Particle therapy

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Particle therapy
ICD-9 92.26

Particle therapy is a form of external beam radiotherapy using beams of energetic neutrons, protons, or other heavier positive ions for cancer treatment. The most common type of particle therapy as of August 2021 is proton therapy. [1]

Contents

In contrast to X-rays (photon beams) used in older radiotherapy, particle beams exhibit a Bragg peak in energy loss through the body, delivering their maximum radiation dose at or near the tumor and minimizing damage to surrounding normal tissues.

Particle therapy is also referred to more technically as hadron therapy, excluding photon and electron therapy. Neutron capture therapy, which depends on a secondary nuclear reaction, is also not considered here. Muon therapy, a rare type of particle therapy not within the categories above, has also been studied theoretically; [2] however, muons are still most commonly used for imaging, rather than therapy. [3]

Method

Unlike electrons or X-rays, the dose from protons to tissue is maximum just over the last few millimeters of the particle's range. Dose Depth Curves.svg
Unlike electrons or X-rays, the dose from protons to tissue is maximum just over the last few millimeters of the particle's range.

Particle therapy works by aiming energetic ionizing particles at the target tumor. [4] [5] These particles damage the DNA of tissue cells, ultimately causing their death. Because of their reduced ability to repair DNA, cancerous cells are particularly vulnerable to such damage.

The figure shows how beams of electrons, X-rays or protons of different energies (expressed in MeV) penetrate human tissue. Electrons have a short range and are therefore only of interest close to the skin (see electron therapy). Bremsstrahlung X-rays penetrate more deeply, but the dose absorbed by the tissue then shows the typical exponential decay with increasing thickness. For protons and heavier ions, on the other hand, the dose increases while the particle penetrates the tissue and loses energy continuously. Hence the dose increases with increasing thickness up to the Bragg peak that occurs near the end of the particle's range. Beyond the Bragg peak, the dose drops to zero (for protons) or almost zero (for heavier ions).

The advantage of this energy deposition profile is that less energy is deposited into the healthy tissue surrounding the target tissue. This enables higher dose prescription to the tumor, theoretically leading to a higher local control rate, as well as achieving a low toxicity rate. [6]

The ions are first accelerated by means of a cyclotron or synchrotron. The final energy of the emerging particle beam defines the depth of penetration, and hence, the location of the maximum energy deposition. Since it is easy to deflect the beam by means of electro-magnets in a transverse direction, it is possible to employ a raster scan method, i.e., to scan the target area quickly, as the electron beam scans a TV tube. If, in addition, the beam energy and hence the depth of penetration is varied, an entire target volume can be covered in three dimensions, providing an irradiation exactly following the shape of the tumor. This is one of the great advantages compared to conventional X-ray therapy.

At the end of 2008, 28 treatment facilities were in operation worldwide and over 70,000 patients had been treated by means of pions, [7] [8] protons and heavier ions. Most of this therapy has been conducted using protons. [9]

At the end of 2013, 105,000 patients had been treated with proton beams, [10] and approximately 13,000 patients had received carbon-ion therapy. [11]

As of April 1, 2015, for proton beam therapy, there are 49 facilities in the world, including 14 in the US with another 29 facilities under construction. For Carbon-ion therapy, there are eight centers operating and four under construction. [11] Carbon-ion therapy centers exist in Japan, Germany, Italy, and China. Two US federal agencies are hoping to stimulate the establishment of at least one US heavy-ion therapy center. [11]

Proton therapy

Proton therapy is a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often to treat cancer. The chief advantage of proton therapy over other types of external beam radiotherapy (e.g., radiation therapy, or photon therapy) is that the dose of protons is deposited over a narrow range of depth, which results in minimal entry, exit, or scattered radiation dose to healthy nearby tissues. High dose rates are key in cancer treatment advancements. PSI demonstrated that for cyclotron-based proton therapy facility using momentum cooling, it is possible to achieve remarkable dose rates of 952 Gy/s and 2105 Gy/s at the Bragg peak (in water) for 70 MeV and 230 MeV beams, respectively. When combined with field-specific ridge filters, Bragg peak-based FLASH proton therapy becomes feasible. [12]

Fast-neutron therapy

Fast neutron therapy utilizes high energy neutrons typically between 50 and 70 MeV to treat cancer. Most fast neutron therapy beams are produced by reactors, cyclotrons (d+Be) and linear accelerators. Neutron therapy is currently available in Germany, Russia, South Africa and the United States. In the United States, the only treatment center still operational is in Seattle, Washington. The Seattle center use a cyclotron which produces a proton beam impinging upon a beryllium target.

Carbon ion radiotherapy

Carbon ion therapy (C-ion RT) was pioneered at the National Institute of Radiological Sciences (NIRS) in Chiba, Japan, which began treating patients with carbon ion beams in 1994. This facility was the first to utilize carbon ions clinically, marking a significant advancement in particle therapy for cancer treatment. The therapeutic advantages of carbon ions were recognized earlier, but NIRS was instrumental in establishing its clinical application. [13] [14]

C-ion RT uses particles more massive than protons or neutrons. [15] Carbon ion radiotherapy has increasingly garnered scientific attention as technological delivery options have improved and clinical studies have demonstrated its treatment advantages for many cancers such as prostate, head and neck, lung, and liver cancers, bone and soft tissue sarcomas, locally recurrent rectal cancer, and pancreatic cancer, including locally advanced disease. It also has clear advantages to treat otherwise intractable hypoxic and radio-resistant cancers while opening the door for substantially hypo-fractionated treatment of normal and radio-sensitive disease.

By mid 2017, more than 15,000 patients have been treated worldwide in over 8 operational centers. Japan has been a conspicuous leader in this field. There are five heavy-ion radiotherapy facilities in operation and plans exist to construct several more facilities in the near future. In Germany this type of treatment is available at the Heidelberg Ion-Beam Therapy Center (HIT) and at the Marburg Ion-Beam Therapy Center (MIT). In Italy the National Centre of Oncological Hadrontherapy (CNAO) provides this treatment. Austria will open a CIRT center in 2017, with centers in South Korea, Taiwan, and China soon to open. No CIRT facility now operates in the United States but several are in various states of development. [16]

Biological advantages of heavy-ion radiotherapy

From a radiation biology standpoint, there is considerable rationale to support use of heavy-ion beams in treating cancer patients. All proton and other heavy ion beam therapies exhibit a defined Bragg peak in the body so they deliver their maximum lethal dosage at or near the tumor. This minimizes harmful radiation to the surrounding normal tissues. However, carbon-ions are heavier than protons and so provide a higher relative biological effectiveness (RBE), which increases with depth to reach the maximum at the end of the beam's range. Thus the RBE of a carbon ion beam increases as the ions advance deeper into the tumor-lying region. [17] CIRT provides the highest linear energy transfer (LET) of any currently available form of clinical radiation. [18] This high energy delivery to the tumor results in many double-strand DNA breaks which are very difficult for the tumor to repair. Conventional radiation produces principally single strand DNA breaks which can allow many of the tumor cells to survive. The higher outright cell mortality produced by CIRT may also provide a clearer antigen signature to stimulate the patient's immune system. [19] [20]

Particle therapy of moving targets

The precision of particle therapy of tumors situated in thorax and abdominal region is strongly affected by the target motion. The mitigation of its negative influence requires advanced techniques of tumor position monitoring (e.g., fluoroscopic imaging of implanted radio-opaque fiducial markers or electromagnetic detection of inserted transponders) and irradiation (gating, rescanning, gated rescanning and tumor tracking). [21]

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Particle radiation is the radiation of energy by means of fast-moving subatomic particles. Particle radiation is referred to as a particle beam if the particles are all moving in the same direction, similar to a light beam.

<span class="mw-page-title-main">Radiation therapy</span> Therapy using ionizing radiation, usually to treat cancer

Radiation therapy or radiotherapy is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.

<span class="mw-page-title-main">External beam radiotherapy</span> Treatment of cancer with ionized radiation

External beam radiation therapy (EBRT) is a form of radiotherapy that utilizes a high-energy collimated beam of ionizing radiation, from a source outside the body, to target and kill cancer cells. A radiotherapy beam is composed of particles which travel in a consistent direction; each radiotherapy beam consists of one type of particle intended for use in treatment, though most beams contain some contamination by other particle types.

<span class="mw-page-title-main">Orthovoltage X-rays</span> High energy (100–500 KeV) X-rays

Orthovoltage X-rays are produced by X-ray tubes operating at voltages in the 100–500 kV range, and therefore the X-rays have a peak energy in the 100–500 keV range. Orthovoltage X-rays are sometimes termed "deep" X-rays (DXR). They cover the upper limit of energies used for diagnostic radiography, and are used in external beam radiotherapy to treat cancer and tumors. They penetrate tissue to a useful depth of about 4–6 cm. This makes them useful for treating skin, superficial tissues, and ribs, but not for deeper structures such as lungs or pelvic organs. The relatively low energy of orthovoltage X-rays causes them to interact with matter via different physical mechanisms compared to higher energy megavoltage X-rays or radionuclide γ-rays, increasing their relative biological effectiveness.

<span class="mw-page-title-main">TRIUMF</span> Particle physics laboratory in Canada

TRIUMF is Canada's national particle accelerator centre. It is considered Canada's premier physics laboratory, and consistently regarded as one of the world's leading subatomic physics research centres. Owned and operated by a consortium of universities, it is on the south campus of one of its founding members, the University of British Columbia in Vancouver, British Columbia, Canada. It houses the world's largest normal conducting cyclotron, a source of 520 MeV protons, which was named an IEEE Milestone in 2010. Its accelerator-focused activities involve particle physics, nuclear physics, nuclear medicine, materials science, and detector and accelerator development.

<span class="mw-page-title-main">Paul Scherrer Institute</span> Swiss federal research institute

The Paul Scherrer Institute (PSI) is a multi-disciplinary research institute for natural and engineering sciences in Switzerland. It is located in the Canton of Aargau in the municipalities Villigen and Würenlingen on either side of the River Aare, and covers an area over 35 hectares in size. Like ETH Zurich and EPFL, PSI belongs to the Swiss Federal Institutes of Technology Domain of the Swiss Confederation. The PSI employs around 3000 people. It conducts basic and applied research in the fields of matter and materials, human health, and energy and the environment. About 37% of PSI's research activities focus on material sciences, 24% on life sciences, 19% on general energy, 11% on nuclear energy and safety, and 9% on particle physics.

<span class="mw-page-title-main">Proton therapy</span> Medical Procedure

In medicine, proton therapy, or proton radiotherapy, is a type of particle therapy that uses a beam of protons to irradiate diseased tissue, most often to treat cancer. The chief advantage of proton therapy over other types of external beam radiotherapy is that the dose of protons is deposited over a narrow range of depth; hence in minimal entry, exit, or scattered radiation dose to healthy nearby tissues.

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<span class="mw-page-title-main">Bragg peak</span> Path length of maximum energy loss of ionizing radiation

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. It is named after William Henry Bragg, who discovered it in 1903 using alpha particles from radium, and wrote the first empirical formula for ionization energy loss per distance with Richard Kleeman.

<span class="mw-page-title-main">Fast neutron therapy</span>

Fast neutron therapy utilizes high energy neutrons typically between 50 and 70 MeV to treat cancer. Most fast neutron therapy beams are produced by reactors, cyclotrons (d+Be) and linear accelerators. Neutron therapy is currently available in Germany, Russia, South Africa and the United States. In the United States, one treatment center is operational, in Seattle, Washington. The Seattle center uses a cyclotron which produces a proton beam impinging upon a beryllium target.

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2He2+ indicating a helium ion with a +2 charge (missing its two electrons). Once the ion gains electrons from its environment, the alpha particle becomes a normal (electrically neutral) helium atom 4
2He.

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<span class="mw-page-title-main">Neutron capture therapy of cancer</span> Nonsurgical therapeutic modality for treating locally invasive malignant tumors

Neutron capture therapy (NCT) is a type of radiotherapy for treating locally invasive malignant tumors such as primary brain tumors, recurrent cancers of the head and neck region, and cutaneous and extracutaneous melanomas. It is a two-step process: first, the patient is injected with a tumor-localizing drug containing the stable isotope boron-10 (10B), which has a high propensity to capture low energy "thermal" neutrons. The neutron cross section of 10B is 1,000 times more than that of other elements, such as nitrogen, hydrogen, or oxygen, that occur in tissue. In the second step, the patient is radiated with epithermal neutrons, the sources of which in the past have been nuclear reactors and now are accelerators that produce higher energy epithermal neutrons. After losing energy as they penetrate tissue, the resultant low energy "thermal" neutrons are captured by the 10B atoms. The resulting decay reaction yields high-energy alpha particles that kill the cancer cells that have taken up enough 10B.

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<span class="mw-page-title-main">The Svedberg Laboratory</span>

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References

  1. ↑ Matsumoto, Y.; Fukumitsu, N.; Ishikawa, H.; Nakai, K.; Sakurai, H. (2021). "A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond". Journal of Personalized Medicine. 11 (8): 825. doi: 10.3390/jpm11080825 . PMC   8399040 . PMID   34442469.
  2. ↑ Woo, Jong-Kwan; Liu, Dong (28 February 2020). "An Investigation of Muon Therapy". New Physics: SAE Mulli. 70 (2): 148–152. doi:10.3938/NPSM.70.148.
  3. ↑ Yang, Guangliang; Clarkson, Tony; Gardner, Simon; Ireland, David; Kaiser, Ralf; Mahon, David; Jebali, Ramsey Al; Shearer, Craig; Ryan, Matthew (28 January 2019). "Novel muon imaging techniques". Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. 377 (2137): 20180062. Bibcode:2019RSPTA.37780062Y. doi:10.1098/rsta.2018.0062.
  4. ↑ Amaldi U, Kraft G (2005). "Radiotherapy with beams of carbon ions". Reports on Progress in Physics. 68 (8): 1861–1882. Bibcode:2005RPPh...68.1861A. doi:10.1088/0034-4885/68/8/R04.
  5. ↑ Jäkel O (2007). "State of the art in hadron therapy". AIP Conference Proceedings. 958 (1): 70–77. Bibcode:2007AIPC..958...70J. doi:10.1063/1.2825836.
  6. ↑ Mohan, Radhe; Grosshans, David (January 2017). "Proton therapy – Present and future". Advanced Drug Delivery Reviews. 109: 26–44. doi:10.1016/j.addr.2016.11.006. PMC   5303653 . PMID   27919760.
  7. ↑ von Essen CF, Bagshaw MA, Bush SE, Smith AR, Kligerman MM (September 1987). "Long-term results of pion therapy at Los Alamos". International Journal of Radiation Oncology, Biology, Physics. 13 (9): 1389–98. doi:10.1016/0360-3016(87)90235-5. PMID   3114189.
  8. ↑ "TRIUMF: Cancer Therapy with Pions". Archived from the original on 2008-12-05.
  9. ↑ PTCOG: Particle Therapy Co-Operative Group
  10. ↑ Jermann M (May 2014). "Particle Therapy Statistics in 2013". International Journal of Particle Therapy. 1 (1): 40–43. doi: 10.14338/IJPT.14-editorial-2.1 .
  11. 1 2 3 Kramer D (2015-06-01). "Carbon-ion cancer therapy shows promise". Physics Today. 68 (6): 24–25. Bibcode:2015PhT....68f..24K. doi: 10.1063/PT.3.2812 . ISSN   0031-9228.
  12. ↑ Maradia, Vivek; Meer, David; Dölling, Rudolf; Weber, Damien C.; Lomax, Antony J.; Psoroulas, Serena (October 2023). "Demonstration of momentum cooling to enhance the potential of cancer treatment with proton therapy". Nature Physics. 19 (10): 1437–1444. Bibcode:2023NatPh..19.1437M. doi:10.1038/s41567-023-02115-2.
  13. ↑ Mohamad, Osama; Sishc, Brock; Saha, Janapriya; Pompos, Arnold; Rahimi, Asal; Story, Michael; Davis, Anthony; Kim, D.W. (9 June 2017). "Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair". Cancers. 9 (6): 66. doi: 10.3390/cancers9060066 . PMC   5483885 . PMID   28598362.
  14. ↑ Malouff, Timothy D.; Mahajan, Anita; Krishnan, Sunil; Beltran, Chris; Seneviratne, Danushka S.; Trifiletti, Daniel Michael (4 February 2020). "Carbon Ion Therapy: A Modern Review of an Emerging Technology". Frontiers in Oncology. 10: 82. doi: 10.3389/fonc.2020.00082 . PMC   7010911 . PMID   32117737.
  15. ↑ Tsujii, Hirohiko (January 2017). "Overview of Carbon-ion Radiotherapy". Journal of Physics: Conference Series. 777: 012032. Bibcode:2017JPhCS.777a2032T. doi:10.1088/1742-6596/777/1/012032.
  16. ↑ Tsujii H (2017). "Overview of Carbon-ion Radiotherapy". Journal of Physics: Conference Series. 777 (1): 012032. Bibcode:2017JPhCS.777a2032T. doi: 10.1088/1742-6596/777/1/012032 .
  17. ↑ Tsujii H, Kamada T, Shirai T, Noda K, Tsuji H, Karasawa K, eds. (2014). Carbon-Ion Radiotherapy : Principles, Practices, and Treatment Planning. Springer. ISBN   978-4-431-54456-2.
  18. ↑ Ando K, Koike S, Oohira C, Ogiu T, Yatagai F (June 2005). "Tumor induction in mice locally irradiated with carbon ions: a retrospective analysis". Journal of Radiation Research. 46 (2): 185–90. Bibcode:2005JRadR..46..185A. doi: 10.1269/jrr.46.185 . PMID   15988136.
  19. ↑ Ebner DK, Kamada T (2016). "The Emerging Role of Carbon-Ion Radiotherapy". Frontiers in Oncology. 6: 140. doi: 10.3389/fonc.2016.00140 . PMC   4894867 . PMID   27376030.
  20. ↑ "Radiation Therapy Side Effects". 17 May 2019.[ self-published source? ]
  21. ↑ Kubiak T (October 2016). "Particle therapy of moving targets-the strategies for tumour motion monitoring and moving targets irradiation". The British Journal of Radiology. 89 (1066): 20150275. doi:10.1259/bjr.20150275. PMC   5124789 . PMID   27376637.
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