APPEAL 10 Future Accelerator Projects

From Accelerator and Particle Physics to Cancer Treatment

Manjit Dosanjh, CERN

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https://www.iceccancer.org/about-icec/leadership/manjit-dosanjh/

https://www.adams-institute.ac.uk/news/manjit-dosanjh-appointed-visiting-professor-john-adams-institute-oxford-physics-department

https://www.youtube.com/watch?v=SPHU17r1iRU

https://indico.lal.in2p3.fr/event/4899/contributions/16507/attachments/13313/16056/Dosanjh-PRAE_Talk-October_2018.pdf

My notes from the lecture (if they don’t make sense then it is entirely my fault)

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Physics technologies involved with the discovery of the Higgs particle

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A way of illustrating the process

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Physics technologies for cancer

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The challenge isn’t the data but the fact that cancer changes and we only want to treat the tumour. The longer we live the more likely we are to get cancer.

Why Cancer and Physics Technologies?

It is a large and a growing societal challenge:

– More than 3 million new cancer cases in Europe in 2015

– Nearly 15 million globally in 2015

– This number will increase to 25 million in 2030

– Currently around 8 million deaths per year

How can physics help?

The Challenge of Treatment

Ideally one needs to treat:

– The tumour

– The whole tumour

– And nothing BUT the tumour”

Treatment has two equally important goals to destroy the tumour and protect the surrounding normal tissue. Therefore “seeing” in order to know where and precise “delivery” to make sure it goes where it should are key

Art of seeing………

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X-ray imaging

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https://en.wikipedia.org/wiki/X-ray

X-rays make up X-radiation, a form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz (3 x 1016 Hz to 3 x 1019 Hz) and energies in the range 100 eV to 100 keV. X-ray wavelengths are shorter than those of UV rays and typically longer than those of gamma rays. In many languages, X-radiation is referred to as Röntgen radiation, after the German scientist Wilhelm Röntgen, who discovered it on November 8, 1895. He named it X-radiation to signify an unknown type of radiation.

https://en.wikipedia.org/wiki/Wilhelm_R%C3%B6ntgen

Wilhelm Conrad Röntgen (27 March 1845 – 10 February 1923) was a German mechanical engineer and physicist, who, on 8 November 1895, produced and detected electromagnetic radiation in a wavelength range known as X-rays or Röntgen rays, an achievement that earned him the first Nobel Prize in Physics in 1901. In honour of his accomplishments, in 2004 the International Union of Pure and Applied Chemistry (IUPAC) named element 111, roentgenium, a radioactive element with multiple unstable isotopes, after him.

Driver of change: X-ray CT

CT – Computed Tomography

https://en.wikipedia.org/wiki/CT_scan

A CT scan or computed tomography scan (formerly computerized axial tomography scan or CAT scan) makes use of computer-processed combinations of many X-ray measurements taken from different angles to produce cross-sectional (tomographic) images (virtual “slices”) of specific areas of a scanned object, allowing the user to see inside the object without cutting. The 1979 Nobel Prize in Physiology or Medicine was awarded jointly to Allan M. Cormack and Godfrey N. Hounsfield “for the development of computer assisted tomography.

2000-2008 “CT Slice War”

CT became very fast with small voxel / pixels

2000: acquire a single transverse slice per rotation

2012: acquire up to 64-500 slices per rotation

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“3D-imaging”

Digital geometry processing is used to further generate a three-dimensional volume of the inside of the object from a small series of two-dimensional radiographic images taken around a single axis of rotation. Medical imaging is the most common application of X-ray CT. Its cross-sectional images are used for diagnostic and therapeutic purposes in various medical disciplines.

Single- , dual-, and spectral CT

https://www.appliedradiology.com/articles/dual-energy-ct-in-practice-basic-principles-and-applications

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Conventional or single energy CT (SECT) uses a single polychromatic X-ray beam (ranging from 70 to 140 kVp with a standard of 120 kVp) emitted from a single source and received by a single detector. The inherent contrast of the image dataset generated by this process depends on differences in photon attenuation of the various materials that constitute the human body (i.e., soft tissue, air, calcium, fat). The degree that a material will attenuate the X-ray beam is dependent on (1) tissue composition and (2) photon energy level and how closely it exceeds the k-edge (i.e., inner electron shell binding energy) of the material. Therefore, tissue attenuation can be manipulated by changing photon energy levels.

https://www.wikilectures.eu/w/Hounsfield%27s_units

https://en.wikipedia.org/wiki/Hounsfield_scale

The name of this unit is in honour of Sir Godfrey Hounsfield (1919-2004) – one of the pioneers of the computerized tomography (CT).

The first CT-images was produced in 1971 in Atkinson Morley’s Hospital in London.

https://en.wikipedia.org/wiki/Godfrey_Hounsfield

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Sir Godfrey Newbold Hounsfield CBE FRS (28 August 1919 – 12 August 2004) was an English electrical engineer who shared the 1979 Nobel Prize for Physiology or Medicine with Allan McLeod Cormack for his part in developing the diagnostic technique of X-ray computed tomography (CT).

https://en.wikipedia.org/wiki/Allan_MacLeod_Cormack

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Dual energy CT offers the potential to analyse material composition through image acquisition at two different energy levels (typically 80 and 140 kVp). Since materials have unique attenuation profiles at different energy levels according to their linear attenuation coefficient, DECT can utilize mathematical algorithms to examine tissues when exposed to both low and high-energy polychromatic X-ray beams (acquire images that can be processed to generate additional datasets.). Materials with low atomic numbers (e.g., water) demonstrate small differences in attenuation between high and low X-ray energies while materials with high atomic numbers (e.g., iodine) show large differences in attenuation at different photon energies.

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https://medipix.web.cern.ch/

Spectral CT is now possible

The overall aim is to reduce the dose of X-rays used

https://www.radiologytoday.net/archive/rt0314p14.shtml

First 3D colour x-ray human image showing a wrist wearing a watch

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Medipix All Resolution System

Energy resolution

Spatial resolution

Temporal resolution

One of spectral CT’s most useful applications may be its ability to eliminate noncontrast exams and reduce radiation exposure by requiring only the contrast exam. In a conventional CT exam, a patient is scanned without contrast to collect noncontrast information for diagnostic purposes. Next, the patient would be injected with contrast, and a second scan would be completed in order to acquire the contrast-enhanced information. This not only increases exam times and impacts workflow but also increases the radiation dose being delivered to the patient. With the IQon Spectral CT, there is potential to identify the iodinated contrast within the image and allow for its selective visualization, thus allowing the elimination of the first step.

Spectral CT can eliminate noncontrast scans in examinations involving the liver and for the detection of kidney stones. You have the ability to remove the contrast agent after the scan based on the dual-energy data that you acquire. You can actually skip the noncontrast scan and only do the contrast-enhanced scan after the acquisitions virtually remove the iodine from the image.

By eliminating the need for a noncontrast exam, technologists can free up their time and resources to focus on better patient care. The true importance in this technique is the impact this can have on the care being delivered to the patient without any sacrifice to the data needed to make a confident diagnosis.

An image’s clarity impacts physicians’ diagnosis as well as their assessment of the best proper treatment for their patients. By discriminating between tissue or material composition, spectral CT may aid physicians in this process, especially when artifacts obstruct the image. For example, conventional CT techniques frequently are challenged by implanted metal hardware, such as a hip or knee prosthesis, and beam-hardening artifacts, which generate streaks or dark banding on an image and may reduce its quality.

On the one hand, conventional CT is a ubiquitous diagnostic tool for the physicians, but on the other hand, it does have challenges. A polychromatic beam is a major cause of beam-hardening artifacts and may result in indeterminate small lesions reducing a physician’s confidence in diagnosis. Spectral CT provides tools for the physicians to overcome these challenges and make CT a more specific diagnostic tool. Because certain energy levels are more sensitive to artifacts than others, combining the images from two different energy levels helps radiologists eliminate them to better assess the diagnostic information.

There is strong evidence in the literature suggesting that spectral CT also may determine kidney stone composition, which can be a significant factor in the physician’s call on best treatment. For example, uric acid stones can be treated with drugs or therapy, whereas the calcium stones need to be destroyed mechanically. This is not information that you can get easily with any other method.

Spectral CT’s use in other potential clinical applications has been demonstrated in further studies, including “optimization of contrast for vascular workup as well as cardiac imaging for enhanced coronary visualization. Spectral CT may increase sensitivity to contrast, which maintains image quality while reducing the amount of contrast given to the patient. This technology also separates calcified plaque from iodine, which may improve plaque assessment, another important tool in treatment decision making.

Radiologists could use spectral CT to aid in lesion characterization, especially in the abdomen. Indeterminate lesions are most common in the abdominal region, and additional testing is sometimes required to accurately interpret them. By separating materials, spectral CT provides access to better diagnostic information to help physicians characterize those lesions and improve their confidence in diagnosis.

Spectral CT may not only assess lesions but also aid in determining the efficacy of cancer treatment. One focus area that would be very exciting would be how to characterize cancer patients’ primary tumours to make an early decision if treatment is effective. Traditionally, you only look at the size of the lesion and if they shrink over time, but that might not be the best parameter to see at an early stage if treatment is effective. Vascularization and iodine uptake might be better parameters to see if the treatment works on the tumour.

Looking Ahead

Spectral CT is a significant step forward in CT technology. However it takes a long time to get things into clinical practice in certain areas, but the volume of publications and studies surrounding spectral CT suggests that it has the potential to bring a new level of preciseness to CT imaging. More diagnostic information means physicians will have greater confidence in determining diagnosis and treatment, which can lead to better care being delivered to the patient—an important value in the current health care reform environment.

Positron Emission Tomography

https://en.wikipedia.org/wiki/Positron_emission_tomography

Positron-emission tomography (PET) is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the body as an aid to the diagnosis of disease. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radioligand, most commonly fluorine-18, which is introduced into the body on a biologically active molecule called a radioactive tracer. Different ligands are used for different imaging purposes, depending on what the radiologist/researcher wants to detect. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis. In modern PET computed tomography scanners, three-dimensional imaging is often accomplished with the aid of a computed tomography X-ray scan performed on the patient during the same session, in the same machine.

If the biologically active tracer molecule chosen for PET is fludeoxyglucose (FDG), an analogue of glucose, the concentrations of tracer imaged will indicate tissue metabolic activity as it corresponds to the regional glucose uptake. Use of this tracer to explore the possibility of cancer metastasis (i.e., spreading to other sites) is the most common type of PET scan in standard medical care (representing 90% of current scans). Metabolic trapping of the radioactive glucose molecule allows the PET scan to be utilized. The same tracer may also be used for PET investigation and diagnosis of types of dementia. Less often, other radioactive tracers, usually but not always labelled with fluorine-18, are used to image the tissue concentration of other types of molecules of interest.

One of the disadvantages of PET scanners is their operating cost. A similar imaging process to PET is single-photon emission computed tomography (SPECT), which also uses radioligands to detect molecules in the brain, and is less expensive.

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18FDG carries the 18F to areas of high metabolic activity

90% of PET scans are in clinical oncology

1974 the first human positron emission tomography

Multimodality Imaging: PET-CT

https://scholar.google.com/citations?user=576nCAMAAAAJ&hl=en David Townsend

https://www.researchgate.net/publication/304750105_Multimodality_Imaging_-PETCT_and_PETMRI_Making_a_Difference

In oncology, PET/CT has swiftly come out as an essential instrument. There are several factors that have made PET/CT as a successful medical imaging technique. For the comprehensive diagnostic anatomical and functional information, patient has the advantage to undergo for the examination in one session. It provides more accurate information as compared to PET or CT separately. In addition, PET/CT allows the radiation oncologist to apply the information obtained from PET for an appropriate plan of radiation treatment. Results of clinical examinations suggest that, PET/CT provides more accurate results in diagnosis of a large of number diseases relative to PET or CT alone. In oncology, PET/CT differentiates very significantly the malignant from benign disease. It identifies more accurately, the locations of disease and detects the primary tumour which was previously unknown. Also, precisely stages the disease, estimates the prognosis, identifies the residual disease and confirms the sites of recurrence. Furthermore, it has a significant impact on foreseeing the early response after the initiation of the treatment, and objectifying the effectiveness of treatment. Thus, it reflects that PET/CT data are very useful in treatment planning in radiotherapy.

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Accelerators for Treatment

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In medicine the multidisciplines makes life difficult

Cancer treatment

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https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/surgery/risks-of-cancer-surgery.html

The biggest problem with surgery is that the cancer has probably spread quite a bit before it is removed

https://www.nhs.uk/conditions/chemotherapy/

There are an awful lot of nasty side effects with chemotherapy

Radiotherapy in 21st Century

https://www.nhs.uk/conditions/radiotherapy/

Radiotherapy is a treatment where ionising radiation is used to kill cancer cells.

There are many different ways you can have radiotherapy, but they all work in a similar way.

They damage cancer cells and stop them from growing or spreading in the body.

Radiotherapy may be used in the early stages of cancer or after it has started to spread.

It can be used to:

try to cure the cancer completely (curative radiotherapy)

make other treatments more effective – for example, it can be combined with chemotherapy (chemoradiation) or used before surgery (neo-adjuvant radiotherapy) reduce the risk of the cancer coming back after surgery (adjuvant radiotherapy) relieve symptoms if a cure isn’t possible (palliative radiotherapy)

Radiotherapy is generally considered the most effective cancer treatment after surgery, but how well it works varies from person to person.

Radiotherapy can be given in several ways. Doctors will recommend the best type for treatment.

The most common types are:

radiotherapy given by a machine (external radiotherapy) – where a machine is used to carefully aim beams of radiation at the cancer radiotherapy implants (brachytherapy) – where small pieces of radioactive metal are (usually temporarily) placed inside the body near the cancer radiotherapy injections, capsules or drinks (radioisotope therapy) – where radioactive liquid is swallowed or injected into the blood

Treatment is usually given in hospital. The patient can normally go home soon after external radiotherapy, but may need to stay in hospital for a few days if implants or radioisotope therapy were used.

Most people have several treatment sessions, which are typically spread over the course of a few weeks.

https://www.21co.com/radiation-therapy-overview/cancer-treatment-options/

3 “Cs” of Radiation

Cure (about 50% cancer cases are cured)

Conservative (non-invasive, fewer side effects)

Cheap (about 10% of total cost of cancer on radiation)

https://www.researchgate.net/scientific-contributions/39887921_J_P_Gerard (J.P.Gérard)

• About 50% patients should be treated with RT

• No substitute for RT in the near future

• No of patients is increasing

DEEP-SEATED TUMOURS Aims of Radiotherapy:

• Irradiate tumour with sufficient dose to stop cancer growth

• Avoid complications and minimise damage to surrounding tissue

Current radiotherapy methods:

• MV photons

• 5 – 25 MeV electrons

• 50 – 300 MeV/u hadrons

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Carbon produces positrons

https://en.wikipedia.org/wiki/Bragg_peak

The Bragg peak is a pronounced peak on the Bragg curve which plots the energy loss of ionizing radiation during its travel through matter. For protons, α-rays, and other ion rays, the peak occurs immediately before the particles come to rest. This is called Bragg peak, after William Henry Bragg who discovered it in 1903.

The phenomenon is exploited in particle therapy of cancer, to concentrate the effect of light ion beams or photons on the tumour being treated while minimizing the effect on the surrounding healthy tissue.

https://en.wikipedia.org/wiki/William_Henry_Bragg

Sir William Henry Bragg OM KBE PRS (2 July 1862 – 12 March 1942) was a British physicist, chemist, mathematician, and active sportsman who uniquely shared a Nobel Prize with his son Lawrence Bragg – the 1915 Nobel Prize in Physics: “for their services in the analysis of crystal structure by means of X-rays”. The mineral Braggite is named after him and his son. He was knighted in 1920.

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The phenomenon is exploited in particle therapy of cancer, to concentrate the effect of light ion beams on the tumour being treated while minimizing the effect on the surrounding healthy tissue.

The graph shows that electrons will have a greater effect at the surface of the body so will be less use for tumours well inside the body. However the energy falls off quite quickly so healthy organs will not be adversely effected. Electrons can be focused

X-rays (i.e. photons) have a Bragg peak at a slightly greater depth than electrons but doesn’t fall off so quickly meaning there is a good chance health organs could be effected.

Bragg peak really needs to be precise

Single beam of photons

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2 opposite photon beams

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Improved Delivery

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Above left shows 1990s: 4 constant intensity fields

Above right shows the current state of RT: Intensity Modulated Radiotherapy (IMRT) – Multiple converging field with planar (2D) intensity variations

Intensity Modulated Radiation Therapy

9 NON-UNIFORM FIELDS

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Intensity-modulated radiation therapy (IMRT) is an advanced mode of high-precision radiotherapy that uses computer-controlled linear accelerators to deliver precise radiation doses to a malignant tumour or specific areas within the tumour. IMRT allows for the radiation dose to conform more precisely to the three-dimensional (3-D) shape of the tumour by modulating—or controlling—the intensity of the radiation beam in multiple small volumes. IMRT also allows higher radiation doses to be focused on the tumour while minimizing the dose to surrounding normal critical structures. Treatment is carefully planned by using 3-D computed tomography (CT) or magnetic resonance (MRI) images of the patient in conjunction with computerized dose calculations to determine the dose intensity pattern that will best conform to the tumour shape. Typically, combinations of multiple intensity-modulated fields coming from different beam directions produce a customized radiation dose that maximizes tumour dose while also minimizing the dose to adjacent normal tissues.

Because the ratio of normal tissue dose to tumour dose is reduced to a minimum with the IMRT approach, higher and more effective radiation doses can safely be delivered to tumours with fewer side effects compared with conventional radiotherapy techniques. IMRT also has the potential to reduce treatment toxicity, even when doses are not increased. Due to its complexity, IMRT does require slightly longer daily treatment times and additional planning and safety checks before the patient can start the treatment when compared with conventional radiotherapy.

https://www.radiologyinfo.org/en/info.cfm?pg=imrt

Modern X-ray Therapy

Two companies produce X-ray accelerators

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Current accelerator system with gantry, patient positioner and X-ray panels to acquire CBCT and planar X-rays.

Intensity modulation is achieved by changing the multi-leaf collimator (MLC) patterns (right), gantry rotation and dose rate. Thus, intensity modulation is achieved through mechanical (slow) means.

The most widespread accelerator

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New Advances are here

The tumour and only the tumour…..

Concept of MRI guided accelerator

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Bas Raaymakers, Utrecht, UMC, ENLIGHT

http://www.radiotherapie.nl/research/who-is-who/raaymakers-bas

https://www.umcutrecht.nl/nl/

https://www.umcutrecht.nl/en/Research

https://www.researchgate.net/publication/324912362_The_ENLIGHT_network_invests_in_training

Seeing what you treat at the moment of treatment

Bringing certainty in the actual treatment

https://www.ncbi.nlm.nih.gov/pubmed/21753236

https://www.youtube.com/watch?v=gbmZkr9_z-E

https://www.christie.nhs.uk/patients-and-visitors/your-treatment-and-care/treatments/radiotherapy/what-we-do/mr-linac/ https://www.christie.nhs.uk/patients-and-visitors/your-treatment-and-care/treatments/radiotherapy/what-we-do/mr-linac/mr-linac-blog/

Hadron Therapy

https://en.wikipedia.org/wiki/Robert_R._Wilson

Robert Rathbun Wilson (March 4, 1914 – January 16, 2000) was an American physicist known for his work on the Manhattan Project during World War II.

After the war, Wilson also helped form the Federation of American Scientists and served as its chairman in 1946. He accepted an appointment as an associate professor at Harvard, but spent the first eight months of 1946 at Berkeley designing a new 150 MeV cyclotron for Harvard to replace the one taken to Los Alamos. At Harvard, Wilson published a seminal paper, “Radiological Use of Fast Protons”, which founded the field of proton therapy

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Both charged and uncharged particles lose energy while passing through matter. Positive ions are considered in most cases.

The force usually increases toward the end of range and reaches a maximum, the Bragg peak, shortly before the energy drops to zero. The curve that describes the force as function of the material depth is called the Bragg curve. This is of great practical importance for radiation therapy.

Why Hadron Therapy?

1946: Robert Wilson

Protons can be used clinically

Accelerators are available

Maximum radiation dose can be placed into the tumour

Particle therapy provides sparing of normal tissues

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Good for:

Tumours near critical organs

Tumours in children

Radio-resistant tumours

Cost is the reason why proton therapy has taken a while

Radio resistance = less oxygen

Ion therapy

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Less impact on surrounding tissue

Reduction of negative side effects

The modified beam shows how the originally monoenergetic beam with the sharp peak is widened by increasing the range of energies, so that a larger tumour volume can be treated. This can be achieved by using variable thickness attenuators like spinning wedges.

https://en.wikipedia.org/wiki/Ernest_Lawrence

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Ernest Orlando Lawrence (August 8, 1901 – August 27, 1958) was a pioneering American nuclear scientist and winner of the Nobel Prize in Physics in 1939 for his invention of the cyclotron. He supported its use in research into medical uses of radioisotopes.

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Diagram showing how a cyclotron works. The magnet’s pole pieces are shown smaller than in reality; they must actually be as wide as the dees to create a uniform field.

https://en.wikipedia.org/wiki/Cyclotron

Ion beams from cyclotrons can be used, as in proton therapy, to penetrate the body and kill tumours by radiation damage, while minimizing damage to healthy tissue along their path. Cyclotron beams can be used to bombard other atoms to produce short-lived positron-emitting isotopes suitable for PET imaging. More recently some cyclotrons currently installed at hospitals for radio isotopes production have been retrofitted to enable them to produce technetium-99m.

As mentioned earlier proton therapy was proposed by R. Wilson in 1946

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The first person was treated at Berkley in 1954

1993- Loma Linda USA (proton therapy)

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https://journals.sagepub.com/doi/pdf/10.1177/15330346070060S411 https://protons.com/ https://protons.com/proton-advantage/about-proton-therapy

https://youtu.be/FuD4z9H8Pcg

https://en.wikipedia.org/wiki/Proton_therapy

https://en.wikipedia.org/wiki/Loma_Linda_University_Medical_Center

Loma Linda University Medical Centre (LLUMC) is the teaching hospital for Loma Linda University

https://en.wikipedia.org/wiki/Loma_Linda_University_Medical_Center#Proton_treatment_and_research_center

First dedicated clinical facility

The James M. Slater Proton Treatment and Research Centre at Loma Linda University Medical Centre (LLUMC) offers proton therapy treatments for prostate, lung, brain and other types of cancers. This centre is the nation’s first hospital-based proton treatment centre. Since its opening in 1990 over 14,500 patients have been treated. Through a multidisciplinary approach, teams of experts including radiation oncologists, nurses, technicians and staff treat patients with care to ensure they experience fewer side effects and better outcomes with the power and precision of proton therapy.

1994 – HIMAC/NIRS Japan (carbon)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876641/

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70412-7/fulltext

https://en.wikipedia.org/wiki/National_Institute_of_Radiological_Sciences

The National Institute of Radiological Sciences (NIRS) is a radiation research institute in Japan. The NIRS was established in 1957 as the Japan’s only one institute of radiology. The NIRS maintains various ion accelerators in order to study the effects of radiation of the human body and medical uses of radiation.

The National Institute of Radiological Sciences hospital established in 1961 is a research hospital with a basic focus on radiation therapy. In 1993 the HIMAC (Heavy Ion Medical Accelerator in Chiba) of NIRS was launched, and in 1997 the Research Centre for Charged Particle Therapy was opened as one of the leading medical centres using carbon ions are in operation.

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https://www.nirs.qst.go.jp/ENG/index.html

1997 – GSI Germany (carbon)

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https://en.wikipedia.org/wiki/GSI_Helmholtz_Centre_for_Heavy_Ion_Research

The GSI Helmholtz Centre for Heavy Ion Research is a federally and state co-funded heavy ion research center in the Wixhausen suburb of Darmstadt, Germany. It was founded in 1969 as the Society for Heavy Ion Research, abbreviated GSI, to conduct research on and with heavy-ion accelerators. It is the only major user research centre in the State of Hesse. The laboratory performs basic and applied research in physics and related natural science disciplines.

An important technology developed at the GSI is the use of heavy ion beams for cancer treatment (from 1997). Instead of using X-ray radiation, carbon ions are used to irradiate the patient. The technique allows tumours which are close to vital organs to be treated, which is not possible with X-rays. This is due to the fact that the Bragg peak of carbon ions is much sharper than the peak of X-ray photons. A facility based on this technology, called Heidelberger Ionenstrahl-Therapiezentrum (HIT), built at the University of Heidelberg Medical Center began treating patients in November 2009.

Three crucial years ………to clinics

PIMMS study at CERN (1996-2000)

https://www.researchgate.net/figure/The-PIMMS-design-study-was-co-ordinated-by-CERN-1996-2000-It-combines-a-number-of_fig4_318665592

https://indico.cern.ch/event/682210/contributions/2960988/attachments/1669941/2678486/vretenar_ion_workshop.pdf

PIMMS = Proton-Ion Medical Machine Study

Started in 1996 as a study group at CERN between CERN, TERA Foundation (Italy), and MedAUSTRON (Austria) with initial close collaboration with GSI (Germany) for the design of a cancer therapy synchrotron.

Goal: understanding key techniques to produce a smooth beam spill for conformal treatment of complex tumours (sub-millimetre accuracy by active scanning); developing the main technical components of the facility.

In 2000 it resulted in the publication of a Technical Design Report, with a CD-ROM of data and technical drawings.

The PIMMS study was the basis for the construction of CNAO (Pavia, Italy) and MedAustron (Wiener Neustadt, Austria).

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Data from www.ptcog.ch Particle therapy co-operative group

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https://enlight.web.cern.ch/what-is-hadron-therapy

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By 2020 it is expected there will be almost 100 centres around the world, with over 30 of these in Europe.

Much remains to be done ……..

Current Challenge: how to ensure high quality radiotherapy globally: Challenging Environments

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Desirable features regarding LINACs designed for LICs

(Pomper MA et al. The Stanley Foundation, CNS, February 2016)

• A developing-world LINAC with modular enhancements,

• Costs could be phased in by starting with a basic unit, and options could be provided for:

– new technology,

– remote diagnosis and adjustment,

– a long-term maintenance contract with the vendor.

David Jaffray, ICARO 2017

Accelerators for “Peace and medical applications”

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Initiated and Championed by Prof. Herwig Schopper, former Director General of CERN

https://en.wikipedia.org/wiki/Herwig_Schopper

Herwig Franz Schopper, (born on 28 February 1924) is an experimental physicist and was the Director General of CERN from 1981 to 1988.

SESAME project: ‘Synchrotron Light for Experimental Science and Applications in the Middle East’

https://en.wikipedia.org/wiki/Synchrotron-Light_for_Experimental_Science_and_Applications_in_the_Middle_East

The Synchrotron-Light for Experimental Science and Applications in the Middle East (SESAME) is an independent laboratory located in Allan in the Balqa governorate of Jordan, created under the auspices of UNESCO on 30 May 2002.

Aimed at promoting peace between Middle Eastern countries, Jordan was chosen as the location for the laboratory, as it was then the only country that maintained diplomatic relations with all the other founding members; Bahrain, Cyprus, Egypt, Iran, Israel, Pakistan, the Palestinian Authority, and Turkey. The project was launched in 1999 and the ground breaking ceremony was held on 6 January 2003. Construction work began the following July, with a scheduled completion date of 2015. However financial and technical infrastructural obstacles forced the project to be delayed. The laboratory was inaugurated on 16 May 2017 under the patronage and presence of King Abdullah II.

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The success of such an initiative is being demonstrated by the SESAME project. It was built in Jordan, unifies nine member states of different political systems and religions in the Middle East: Bahrain, Cyprus, Egypt, Israel, Iran, Jordan, Pakistan, Palestinian Authority, Turkey and has achieved all of them to peacefully work together

The founding father of the SESAME project is also Prof. Herwig Schopper

Candidate Members for the South-East European International Institute for Sustainable Technologies

Republic of Albania; Bosnia and Montenegro; Republic of Bulgaria; Kosovo*; FYR of Macedonia; Montenegro; Republic of Serbia; Republic of Slovenia all signed a Declaration of Intent

Republic of Croatia agreed ‘ad referendum’

Hellenic Republic is an observer

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Main objectives

To promote collaboration between science, technology and industry, but also to provide platforms for the development of the education of young scientists and engineers based on knowledge and technology transfer from European laboratories like CERN and others

Bringing people from different countries to work together

To mitigate tensions between countries in the region

‘CERN model’ for SESAME in the Middle East and for South East Europe

What do we need in the future?

Treat the tumour and only the tumour: Control and monitor the ideal dose to the tumour; Minimal collateral radiation “outside” the tumour; Minimal radiation to nearby critical organs; Even if the tumour is moving

Be affordable: Keep capital and operating costs as low as possible: Increase the number of treated patients per year?

Compact: Fit into a large hospital? Reduce the size of the equipment

Improve patient through-put Increase effectiveness Decrease cost

Current Hot topics: VHEE, FLASH, Compact Machine ……….

With recent High-Gradient linac technology developments, Very High Energy Electrons (VHEE) in the range 100–250 MeV offer the promise to be a cost-effective option for Radiation Therapy

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CLIC RF X-band cavity prototype (12 Ghz, 100 MV/m) Compact Linear Collider

https://iopscience.iop.org/article/10.1088/0031-9155/59/19/5811/meta

Very high energy electrons (VHEE) in the range from 100–250 MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetry properties compared with MV photons from contemporary medical linear accelerators.

Courtesy of A. Lagzda

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Above right shows dose profiles for various particle beams in water (beam widths r = 0.5cm)

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Depth dose curve for various particle beams in water (beam widths r = 0.5cm)

FLASH radiotherapy is based on the observation that healthy tissue is less damaged if treatment occurs very fast

https://www.clinicaloncologyonline.net/article/S0936-6555(19)30203-1/fulltext

FLASH radiotherapy involves the ultra-fast delivery of radiation treatment at dose rates several orders of magnitude greater than those currently in routine clinical practice. In order to eradicate tumours, all cancerous cells must be killed with normal tissue being spared from radiation damage as much as possible. Ultra-fast dose rates allow normal tissue tolerance levels to be exceeded, at least in animal models, with a greater probability of tumour control and little or no normal tissue damage.

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Cyclotrons for proton therapy

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The isochronous cyclotron: principles and recent developmentshttps://www.sciencedirect.com/science/article/abs/pii/S0895611100000562

https://www.wikiwand.com/en/Cyclotron#/Isochronous_cyclotron

An isochronous cyclotron has a magnetic field that increases with radius rather than with time.

https://en.wikipedia.org/wiki/Synchrocyclotron

A synchrocyclotron is a special type of cyclotron, patented by Edwin McMillan, in which the frequency of the driving RF electric field is varied to compensate for relativistic effects as the particles’ velocity begins to approach the speed of light. This is in contrast to the classical cyclotron, where this frequency is constant.

https://en.wikipedia.org/wiki/Edwin_McMillan

Laser driven proton accelerator

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The process uses 6 x 1017 W/mm2 which is equivalent to the total solar power on earth, focused at 1 mm2

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But:

– 100x more power is needed

– Energy spectrum: not homogenous.

The process takes time!!

https://accelconf.web.cern.ch/accelconf/IPAC10/papers/mopea013.pdf

https://www.med.physik.uni-muenchen.de/research/laser-acceleration/1100_old/targetry-workshop/index.html

https://www.med.physik.uni-muenchen.de/research/laser-acceleration/1100_old/targetry-workshop/program/book-of-abstracts.pdf

To provide equipment for medical applications such as the production of radiopharmaceuticals

https://www.tandfonline.com/doi/full/10.1080/0284186X.2017.1355111

An intense laser pulse is focused on the front side of a thin solid laser target. The electrically neutral atoms of the laser target are ionized by the electric field of the incoming light pulse and a plasma is generated. The electrons in this front-side plasma are accelerated dominantly in forward direction by the electromagnetic field of the laser pulse, because at sufficient high intensities the electron quiver motion in the oscillating laser field becomes fully relativistic and the Lorentz force bends the electron motion into the foil. The ions acceleration is negligible at first because their mass is more than three orders of magnitude higher than the electron mass. As the laser pulse cannot penetrate the foil, the electrons pass through the foil, leaving the target, which leads to a strong local charge imbalance. A local sheath field is formed at the foil surface, providing a quasi-static acceleration field for surface ions, several orders of magnitude higher than the electrical fields used in conventional accelerators. Ions from the back side of the laser target are finally accelerated by this electrical field. At the end, a neutral cloud consisting of different ions, either from (organic) contaminations or targeted coatings of the rear laser target surface or from the target itself, as well as electrons, is propagating perpendicular to the laser target.

Because the accelerated ions are originating from different positions on the rear laser target surface, they experience different electric field strengths over different time durations. Finally, if the laser target is a plain foil the accelerated ions show an approximately exponentially decreasing energy spectrum up to an ion specific maximum cutoff energy. Another consequence of the acceleration process is a large laminar divergence of the ion beam (opening angles of few degrees).

Ion acceleration – options

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https://www.avoplc.com/Our-Company/Our-History

https://en.wikipedia.org/wiki/John_Adams_(physicist)

https://home.cern/science/accelerators/proton-synchrotron

https://www.iba-radiopharmasolutions.com/products/cyclotrons

https://www.iba-radiopharmasolutions.com/news/iba-launches-evolutionary-new-cyclotron

https://en.wikipedia.org/wiki/Fixed-field_alternating_gradient_accelerator

A Fixed-Field alternating gradient Accelerator (FFA) is a circular particle accelerator concept on which development was started in the early 50s, and that can be characterized by its time-independent magnetic fields (fixed-field, like in a cyclotron) and the use of strong focusing (alternating gradient, like in a synchrotron). Thus, FFA accelerators combine the cyclotron’s advantage of continuous, unpulsed operation, with the synchrotron’s relatively inexpensive small magnet ring, of narrow bore.

https://stfc.ukri.org/research/accelerator-science/ffag/

Improved synchrotron and linac are more advanced (less development time needed) and are within the CERN competences and are not in competition with commercial companies.

Treating moving targets

Courtesy of Christian Graeff, GSI, Germany

https://www.gsi.de/en/work/research/biophysics/team_details.htm?no_cache=1&name=graeff&vorname=christian

https://www.liverpool.ac.uk/oma-project/network-structure/steering-committee/christian_graeff/

Particle therapy of moving targets—the strategies for tumour motion monitoring and moving targets irradiation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124789/

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