that allows radiation oncologists to identify more accurately tumor volumes and their relationship with other critical normal organs. • 3DCRT (Three Dimensional Conformal Radiation Therapy).Several technologic developments have combined to move radiation oncology into the 3D conformal radiation therapy (3DCRT) era. • 3D radiation therapy treatment planning (3DRTP)systems have been commercially available for over the end of 20th century and were rapidly replacing the conventional radiation therapy (2D) dose planning process. • MLC:A new generation linear accelerators have computer-controlled multileaf collimators (MLC) providing aperture and beam-intensity modulation features giving precise shaping of dose distributions • Three-dimensional CRT plansusually use an increased number of radiation beams that are shaped using beams-eye-view (BEV) planning to conform to the target volume. Conventional 3DCRT was replaced with a newer, more advanced form of conformal therapy, called intensity-modulated radiation therapy (IMRT)

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch At the end of the XX century

• IMRT (Intensity Modulated Radiation Therapy) IMRT is a type of conformal radiation, which shapes radiation beams to closely approximate the shape of the tumor. • The intensity of the radiation in IMRT can be changed during treatment to spare more adjoining normal tissue than is spared during conventional radiation therapy. Because of this an increased dose of radiation can be delivered to the tumor using IMRT. IMRT is a state-of-the- art cancer treatment method that delivers high doses of radiation directly to cancer cells in a very targeted way, much more precisely than is possible with conventional radiotherapy. • IMRT utilizes beams or multileaf collimators that can turn on or off or be blocked during treatment, varying the radiation beam intensity across the targeted field. • The radiation beams may be moved dozens or hundreds of times and each may have a different intensity, resulting in radiation sculpted in three dimensions

• IGRT (Image GuidedRadiation Therapy)was a one step progress been made after IMRT. Traditionally, imaging technology has been used to produce three-dimensional scans of the patient’s anatomy to identify the exact location of the cancer tumor prior to treatment. However, difficulty arises for example, from movement caused by breathing.. IGRT combines with IMRT a new form of scanning technology, which allows planar or X-ray Volume Imaging (XVI), This enables to adjust the radiation beam based on the position of the target tumor and critical organs, while the patient is in the treatment position.

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Radiobiology: Cell Cycle and irradiation

up Fractionated-dose irradiation works Grow Fractionated-dose irradiation works Cells because cell cycle because cell cycle (unknow in C. Regaud’s times) • Hi (unknow in C. Regaud’s times) up Grow • Tumor: tissue: rapid renewal and Cells multi-plication of cells • Healthy tissue: slow renewal of cells

Period of cell radio-sensitivity :

High

Important

Low / null

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Tumoral / Normal Differential Effect

Healthy Tissues

Tumor

Tumor healing threshold

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Situation Now..

Courtesy Ugo Ugo Amaldi Amaldi

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch An Example of Modern Linac

• The TrueBeam Machine you can find in many hospitals… Varian’s TrueBeam is an innovative medical technology that integrates and synchronizes performance of imaging and treatment technology. • The system’s imager is used to guide patient placement and treatment delivery.(Pictures on the left) •The machine rotates around the patient to deliver the radiation treatments from nearly any angle. • The radiation beam is sculpted and shaped to match the three- dimensional shape of the tumor. This is accomplished using an important accessory called a multileaf collimator (MLC), a device with 120 computer-controlled mechanical “leaves” or “fingers” that can move to create apertures of different shapes and sizes. The MLC aperture changes during the course of treatment, to carefully target the tumor and protect surrounding tissues to the greatest extent possible. Uwe Oelfke will explain details about IMRT, IGRT, VMAT … Multileaf collimator

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Medical Accelerators for Proton Therapy The first suggestion that energetic protons could be an effective treatment method was made by Robert Wilson in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory (HCL). The first treatments were performed with particle accelerators built for physics research, notably Berkeley Radiation Laboratory. In 1961, a collaboration began between HCL and the Massachusetts General Hospital (MGH) to pursue proton therapy. a Later, The Northeast Proton Therapy Center at Massachusetts MGH f t General Hospital was brought online, HCL was Merged to it (9K patients). e r The world's first hospital-based proton therapy center with Loma Linda sufficient high energy was in 1990 at the Loma Linda 1 University9 University Medical Center (LLUMC) Medical Center

LLUMC Synchrotron

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Why Protons and Carbon Ions instead of X-Rays ?

Direct effects are those caused by ionizing particles and rays themselves, while the indirect effects are those that are caused by free radicals, generated especially in water radiolysis

Longitudinally and transversally the carbon peak is about 3 times narrower than the POOR proton peak: GOOD the widths are Size of Double ADN Helix is : 2 nm prop. to 1/√M

Excellent ! Courtesy Ugo Amaldi RBE (C/ = 5/1=5

Courtesy Ugo Amaldi 26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Pioneers’ Work in IonTherapy

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Specificity of Carbon Ions

Courtesy Ugo Amaldi

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Increasing Number of Particle Therapy Centres in one Decade

Particle Therapy Centres in Europe 2002 Particle Therapy Centres in Europe 2012 Ion Centres Proton Centres

In Europe Proton centres multipled by 3 In Europe Ion centres multipled by 4

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Worldwide Perspective …

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch In The Whole World

East Europe CCCP Mongolia

China Cuba India

(Mainly CO60)

Possible explanation : In the « Communist times » A Czech firm was producing « cobalt Bomb » at low price dispatched to « friends of Moscow » in his «Atom for Peace» program during the cold war…. 26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch World Equipment Type

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Mainly Rich Countries …

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch UN Countries / RT Centres

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Back in Europe

Particle Therapy Centres : 4 times more than in 2002

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Only the future can validate the past ... (Confucius ?) …and vice versa

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch Discussion / Comments

Now opens the time reserved for discussion and/or free comments…

26/07/2018 Yves Lemoigne, PhD, IFMP Ambilly Fr & TERA @ CERN, Geneva, Ch

Physics for Medical Imaging Applications Nato Science Series (II Mathematics, Physics and Chemistry Yves Lemoigne, Alessandra Caner and Ghita Rahal (5 janvier 2007)

SPRINGER P.O. Box 17,3300 AA Dordrecht, The Netherlands

Amazon Price: 64 € (Kindle format), 121 € (Broché)

Molecular Imaging: Computer Reconstruction &Practice Nato Science Series (II Mathematics, Physics and Chemistry Yves Lemoigne et Alessandra Caner (18 août 2008)

SPRINGER P.O. Box 17,3300 AA Dordrecht, The Netherlands

Amazon Price: 68 €

Radiotherapy and Brachytherapy (NATO Science for Peace and Security Series - B: Physics and Biophysics) Yves Lemoigne et Alessandra Caner (11 september 2009)

SPRINGER P.O. Box 17,3300 AA Dordrecht, The Netherlands

Amazon Price:67€

Radiation Protection In Medical Physics (Nato Science For Peace And Security Series B: Physics and Biophysics) ... Yves Lemoigne et Alessandra Caner (1 décembre 2010)

SPRINGER P.O. Box 17,3300 AA Dordrecht, The Netherlands

Amazon Price:63€

Radiation Protection in Medical Physics: Editors: Lemoigne, Yves, Caner, Alessandra Connect to https://www.springer.com/gp/book/9789400702462 or