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Particle beam – proton,neutron & heavy ion therapy



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particle therapy is advanced external beam therapy used to treat cancer , which uses beams of protons or other charged particles such as helium, carbon or other ions instead of photons. charged particles have different depth-dose distributions compared to photons. They deposit most of their energy in the last final millimeters of their trajectory (when their speed slows). This results in a sharp and localized peak of dose, known as the Bragg peak.

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Particle beam – proton,neutron & heavy ion therapy

  2. 2. 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
  3. 3. • 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)
  4. 4. 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 protons 1948 Extensive studies at Berkeley confirm Wilson 1954 Protons used on patients in Berkeley 1957 Uppsala duplicates Berkeley results on patients 1961 First treatment at Harvard (By the time the facility closed in 2002, 9,111patients had been treated.) 1968 Dubna proton facility opens 1969 Moscow proton facility opens 1972 Neutron therapy initiated at MD Anderson (Soon 6 places in USA.) 1974 Patient treated with pi meson beam at Los Alamos (Terminated in 1981) (Starts and stops also at PSI and TRIUMF)
  5. 5. 1. HISTORY OF HADRON THERAPY (CONT) A TIME LINE OF HADRON THERAPY 1975 St. Petersburg proton therapy facility opens 1975 Harvard team pioneers eye cancer treatment with protons 1976 Neutron therapy initiated at Fermilab. (By the time the facility closed in 2003, 3,100 patients had been treated) 1977 Bevalac starts ion treatment of patients. (By the time the facility closed in 1992, 223 patients had been treated.) 1979 Chiba opens with proton therapy 1988 Proton therapy approved by FDA 1989 Proton therapy at Clatterbridge 1990 Medicare covers proton therapy and Particle Therapy Cooperative Group (PTCOG) is formed: 1990 First hospital-based facility at Loma Linda (California) 1991 Protons at Nice and Orsay
  6. 6. 1. HISTORY OF HADRON THERAPY (CONT) A TIME LINE OF HADRON THERAPY 1992 Berkeley cyclotron closed after treating more than 2,500 patients 1993 Protons at Cape Town 1993 Indiana treats first patient with protons 1994 Ion (carbon) therapy started at HIMAC (By 20088 more than 3,000patients treated.) 1996 PSI proton facility 1998 Berlin proton facility 2001 Massachusetts General opens proton therapy center 2006 MD Anderson opens 2007 Jacksonville, Florida opens 2008 Neutron therapy re-stated at Fermilab (due to an ear mark).
  7. 7. 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.
  8. 8. 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
  10. 10. WHERE IS THE ENERGY DEPOSITED? 100 80 60 40 20 0 0 5 10 15 20 25 30 35 )Depth in Phantom (cm Dose, Normalized to Dmax (%) SAD = 190 cm SSD = 180 cm Photons Neutrons Protons
  11. 11. 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.
  12. 12. 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.
  13. 13. 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 Medical Center
  14. 14. 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.
  15. 15. 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.
  16. 16. In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor
  17. 17. 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.
  18. 18. 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.
  19. 19. 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.
  20. 20. 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)
  21. 21. 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
  22. 22. 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.
  23. 23. 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 .
  25. 25. 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
  26. 26. APPLICATION CARBON ION THERAPY • Prostate cancer • Lung cancer • Specific bone and soft-tissue sarcomas
  27. 27. 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.
  28. 28. NEUTRON RADIOTHERAPY • Fast Neutron Therapy Beams • Boron Neutron Capture Therapy
  29. 29. 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.
  30. 30. 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.
  31. 31. 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. B 10 5 Be 9 4 n + g
  32. 32. 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. B 9 5 Be 9 P 4 n + + g
  33. 33. Why are Neutrons Needed? 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
  34. 34. 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
  35. 35. 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
  36. 36. 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.
  37. 37. ADVANTAGES(CONT) • Oxygen effect Neutron irradiation overcomes the effect of tumor hypoxia
  38. 38. 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.
  39. 39. BNCT-PRINCIPLES 42/18 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. Incident epithermal neutrons Air Tissue 10B 11*B α t =10-12 sec 7Li E7 Li=0,84 MeV Eα=1,47 MeV γ Eγ=0,48 MeV Thermal neutrons
  40. 40. 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.
  41. 41. 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 Polyethylene 5% maze ceiling, and floor). Boron Steel Casing Lead Maze
  42. 42. 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
  43. 43. APPLICATION • Brain tumors • head and neck cancers • Melanoma • Colon cancer
  44. 44. REFERENCE • PROTON THERAPY PHYSICS - Edited by Harald Paganetti • RADIATION ONCOLOGY PHYSICS (A handbook for • teachers and students) • WIKIPEDIA
  45. 45. THANK YOU