PARTICLE BEAM – PROTON,NEUTRON & HEAVY ION THERAPY

ASWATHI C P

M.SC RADIATION PHYSICS

CALICUT UNIVERSITY

INTRODUCTION

• Particle therapy is a form of external beam radiotherapy using beams of energetic protons, neutrons, or positive ions for cancer treatment .

- neutrons produced by neutron generators and cyclotrons,

- protons produced by cyclotrons and synchrotrons ,and

- heavy ions ( helium,carbon,nitrogen,argon,neon)

produced by synchro -cyclotrons and synchrotons

• The most common type of particle therapy as of 2012 is proton therapy.

• Although a photon, used in x-ray or gamma ray therapy, can also be considered a particle, photon therapy is not considered here. Additionally, electron therapy is generally put into its own category. Because of this, particle therapy is sometimes referred to, more correctly, as hadron therapy (that is, therapy with particles that are made of quarks)

1. HISTORY OF HADRON THERAPY

A TIME LINE OF HADRON THERAPY

1938 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)

1. HISTORY OF HADRON THERAPY (CONT)

A TIME LINE OF HADRON THERAPY1975 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)1991 Protons at Nice and Orsay

1. HISTORY OF HADRON THERAPY (CONT)

A TIME LINE OF HADRON THERAPY

1992 Berkeley cyclotron closed after treating more than 2,500 patients1993 Protons at Cape Town1993 Indiana treats first patient with protons1994 Ion (carbon) therapy started at HIMAC (By 20088 more than 3,000patients treated.)1996 PSI proton facility1998 Berlin proton facility2001 Massachusetts General opens proton therapy center2006 MD Anderson opens2007 Jacksonville, Florida opens2008 Neutron therapy re-stated at Fermilab (due to an ear mark).

PHYSICAL BASIS OF PARTICLE THERAPY

•In particle therapy (Proton therapy), energetic ionizing particles (protons or carbon ions) are directed at the target tumor.

•The dose increases while the particle penetrates the tissue, up to a maximum (the Bragg peak) that occurs near the end of the particle's range, and it then drops to (almost) zero.

•The advantage of this energy deposition profile is that less energy is deposited into the healthy tissue surrounding the target tissue.

LINEAR ENERGY TRANSFER

• It is defined as the average energy deposited per unit length of track of radiation and the unit is keV/μm.

• The energy loss per unit distance increases as the particle slow down in the medium, such that there is a peak of energy deposition at the end of the track of a charged particle, called Braggs peak.

• Charged particles generally have higher LET than X and γ rays because of their greater energy deposition along the track.

• biological effect of a radiation (its relative biological effectiveness, RBE) depends on its average LET

DOSE DISTRIBUTIONS OF DIFFERENT BEAM QUALITIES IN TISSUE

WHERE IS THE ENERGY DEPOSITED?

0

20

40

60

80

100

0 5 10 15 20 25 30 35

( Depth in Phantom)cm

Dose, N

orm

alize

d t

o D

max (%

)

SAD = 190 cm

SSD = 180 cm

Photons

Neutrons

Protons

PROTON THERAPY

Proton therapy (also called proton beam therapy) is a type of radiation treatment that uses protons rather than x-rays to treat cancer.

A proton is a positively charged particle that is part of an atom, the basic unit of all chemical elements, such as hydrogen or oxygen. At high energy, protons can destroy cancer cells.

HISTORY

• In 1946 Harvard physicist Robert Wilson (1914-2000) suggested*:• Protons can be used

clinically• Accelerators are available• Maximum radiation dose

can be placed into the tumor

• Proton therapy provides sparing of normal tissues

• Modulator wheels can spread narrow Bragg peak

*Wilson, R.R. (1946), “Radiological use of fast protons,” Radiology 47, 487.

SHORT HISTORY OF PROTON BEAM THERAPY

• 1946R. Wilson suggests use of protons• 1954First treatment of pituitary glands in Berkeley, USA• 1956Treatment of pituitary tumors in Berkeley, USA• 1958 First use of protons as a neurosurgical tool in

Sweden• 1967First large-field proton treatments in Sweden• 1974Large-field fractionated proton treatments

program begins at HCL, Cambridge, MA• 1990First hospital-based proton treatment center

opens at Loma Linda University MedicalCenter

DESCRIPTION

• Proton therapy is a type of external beam radiotherapy using ionizing radiation.

• During treatment, a particle accelerator is used to target the tumor with a beam of protons. These charged particles damage the DNA of cells, ultimately causing their death or interfering with their ability to proliferate.

• Due to their relatively large mass, protons have little lateral side scatter in the tissue; the beam does not broaden much, stays focused on the tumor shape and delivers only low-dose side-effects to surrounding tissue.

DESCRIPTION (CONT)

• All protons of a given energy have a certain range; very few protons penetrate beyond that distance. Furthermore, the dose delivered to tissue is maximum just over the last few millimeters of the particle’s range; this maximum is called the Bragg peak.

• The accelerators used for proton therapy typically produce protons with energies in the range of 70 to 250 MeV

• By adjusting the energy of the protons during application of treatment, the cell damage due to the proton beam is maximized within the tumor itself.

In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor

SPREAD OUT BRAGG PEAK (SOBP)

• In a typical treatment plan for proton therapy, the Spread Out Bragg Peak (SOBP, dashed blue line), is the therapeutic radiation distribution. The SOBP is the sum of several individual Bragg peaks (thin blue lines) at staggered depths.

• The depth-dose plot of an x-ray beam (red line) is provided for comparison. The pink area represents the additional dose delivered by x-ray radiotherapy which can be the source of damage to normal tissues and of secondary cancers, especially of the skin.

APPLICATION

• Proton therapy goes to a specific area of the patient's body, so this therapy can best shrink tumors that have not spread to other parts of the body

• proton therapy alone, or they may combine with standard radiation therapy, surgery, and/or chemotherapy are used clinically .

• Proton therapy is particularly useful for treating cancer in children because it lessens the chance of harming healthy, developing tissue.

PROTON THERAPY MAY BE USED TO TREAT THESE CANCERS:

• Central nervous system cancers (including chordoma, chondrosarcoma, and malignant meningioma)

• Eye cancer (including uveal melanoma or choroidal melanoma)

• Head and neck cancers (including nasal cavity and paranasal sinus cancer and some nasopharyngeal cancers)

• Lung cancer

• Liver cancer

• Prostate cancer

• Spinal and pelvic sarcomas (cancers that occur in the soft-tissue and bone)

• Some noncancerous tumors of the brain may also benefit from proton therapy.

WHY PROTONS ARE ADVANTAGEOUS

• Relatively low entrance dose (plateau)

• Maximum dose at depth (Bragg peak)

• Rapid distal dose fall-off

• Energy modulation (Spread-out Bragg peak)

ADVANTAGES

When compared to standard x-ray radiation:

1.Fewer short –and long-term side effects

2.Improved quality of life during and after treatment

3.Proven to be effective in adults and children

4.Reduces the likelihood of secondary tumors caused by treatment

5.Can be used to treat recurrent tumors even in patients who have already received radiation

6.Targets tumors and cancer cells with precision,

reducing the risk of damage to surrounding healthy tissues and organs

DRAWBACKS

• Limited availability- This treatment requires highly specialized, expensive equipment. As a result, proton therapy is available at just a few medical centers in the United States

• Higher expense- Proton therapy costs more than conventional radiation therapy. equipment for production of protons, neutrons and heavy ions is considerably more expensive than standard radiotherapy equipment, both in capital costs and in maintenance and servicing costs.

HEAVY ION THERAPY

• Heavy-ion therapy is the use of particles more massive than protons or neutrons, such as carbon ions

• They are produced in ion sources and accelerated up to 50% of the speed of light in order to reach the necessary depth in the patient.

• A typical therapy beam consists of 1 million to 10 million carbon ions per second .

PHYSICAL BASIS OF HEAVY ION THERAPY

ADVANTAGES

As compared to conventional radiotherapy, heavy ion radiotherapy has the following advantages:

• Higher tumor dose and improved sparing of normal tissue in the entrance channel

• More precise concentration of the dose in the target volume with steeper gradients to the normal tissue

• Higher radiobiological effectiveness for tumors which are radio-resistant during conventional

APPLICATION CARBON ION THERAPY

• Prostate cancer

• Lung cancer

• Specific bone and soft-tissue sarcomas

DISADVANTAGE

Compared to protons, carbon ions have the disadvantage that beyond the Bragg peak, the dose does not decrease to zero, since nuclear reactions between the carbon ions and the atoms of the tissue lead to production of lighter ions which have a higher range. Therefore, some damage occurs also beyond the Bragg peak.

NEUTRON RADIOTHERAPY

• Fast Neutron Therapy Beams

• Boron Neutron Capture Therapy

FAST NEUTRONS METHODS OF PRODUCTION

• Neutrons can be produced in a cyclotron by accelerating deuterons or protons and impinging them on a beryllium target.

• Protons or deuterons must be accelerated to ≥50 MeV to produce neutron beams with penetration comparable to megavoltage x-rays.

FAST NEUTRONS METHODS OF PRODUCTION

• Accelerating deuterons to ≥50MeV • Requires very large

cyclotron, too large for hospital.

• Accelerating protons to ≥50MeV • Much smaller cyclotron

b/c proton has ½ the mass of deuteron.

P+

n

FAST NEUTRONS FROM DEUTERON BOMBARDMENT OF BE

• Stripping Process – • Proton is stripped from the deuteron.• Recoil neutron retains some of the incident kinetic

energy of the accelerated deuteron. • For each neutron produced, one atom of Be is

converted to B.B105

Be94 n

+ g

FAST NEUTRONS FROM PROTON BOMBARDMENT OF BE

• Knock-out Process • Protons impinge target of beryllium, where they

knock-out neutrons.• For each neutron “knocked-out”, one atom of Be is

converted to B.

B95Be94 nP+

+ g

LARGE RADIORESISTANT TUMORS ARE NOT WELL CONTROLLED BY PHOTON (OR PROTON)

THERAPY

• Resting cells are radioresistant• Hypoxic (low oxygen) cells are

radioresistant

Neutron therapy is less affected by cell cycle or oxygen content

Why are Neutrons Needed?

RADIOBIOLOGICAL ASPECTS OF NEUTRON THERAPY

• Neutrons are more effective per unit dose than x-rays

• Cell survival curves for neutrons are more nearly exponential than those of x-rays

• The modifying effect of hypoxia is smaller for neutrons than for photons

• Cell sensitivity to neutrons is much less dependent on cell growth stage than cell sensitivity to photons

APPLICATION

Neutrons have effective for patients with slower growing tumors such as

• adenoidcystic carcinoma (cancer of parotid glands)• locally advanced prostate cancer • locally advanced head and neck tumors • inoperable sarcomas • cancer of the salivary glands

ADVANTAGES

• LET comparisons of low LET electrons and high LET electrons

electrons produced from X-rays have high energy and low LET cause only few ionizations , when they interact with a cell , and so single strand breaks of the DNA molecule are possible , which can be readily repaired.

The high LET charged particles produced from neutron irradiation cause many ionizations as they traverse a cell, and so double-strand breaks of the DNA molecule are possible. DNA repair of double-strand breaks are much more difficult for a cell to repair, and more likely to lead to cell death.

ADVANTAGES(CONT)

• Oxygen effect

Neutron irradiation overcomes the effect of tumor hypoxia

BORON NEUTRON CAPTURE THERAPY (BNCT)

• Neutron capture therapy might be considered a type of particle therapy, as the damage it does to tumors is mostly from energetic ions produced by the secondary nuclear reaction after the neutrons in the external beam are absorbed into boron-10 (or occasionally some other nuclide), and not due primarily to the neutrons themselves. It is therefore a type of secondary particle therapy.

BNCT-PRINCIPLES

BNCT is a form of cancer therapy which uses a boron-containing compound that preferentially concentrates in tumor sites. The neutrons irradiated interact with the boron in the tumor to cause the boron atom to split into an alpha particle and lithium nucleus. Both of these particles have a very short range (about one cellular diameter) and cause significant damage to the cell in which it is contained.

42/18

TissueAir

Incident epithermal

neutrons

10B 11*B7Lit =10-12 sec

E7Li=0,84 MeV

Eα=1,47 MeVα

γEγ=0,48 MeV

Thermal neutrons

WHY BORON???

1. it is non-radioactive and readily available, comprising approximately 20% of naturally occurring boron;

2.Emitted particles (a and 7Li) have high LET

3.Chemistry of boron is well understood and allows it to be readily incorporated into a multitude of different chemical structures.

DOOR DESIGN FOR NEUTRON SHIELDING DETAILS

1. Boronated polyethylene: The polyethylene (high H content)

slows (moderates) the fast and intermediate energy neutrons to thermal energies.

The 5% Boron absorbs the low energy neutrons (high cross section for thermal neutron absorption).

2. Lead absorbs the 0.48 MeV photon that results from the (n,a) and capture gammas ( from maze ceiling, and floor).

Polyethylene 5% Boron

Steel Casing

Lead

Maze

Click icon to add picture

NEUTRON SOURCES nuclear research reactors accelerators radioisotopes (in particular 252Cf)

Neutron beam requirements epithermal neutron flux 109 neutrons/cm2s

(at the therapy position) neutron energy ~ 1 eV to ~ 10.0 keV gamma dose rate 2х10-13 Gy/cm2

fast neutron dose rate 2х10-13 Gy/cm2

current:flux (J/) ratio > 0.8

APPLICATION

• Brain tumors

• head and neck cancers

• Melanoma

• Colon cancer

REFERENCE

• PROTON THERAPY PHYSICS - Edited by Harald Paganetti

• RADIATION ONCOLOGY PHYSICS (A handbook for

• teachers and students)

• WIKIPEDIA

THANK YOU