Proton therapy

Proton therapy
Proton therapy equipment at the Mayo Clinic in Rochester, Minnesota
Other namesProton beam therapy
ICD-10-PCSZ92.3

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.

When evaluating whether to treat a tumor with photon or proton therapy, physicians may choose proton therapy if it is important to deliver a higher radiation dose to targeted tissues while significantly decreasing radiation to nearby organs at risk.[1] The American Society for Radiation Oncology Model Policy for Proton Beam therapy says proton therapy is considered reasonable if sparing the surrounding normal tissue "cannot be adequately achieved with photon-based radiotherapy" and can benefit the patient.[2] Like photon radiation therapy, proton therapy is often used in conjunction with surgery and/or chemotherapy to most effectively treat cancer.

Description[edit]

In a typical treatment plan for proton therapy, the spread out Bragg peak (SOBP, dashed blue line) shows how the radiation is distributed. The SOBP is the sum of several individual Bragg peaks (thin blue lines) at staggered depths. Note that the vast majority of the proton radiation is delivered to the tumor, not to the skin and shallow tissues in front of the tumor or to the deep tissues behind the tumor. The red line shows the depth-dose plot of an X-ray beam (photon or conventional radiation therapy) for comparison. The pink area represents additional doses of X-ray radiotherapy in front and behind the tumor – which can damage normal tissues and cause secondary cancers, especially of the skin.[3]

Proton therapy is a type of external beam radiotherapy that uses ionizing radiation. In proton therapy, medical personnel use a particle accelerator to target a tumor with a beam of protons.[4][5] These charged particles damage the DNA of cells, ultimately killing them by stopping their reproduction and thus eliminating the tumor. Cancerous cells are particularly vulnerable to attacks on DNA because of their high rate of division and their limited ability to repair DNA damage. Some cancers with specific defects in DNA repair may be more sensitive to proton radiation.[6]

Proton therapy lets physicians deliver a highly conformal beam, i.e. delivering radiation that conforms to the shape and depth of the tumor and sparing much of the surrounding, normal tissue.[7] For example, when comparing proton therapy to the most advanced types of photon therapy—intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)—proton therapy can give similar or higher radiation doses to the tumor with a 50%-60% lower total body radiation dose.[8][1]

Protons can focus energy delivery to fit the tumor shape, delivering only low-dose radiation to surrounding tissue. As a result, the patient has fewer side effects. All protons of a given energy have a certain penetration range; very few protons penetrate beyond that distance.[9] Also, the dose delivered to tissue is maximized only over the last few millimeters of the particle's range; this maximum is called the spread out Bragg peak, often called the SOBP (see visual).[10]

To treat tumors at greater depth, one needs a beam with higher energy, typically given in MeV (mega electron volts). Accelerators used for proton therapy typically produce protons with energies of 70 to 250 MeV. Adjusting proton energy during the treatment maximizes the cell damage within the tumor. Tissue closer to the surface of the body than the tumor gets less radiation, and thus less damage. Tissues deeper in the body get very few protons, so the dose becomes immeasurably small.[9]

In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor. These Bragg peaks are shown as thin blue lines in the figure in this section. It is important to understand that, while tissues behind (or deeper than) the tumor get almost no radiation, the tissues in front of (shallower than) the tumor get radiation dosage based on the SOBP.

Equipment[edit]

Most installed proton therapy systems use isochronous cyclotrons.[11][12] Cyclotrons are considered simple to operate, reliable and can be made compact, especially with use of superconducting magnets.[13] Synchrotrons can also be used, with the advantage of easier production at varying energies.[14] Linear accelerators, as used for photon radiation therapy, are becoming commercially available as limitations of size and cost are resolved.[15] Modern proton systems incorporate high-quality imaging for daily assessment of tumor contours, treatment planning software illustrating 3D dose distributions, and various system configurations, e.g. multiple treatment rooms connected to one accelerator. Partly because of these advances in technology, and partly because of the continually increasing amount of proton clinical data, the number of hospitals offering proton therapy continues to grow.

FLASH therapy[edit]

FLASH radiotherapy is a technique under development for photon and proton treatments, using very high dose rates (necessitating large beam currents). If applied clinically, it could shorten treatment time to just one to three 1-second sessions, and further reducing side effects.[16][17][18][19]

History[edit]

The first suggestion that energetic protons could be an effective treatment was made by Robert R. Wilson in a paper published in 1946[20] while he was involved in the design of the Harvard Cyclotron Laboratory (HCL).[21] The first treatments were performed with particle accelerators built for physics research, notably Berkeley Radiation Laboratory in 1954 and at Uppsala in Sweden in 1957. In 1961, a collaboration began between HCL and Massachusetts General Hospital (MGH) to pursue proton therapy. Over the next 41 years, this program refined and expanded these techniques while treating 9,116 patients[22] before the cyclotron was shut down in 2002. In the USSR a therapeutic proton beam with energies up to 200 MeV was obtained at the synchrocyclotron of JINR in Dubna in 1967. The ITEP center in Moscow, Russia, which began treating patients in 1969, is the oldest proton center still in operation. The Paul Scherrer Institute in Switzerland was the world's first proton center to treat eye tumors beginning in 1984. In addition, they invented pencil beam scanning in 1996, which is now the state-of-the art form of proton therapy.[23]

The world's first hospital-based proton therapy center was a low energy cyclotron centre for eye tumors at Clatterbridge Centre for Oncology in the UK, opened in 1989,[24] followed in 1990 at the Loma Linda University Medical Center (LLUMC) in Loma Linda, California. Later, the Northeast Proton Therapy Center at Massachusetts General Hospital was brought online, and the HCL treatment program was transferred to it in 2001 and 2002. At the beginning of 2023, there were 41 proton therapy centers in the United States,[25] and a total of 89 worldwide.[26] As of 2020, six manufacturers make proton therapy systems: Hitachi, Ion Beam Applications, Mevion Medical Systems, ProNova Solutions, ProTom International and Varian Medical Systems.

Types[edit]

The newest form of proton therapy, pencil beam scanning, gives therapy by sweeping a proton beam laterally over the target so that it gives the required dose while closely conforming to shape of the targeted tumor. Before the use of pencil beam scanning, oncologists used a scattering method to direct a wide beam toward the tumor. [27]

Passive scattering beam delivery[edit]

The first commercially available proton delivery systems used a scattering process, or passive scattering, to deliver the therapy. With scattering proton therapy the proton beam is spread out by scattering devices, and the beam is then shaped by putting items such as collimators and compensators in the path of the protons. The collimators were custom made for the patient with milling machines.[28] Passive scattering gives homogeneous dose along the target volume. Therefore, passive scattering gives more limited control over dose distributions proximal to target. Over time many scattering therapy systems have been upgraded to deliver pencil beam scanning. Because scattering therapy was the first type of proton therapy available, most clinical data available on proton therapy—especially long-term data as of 2020—were acquired via scattering technology.

Pencil beam scanning beam delivery[edit]

A newer and more flexible delivery method is pencil beam scanning, using a beam that sweeps laterally over the target so that it delivers the needed dose while closely conforming to the tumor's shape. This conformal delivery is achieved by shaping the dose through magnetic scanning of thin beamlets of protons without needing apertures and compensators. Multiple beams are delivered from different directions, and magnets in the treatment nozzle steer the proton beam to conform to the target volume layer as the dose is painted layer by layer. This type of scanning delivery provides greater flexibility and control, letting the proton dose conform more precisely to the shape of the tumor.[28]

Delivery of protons via pencil beam scanning, in use since 1996 at the Paul Scherrer Institute,[28] allows for the most precise type of proton delivery: intensity-modulated proton therapy (IMPT). IMPT is to proton therapy what IMRT is to conventional photon therapy—treatment that more closely conforms to the tumor while avoiding surrounding structures.[29] Virtually all new proton systems now provide pencil beam scanning exclusively. A study led by Memorial Sloan Kettering Cancer Center suggests that IMPT can improve local control when compared to passive scattering for patients with nasal cavity and paranasal sinus malignancies.[30]

Application[edit]

It was estimated that by the end of 2019, a total of ~200,000 patients had been treated with proton therapy. Physicians use protons to treat conditions in two broad categories:

  • Disease sites that respond well to higher doses of radiation, i.e., dose escalation. Dose escalation has sometimes shown a higher probability of "cure" (i.e. local control) than conventional radiotherapy.[31] These include, among others, uveal melanoma (ocular tumor), skull base and paraspinal tumor (chondrosarcoma and chordoma), and unresectable sarcoma. In all these cases proton therapy gives significant improvement in the probability of local control, over conventional radiotherapy.[32][33][34] For eye tumors, proton therapy also has high rates of maintaining the natural eye.[35]
  • Treatment where proton therapy's increased precision reduces unwanted side effects by lessening the dose to normal tissue. In these cases, the tumor dose is the same as in conventional therapy, so there is no expectation of increased probability of curing the disease. Instead, emphasis is on reducing the dose to normal tissue, thus reducing unwanted effects.[31]

Two prominent examples are pediatric neoplasms (such as medulloblastoma) and prostate cancer.

Pediatric[edit]

Irreversible long-term side effects of conventional radiation therapy for pediatric cancers are well documented and include growth disorders, neurocognitive toxicity, ototoxicity with subsequent effects on learning and language development, and renal, endocrine and gonadal dysfunctions. Radiation-induced secondary malignancy is another very serious adverse effect that has been reported. As there is minimal exit dose when using proton radiation therapy, dose to surrounding normal tissues can be significantly limited, reducing the acute toxicity which positively impacts the risk for these long-term side effects. Cancers requiring craniospinal irradiation, for example, benefit from the absence of exit dose with proton therapy: dose to the heart, mediastinum, bowel, bladder and other tissues anterior to the vertebrae is eliminated, hence a reduction of acute thoracic, gastrointestinal and bladder side effects.[36][37][38]

Eye tumor[edit]

Proton therapy for eye tumors is a special case since this treatment requires only relatively low energy protons (~70 MeV). Owing to this low energy, some particle therapy centers only treat eye tumors.[22] Proton, or more generally, hadron therapy of tissue close to the eye affords sophisticated methods to assess the alignment of the eye that can vary significantly from other patient position verification approaches in image guided particle therapy.[39] Position verification and correction must ensure that the radiation spares sensitive tissue like the optic nerve to preserve the patient's vision.

For ocular tumors, selecting the type of radiotherapy depends on tumor location and extent, tumor radioresistance (calculating the dose needed to eliminate the tumor), and the therapy's potential toxic side effects on nearby critical structures.[40] For example, proton therapy is an option for retinoblastoma [41] and intraocular melanoma.[42] The advantage of a proton beam is that it has the potential to effectively treat the tumor while sparing sensitive structures of the eye.[43] Given its effectiveness, proton therapy has been described as the "gold standard" treatment for ocular melanoma.[44][45] The implementation of momentum cooling technique in proton therapy for eye treatment can significantly enhance its effectiveness.[46] This technique aids in reducing the radiation dose administered to healthy organs while ensuring that the treatment is completed within a few seconds. Consequently, patients experience improved comfort during the procedure.

Base of skull cancer[edit]

When receiving radiation for skull base tumors, side effects of the radiation can include pituitary hormone dysfunction and visual field deficit—after radiation for pituitary tumors—as well as cranial neuropathy (nerve damage), radiation-induced osteosarcoma (bone cancer), and osteoradionecrosis, which occurs when radiation causes part of the bone in the jaw or skull base to die.[47] Proton therapy has been very effective for people with base of skull tumors.[48] Unlike conventional photon radiation, protons do not penetrate beyond the tumor. Proton therapy lowers the risk of treatment-related side effects from when healthy tissue gets radiation. Clinical studies have found proton therapy to be effective for skull base tumors.[49][50][51]

Head and neck tumor[edit]

Proton particles do not deposit exit dose, so proton therapy can spare normal tissues far from the tumor. This is particularly useful for head and neck tumors because of the anatomic constraints found in nearly all cancers in this region. The dosimetric advantage unique to proton therapy translates into toxicity reduction. For recurrent head and neck cancer requiring reirradiation, proton therapy is able to maximize a focused dose of radiation to the tumor while minimizing dose to surrounding tissues, hence a minimal acute toxicity profile, even in patients who got multiple prior courses of radiotherapy.[52]

Left-side breast cancer[edit]

When breast cancer — especially in the left breast — is treated with conventional radiation, the lung and heart, which are near the left breast, are particularly susceptible to photon radiation damage. Such damage can eventually cause lung problems (e.g. lung cancer) or various heart problems. Depending on location of the tumor, damage can also occur to the esophagus, or to the chest wall (which can potentially lead to leukemia).[53] One recent study showed that proton therapy has low toxicity to nearby healthy tissues and similar rates of disease control compared with conventional radiation.[54] Other researchers found that proton pencil beam scanning techniques can reduce both the mean heart dose and the internal mammary node dose to essentially zero.[55]

Small studies have found that, compared to conventional photon radiation, proton therapy delivers minimal toxic dose to healthy tissues[56] and specifically decreased dose to the heart and lung.[57] Large-scale trials are underway to examine other potential benefits of proton therapy to treat breast cancer.[58]

Lymphoma[edit]

Though chemotherapy is the main treatment for lymphoma, consolidative radiation is often used in Hodgkin lymphoma and aggressive non-Hodgkin lymphoma, while definitive treatment with radiation alone is used in a small fraction of lymphoma patients. Unfortunately, treatment-related toxicities caused by chemotherapy agents and radiation exposure to healthy tissues are major concerns for lymphoma survivors. Advanced radiation therapy technologies such as proton therapy may offer significant and clinically relevant advantages such as sparing important organs at risk and decreasing the risk for late normal tissue damage while still achieving the primary goal of disease control. This is especially important for lymphoma patients who are being treated with curative intent and have long life expectancy following therapy.[59]

Prostate cancer[edit]

In prostate cancer cases, the issue is less clear. Some published studies found a reduction in long term rectal and genito-urinary damage when treating with protons rather than photons (meaning X-ray or gamma ray therapy). Others showed a small difference, limited to cases where the prostate is particularly close to certain anatomical structures.[60][61] The relatively small improvement found may be the result of inconsistent patient set-up and internal organ movement during treatment, which offsets most of the advantage of increased precision.[61][62][63] One source suggests that dose errors around 20% can result from motion errors of just 2.5 mm (0.098 in).[citation needed] and another that prostate motion is between 5–10 mm (0.20–0.39 in).[64]

The number of cases of prostate cancer diagnosed each year far exceeds those of the other diseases referred to above, and this has led some, but not all, facilities to devote most of their treatment slots to prostate treatments. For example, two hospital facilities devote ~65%[65] and 50%[66] of their proton treatment capacity to prostate cancer, while a third devotes only 7.1%.[67]

Worldwide numbers are hard to compile, but one example says that in 2003 ~26% of proton therapy treatments worldwide were for prostate cancer.[68]

Gastrointestinal malignancy[edit]

A growing amount of data shows that proton therapy has great potential to increase therapeutic tolerance for patients with GI malignancy. The possibility of decreasing radiation dose to organs at risk may also help facilitate chemotherapy dose escalation or allow new chemotherapy combinations. Proton therapy will play a decisive role for ongoing intensified combined modality treatments for GI cancers. The following review presents the benefits of proton therapy in treating hepatocellular carcinoma, pancreatic cancer and esophageal cancer.[69]

Hepatocellular carcinoma[edit]

Post-treatment liver decompensation, and subsequent liver failure, is a risk with radiotherapy for hepatocellular carcinoma, the most common type of primary liver cancer. Research shows that proton therapy gives favorable results related to local tumor control, progression-free survival, and overall survival.[70][71][72][73] Other studies, which examine proton therapy compared with conventional photon therapy, show that proton therapy gives improved survival and/or fewer side effects; hence proton therapy could significantly improve clinical outcomes for some patients with liver cancer.[74][75]

Reirradiation for recurrent cancer[edit]

For patients who get local or regional recurrences after their initial radiation therapy, physicians are limited in their treatment options due to their reluctance to give additional photon radiation therapy to tissues that have already been irradiated. Re-irradiation is a potentially curative treatment option for patients with locally recurrent head and neck cancer. In particular, pencil beam scanning may be ideally suited for reirradiation.[76] Research shows the feasibility of using proton therapy with acceptable side effects, even in patients who have had multiple prior courses of photon radiation.[77][78][79]

Comparison with other treatments[edit]

A large study on comparative effectiveness of proton therapy was published by teams of the University of Pennsylvania and Washington University in St. Louis in JAMA Oncology, assessing if proton therapy in the setting of concurrent chemoradiotherapy is associated with fewer 90-day unplanned hospitalizations and overall survival compared with concurrent photon therapy and chemoradiotherapy.[80] The study included 1483 adult patients with nonmetastatic, locally advanced cancer treated with concurrent chemoradiotherapy with curative intent and concluded, "proton chemoradiotherapy was associated with significantly reduced acute adverse events that caused unplanned hospitalizations, with similar disease-free and overall survival". A significant number of randomized controlled trials is currently recruiting, but only a limited number have been completed as of August 2020. A phase III randomized controlled trial of proton beam therapy versus radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma organized by the National Cancer Center in Korea showed better 2-year local progression-free survival for the proton arm and concluded that proton beam therapy (PBT) is "not inferior to RFA in terms of local progression-free survival and safety, denoting that either RFA or PBT can be applied to recurrent small HCC patients".[70] A phase IIB randomized controlled trial of proton beam therapy versus IMRT for locally advanced esophageal cancer organized by University of Texas MD Anderson Cancer Center concluded that proton beam therapy reduced the risk and severity of adverse events compared with IMRT while maintaining similar progression free survival.[81] Another Phase II Randomized Controlled Trial comparing photons versus protons for Glioblastoma concluded that patients at risk of severe lymphopenia could benefit from proton therapy.[82] A team from Stanford University assessed the risk of secondary cancer after primary cancer treatment with external beam radiation using data from the National Cancer Database for 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system.[83] The study included a total of 450,373 patients and concluded that proton therapy was associated with a lower risk of second cancer.

The issue of when, whether, and how best to apply this technology is still under discussion by physicians and researchers. One recently introduced method, 'model-based selection', uses comparative treatment plans for IMRT and IMPT in combination with normal tissue complication probability (NTCP) models to identify patients who may benefit most from proton therapy.[84][85]

Clinical trials are underway to examine the comparative efficacy of proton therapy (vs photon radiation) for the following:

  • Pediatric cancers—by St. Jude Children's Research Hospital,[86] Samsung Medical Center [87]
  • Base of skull cancer—by Heidelberg University [88]
  • Head and neck cancer—by MD Anderson,[89] Memorial Sloan Kettering and other centers[90]
  • Brain and spinal cord cancer—by Massachusetts General Hospital,[91] Uppsala University and other centers,[92] NRG Oncology[93][94]
  • Hepatocellular carcinoma (liver)—by NRG Oncology,[95] Chang Gung Memorial Hospital,[96] Loma Linda University [97]
  • Lung cancer—by Radiation Therapy Oncology Group (RTOG),[98] Proton Collaborative Group (PCG),[99] Mayo Clinic[100]
  • Esophageal cancer—by NRG Oncology,[101] Abramson Cancer Center, University of Pennsylvania[102]
  • Breast cancer—by University of Pennsylvania,[103] Proton Collaborative Group (PCG)[104]
  • Pancreatic cancer—by University of Maryland,[105] Proton Collaborative Group (PCG)[106]

X-ray radiotherapy[edit]

Irradiation of nasopharyngeal carcinoma by photon (X-ray) therapy (left) and proton therapy (right)

The figure at the right of the page shows how beams of X-rays (IMRT; left frame) and beams of protons (right frame), of different energies, penetrate human tissue. A tumor with a sizable thickness is covered by the IMRT spread out Bragg peak (SOBP) shown as the red lined distribution in the figure. The SOBP is an overlap of several pristine Bragg peaks (blue lines) at staggered depths.

Megavoltage X-ray therapy has less "skin sparing potential" than proton therapy: X-ray radiation at the skin, and at very small depths, is lower than for proton therapy. One study estimates that passively scattered proton fields have a slightly higher entrance dose at the skin (~75%) compared to therapeutic megavoltage (MeV) photon beams (~60%).[3] X-ray radiation dose falls off gradually, needlessly harming tissue deeper in the body and damaging the skin and surface tissue opposite the beam entrance. The differences between the two methods depends on:

  • Width of the SOBP
  • Depth of the tumor
  • Number of beams that treat the tumor

The X-ray advantage of less harm to skin at the entrance is partially counteracted by harm to skin at exit point.

Since X-ray treatments are usually done with multiple exposures from opposite sides, each section of skin is exposed to both entering and exiting X-rays. In proton therapy, skin exposure at the entrance point is higher, but tissues on the opposite side of the body to the tumor get no radiation. Thus, X-ray therapy causes slightly less damage to skin and surface tissues, and proton therapy causes less damage to deeper tissues in front of and beyond the target.[5]

An important consideration in comparing these treatments is whether the equipment delivers protons via the scattering method (historically, the most common) or a spot scanning method. Spot scanning can adjust the width of the SOBP on a spot-by-spot basis, which reduces the volume of normal (healthy) tissue inside the high dose region. Also, spot scanning allows for intensity modulated proton therapy (IMPT), which determines individual spot intensities using an optimization algorithm that lets the user balance the competing goals of irradiating tumors while sparing normal tissue. Spot scanning availability depends on the machine and the institution. Spot scanning is more commonly known as pencil-beam scanning and is available on IBA, Hitachi, Mevion (known as HYPERSCAN[107] which became US FDA approved in 2017) and Varian.

Surgery[edit]

Physicians base the decision to use surgery or proton therapy (or any radiation therapy) on tumor type, stage, and location. Sometimes surgery is superior (such as cutaneous melanoma), sometimes radiation is superior (such as skull base chondrosarcoma), and sometimes are comparable (for example, prostate cancer). Sometimes, they are used together (e.g., rectal cancer or early stage breast cancer).

The benefit of external beam proton radiation is in the dosimetric difference from external beam X-ray radiation and brachytherapy in cases where use of radiation therapy is already indicated, rather than as a direct competition with surgery.[31] In prostate cancer, the most common indication for proton beam therapy, no clinical study directly comparing proton therapy to surgery, brachytherapy, or other treatments has shown any clinical benefit for proton beam therapy. Indeed, the largest study to date showed that IMRT compared with proton therapy was associated with less gastrointestinal morbidity.[108]

Side effects and risks[edit]

Proton therapy is a type of external beam radiotherapy, and shares risks and side effects of other forms of radiation therapy. The dose outside of the treatment region can be significantly less for deep-tissue tumors than X-ray therapy, because proton therapy takes full advantage of the Bragg peak. Proton therapy has been in use for over 40 years, and is a mature technology. As with all medical knowledge, understanding of the interaction of radiations with tumor and normal tissue is still imperfect.[109]

Costs[edit]

Historically, proton therapy has been expensive. An analysis published in 2003 found that the cost of proton therapy is ~2.4 times that of X-ray therapies.[110] Newer, less expensive, and dozens more proton treatment centers are driving costs down and they offer more accurate three-dimensional targeting. Higher proton dosage over fewer treatments sessions (1/3 fewer or less) is also driving costs down.[111][112] Thus the cost is expected to reduce as better proton technology becomes more widely available. An analysis published in 2005 determined that the cost of proton therapy is not unrealistic and should not be the reason for denying patients access to the technology.[113] In some clinical situations, proton beam therapy is clearly superior to the alternatives.[114][115]

A study in 2007 expressed concerns about the effectiveness of proton therapy for prostate cancer,[116] but with the advent of new developments in the technology, such as improved scanning techniques and more precise dose delivery ('pencil beam scanning'), this situation may change considerably.[117] Amitabh Chandra, a health economist at Harvard University, said, "Proton-beam therapy is like the Death Star of American medical technology... It's a metaphor for all the problems we have in American medicine."[118] Proton therapy is cost-effective for some types of cancer, but not all.[119][120] In particular, some other treatments offer better overall value for treatment of prostate cancer.[119]

As of 2018, the cost of a single-room particle therapy system is US$40 million, with multi-room systems costing up to US$200 million.[121][122]

Treatment centers[edit]

Control panel of the synchrocyclotron at the Orsay proton therapy center, France

As of August 2020, there are over 89 particle therapy facilities worldwide,[123] with at least 41 others under construction.[124] As of August 2020, there are 34 operational proton therapy centers in the United States. As of the end of 2015 more than 154,203 patients had been treated worldwide.[125]

One hindrance to universal use of the proton in cancer treatment is the size and cost of the cyclotron or synchrotron equipment necessary. Several industrial teams are working on development of comparatively small accelerator systems to deliver the proton therapy to patients.[126] Among the technologies being investigated are superconducting synchrocyclotrons (also known as FM Cyclotrons), ultra-compact synchrotrons, dielectric wall accelerators,[126] and linear particle accelerators.[112]

United States[edit]

Proton treatment centers in the United States as of 2024 (in chronological order of first treatment date) include:[24][127]

Institution Location Year of first treatment Comments
Loma Linda University Medical Center[128] Loma Linda, CA 1990 First hospital-based facility in USA; uses Spread Out Bragg's Peak (SOBP)
Crocker Nuclear Laboratory[129] Davis, CA 1994 Ocular treatments only (low energy accelerator); at University of California, Davis
Francis H. Burr Proton Center Boston, MA 2001 At Massachusetts General Hospital and formerly known as NPTC; continuation of Harvard Cyclotron Laboratory/MGH treatment program that began in 1961; Manufactured by Ion Beam Applications[130]
University of Florida Health Proton Therapy Institute-Jacksonville[131] Jacksonville, FL 2006 The UF Health Proton Therapy Institute is a part of a non-profit academic medical research facility affiliated with the University of Florida College of Medicine-Jacksonville. It is the first treatment center in the Southeast U.S. to offer proton therapy. Manufactured by Ion Beam Applications[130]
University of Texas MD Anderson Cancer Center[132] Houston, TX
Oklahoma Proton Center[133] Oklahoma City, OK 2009 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
Northwestern Medicine Chicago Proton Center Warrenville, IL 2010 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
Roberts Proton Therapy Center[134] Philadelphia, PA The largest proton therapy center in the world, the Roberts Proton Therapy Center, which is a part of Penn's Abramson Cancer Center, University of Pennsylvania Health System; 5 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
Hampton University Proton Therapy Institute Hampton, VA 5 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
ProCure Proton Therapy Center[135] Somerset, NJ 2012 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
SCCA Proton Therapy Center Seattle, WA 2013 At Seattle Cancer Care Alliance; part of Fred Hutchinson Cancer Research Center; 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
Siteman Cancer Center[111] St. Louis, MO First of the new single suite, ultra-compact, superconducting synchrocyclotron,[136] lower cost facilities to treat a patient using the Mevion Medical System's S250.[137]
Provision Proton Therapy Center[138] Knoxville, TN 2014 3 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
California Protons Cancer Therapy Center[139] San Diego, CA 5 treatment rooms, manufactured by Varian Medical Systems[140]
Ackerman Cancer Center Jacksonville, FL 2015 Ackerman Cancer Center is the world's first private, physician-owned practice to provide proton therapy, in addition to conventional radiation therapy and on-site diagnostic services.
The Laurie Proton Therapy Center New Brunswick, NJ The Laurie Proton Therapy Center, part of Robert Wood Johnson University Hospital, is home to the world's third MEVION S250 Proton Therapy System.
Texas Center for Proton Therapy Dallas Fort Worth, TX A collaboration by "Texas Oncology and The US Oncology Network, supported by McKesson Specialty Health, and Baylor Health Enterprises"; three pencil beam rooms and cone beam CT imaging.[141] 3 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[130]
Mayo Clinic Jacobson Building Rochester, MN 4 treatment rooms.[142] Manufactured by Hitachi.[143]
St. Jude Red Frog Events Proton Therapy Center Memphis, TN 3 treatment rooms
Mayo Clinic Cancer Center Phoenix, AZ 2016 4 treatment rooms.[144] Manufactured by Hitachi.[145]
The Marjorie and Leonard Williams Center for Proton Therapy Orlando, FL http://www.ufhealthcancerorlando.com/centers/proton-therapy-center
Cancer and Blood Diseases Institute Liberty Township, OH Collaboration of University of Cincinnati Cancer Institute and Cincinnati Children's Hospital Medical Center,[146][147] manufactured by Varian Medical Systems
Maryland Proton Treatment Center Baltimore, MD 5 treatment rooms, affiliated with the University of Maryland Greenebaum Comprehensive Cancer Center, manufactured by Varian Medical Systems.
Proton Therapy Center at University Hospitals Seidman Cancer Center Cleveland, OH Only proton therapy center in Northern Ohio. One treatment room with the Mevion S250 Proton Therapy System. Part of the NCI-designated Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center is one of the nation's leading freestanding cancer hospitals.
Miami Cancer Institute Miami, FL 2017 3 treatment rooms, all using pencil-beam scanning[148] Manufactured by Ion Beam Applications[130]
Beaumont Proton Therapy Center Royal Oak, MI Single treatment room, Proteus ONE system manufactured by Ion Beam Applications[130]
Emory Proton Therapy Center Archived 2018-03-07 at the Wayback Machine Atlanta, GA 2018 Five treatment rooms, ProBeam Superconducting Cyclotron[149] manufactured by Varian Medical Systems
Provision CARES Proton Therapy Center Nashville, TN Three treatment rooms, Two Gantries and One Fixed Beam, All Pencil Beam Scanning, manufactured by ProNova Solutions, LLC
McLaren Proton Therapy Center Flint, MI The McLaren Proton Therapy System uses the industry's highest energy 330 MeV proton synchrotron to accelerate and deliver proton beam to two treatment rooms, with an opportunity to extend into a planned third room. Both operating treatment rooms are equipped with proton pencil beam scanning, cone beam computed tomography for image guidance, patient positioning system with 6-degrees of freedom that coupled with 180-degree partial gantry allows for complete flexibility of treatment angles.
New York Proton Center New York, NY 2019 A partnership between Memorial Sloan Kettering, Montefiore Health, and Mount Sinai Health System. 4 treatment rooms, manufactured by Varian Medical Systems
Johns Hopkins Proton Therapy Center Washington, DC 3 treatment rooms and 1 research gantry. Manufactured by Hitachi.
South Florida Proton Therapy Institute Delray Beach, FL One treatment room, manufactured by Varian Medical Systems
UAB Proton Therapy Center Birmingham, AL 2020 One treatment room, manufactured by Varian Medical Systems
Dwoskin PTC - University of Miami Miami, FL One treatment room, manufactured by Varian Medical Systems
The Inova Mather Proton Therapy Center Fairfax, VA Two treatment rooms, manufactured by Ion Beam Applications
The University of Kansas Cancer Center Kansas City, KS 2022 Announced Feb 2019[150]
Penn Medicine Lancaster General Health Ann B. Barshinger Cancer Institute Lancaster, PA One treatment room, manufactured by Varian Medical Systems
Penn Medicine Virtua Health Voorhees, NJ One treatment room, manufactured by Varian Medical Systems
Ohio State, Nationwide Children's Hospital Columbus, OH 2023 Three treatment rooms, manufactured by Varian Medical Systems
OSF Healthcare Peoria, IL 2024 One treatment room, manufactured by Varian Medical Systems
Froedtert Hospital Wauwatosa, WI 2024 (Estimated) Announced May 2022[151]
Mayo Clinic Florida Jacksonville, FL 2025 (Estimated) Announced June 2019[152]

The Indiana University Health Proton Therapy Center in Bloomington, Indiana opened in 2004 and ceased operations in 2014.

Outside the US[edit]

Proton therapy Centres (partial list)[24]
Institution Maximum energy (MeV) Year of first treatment Location
Paul Scherrer Institute 250 1984 Villigen, Switzerland
Clatterbridge Cancer Centre NHS Foundation Trust, low-energy for ocular[153] 62 1989 Liverpool, United Kingdom
Centre de protonthérapie de l'Institut Curie 235 1991 Orsay, France
Centre Antoine Lacassagne 63 1991 Nice, France
Research Center for Charged Particle Therapy 350–400 1994 Chiba, Japan
TRIUMF[154] 74 1995 Vancouver, Canada
Helmholtz-Zentrum Berlin 72 1998 Berlin, Germany
Proton Medical Research Center University of Tsukuba 250 2001 Tsukuba, Japan
Centro di adroterapia oculare 60 2002 Catania, Italy
Wanjie Proton Therapy Center 230 2004 Zibo, China
Proton Therapy Center, Korea National Cancer Center 230 2007 Seoul, Korea
Heidelberg Ion-Beam Therapy Center (HIT) 230 2009 Heidelberg, Germany
Medipolis Proton Therapy and Research Center 235 2011 Kagoshima, Japan
Instytut Fizyki Jądrowej 230 2011 Kraków, Poland
Centro Nazionale di Adroterapia Oncologica 250 2011 Pavia, Italy
Protonové centrum v Praze (PTC, Prague) 230 2012 Prague, Czech Republic
Westdeutsches Protonentherapiezentrum Essen 230 2013 Essen, Germany
PTC Uniklinikum Dresden 230 2014 Dresden, Germany
Centro di Protonterapia, APSS Trento[155] 230 2014 Trento, Italy
Shanghai Proton and Heavy Ion Center 230 2014 Shanghai, China
Centrum Cyklotronowe Bronowice 230 2015 Kraków, Poland
Samsung Medical Center Proton Therapy Center 230 2015 Seoul, Korea
Proton and Radiation Therapy Center, Linkou Chang Gung Memorial Hospital 230 2015 Taipei, Taiwan
Yung-Ching Proton Center, Kaohsiung Chang Gung Memorial Hospital[156] 230 2018 Kaohsiung, Taiwan
Skandionkliniken[157] 230 2015 Uppsala, Sweden
A. Tsyb Medical Radiological Research Centre 250 2016 Obninsk, Russia
MedAustron 250 2016 Wiener Neustadt, Austria [1]
Clinical Proton Therapy Center Dr. Berezin Medical Institute[158] 250 2017 Saint-Petersburg, Russia
Holland Proton Therapy Center[159] 250 2018 Delft, Netherlands
UMC Groningen Protonen Therapie Centrum[160] 230 2018 Groningen, Netherlands
The Christie[161] 250 2018 Manchester, United Kingdom
Danish Centre for Particle Therapy[162] 250 2019 Aarhus, Denmark
Apollo Proton Cancer Centre[163] 230 2019 Chennai, India
MAASTRO Clinic Proton Therapy[164] 230 2019 Maastricht, Netherlands
Clínica Universidad de Navarra 230 2019 Madrid, Spain
Centro de Protonterapia de Quirónsalud[165] 230 2019 Madrid, Spain
King Chulalongkorn Memorial Hospital [166] 250 2021 Bangkok, Thailand
University College London Hospitals[167] 250 2021 London, United Kingdom
Hefei Ion Medical Center[168] 250 2022 Hefei, China
Proton Clinical Research Center of the Shandong Cancer Hospital 250 2022 Jinan, China
Singapore Institute of Advanced Medicine Holdings - Proton Therapy SG[169] 250 2023 Singapore
Mount Elizabeth Proton Therapy Centre[170] 230 2023 Singapore
National Cancer Centre Singapore - Goh Cheng Liang Proton Therapy Centre[171] 2023 Singapore
Central Japan International Medical Center [172] 230 2024 Minokamo, Japan
Australian Bragg Centre for Proton Therapy & Research[173][174] 330 2023–2025 Adelaide, Australia

Australia[edit]

In July 2020, construction began for "SAHMRI 2", the second building for the South Australian Health and Medical Research Institute. The building will house the Australian Bragg Centre for Proton Therapy & Research, a A$500+ million addition to the largest health and biomedical precinct in the Southern Hemisphere, Adelaide's BioMed City. The proton therapy unit is being supplied by ProTom International, which will install its Radiance 330 proton therapy system, the same system used at Massachusetts General Hospital. When in full operation, it will have the ability to treat approximately 600-700 patients per year with around half of these expected to be children and young adults. The facility is expected to be completed in late 2023, with its first patients treated in 2025.[174] In 2024 the South Australian government expressed concerns about the delivery of the project. [175]

India[edit]

Apollo Proton Cancer Centre (APCC) in Chennai, Tamil Nadu, a unit under Apollo Hospitals, is a Cancer specialty hospital.[176] APCC is the only cancer hospital in India with Joint Commission International accreditation.[177]

Israel[edit]

In January 2020, it was announced that a proton therapy center would be built in Ichilov Hospital, at the Tel Aviv Sourasky Medical Center. The project's construction was fully funded by donations. It will have two treatment rooms.[178] According to a newspaper report in 2023, it should be ready in three to four years. The report also mentions that "Proton therapy for cancer treatment has arrived in Israel and the Middle East with a clinical trial underway that sees Hadassah Medical Center partnering with P-Cure, an Israeli company that has developed a unique system designed to fit into existing hospital settings".[179]

Spain[edit]

In October 2021, the Amancio Ortega Foundation arranged with the Spanish government and several autonomous communities to donate 280 million euros to install ten proton accelerators in the public health system.[180]

United Kingdom[edit]

Prince Charles and Dr. Yen-Ching Chang at the University College London Hospitals NHS Foundation Trust proton centre opening ceremony

In 2013 the British government announced that £250 million had been budgeted to establish two centers for advanced radiotherapy: The Christie NHS Foundation Trust (the Christie Hospital) in Manchester, which opened in 2018; and University College London Hospitals NHS Foundation Trust, which opened in 2021. These offer high-energy proton therapy, and other types of advanced radiotherapy, including intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT).[181] In 2014, only low-energy proton therapy was available in the UK, at Clatterbridge Cancer Centre NHS Foundation Trust in Merseyside. But NHS England has paid to have suitable cases treated abroad, mostly in the US. Such cases rose from 18 in 2008 to 122 in 2013, 99 of whom were children. The cost to the National Health Service averaged ~£100,000 per case.[182]

See also[edit]

References[edit]

  1. ^ a b Tai-Ze Yuan (2019). "New frontiers in proton therapy: applications in cancers". Cancer Commun. 39 (61): 61. doi:10.1186/s40880-019-0407-3. PMC 6805548. PMID 31640788.
  2. ^ "PROTON BEAM THERAPY (PBT)" (PDF). astro.org. American Medical Association. 2013. Retrieved 1 February 2021.
  3. ^ a b Adapted, Levin W. P., Kooy H., Loeffler J. S., DeLaney T. F. (2005). "Proton Beam Therapy". British Journal of Cancer. 93 (8): 849–854. doi:10.1038/sj.bjc.6602754. PMC 2361650. PMID 16189526.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Jakel 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.
  5. ^ a b "Zap! You're Not Dead". The Economist. Vol. 384, no. 8545. 8 September 2007. pp. 13–14.
  6. ^ Liu Q (2015). "Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation". Int J Radiation Oncol Biol Phys. 91 (5): 1081–1089. doi:10.1016/j.ijrobp.2014.12.046. PMID 25832698.
  7. ^ Slater Jason M (2019). "Hypofractionated Proton Therapy in Early Prostate Cancer: Results of a Phase I/II Trial at Loma Linda University". Int J Particle Ther. 6 (1): 1–9. doi:10.14338/IJPT-19-00057. PMC 6871628. PMID 31773043.
  8. ^ Kandula Shravan (2013). "Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: a treatment planning comparison". Med Dosim. 38 (4): 390–394. doi:10.1016/j.meddos.2013.05.001. PMID 23916884.
  9. ^ Camphausen, K. A.; Lawrence, R. C. (2008). "Principles of Radiation Therapy". In Pazdur, R.; Wagman, L. D.; Camphausen, K. A.; Hoskins, W. J. (eds.). Cancer Management: A Multidisciplinary Approach (11th ed.). Archived from the original on 2009-05-15. Retrieved 2018-04-02.
  10. ^ Smith, Alfred R. (26 January 2009). "Vision 20/20: Proton therapy". Medical Physics. 36 (2): 556–568. Bibcode:2009MedPh..36..556S. doi:10.1118/1.3058485. PMID 19291995. S2CID 1490932.
  11. ^ Degiovanni, Alberto; Amaldi, Ugo (June 2015). "History of hadron therapy accelerators". Physica Medica. 31 (4): 322–332. doi:10.1016/j.ejmp.2015.03.002. PMID 25812487.
  12. ^ Peach, K; Wilson, P; Jones, B (December 2011). "Accelerator science in medical physics". The British Journal of Radiology. 84 (special_issue_1): S4–S10. doi:10.1259/bjr/16022594. PMC 3473892. PMID 22374548.
  13. ^ Liu, Hui; Chang, Joe Y. (5 May 2011). "Proton therapy in clinical practice". Chinese Journal of Cancer. 30 (5): 315–326. doi:10.5732/cjc.010.10529. PMC 4013396. PMID 21527064.
  14. ^ Owen, Hywel; Lomax, Antony; Jolly, Simon (February 2016). "Current and future accelerator technologies for charged particle therapy". Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 809: 96–104. Bibcode:2016NIMPA.809...96O. doi:10.1016/j.nima.2015.08.038. S2CID 53615768.
  15. ^ "FLASH radiotherapy with protons protects normal tissue while killing cancer". Physics World. 15 January 2020.
  16. ^ Vozenin, M.-C.; Hendry, J.H.; Limoli, C.L. (July 2019). "Biological Benefits of Ultra-high Dose Rate FLASH Radiotherapy: Sleeping Beauty Awoken". Clinical Oncology. 31 (7): 407–415. doi:10.1016/j.clon.2019.04.001. PMC 6850216. PMID 31010708.
  17. ^ Atkinson, Jake; Bezak, Eva; Le, Hien; Kempson, Ivan (2023-05-09). "The current status of FLASH particle therapy: a systematic review". Physical and Engineering Sciences in Medicine. 46 (2): 529–560. doi:10.1007/s13246-023-01266-z. ISSN 2662-4737. PMC 10209266. PMID 37160539.
  18. ^ Wilson, Joseph D.; Hammond, Ester M.; Higgins, Geoff S.; Petersson, Kristoffer (17 January 2020). "Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?". Frontiers in Oncology. 9: 1563. doi:10.3389/fonc.2019.01563. PMC 6979639. PMID 32010633.
  19. ^ Wilson, Robert R. (1946). "Radiological Use of Fast Protons". Radiology. 47 (5): 487–491. doi:10.1148/47.5.487. ISSN 0033-8419. PMID 20274616.
  20. ^ Wilson, Richard (2004). A Brief History of the Harvard University Cyclotrons. Harvard University Press. p. 9. ISBN 978-0-674-01460-2.
  21. ^ a b "PTCOG: Particle Therapy Co-Operative Group". Ptcog.web.psi.ch. Retrieved 2009-09-03.
  22. ^ "Treating Cancer with Proton Therapy" (PDF). Paul Scherrer Institute. Retrieved 2020-08-01.
  23. ^ a b c "Particle therapy facilities in operation". Particle Therapy Co-Operative Group. 2013-08-27. Retrieved 2014-09-01.
  24. ^ "Proton Therapy Centers in the United States". Proton Beam Therapy. Retrieved 2020-08-01.
  25. ^ "Particle therapy facilities in clinical operation". Particle Therapy Co-Operative Group. Retrieved 2023-05-10.
  26. ^ "ASTRO model policies PBT" (PDF). ASTRO. 2017-06-01. Retrieved 2020-08-01.
  27. ^ a b c Radhe Mohan (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.
  28. ^ Eric S Wisenbaugh (2014). "Proton Beam Therapy for Localized Prostate Cancer 101: Basics, Controversies, and Facts". Rev. Urol. 16.
  29. ^ Ming Fan (2020). "Outcomes and Toxicities of Definitive Radiotherapy and Reirradiation Using 3-Dimensional Conformal or Intensity-Modulated (Pencil Beam) Proton Therapy for Patients With Nasal Cavity and Paranasal Sinus Malignancies". Cancer. 126 (9): 1905–1916. doi:10.1002/cncr.32776. PMC 7304541. PMID 32097507.
  30. ^ a b c Levy, Richard P.; Blakely, Eleanor A.; et al. (March 2009). "The current status and future directions of heavy charged particle therapy in medicine". AIP Conference Proceedings. 1099 (410): 410–425. Bibcode:2009AIPC.1099..410L. doi:10.1063/1.3120064.
  31. ^ Hug E. B.; et al. (1999). "Proton radiation therapy for chordomas and chondrosarcomas of the skull base". J. Neurosurg. 91 (3): 432–439. doi:10.3171/jns.1999.91.3.0432. PMID 10470818.
  32. ^ Gragoudas, Evangelos; et al. (2002). "Evidence-based estimates of outcomes in patients treated for intraocular melenoma". Arch. Ophthalmol. 120 (12): 1665–1671. doi:10.1001/archopht.120.12.1665. PMID 12470140.
  33. ^ Munzenrider J. E.; Liebsch N. J. (1999). "Proton radiotherapy for tumors of the skull base". Strahnlenther. Onkol. 175: 57–63. doi:10.1007/bf03038890. PMID 10394399. S2CID 34755628.
  34. ^ "Proton Therapy for Ocular Tumors". ucsf.edu. Department of Radiation Oncology; University of California, San Francisco. Archived from the original on 2017-10-06. Retrieved 2017-10-05.
  35. ^ Lisa S Kahalley (2019). "Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma". Journal of Clinical Oncology. 38 (5): 454–461. doi:10.1200/JCO.19.01706. PMC 7007288. PMID 31774710.
  36. ^ Bree R Eaton (2016). "Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma". Neuro-Oncol. 18 (6): 881–7. doi:10.1093/neuonc/nov302. PMC 4864263. PMID 26688075.
  37. ^ Christine E Hill-Kayser (2019). "Outcomes after Proton Therapy for Treatment of Pediatric High-Risk Neuroblastoma". International Journal of Radiation Oncology, Biology, Physics. 104 (2): 401–408. doi:10.1016/j.ijrobp.2019.01.095. PMID 30738983. S2CID 73417717.
  38. ^ Selby, Boris Peter; et al. (2007). "Pose estimation of eyes for particle beam treatment of tumors". Bildverarbeitung für die Medizin (Medical Image Processing). Munich: Springer Berlin Heidelberg: 368–373.
  39. ^ Juliette Thariat (2019). "Which irradiation technique for which ocular tumor". Acta Ophthalmologica. 97 (263). doi:10.1111/j.1755-3768.2019.8284.
  40. ^ "Retinoblastoma Treatment". www.cancers.gov. 27 Aug 2020.
  41. ^ "Treatment Options for Intraocular (Uveal) Melanoma". www.cancers.gove. 27 Aug 2020.
  42. ^ Thanos Papakostas (2017). "Long-term Outcomes After Proton Beam Irradiation in Patients With Large Choroidal Melanomas". JAMA Ophthalmol. 135 (11): 1191–1196. doi:10.1001/jamaophthalmol.2017.3805. PMC 5710395. PMID 29049518.
  43. ^ Kavita K Mishra (2016). "Proton therapy for the management of uveal melanoma and other ocular tumors". Chinese Clinical Oncology. 5 (4): 50. doi:10.21037/cco.2016.07.06. PMID 27558251.
  44. ^ "Proton Therapy for Ocular Tumors". radonc.ucsf.edu. 27 Aug 2020. Archived from the original on 6 October 2017. Retrieved 5 October 2017.
  45. ^ Maradia, Vivek; Meer, David; Dölling, Rudolf; Weber, Damien C.; Lomax, Antony J.; Psoroulas, Serena (2023-07-03). "Demonstration of momentum cooling to enhance the potential of cancer treatment with proton therapy". Nature Physics. 19 (10). Springer Science and Business Media LLC: 1437–1444. Bibcode:2023NatPh..19.1437M. doi:10.1038/s41567-023-02115-2. hdl:20.500.11850/623775. ISSN 1745-2473. S2CID 259600479.
  46. ^ K J Stelzer (2000). "Acute and long-term complications of therapeutic radiation for skull base tumors". Neurosurg Clin N Am. 11 (4): 597–604. doi:10.1016/S1042-3680(18)30085-8. PMID 11082170.
  47. ^ "Skull Base Tumors". www.mskcc.org. 27 Aug 2020.
  48. ^ Maurizio Amichetti (2010). "A systematic review of proton therapy in the treatment of chondrosarcoma of the skull base". Neurosurg Rev. 33 (2): 155–165. doi:10.1007/s10143-009-0235-z. PMID 19921291. S2CID 10849293.
  49. ^ Damien Weber (2016). "Long term outcomes of patients with skull-base low-grade chondrosarcoma and chordoma patients treated with pencil beam scanning proton therapy". Radiother Oncol. 120 (1): 169–174. doi:10.1016/j.radonc.2016.05.011. PMID 27247057.
  50. ^ Jinpeng Zhou (2018). "Comparison of the Effectiveness of Radiotherapy with Photons and Particles for Chordoma After Surgery: A Meta-Analysis". World Neurosurg. 117: 46–53. doi:10.1016/j.wneu.2018.05.209. PMID 29879512. S2CID 46970649.
  51. ^ "TREATING HEAD AND NECK CARCINOMA WITH PROTON THERAPY". IBA White Paper. 2016-10-04. Archived from the original on 2018-04-24. Retrieved 2018-04-23.
  52. ^ Zachary Brownlee (2018). "Late complications of radiation therapy for breast cancer: evolution in techniques and risk over time". Gland Surgery. 7 (4): 371–378. doi:10.21037/gs.2018.01.05. PMC 6107587. PMID 30175054.
  53. ^ Rachel B. Jimenez (2019). "Phase II Study of Proton Beam Radiation Therapy for Patients With Breast Cancer Requiring Regional Nodal Irradiation". Journal of Clinical Oncology. 37 (30): 2778–2785. doi:10.1200/JCO.18.02366. PMC 7351324. PMID 31449469.
  54. ^ Line B. Stick (2016). "Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer". International Journal of Radiation Oncology, Biology, Physics. 97 (4): 754–761. doi:10.1016/j.ijrobp.2016.12.008. PMC 5625081. PMID 28244411.
  55. ^ David A Bush (2014). "Partial breast radiation therapy with proton beam: 5-year results with cosmetic outcomes". Int J Radiat Oncol Biol Phys. 90 (3): 501–505. doi:10.1016/j.ijrobp.2014.05.1308. PMID 25084608.
  56. ^ Julie A Bradley (2015). "Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons". Int J Radiat Oncol Biol Phys. 95 (5): 411–421. doi:10.1016/j.ijrobp.2015.09.018. PMID 26611875.
  57. ^ "Pragmatic Randomized Trial of Proton vs. Photon Therapy for Patients With Non-Metastatic Breast Cancer: A Radiotherapy Comparative Effectiveness (RADCOMP) Consortium Trial". ClinicalTrials.gov. 21 August 2020.
  58. ^ "TREATING HODGKIN AND NON-HODGKIN LYMPHOMA WITH PROTON THERAPY". IBA White Paper. September 2016. Archived from the original on 2018-05-02. Retrieved 2018-05-02.
  59. ^ Slater, J. D.; et al. (2004). "Proton therapy for prostate cancer; the initial Loma Linda University experience". Int. J. Radiat. Oncol. Biol. Phys. 59 (2): 348–352. doi:10.1016/j.ijrobp.2003.10.011. PMID 15145147.
  60. ^ a b Zietman, A. L.; et al. (2005). "Comparisons of conventional-dose vs. high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial". JAMA. 294 (10): 1233–1239. doi:10.1001/jama.294.10.1233. PMID 16160131.
  61. ^ deCrevoisier, R.; et al. (2005). "Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy". Int. J. Radiat. Oncol. Biol. Phys. 62 (4): 965–973. doi:10.1016/j.ijrobp.2004.11.032. PMID 15989996.
  62. ^ Lambert; et al. (2005). "Intrafractional motion during proton beam scanning". Phys. Med. Biol. 50 (20): 4853–4862. Bibcode:2005PMB....50.4853L. doi:10.1088/0031-9155/50/20/008. PMID 16204877. S2CID 12140561.
  63. ^ Byrne, Thomas E. (2005). "A Review of Prostate Motion with Considerations for the Treatment of Prostate Cancer". Medical Dosimerty. 30 (3): 155–161. doi:10.1016/j.meddos.2005.03.005. PMID 16112467.
  64. ^ Van Dyk, Jacob (1999). The modern technology of radiation oncology: A Compendium for Medical Physicists and Radiation Oncologists. Medical Physics Publishing Corporation. p. 826. ISBN 978-0944838389. Proton Patient Summary – Inception Through December 1998...Prostate...2591 64.3%
  65. ^ "The Promise of Proton-Beam Therapy". U.S. News & World Report. 2008-04-16. Retrieved 2008-02-20.
  66. ^ Delaney, T (2011). Francis H. Burr Proton Therapy Center (PDF of PowerPoint presentation). Massachusetts General Hospital; Harvard Medical School. Bibcode:2012ibt..book..597F – via Particle Therapy Co-Operative Group.
  67. ^ Sisterson, Janet (December 2005). "Ion beam therapy in 2004". Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms. 241 (1–4): 713–716. Bibcode:2005NIMPB.241..713S. doi:10.1016/j.nimb.2005.07.121.
  68. ^ "TREATING GASTROINTESTINAL MALIGNANCY WITH PROTON THERAPY". IBA White Paper. September 2016. Archived from the original on 2018-05-02. Retrieved 2018-05-02.
  69. ^ a b Tae Hyung Kim (2020). "Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: a randomized phase III trial". Journal of Hepatology. 74 (3): 603–612. doi:10.1016/j.jhep.2020.09.026. PMID 33031846.
  70. ^ Kuniaki Fuduka (2016). "Long-term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma". Cancer Science. 108 (3): 497–503. doi:10.1111/cas.13145. PMC 5378259. PMID 28012214.
  71. ^ Jeong Il Yu (2018). "Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma". Radiat Oncol J. 36 (1): 25–34. doi:10.3857/roj.2017.00409. PMC 5903361. PMID 29580046.
  72. ^ Awalpreet S Chadha (2019). "Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma". Radiotherapy and Oncology. 133: 54–61. doi:10.1016/j.radonc.2018.10.041. PMC 6446916. PMID 30935582.
  73. ^ Nina N Sanford (2018). "Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival". Int J Radiation Oncol Biol Phys. 105 (1): 64–72. doi:10.1016/j.ijrobp.2019.01.076. PMID 30684667.
  74. ^ Chuong (2019). "Consensus Report From the Miami Liver Proton Therapy Conference". Front. Oncol. 9: 457. doi:10.3389/fonc.2019.00457. PMC 6557299. PMID 31214502.
  75. ^ Shaed N Badiyan (2019). "Clinical Outcomes of Patients With Recurrent Lung Cancer Reirradiated With Proton Therapy on the Proton Collaborative Group and University of Florida Proton Therapy Institute Prospective Registry Studies". Pract Radiat Oncol. 9 (4): 280–288. doi:10.1016/j.prro.2019.02.008. PMID 30802618. S2CID 73499968.
  76. ^ Paul B Romesser (2016). "Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes". International Journal of Radiation Oncology, Biology, Physics. 95 (1): 386–395. doi:10.1016/j.ijrobp.2016.02.036. PMC 4997784. PMID 27084656.
  77. ^ Vivek Verma (2017). "Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation". Radiotherapy and Oncology. 125 (1): 21–30. doi:10.1016/j.radonc.2017.08.005. PMID 28941560.
  78. ^ Hann-Hsiang Chao (2017). "Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non-Small Cell Lung Cancer". J Thorac Oncol. 12 (2): 281–292. doi:10.1016/j.jtho.2016.10.018. PMID 27826034.
  79. ^ Baumann BC (2020). "Comparative Effectiveness of Proton vs Photon Therapy as Part of Concurrent Chemoradiotherapy for Locally Advanced Cancer". JAMA Oncology. 6 (2): 237–246. doi:10.1001/jamaoncol.2019.4889. PMC 6990870. PMID 31876914.
  80. ^ Steven H Lin (2020). "Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer". Journal of Clinical Oncology. 38 (14): 1569–1579. doi:10.1200/JCO.19.02503. PMC 7213588. PMID 32160096.
  81. ^ Radhe Mohan (2020). "Proton Therapy Reduces the Likelihood of High-Grade Radiation-Induced Lymphopenia in Glioblastoma Patients: Phase II Randomized Study of Protons vs. Photons". Neuro-Oncology. 23 (2): 284–294. doi:10.1093/neuonc/noaa182. PMC 7906048. PMID 32750703.
  82. ^ Michael Xiang (2020). "Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy". Cancer. 126 (15): 3560–3568. doi:10.1002/cncr.32938. PMID 32426866. S2CID 218690280.
  83. ^ Makbule Tambas (2020). "First experience with model-based selection of head and neck cancer patients for proton therapy". Radiotherapy and Oncology. 126 (15): 206–213. doi:10.1016/j.radonc.2020.07.056. PMID 32768508.
  84. ^ Johannes A Langendijk (2013). "Selection of patients for radiotherapy with protons aiming at reduction of side effects: The model-based approach". Radiotherapy and Oncology. 107 (3): 267–273. doi:10.1016/j.radonc.2013.05.007. PMID 23759662.
  85. ^ "Evaluation of Proton Therapy in Pediatric Cancer Patients". ClinicalTrials.gov. August 2020.
  86. ^ "Registry for Analysis of Quality of Life, Normal Organ Toxicity and Survival of Pediatric Patients Treated With Proton Therapy". ClinicalTrials.gov. August 2020.
  87. ^ "Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base (HIT-1)". ClinicalTrials.gov. August 2020.
  88. ^ "Intensity-Modulated Proton Therapy for Oropharyngeal Cancer". mdanderson.org. August 2020. Archived from the original on 2020-08-14. Retrieved 2020-08-21.
  89. ^ "Study of Proton Versus Photon Beam Radiotherapy in the Treatment of Head and Neck Cancer". ClinicalTrials.gov. August 2020.
  90. ^ Md, Helen A. Shih (August 2020). "A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas". ClinicalTrials.gov.
  91. ^ "Proton Radiotherapy for Primary Central Nervous System Tumours in Adults (PRO-CNS)". ClinicalTrials.gov. August 2020.
  92. ^ "Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastom". ClinicalTrials.gov. August 2020.
  93. ^ "Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma". ClinicalTrials.gov. August 2020.
  94. ^ "Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer". ClinicalTrials.gov. August 2020.
  95. ^ Lin, Shi-Ming (August 2020). "Proton Radiotherapy Versus Radiofrequency Ablation for Patients With Medium or Large Hepatocellular Carcinoma". ClinicalTrials.gov.
  96. ^ Md, Michael Devera (August 2020). "Transarterial Chemoembolization Versus Proton Beam Radiotherapy for the Treatment of Hepatocellular Carcinoma". ClinicalTrials.gov.
  97. ^ "Comparing Photon Therapy To Proton Therapy To Treat Patients With Lung Cancer". ClinicalTrials.gov. August 2020.
  98. ^ "A Phase I/II Study of Hypofractionated Proton Therapy for Stage II-III Non-Small Cell Lung Cancer". ClinicalTrials.gov. August 2020.
  99. ^ Schild, Steven (August 2020). "Phase II Trial of Standard Chemotherapy (Carboplatin & Paclitaxel) +Various Proton Beam Therapy (PBT) Doses". ClinicalTrials.gov.
  100. ^ "Comparing Proton Therapy to Photon Radiation Therapy for Esophageal Cancer". ClinicalTrials.gov. August 2020.
  101. ^ "Dose Escalation of Neoadjuvant Proton Beam Radiotherapy With Concurrent Chemotherapy in Locally Advanced Esophageal Cancer". ClinicalTrials.gov. August 2020.
  102. ^ "Pragmatic Randomized Trial of Proton vs. Photon Therapy for Patients With Non-Metastatic Breast Cancer: A Radiotherapy Comparative Effectiveness (RADCOMP) Consortium Trial". ClinicalTrials.gov. August 2020.
  103. ^ "Phase II Protocol of Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer". ClinicalTrials.gov. August 2020.
  104. ^ "Phase I Nab-Paclitaxel Plus Gemcitabine With Proton Therapy for Locally Advanced Pancreatic Cancer (LAPC)". ClinicalTrials.gov. August 2020.
  105. ^ "Proton Radiation for Unresectable, Borderline Resectable, or Medically Inoperable Carcinoma of the Pancreas". ClinicalTrials.gov. August 2020.
  106. ^ "Introducing Hyperscan". mevion.com. Mevion Medical Systems. 2015-04-19.
  107. ^ Sheets, NC; Goldin, GH; Meyer, AM; Wu, Y; et al. (April 18, 2012). "Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer". The Journal of the American Medical Association. 307 (15): 1611–20. doi:10.1001/jama.2012.460. PMC 3702170. PMID 22511689.
  108. ^ Tepper, Joel E.; Blackstock, A. William (20 October 2009). "Editorial: Randomized Trials and Technology Assessment". Annals of Internal Medicine. 151 (8): 583–584. doi:10.7326/0003-4819-151-8-200910200-00146. PMID 19755346.
  109. ^ Goitein, M.; Jermann, M. (2003). "The Relative Costs of Proton and X-ray Radiation Therapy". Clinical Oncology. 15 (1): S37–50. doi:10.1053/clon.2002.0174. PMID 12602563.
  110. ^ a b Bassett, Anne. "Siteman Cancer Center Treats First Patient With First-of-Its-Kind Proton Therapy System". PRWeb.com (Press release). Barnes-Jewish Hospital. Retrieved 2017-10-05.
  111. ^ a b Roland, Denise (September 25, 2013). "God particle technology to cancer patients". The Telegraph. Retrieved 2017-10-05.
  112. ^ Lievens, Y.; Van den Bogaert, W; et al. (2005). "Proton beam therapy: Too expensive to become true?". Radiotherapy and Oncology. 75 (2): 131–133. doi:10.1016/j.radonc.2005.03.027. PMID 15890422.
  113. ^ St Clair, W. H.; Adams, J. A.; Bues, M.; Fullerton, B. C.; La Shell, S.; Kooy, H. M.; Loeffler, J. S.; Tarbell, N. J. (2004). "Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma". Int. J. Radiat. Oncol. Biol. Phys. 58 (3): 727–734. doi:10.1016/S0360-3016(03)01574-8. PMID 14967427.
  114. ^ Merchant, T. E.; Hua, C. H.; Shukla, H.; Ying, X.; Nill, S.; Oelfke, U. (2008). "Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function". Pediatr. Blood Cancer. 51 (1): 110–117. doi:10.1002/pbc.21530. PMID 18306274. S2CID 36735536.
  115. ^ Konski A.; Speier W.; Hanlon A.; Beck J. R.; Pollack A. (2007). "Is proton beam therapy cost effective in the treatment of adenocarcinoma of the prostate?". J. Clin. Oncol. 25 (24): 3603–3608. doi:10.1200/jco.2006.09.0811. PMID 17704408. S2CID 19423315.
  116. ^ Nguyen, P. L.; Trofimov, A.; Zietman, A. L. (June 22, 2008). "Proton-Beam vs. Intensity-Modulated Radiation Therapy, Which Is Best for Treating Prostate Cancer?". Oncology (Williston Park). 22 (7): 748–754, discussion 754, 757. PMID 18619120.
  117. ^ Langreth, Robert (March 26, 2012). "Prostate Cancer Therapy Too Good to Be True Explodes Health Cost". Bloomberg.com. Retrieved 2013-05-16.
  118. ^ a b Muralidhar, Vinayak; Nguyen, Paul L. (February 2017). "Maximizing resources in the local treatment of prostate cancer: A summary of cost-effectiveness studies". Urologic Oncology. 35 (2): 76–85. doi:10.1016/j.urolonc.2016.06.003. ISSN 1873-2496. PMID 27473636.
  119. ^ Yuan, Tai-Ze; Zhan, Ze-Jiang; Qian, Chao-Nan (22 October 2019). "New frontiers in proton therapy: applications in cancers". Cancer Communications. 39 (1): 61. doi:10.1186/s40880-019-0407-3. ISSN 2523-3548. PMC 6805548. PMID 31640788.
  120. ^ Hancock, Jay (April 27, 2018). "For Cancer Centers, Proton Therapy's Promise Is Undercut by Lagging Demand". The New York Times.
  121. ^ "Wise Buy? Proton Beam Therapy". www.medpagetoday.com. May 19, 2017.
  122. ^ "Particle therapy facilities in operation". PTCOG.ch. Particle Therapy Co-Operative Group. August 2020. Retrieved 2020-08-01.
  123. ^ "Particle therapy facilities under construction". PTCOG.ch. Particle Therapy Co-Operative Group. June 2017. Retrieved 2017-10-06.
  124. ^ "Statistics of patients treated in particle therapy facilities worldwide". PTCOG.ch. Particle Therapy Co-Operative Group. 2016. Retrieved 2017-10-06.
  125. ^ a b Matthews, J. N. A. (March 2009). "Accelerators shrink to meet growing demand for proton therapy". Physics Today. p. 22.
  126. ^ Nafziger, Brendon (March 20, 2012). "N.J. proton therapy center opens today". DotMed.com. Retrieved 2012-03-30.
  127. ^ "Proton Therapy Treatment and Research Center". Loma Linda University Medical Center. Retrieved 2013-11-05.
  128. ^ "Cyclotron Services". crocker.udavis.edu. University of California, Davis, Crocker Nuclear Laboratory. Retrieved 2017-10-05.
  129. ^ a b c d e f g h i j k l "Best proton therapy centers – IBA proton therapy". iba-worldwide.com. Retrieved 2018-03-16.
  130. ^ "Proton Therapy Jacksonville | Cancer Treatment". University of Florida Proton Therapy Institute. Retrieved 2013-11-05.
  131. ^ "Proton Therapy Center". University of Texas MD Anderson Cancer Center. Retrieved 2013-11-05.
  132. ^ "Oklahoma Proton Therapy Treatment Center". ProCure. Retrieved 2013-11-05.
  133. ^ "Proton Therapy at Penn Medicine". Perelman Center for Advanced Medicine. Retrieved 2013-11-05.
  134. ^ "New Jersey Proton Therapy Treatment Center". ProCure. Archived from the original on 2010-11-26. Retrieved 2013-11-05.
  135. ^ "Elegant and Precise". Mevion Medical Systems. Archived from the original on 2015-04-14. Retrieved 2015-04-19.
  136. ^ "Introducing the Mevion S250". Mevion. Archived from the original on 2015-04-14. Retrieved 2015-04-19.
  137. ^ "Proton therapy cancer treatment center opens, first of its kind in Tennessee". WATE-TV. Archived from the original on 2014-01-26. Retrieved 2014-01-25.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  138. ^ "California Protons Cancer Therapy Center". California Protons Cancer Therapy Center. Retrieved 2017-12-18.
  139. ^ "Oncology, Solutions, Proton Therapy". Varian Medical Systems. Archived from the original on 2019-01-07. Retrieved 2015-04-19.
  140. ^ "Texas Center for Proton Therapy Treats First Patient with Isocentric Cone Beam CT and Pencil Beam Scanning" (Press release). Irving, Texas: McKesson. May 9, 2016. Retrieved 2017-10-05.
  141. ^ "Mayo Clinic launches Proton Beam Therapy Program". mayoclinic.org. Mayo Clinic. Retrieved 2017-10-05.
  142. ^ "Hitachi's Advanced Proton Beam Therapy System "PROBEAT-V" Begins Treatments at Mayo Clinic in Rochester, MN" (Press release). Tokyo, Japan: Hitachi. September 15, 2015. Retrieved 2018-05-01.
  143. ^ "Mayo Clinic Cancer Center". mayoclinic.org. Mayo Clinic.
  144. ^ "Hitachi "PROBEAT-V" Advanced Proton Beam Therapy System Now In Use at Mayo Clinic in Arizona" (Press release). Tokyo, Japan: Hitachi. March 15, 2016. Retrieved 2018-05-01.
  145. ^ "Proton Therapy at University of Cincinnati Medical Center". uchealth.com. University of Cincinnati Cancer Institute, UC Health. Retrieved 2017-10-05.
  146. ^ "Pediatric Proton Therapy Center". cincinnatichildrens.org. Cincinnati Children's Hospital Medical Center. Retrieved 2017-10-05.
  147. ^ "Proton Therapy at Miami Cancer Institute". Baptist Health South Florida. Archived from the original on 2017-10-06.
  148. ^ "Emory Proton Therapy Center Fact Sheet" (PDF). winshipcancer.emory.edu. Emory Winship Cancer Institute. Archived from the original (PDF) on 2017-10-14. Retrieved 2018-03-05.
  149. ^ "KU Health System to offer innovative, new proton therapy cancer treatment". 26 February 2019. Retrieved 2019-05-29.
  150. ^ "The Froedtert & MCW health network to offer new generation radiation therapy to patients". froedtert.com. 16 May 2022.
  151. ^ "Integrated oncology facility with proton beam therapy planned for Mayo Clinic's Florida campus". newsnetwork.mayoclinic.org. 24 June 2019.
  152. ^ "Proton therapy". clatterbridgecc.nhs.uk. Clatterbridge Cancer Centre NHS Foundation Trust. Archived from the original on 2014-01-15. Retrieved 2017-10-05.
  153. ^ "Proton Therapy". TRIUMF.ca. Archived from the original on 2017-06-27. Retrieved 2017-10-05.
  154. ^ "Proton Therapy Center - Trento". protonterapia.provincia.tn.it.
  155. ^ "Kaohsiung Branch-Yung-Ching Proton Center". www.chang-gung.org.
  156. ^ "Skandionkliniken — Nordens första klinik för protonstrålning". Startsida.
  157. ^ "Протонный центр МИБС". protherapy.ru.
  158. ^ "Welkom bij HollandPTC". HPTC. Archived from the original on 2022-04-07. Retrieved 2020-08-27.
  159. ^ "Corporate information". www.umcg.nl. Archived from the original on 2020-08-18. Retrieved 2020-08-27.
  160. ^ "The Christie". Archived from the original on 2019-05-31. Retrieved 2019-05-31.
  161. ^ "Danish Centre for Particle Therapy". www.en.auh.dk.
  162. ^ Proton Therapy Centre Apollo Hospitals
  163. ^ "Maastro is the first true compact proton therapy system in Europe" (PDF). www.maastro.nl/. Archived from the original (PDF) on 2021-08-17. Retrieved 2020-12-21.
  164. ^ "Proton therapy delivered to patient for the first time in Spain". 15 January 2020.
  165. ^ "Department of Radiology". King Chulalongkorn Memorial Hospital, The Thai Red Cross Society.
  166. ^ "University College London Hospitals". Archived from the original on 2016-04-14. Retrieved 2019-05-31.
  167. ^ "Hefei Ion Medical Center". hefeihightech.chinadaily.com.cn.
  168. ^ "Singapore Institute of Advanced Medicine Holdings - Proton Therapy SG". www.advancedmedicine.sg.
  169. ^ "Mount Elizabeth Proton Therapy Centre". www.mountelizabeth.com.sg.
  170. ^ "Goh Cheng Liang Proton Therapy Centre". www.nccs.com.sg.
  171. ^ "Cancer Treatment". cjimc-hp.jp.
  172. ^ "Australian Bragg Centre for Proton Therapy". Australian Bragg Centre for Proton Therapy.
  173. ^ a b Spence, Andrew (10 June 2020). "Proton therapy focus of 'SAHMRI 2'". InDaily. Retrieved 6 July 2020.
  174. ^ Kelsall, Thomas (22 Feb 2024). "Warnings over Adelaide proton therapy unit in 2017 as government looks for plan B". InDaily. Retrieved 5 March 2024.
  175. ^ www.ETHealthworld.com. "Modern cancer treatments ensure that every single mm of the tissue beyond the tumor is preserved: Dr.Rakesh Jalali - ET HealthWorld". ETHealthworld.com. Retrieved 2021-12-06.
  176. ^ "Apollo Proton Centre gets JCI accreditation". The Hindu. 2020-07-04. ISSN 0971-751X. Retrieved 2021-12-06.
  177. ^ Filut, Adrian (January 27, 2020). "Israel to Establish National Center for Proton Radiation Cancer Therapy". CTECH - www.calcalistech.com.
  178. ^ Ghert-Zand, Renee (18 May 2023). "Proton therapy, touted as cancer killer without side effects, set for Israel debut". The Times of Israel. Retrieved 4 Oct 2023.
  179. ^ "Programme for the implementation of proton therapy in the Spanish public health system". Fundación Amancio Ortega.
  180. ^ "Manchester and London proton beam therapy units confirmed", Press release, Press Association, Cancer Research UK, 1 August 2013
  181. ^ "Ashya King case: What is proton beam therapy?" BBC news story with NHS England figures, 31 August 2014

Further reading[edit]

External links[edit]