View source for Physics:Particle therapy

{{Short description|Fighting cancer with high-energy particles}}
{{Infobox medical intervention
| Name = Particle therapy
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| ICD9unlinked = {{ICD9proc|92.26}}
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'''Particle therapy''' is a form of [[Medicine:External beam radiotherapy|external beam radiotherapy]] using beams of energetic [[Physics:Neutron|neutron]]s, [[Physics:Proton|proton]]s, or other heavier positive [[Physics:Ion|ion]]s for cancer treatment. The most common type of particle therapy as of August 2021 is [[Physics:Proton therapy|proton therapy]].<ref>{{cite journal | pmc=8399040 | year=2021 | last1=Matsumoto | first1=Y. | last2=Fukumitsu | first2=N. | last3=Ishikawa | first3=H. | last4=Nakai | first4=K. | last5=Sakurai | first5=H. | title=A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond | journal=Journal of Personalized Medicine | volume=11 | issue=8 | page=825 | doi=10.3390/jpm11080825 | pmid=34442469 | doi-access=free }}</ref>

In contrast to [[Physics:X-ray|X-ray]]s ([[Physics:Photon|photon]] beams) used in older radiotherapy, particle beams exhibit a [[Physics:Bragg peak|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 '''[[Physics:Hadron|hadron]] therapy''', excluding photon and [[Medicine:Electron therapy|electron therapy]]. Neutron capture therapy, which depends on a secondary nuclear reaction, is also not considered here. [[Physics:Muon|Muon]] therapy, a rare type of particle therapy not within the categories above, has also been attempted;<ref>{{cite journal | url=https://www.npsm-kps.org/journal/view.html?doi=10.3938/NPSM.70.148 | doi=10.3938/NPSM.70.148 | title=An Investigation of Muon Therapy | year=2020 | last1=Liu | first1=Dong | last2=Woo | first2=Jong-Kwan | journal=New Physics: SAE Mulli | volume=70 | issue=2 | pages=148–152 | s2cid=214039747 }}</ref> however, muons are still most commonly used for imaging, rather than therapy.<ref>{{cite journal | doi=10.1098/rsta.2018.0062 | title=Novel muon imaging techniques | year=2019 | last1=Yang | first1=Guangliang | last2=Clarkson | first2=Tony | last3=Gardner | first3=Simon | last4=Ireland | first4=David | last5=Kaiser | first5=Ralf | last6=Mahon | first6=David | last7=Jebali | first7=Ramsey Al | last8=Shearer | first8=Craig | last9=Ryan | first9=Matthew | journal=Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | volume=377 | issue=2137 | pmid=30530538 | pmc=6335303 | bibcode=2019RSPTA.37780062Y }}</ref>

== Method ==
[[File:Dose Depth Curves.svg|thumb|300px|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.<ref name=Amaldi>{{cite journal | vauthors = Amaldi U, Kraft G | title = Radiotherapy with beams of carbon ions | journal = Reports on Progress in Physics | volume = 68 | date = 2005 | issue = 8 | pages = 1861–1882 | doi = 10.1088/0034-4885/68/8/R04 | bibcode = 2005RPPh...68.1861A }}</ref><ref name="Jäkel">{{cite journal | vauthors = Jäkel O | title = State of the art in hadron therapy | journal = AIP Conference Proceedings | volume = 958 | issue = 1 | date = 2007 | pages = 70–77 | doi = 10.1063/1.2825836 | bibcode = 2007AIPC..958...70J }}</ref> These particles damage the [[Biology:DNA|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 [[Medicine:Electron therapy|electron therapy]]). [[Physics:Bremsstrahlung|Bremsstrahlung]] X-rays penetrate more deeply, but the [[Physics:Absorbed dose|dose]] absorbed by the tissue then shows the typical [[Exponential decay|exponential decay]] with increasing thickness. For protons and heavier ions, on the other hand, the dose increases while the particle penetrates the tissue and [[Physics:Stopping power (particle radiation)|loses energy]] continuously. Hence the dose increases with increasing thickness up to the [[Physics:Bragg peak|Bragg peak]] that occurs near the end of the particle's [[Physics:Range (particle radiation)|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.<ref>{{cite journal |last1=Mohan |first1=Radhe |last2=Grosshans |first2=David |title=Proton therapy – Present and future |journal=Advanced Drug Delivery Reviews |date=January 2017 |volume=109 |pages=26–44 |doi=10.1016/j.addr.2016.11.006 |pmid=27919760|pmc=5303653 }}</ref>

The ions are first accelerated by means of a [[Physics:Cyclotron|cyclotron]] or [[Physics:Synchrotron|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|raster scan]] method, i.e., to scan the target area quickly like 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 [[Physics:Pion|pion]]s,<ref>{{cite journal | vauthors = von Essen CF, Bagshaw MA, Bush SE, Smith AR, Kligerman MM | title = Long-term results of pion therapy at Los Alamos | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 13 | issue = 9 | pages = 1389–98 | date = September 1987 | pmid = 3114189 | doi = 10.1016/0360-3016(87)90235-5 }}</ref><ref>{{cite web |url=http://triumf.ca/welcome/pion_trtmt.html |title=TRIUMF: Cancer Therapy with Pions |url-status=dead |archive-url=https://web.archive.org/web/20081205175608/http://www.triumf.ca/welcome/pion_trtmt.html |archive-date=2008-12-05 }}</ref> protons and heavier ions. Most of this therapy has been conducted using protons.<ref name=PTCOG>[http://ptcog.web.psi.ch/ PTCOG: Particle Therapy Co-Operative Group]</ref>

At the end of 2013, 105,000 patients had been treated with proton beams,<ref>{{cite journal |last1=Jermann |first1=Martin | name-list-style = vanc |title=Particle Therapy Statistics in 2013 |journal=International Journal of Particle Therapy |date=May 2014 |volume=1 |issue=1 |pages=40–43 |doi=10.14338/IJPT.14-editorial-2.1|doi-access=free }}</ref> and approximately 13,000 patients had received carbon-ion therapy.<ref name="Kramer 24–25">{{Cite journal|title = Carbon-ion cancer therapy shows promise|journal = Physics Today|date = 2015-06-01|issn = 0031-9228|pages = 24–25|volume = 68|issue = 6|doi = 10.1063/PT.3.2812|first = David|last = Kramer |bibcode = 2015PhT....68f..24K| name-list-style = vanc |doi-access = free}}</ref>

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.<ref name="Kramer 24–25"/> 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.<ref name="Kramer 24–25"/>

==Proton therapy==
{{main article|Proton therapy}}'''Proton therapy''' is a type of particle therapy that uses a beam of [[Physics:Proton|proton]]s to [[Biology:Irradiation|irradiate]] diseased [[Biology:Tissue|tissue]], most often to treat [[Medicine:Cancer|cancer]]. The chief advantage of proton therapy over other types of [[Medicine:External beam radiotherapy|external beam radiotherapy]] (e.g., [[Physics:Radiation therapy|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.<ref>Maradia, V., Meer, D., Dölling, R. et al. Demonstration of momentum cooling to enhance the potential of cancer treatment with proton therapy. Nat. Phys. (2023). https://doi.org/10.1038/s41567-023-02115-2</ref>

==Fast-neutron therapy==
{{main article|Fast neutron therapy}}'''Fast neutron therapy''' utilizes high energy [[Physics:Neutron|neutron]]s typically between 50 and 70 [[Physics:MeV|MeV]] to treat [[Medicine:Cancer|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, three treatment centers are operational in Seattle, Washington, Detroit, Michigan and Batavia, Illinois. The Detroit and Seattle centers use a cyclotron which produces a proton beam impinging upon a [[Chemistry:Beryllium|beryllium]] target; the Batavia center at [[Organization:Fermilab|Fermilab]] uses a proton linear accelerator.

==Carbon ion radiotherapy==
[[Chemistry:Carbon|Carbon]] [[Physics:Ion|ion]] therapy (C-ion RT) uses particles more massive than protons or neutrons. 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.<ref>{{cite journal | first = Hirohiko | last = Tsujii | name-list-style = vanc | title = Overview of Carbon-ion Radiotherapy | journal = Journal of Physics: Conference Series | volume = 777 | pages = 012032 | number = 1 | doi = 10.1088/1742-6596/777/1/012032 | year = 2017 | bibcode = 2017JPhCS.777a2032T | doi-access = free }}</ref>

==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.<ref>{{cite book | veditors = Tsujii H, Kamada T, Shirai T, Noda K, Tsuji H, Karasawa K |title=Carbon-Ion Radiotherapy : Principles, Practices, and Treatment Planning | publisher = Springer | year = 2014 |isbn=978-4-431-54456-2}}</ref> CIRT provides the highest linear energy transfer (LET) of any currently available form of clinical radiation.<ref name="pmid15988136">{{cite journal | vauthors = Ando K, Koike S, Oohira C, Ogiu T, Yatagai F | title = Tumor induction in mice locally irradiated with carbon ions: a retrospective analysis | journal = Journal of Radiation Research | volume = 46 | issue = 2 | pages = 185–90 | date = June 2005 | pmid = 15988136 | doi = 10.1269/jrr.46.185| bibcode = 2005JRadR..46..185A | doi-access = free }}</ref> 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.<ref name="pmid27376030">{{cite journal | vauthors = Ebner DK, Kamada T | title = The Emerging Role of Carbon-Ion Radiotherapy | journal = Frontiers in Oncology | volume = 6 | pages = 140 | date = 2016 | pmid = 27376030 | pmc = 4894867 | doi = 10.3389/fonc.2016.00140 | doi-access = free }}</ref><ref>{{cite web| url=https://ourcamwell.com/blog/radiation-therapy-side-effects/ |title= Radiation Therapy Side Effects |date= 17 May 2019 }} Saturday, 3 August 2019</ref>

== 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).<ref>{{cite journal | vauthors = Kubiak T | title = Particle therapy of moving targets-the strategies for tumour motion monitoring and moving targets irradiation | language = EN | journal = The British Journal of Radiology | volume = 89 | issue = 1066 | pages = 20150275 | date = October 2016 | pmid = 27376637 | pmc = 5124789 | doi = 10.1259/bjr.20150275 }}</ref>

== References ==
{{Reflist}}

== External links ==
*[https://web.archive.org/web/20120314084649/http://www.touro.edu/media/pr/releases/PR-ParticleTherapy.asp Touro University announces first combined particle therapy center in U.S.]
*[https://ptcog58.org PTCOG annual conference]
{{Radiation oncology}}

[[Category:Medical physics]]
[[Category:Particle physics]]

{{Sourceattribution|Particle therapy}}