Proton therapy

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

In the field of medical treatment, 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 (e.g., radiation 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.

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 states that proton therapy is considered reasonable in instances where 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

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 thereby eliminating the tumor. Cancerous cells are particularly vulnerable to attacks on DNA because of their high rate of division and their limited abilities to repair DNA damage. Some cancers with specific defects in DNA repair may be more sensitive to proton radiation.[6]

Proton therapy offers physicians the ability to 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 deliver similar or higher radiation doses to the tumor with a 50%-60% lower total body radiation dose.[8][1]

Protons have the ability to focus energy delivery to conform to the tumor shape, delivering only low-dose radiation to surrounding tissue. As a result, the patient experiences fewer side effects. All protons of a given energy have a certain penetration range; very few protons penetrate beyond that distance.[9] Furthermore, 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 referred to as the SOBP (see visual).[10]

To treat tumors at greater depths, the proton accelerator must produce a beam with higher energy, typically given in eV (electron volts). Accelerators used for proton therapy typically produce protons with energies in the range of 70 to 250 MeV. Adjusting proton energy during the treatment maximizes the cell damage the proton beam causes within the tumor. Tissue closer to the surface of the body than the tumor receives reduced radiation, and therefore reduced damage. Tissues deeper in the body receive very few protons, so the dosage 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 receive almost no radiation from proton therapy, the tissues in front of (shallower than) the tumor receive radiation dosage based on the SOBP.

Equipment

Most installed proton therapy systems utilise isochronous cyclotrons.[11][12] Cyclotrons are considered simple to operate, reliable and can be made compact, especially with the 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 advancements in technology, and partly because of the continually increasing amount of proton clinical data, the number of hospitals offering proton therapy continues to increase.

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

History

The first suggestion that energetic protons could be an effective treatment method was made by Robert R. Wilson[19] in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory (HCL).[20] 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 the 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[21] 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 the 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 ocular 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. [22]

The world's first hospital-based proton therapy center was a low energy cyclotron centre for ocular tumours at the Clatterbridge Centre for Oncology in the UK, opened in 1989,[23] 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 during 2001 and 2002. At the beginning of 2020, there were 37 proton therapy centers in the United States alone,[24] and a total of 89 worldwide.[25] As of 2020, five manufacturers make proton therapy systems: Mevion Medical Systems, Ion Beam Applications, Hitachi, ProTom International and Varian Medical Systems.

Types of proton therapy

The newest form of proton therapy, pencil beam scanning, delivers therapy by sweeping a proton beam laterally over the target so that it delivers the required dose while closely conforming to shape of the targeted tumor. Prior to the use of pencil beam scanning, oncologists used a scattering method to direct a wide beam toward the tumor. [26]

Passive scattering beam delivery

The first commercially available proton delivery systems used a scattering process, also known as 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 placing items such as collimators and compensators into the path of the protons.[27] Passive scattering delivers homogenous dose along the target volume. Consequently, passive scattering provides more limited control over dose distributions proximal to the target. Over time many scattering therapy systems have been upgraded to deliver pencil beam scanning. However, 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

A newer and more flexible delivery method for proton therapy is pencil beam scanning, using a beam that sweeps laterally over the target so that it delivers the required dose while closely conforming to shape of the targeted tumor. This conformal delivery is achieved by shaping the dose through magnetic scanning of thin beamlets of protons without the need for 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, allowing the proton dose to conform more precisely to the shape of the tumor.[27]

Delivery of protons via pencil beam scanning, which has been in use since 1996 at the Paul Scherrer Institute,[27] allows for the most precise type of proton delivery known as intensity-modulated proton therapy (IMPT). IMPT is to proton therapy what IMRT is to conventional photon therapy—treatment that more closely conforms to the target tumor while avoiding surrounding structures.[28] 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.[29]

Application

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. In some instances, dose escalation has demonstrated a higher probability of "cure" (i.e., local control) than conventional radiotherapy.[30] These include, among others, uveal melanoma (ocular tumors), skull base and paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas. In all these cases proton therapy achieves significant improvements in the probability of local control over conventional radiotherapy.[31][32][33] In treatment of ocular tumors, proton therapy also has high rates of maintaining the natural eye.[34]
  • Treatments 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 an increased probability of curing the disease. Instead, the emphasis is on reducing the integral dose to normal tissue, thus reducing unwanted effects.[30]

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

Pediatric treatments

Irreversible long-term side effects of conventional radiation therapy for pediatric cancers have been 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, the 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, resulting in a reduction of acute thoracic, gastrointestinal and bladder side effects.[35][36][37]

Eye tumors

Proton therapy for ocular (eye) tumors is a special case since this treatment requires only comparatively low energy protons (about 70 MeV). Owing to this low energy requirement, some particle therapy centers only treat ocular tumors.[21] 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.[38] 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 radiotherapy's potential toxic side effects of nearby critical structures.[39] For example, proton therapy is an option for retinoblastoma [40] and intraocular melanoma.[41] The advantage of using a proton beam is that it has the potential to effectively treat the tumor while sparing sensitive structures of the eye.[42] Given its effectiveness, proton therapy has been described as the "gold standard" treatment for ocular melanomas.[43][44]

Base of skull cancer

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 osteosarcomas (bone cancer), and osteoradionecrosis, which occurs when radiation causes part of the bone in the jaw or skull base to die.[45] Proton therapy has been very effective for people with base of skull tumors.[46] Unlike conventional photon radiation, protons do not penetrate beyond the tumor. Proton therapy lowers the risk of treatment-related side effects caused when healthy tissue receives radiation. Clinical studies have found proton therapy to be effective for skull base tumors.[47][48][49]

Head and neck tumors

Proton particles do not deposit exit dose, which allows proton therapy to spare normal tissues distal to the tumor target. This is particularly useful for treating head and neck tumors because of the anatomic constraints encountered 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 which results in a minimal acute toxicity profile, even in patients who have received multiple prior courses of radiotherapy.[50]

Left-sided breast cancer

When breast cancer — especially cancer 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 the location of the tumor, damage can also occur to the esophagus, or to the chest wall (which can potentially lead to leukemia).[51] One recent study revealed that proton therapy has low rates of toxicity to nearby healthy tissues and similar rates of disease control compared with conventional radiation.[52] 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.[53]

Small studies have found that, compared to conventional photon radiation, proton therapy delivers minimal toxic dose to healthy tissues[54] and specifically decreased dose to the heart and lung.[55] Large-scale trials are underway to examine other potential benefits of proton therapy to treat breast cancer.[56]

Lymphoma (Tumors of lymphoid tissue)

Although chemotherapy is the primary treatment for patients with 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 expectancies following therapy.[57]

Prostate cancer

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.[58][59] 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.[59][60][61] One source suggests that dose errors around 20% can result from motion errors of just 2.5 mm (0.098 in). and another that prostate motion is between 5–10 mm (0.20–0.39 in).[62]

However, 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 a majority of their treatment slots to prostate treatments. For example, two hospital facilities devote roughly 65%[63] and 50%[64] of their proton treatment capacity to prostate cancer, while a third devotes only 7.1%.[65]

Overall worldwide numbers are hard to compile, but one example states that in 2003 roughly 26% of proton therapy treatments worldwide were for prostate cancer.[66]

Gastrointestinal malignancy

An increasing amount of data has shown that proton therapy has great potential to increase therapeutic tolerance for patients with GI malignancies. The possibility of decreasing radiation dose to organs at risk may also help facilitate chemotherapy dose escalation or allow for new chemotherapy combinations. Proton therapy will play a decisive role in the context of 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.[67]

Hepatocellular carcinoma

Post-treatment liver decompensation, and subsequent liver failure, is a risk when delivering radiotherapy for hepatocellular carcinoma, the most common type of primary liver cancer. Research shows that use of proton therapy results in favorable results related to local tumor control, progression-free survival, and overall survival.[68][69][70][71] Other studies, which examined proton therapy compared with conventional photon therapy, show that proton therapy is associated with improved survival and/or fewer side effects; therefore proton therapy has the potential to significantly improve clinical outcomes for some patients with liver cancer.[72][73]

Reirradiation for recurrent cancer

For patients who develop local or regional recurrences after their initial radiation therapy, physicians are limited in their treatment options due to their reluctance to deliver 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.[74] Research has shown the feasibility of using proton therapy with acceptable side effects, even in patients who have had multiple prior courses of photon radiation.[75][76][77]

Comparison with other treatments

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 whether 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.[78] The study included 1483 adult patients with nonmetastatic, locally advanced cancer treated with concurrent chemoradiotherapy with curative intent and concluded that '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 to date (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'.[68] A phase IIB randomized controlled trial of proton beam therapy versus IMRT for locally advanced esophageal cancer organized by the 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.[79] 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.[80] 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 from 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system.[81] 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 called 'model-based selection' uses comparative treatment plans for IMRT and IMPT in combination with normal tissue complication probability (NTCP) models to identify patients that may benefit most from proton therapy.[82][83]

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,[84] Samsung Medical Center [85]
  • Base of skull cancer—by Heidelberg University [86]
  • Head and neck cancer—by MD Anderson,[87] Memorial Sloan Kettering and other centers[88]
  • Brain and spinal cord cancer—by Massachusetts General Hospital,[89] Uppsala University and other centers,[90] NRG Oncology[91][92]
  • Hepatocellular carcinoma (liver)—by NRG Oncology,[93] Chang Gung Memorial Hospital,[94] Loma Linda University [95]
  • Lung cancer—by Radiation Therapy Oncology Group (RTOG),[96] Proton Collaborative Group (PCG),[97] Mayo Clinic[98]
  • Esophageal cancer—by NRG Oncology,[99] Abramson Cancer Center, University of Pennsylvania[100]
  • Breast cancer—by University of Pennsylvania,[101] Proton Collaborative Group (PCG)[102]
  • Pancreatic cancer—by University of Maryland,[103] Proton Collaborative Group (PCG)[104]

X-ray radiotherapy

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 scarring 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, unnecessarily damaging tissue deeper in the body and damaging the skin and surface tissue opposite the beam entrance. The differences between the two methods depends on the:

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

The X-ray advantage of reduced damage to skin at the entrance is partially counteracted by damage to skin at the 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 receive no radiation. Thus, X-ray therapy causes slightly less damage to the 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[105] which became US FDA approved in 2017) and Varian.

Surgery

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

The benefit of external beam proton radiation lies in the dosimetric difference from external beam X-ray radiation and brachytherapy in cases where the use of radiation therapy is already indicated, rather than as a direct competition with surgery.[30] However, in the case of 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.[106]

Side effects and risks

Proton therapy is a type of external beam radiotherapy, and shares risks and side effects of other forms of radiation therapy. However 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 treatment technology. However, as with all medical knowledge, understanding of the interaction of radiation (proton, X-ray, etc.) with tumor and normal tissue is still imperfect.[107]

Costs

Historically, proton therapy has been expensive. An analysis published in 2003 determined the relative cost of proton therapy is approximately 2.4 times that of X-ray therapies.[108] 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.[109][110] 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.[111] In some clinical situations, proton beam therapy is clearly superior to the alternatives.[112][113]

A study in 2007 expressed concerns about the effectiveness of proton therapy for treating prostate cancer,[114] 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.[115] Amitabh Chandra, a health economist at Harvard University, stated, "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."[116] Proton therapy is cost-effective for some types of cancer, but not all.[117][118] In particular, some other treatments offer better overall value for treatment of prostate cancer.[117]

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.[119][120]

Treatment centers

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

As of August 2020, there are over 89 particle therapy facilities worldwide,[121] with at least 41 others under construction.[122] 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.[123]

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.[124] Among the technologies being investigated are superconducting synchrocyclotrons (also known as FM Cyclotrons), ultra-compact synchrotrons, dielectric wall accelerators,[124] and linear particle accelerators.[110]

United States

Proton treatment centers in the United States as of 2020 (in chronological order of first treatment date) include:[23][125]

Institution Location Year of first treatment Comments
Loma Linda University Medical Center[126] Loma Linda, CA 1990 First hospital-based facility in USA; uses Spread Out Bragg's Peak (SOBP)
Crocker Nuclear Laboratory[127] 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[128]
University of Florida Health Proton Therapy Institute-Jacksonville[129] 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[128]
University of Texas MD Anderson Cancer Center[130] Houston, TX
Oklahoma Proton Center[131] Oklahoma City, OK 2009 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[128]
Northwestern Medicine Chicago Proton Center Warrenville, IL 2010 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[128]
Roberts Proton Therapy Center[132] 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[128]
Hampton University Proton Therapy Institute Hampton, VA 5 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[128]
ProCure Proton Therapy Center[133] Somerset, NJ 2012 4 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[128]
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[128]
Siteman Cancer Center[109] St. Louis, MO First of the new single suite, ultra-compact, superconducting synchrocyclotron,[134] lower cost facilities to treat a patient using the Mevion Medical System's S250.[135]
Provision Proton Therapy Center[136] Knoxville, TN 2014 3 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[128]
California Protons Cancer Therapy Center[137] San Diego, CA 5 treatment rooms, manufactured by Varian Medical Systems[138]
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.[139] 3 treatment rooms, Proteus PLUS system manufactured by Ion Beam Applications[128]
Mayo Clinic Jacobson Building Rochester, MN 4 treatment rooms.[140] Manufactured by Hitachi.[141]
St. Jude Red Frog Events Proton Therapy Center Memphis, TN 3 treatment rooms
Mayo Clinic Cancer Center Phoenix, AZ 2016 4 treatment rooms.[142] Manufactured by Hitachi.[143]
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,[144][145] 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[146] Manufactured by Ion Beam Applications[128]
Beaumont Proton Therapy Center Royal Oak, MI Single treatment room, Proteus ONE system manufactured by Ion Beam Applications[128]
Emory Proton Therapy Center Atlanta, GA 2018 Five treatment rooms, ProBeam Superconducting Cyclotron[147] 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 University of Kansas Cancer Center Kansas City, KS 2021 (Estimated) Announced Feb 2019[148]
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 2022 (Estimated) One treatment room, manufactured by Varian Medical Systems
Mayo Clinic Florida Jacksonville, FL 2023 (Estimated) Announced June 2019[149]
Ohio State, Nationwide Children's Hospital Columbus, OH Three treatment rooms, manufactured by Varian Medical Systems

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

Outside the US

Proton therapy Centres (partial list)[23]
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[150] 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[151] 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
Rinecker Proton Therapy Center 250 2009 Munich, 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[152] 230 2014 Trento, Italy
Shanghai Proton and Heavy Ion Center 230 2014 Shanghai, China
Centrum Cyklotronowe Bronowice 230 2015 Kraków, Poland
SMC 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[153] 230 2018 Kaohsiung, Taiwan
Skandionkliniken[154] 230 2015 Uppsala, Sweden
A. Tsyb Medical Radiological Research Centre 250 2016 Obninsk, Russia
MedAustron 250 2016 Wiener Neustadt, Austria
Clinical Proton Therapy Center Dr. Berezin Medical Institute[155] 250 2017 Saint-Petersburg, Russia
Holland Proton Therapy Center[156] 250 2018 Delft, Netherlands
UMC Groningen Protonen Therapie Centrum[157] 230 2018 Groningen, Netherlands
The Christie[158] 250 2018 Manchester, United Kingdom
Danish Centre for Particle Therapy[159] 250 2019 Aarhus, Denmark
Apollo Proton Cancer Centre[160] 230 2019 Chennai, India
MAASTRO Clinic Proton Therapy[161] 230 2019 Maastricht, Netherlands
Clínica Universidad de Navarra 230 2019 Madrid, Spain
Centro de Protonterapia de Quirónsalud[162] 230 2019 Madrid, Spain
King Chulalongkorn Memorial Hospital [163] 250 2021 Bangkok, Thailand
University College London Hospitals[164] 250 2021 London, United Kingdom
Singapore Institute of Advanced Medicine[165] 250 2021 Singapore
Hefei Ion Medical Center[166] 250 2021 Hefei, China
Australian Bragg Centre for Proton Therapy & Research[167][168] 330 2023–2025 Adelaide, Australia

Australia

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.[168]

India

Apollo Proton Cancer Centre (APCC) in Chennai, Tamil Nadu, a unit under Apollo Hospitals, is a Cancer specialty hospital.[169] APCC is the only cancer hospital in India with Joint Commission International accreditation.[170]

Israel

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.[171]

Spain

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.[172]

United Kingdom

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, as well as other types of advanced radiotherapy, including intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT).[173] In 2014, only low-energy proton therapy was available in the UK, at the 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 have risen from 18 in 2008 to 122 in 2013, 99 of whom were children. The cost to the National Health Service averaged around £100,000 per case.[174]

See also

References

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Further reading

  • Greco C.; Wolden S. (Apr 2007). "Current status of radiotherapy with proton and light ion beams". Cancer. 109 (7): 1227–1238. doi:10.1002/cncr.22542. PMID 17326046. S2CID 36256866.
  • "Use of Protons for Radiotherapy", A.M. Koehler, Proc. of the Symposium on Pion and Proton Radiotherapy, Nat. Accelerator Lab., (1971).
  • A.M. Koehler, W.M. Preston, "Protons in Radiation Therapy: comparative Dose Distributions for Protons, Photons and Electrons Radiology 104(1):191–195 (1972).
  • "Bragg Peak Proton Radiosurgery for Arteriovenous Malformation of the Brain" R.N. Kjelberg, presented at First Int. Seminar on the Use of Proton Beams in Radiation Therapy, Moskow (1977).
  • Austin-Seymor, M.J. Munzenrider, et al. "Fractionated Proton Radiation Therapy of Cranial and Intracrainial Tumors" Am. J. of Clinical Oncology 13(4):327–330 (1990).
  • "Proton Radiotherapy", Hartford, Zietman, et al. in Radiotheraputic Management of Carcinoma of the Prostate, A. D'Amico and G.E. Hanks. London, UK, Arnold Publishers: 61–72 (1999).
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