Table of contents
Answers to frequently asked questions ................................................................................................ 2
1
What is proton therapy? .................................................................................................................................. 2
2
How does proton therapy work? ...................................................................................................................... 3
3
What are the clinical advantages of proton therapy? ...................................................................................... 4
4
Which cancer indications can be treated with proton therapy? ....................................................................... 5
5
Where can I receive treatment? ...................................................................................................................... 6
6
Are there clinical trials under way? .................................................................................................................. 8
7
What is the proton therapy treatment process? How long does it take? ....................................................... 10
8
Are there side effects? ................................................................................................................................... 10
9
Does proton therapy cost more than conventional forms of cancer treatment? Is proton therapy
covered by insurance? .......................................................................................................................................... 10
10
When was the first patient treated with proton therapy? ........................................................................... 11
11
How many patients can be treated with proton therapy? .......................................................................... 11
12
Is proton therapy the most appropriate treatment for me? ........................................................................ 14
13
Can proton therapy be used in combination with other forms of cancer treatment? ................................. 14
14
What is the future of proton therapy? ........................................................................................................ 14
a)
Compact and affordable proton therapy .................................................................................................... 14
b)
Intensity modulated treatments ................................................................................................................. 14
Key figures on proton therapy ................................................................................................................. 17
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ANSWERS TO FREQUENTLY ASKED QUESTIONS
1. What is proton therapy?
Proton therapy is an advanced form of radiotherapy that uses a high-energy proton beam for cancer
treatment. These protons damage the DNA of cancer cells, ultimately inducing cell death. Cancerous
cells are particularly vulnerable to such attacks.
While conventional X-ray radiation can damage healthy tissues, proton beams deliver their maximum
energy within a precisely controlled range, known as the Bragg peak, thereby reducing adverse effects
to adjacent healthy tissues. There is virtually no energy deposition past the Bragg peak as the proton
has delivered all its energy to the tumor. X-ray radiation releases much of its energy quickly after
penetrating the skin, disrupting the cells of healthy tissues and organs. The unnecessary dose of Xrays (photons) is shown in purple.
The Bragg peak can be precisely calculated as a function of the beam’s initial energy. Proton beams
release the majority of their destructive energy within a small range inside the tumor, depositing lower
entrance dose and no exit dose.
This unique characteristic of the proton beam enables it to treat tumors with unequaled
precision, safety and efficiency.
Proton therapy advantages include:
•
precise delivery of an optimal radiation dose to the tumor;
•
safely escalating the dose within the tumor, with minimal exit dose;
•
reducing the probability and/or severity of side effects on healthy surrounding tissues;
•
an increase of long-term, progression-free survival rates for certain types of tumors.
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2. How does proton therapy work?
Proton therapy uses the protons from hydrogen atoms that remain after the electrons are removed. In
proton therapy centers equipped by IBA, the cyclotron accelerates protons to an extremely high
speed, generating a controlled beam. The IBA Energy Selection System (ESS) makes it possible to
transform the fixed energy generated by the cyclotron into the exact energy needed for a particular
treatment.
This proton beam travels through a beam transport system to individual treatment rooms. The beam is
then delivered through a nozzle to the targeted tumor.
As each proton enters the body, there is a low dose of radiation released at the surface, followed by a
sharp burst released as the proton hits its target. The proton beam can be contoured to the shape of
the tumor, further decreasing the exposure of healthy cells to radiation and limiting side effects.
The IBA isochronous cyclotron is today the simplest and most effective way to produce 230 MeV protons.
A.
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3. What are the clinical advantages of proton therapy?
Proton therapy offers the same tumor-killing properties as traditional radiation treatment, but with
decreased side effects and complications.
The difference in the effectiveness of proton therapy versus radiation treatment is determined by what
takes place before and after the radiation reaches the tumor. Radiation releases much of its energy
quickly after penetrating the skin, disrupting the molecules of healthy tissues and organs. Proton
therapy allows most of its energy to be released only when it reaches the tumor. And unlike radiation,
which passes completely through the body, protons do not go further than the tumor thus sparing
surrounding healthy tissues.
Key advantages of the proton beam in cancer treatment:
•
high-energy radiation doses delivered directly to the tumor;
•
little or no radiation beyond the tumor;
•
compassionate cancer treatment with fewer side effects on surrounding healthy tissues and
vital organs, hence allowing a better quality of life during and after treatment.
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4. Which cancer indications can be treated with proton therapy?
Proton therapy is used today to treat many cancers and is particularly appropriate in situations where
treatment options are limited and conventional radiotherapy presents unacceptable risks to patients.
Because proton therapy targets tumors better than traditional treatments, it is ideal for the treatment of
tumors that are located near a vital organ.
These situations include eye or brain cancers, tumors close to the brain stem or spinal cord, head and
neck cancers, prostate cancers, and pediatric cancers. Recent phase II studies have also shown the
key impact proton therapy can have on lung tumors, a medical condition that is today poorly treated
with conventional radiation therapy.
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5. Where can I receive treatment?
IBA has designed and installed the majority of clinically operating proton therapy centers in the world.
Today, numerous reference centers all over the world are treating patients with IBA equipment. [Link
to document Proton Therapy Facilities list of the Press Kit]
The National Association for Proton Therapy displays the map of existing proton therapy centers on the following
link: http://www.proton-therapy.org/map.htm
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Number of proton therapy centers worldwide:
Source: PTCOG, Press Releases of manufacturers.
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6. Are there clinical trials under way?
Over the years it has become increasingly clear that the strength of proton therapy lies in the reduced
side effects of the superior dose deposition efficiency (i.e. the Bragg peak). Protons have a significant
advantage over more traditional therapies when the tumor lies adjacent to an organ at risk. This is not
so much because of the better penumbra with respect to high energy X-rays but due to the reduced
dose that protons deliver outside the target volume. In addition, when the target volume is wrapped
around a sensitive organ, proton will offer the best treatment. Due to the sharp distal fall-off (protons
have a finite range), the dose distribution can be shaped to create complexly shaped dose
distributions.
At the Francis H. Burr Proton Therapy Center, linked to Massachusetts General Hospital in Boston
(USA), the medical staff can rely on almost 40 years of proton therapy practice at the Harvard
Cyclotron Laboratory. The equipment designed and installed by IBA started treating patients in
November 2001. To date more than 5600 patients have received proton treatment there.
Table 1 gives a list of conditions which can be treated at the Francis H. Burr Proton Therapy Center.
Table 1: Proton beams at the Francis H. Burr Proton Therapy Center that will be used for the following
treatment sites: (* Sites already treated at Harvard Cyclotron Laboratory)



















Chordoma and chondrosarcoma*
Craniopharyngioma*
Meningioma*
Thoracic and lumbar spine tumors*
Pediatric tumors*
Prostate tumors*
Choroidal melanoma*
Retinoblastoma*
Age related Macular Degeneration*
Malignant tumors of the orbit*
Arteriovenous malformations (AVMs)*
Pituitary tumors*
Paranasal sinus*
Nasopharynx
Carcinoma of the rectum
Medulloblastoma
Non small cell lung cancer (NSCLC)
Hepatocellular carcinoma
Pediatric soft tissue sarcomas
Good long-term follow-up data is available for several clinical sites. Five-year survival rates for
chordomas and chondrosarcomas of the base of the skull are approximately twice as high with proton
therapy compared to conventional X-rays.
Good results are obtained for choroidal melanomas (tumors of the eye), which are often treated by
surgically removing the eye.
Protons have also been shown to be very effective in the treatment of arteriovenous malformations,
prostate and paranasal sinus.
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Clinical trials for several treatment sites are in progress at different centers in the world, and cover
multiple indications, as can be seen below:
Hodgkins Lymphoma
1%
CNS
2%
Clinical Trials Repartition
AVM
2%
Spine Cervix Bladder
1%
1%
1%
Colorectal
2%
Eye
3%
Nasopharynx/Sinus
4%
Head & Neck
20%
Sarcomas
5%
Liver
6%
Prostate
12%
Others/General
7%
Lung
11%
Pancreas
7%
Breast
7%
Pediatrics
8%
Source: ClinicalTrials.gov - Over a total of 110 clinical trials - Accessed on May 2nd 2012
The clinical benefits of proton therapy over conventional radiation therapy can be summarized as
follows.
Increased tumor control, due to the ability of depositing a higher dose in the targeted volume.
Reduced occurrence of treatment-related side effects due to the precision of the dose delivery and the
resulting limited amount of radiation delivered to healthy tissues adjacent to the treatment volume.
Increased long-term disease free survival rates for many types of tumors, due to the superior local
tumor control rate in proton therapy.
Several articles have been published and an extensive list of clinical references can be provided upon
request.
Moreover, OncoLink offers a free, confidential, personalized service that quickly searches for clinical
trials that match specific cancer diagnosis and treatment history:
http://www.oncolink.org/treatment/trials.cfm
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7. What is the proton therapy treatment process? How long does it take?
Radiation oncologists use advanced imaging techniques to determine the exact location of the tumor
to be treated. Proton therapy sessions may take anywhere from one day to several weeks. Over time,
practitioners will be able to deliver heavier doses thereby decreasing the length of treatment.
Because treatments are noninvasive, patients are able to continue with their daily activities. The actual
proton beam time is about one to two minutes, but total treatment time may last up to an hour, due to
the time spent positioning the patient.
8. Are there side effects?
Depending on the patient’s age, medical history and condition, he or she may experience minor side
effects such as fatigue, skin irritation, or slight hair loss.
9. Does proton therapy cost more than conventional forms of cancer
treatment? Is proton therapy covered by insurance?
Given the advanced technologies of proton therapy, the reimbursement rate has been planned
accordingly. Some countries plan reimbursement on a given number of indications (usually Uveal
Mellanoma Pediatric Cancers, Head and Neck, Non Small Cell Lung Cancer and Hepatocellular
Carcinoma) while others plan reimbursement of proton therapy with a general rate (as is the case, for
example, in the United States where MediCare reimburses proton therapy at around 1100$ per
fraction and makes the distinction between “simple” and “complex” cases).
Source: Various government agencies, IBA internal.
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10. When was the first patient treated with proton therapy?
In 1946 Robert Wilson proposed that proton beams would provide superior dose distributions and
should be considered for clinical radiation treatment. First tests were directed at intracranial targets
and used single fractionation. The first treatments using proton or helium ion beams were carried out
at the University of California in Berkeley, USA (1955), University of Uppsala, Sweden (1957),
Massachusetts General Hospital, USA (1961), Physics Research Institute, Dubna, Russia (1964) and
the Institute for Experimental and Theoretical Physics, Moscow, Russia (1969).
Today about 39 clinical proton treatment centers are established worldwide, while approximately 25
research centers have some proton therapy related activities. The Particle Therapy Cooperative
Group (PTCOG)1 is collecting valuable information about the total number of patients receiving particle
therapy, i.e. protons and heavy ions. According to the most recent information, more than 100,000
patients have received treatment by particle therapy.
11. How many patients can be treated with proton therapy?
As proton therapy is an emerging technology, a difference can be made between Essential Indications
for which this technique is today the standard of care and Potential Indications, for which proton
therapy has been demonstrated superior in treatment planning terms and over a smaller cohort of
patients, and for which clinical studies are currently ongoing.
As reported in the UK National Radiotherapy Advisory Group 2, Essential Indications for proton therapy
can be found for pediatric cancers and head & neck chordomas, and amount to 31.5 patients / million
inhabitants. In a city of 7 million inhabitants, this would equate to 220 patients treated per year, or one
treatment room.
As reported in the Dutch Gezondheidsraad report on Proton Therapy 3, Potential Indications would
amount to 411 patients / million inhabitants, equating to about 2880 patients a year in a city of 7 million
inhabitants, which would necessitate around 10 treatment rooms.
Furthermore, with future developing technologies (such as Intensity Modulated Proton Therapy (IMPT)
or different uses of these particles such as mild hypo-fractionation), both the effectiveness and the
cost per treatment will decrease, indicating that proton therapy could be used for up to 30% of
radiation therapy patients, which would mean in excess of 900 patients/million inhabitants.
Today, the total number of treatment rooms ordered worldwide amounts to more than 160 with
approximately 96,000 patients treated in all facilities, as illustrated in the tables below.
1
Particle Therapy Cooperative Group (PTCOG), http://ptcog.web.psi.ch/.
2
http://www.cancer.nhs.uk/documents/nrag_files/proton%20subgroup%20report%20-%20fin.pdf
3
http://www.gezondheidsraad.nl/sites/default/files/proton%20radiotherapy200917E_0.pdf
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Number of treatment rooms ordered - Number of patients treated per year:
Source: PTCOG and various company websites.
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Patient Statistics (for the facilities in operation end of 2011):
Source: “Hadron Therapy Patient Statistics (data received per March 2012)”, Martin Jermann, March
2012,
Particle
Therapy
Cooperative
Group
(PTCOG)
Secretary,
http://ptcog.web.psi.ch/patient_statistics.html, visited on May 2012.
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12. Is proton therapy the most appropriate treatment for me?
This question must be answered by your doctor. He is the one who can identify the most appropriate
treatment based on the cancer diagnosis. Further information on this subject is provided by
international organizations such as oncolink.com. Patients are encouraged to read as much as
possible about treatment options and discuss the question thoroughly with their doctor.
13. Can proton therapy be used in combination with other forms of cancer
treatment?
Yes, in multiple cases proton therapy can be used in conjunction with other forms of treatment.
Depending on the situation, proton therapy may be used in combination with traditional radiation,
chemotherapy and/or as a follow-up to surgery.
14. What is the future of proton therapy?
A. Compact and affordable proton therapy
Although the first discoveries about the use of the proton beams in cancer treatment date from 1946, it
was only in 1990 that the world's first hospital-based proton therapy center was built. Since then, IBA
has installed 12 proton therapy centers worldwide and 10 more are in various stages of development.
Today, the number of proton therapy facilities worldwide is still relatively limited. Existing proton
therapy facilities therefore attract patients from around the world, in addition to treating patients from
their region. While the potential number of patients that could benefit from proton therapy is large, the
heavy investment required for this technology has limited access up until now. This is the reason why
IBA is dedicated to making proton therapy more available to patients, as well as more affordable to
healthcare systems.
For example, IBA is currently designing ProteusONE 4 , a smaller, more affordable proton therapy
system. This new single-room system substantially reduces the cost, space and installation time
required to build a proton therapy center. The first ProteusONE solution installed by IBA will be at a
proton facility being developed by Willis-Knighton Cancer Center in Shreveport, Louisiana. IBA is
committed to making proton therapy the most precise cancer treatment available worldwide.
B. Intensity modulated treatments
Technological advances in conventional external beam radiotherapy have led to a new approach of
Intensity Modulated Radiation Therapy (IMRT). While IMRT is certainly a large improvement over
conventional radiotherapy and given the fact that some medical professionals may estimate that
photon IMRT and its recent developments make proton therapy redundant, we need to evaluate some
of the physics aspects.
While IMRT may come close to the dose distribution achieved in passive scattering methods with
protons, a recent comparative study between IMRT and Intensity Modulated Proton Therapy (IMPT)
shows the advantage of protons in terms of its reduced dose burden outside the target volume.
Looking at the treatment plans for the different approaches, as shown in Figure 1 below, it takes 9
photon fields to construct a highly conformal dose distribution with good sparing of the brain stem for
the treatment of a nasopharyngeal tumor.
The availability of large degrees of freedom in the beam delivery and the strength of the mathematical
methods make it possible to produce very satisfying dose distributions, shaped in all 3 dimensions to
conform precisely to the target volume.
4
Subject to review by Competent Authorities (FDA, European Notified Bodies, et al.) before being put on the market.
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Figure 1: An example of intensity modulated treatment planning with photons. Through the
addition of 9 fields it is possible to construct a highly conformal dose distribution with good
dose sparing in the region of the brain stem
Protons are charged particles and narrow beams can be magnetically scanned onto any target
volume. In Figure 2, using the same patient as in 1, a very high degree of conformity with target
volume is shown using only four dose fields with protons.
Figure 2: Example of intensity modulated proton therapy (IMPT). A high degree of conformity is
achieved using a low number of dose fields. The advantage compared with photons is the
general reduction of dose burden outside of the target volume.
Another important comparison point is the integral dose delivered during the course of the treatments
in the different treatment modalities. While IMRT may come close in target conformity to standard
methods of delivering proton therapy, the total dose delivered in the treatments is substantially higher.
The possibility of also delivering proton in an intensity modulated treatment will allow a small reduction
of the integral dose while increasing substantially conformity to the target volume. Figure 3, illustrating
these principles was presented by Dr. J. Loeffler from the NPTC at the ASTRO conference in 2001.
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Conformity
IMPT
3D PT
IMXT
3D-XRT
LOW
Integral Dose
HIGH
Figure 3: Illustration of the expected integral dose versus tumor conformity in the different
treatment modalities.
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KEY FIGURES ON PROTON THERAPY5
5
•
Cancer is a leading cause of death worldwide.
•
There are more than 100 types of cancers; any part of the body can be affected.
•
In 2008, 7.6 million people died of cancer, representing 13% of all deaths worldwide.
•
By 2020, 1/3 of the population will be affected by cancer.
•
In 2020, 19 million patients will be newly diagnosed with cancer every year.
•
Today, we have identified 3 ways to fight cancer: chemotherapy, surgery and radiation
therapy. Depending on the cancer diagnosis, doctors identify the most appropriate treatment.
•
Proton therapy is an advanced form of radiation therapy that uses a micro-precision proton
beam for cancer treatment. While conventional X-ray radiation can damage healthy tissues,
proton therapy delivers the beam very precisely, thereby treating without harming healthy
surrounding tissues. With proton therapy, there is significant potential to reduce side effects,
improve overall outcomes in cancer treatment and improve the quality of life for patients.
Depending on the case, proton therapy can be used stand-alone or in combination with
traditional radiation, chemotherapy and/or as a follow-up to surgery.
•
With the use of proton therapy, 10-year cure rates for patients with tumors at the base of their
skulls have increased from 35 percent to 75 percent.
•
The overall disease-free survival rate of patients with prostate cancer who received proton
therapy has reached 89 percent. And patients are experiencing fewer side effects than with
traditional treatments.
•
Thanks to its precise dose distribution, proton therapy reduces the severity of radiotherapy
late effects, which is extremely beneficial in the treatment of children.
•
In the case of pediatric tumors, conventional radiation has a major effect on growth and IQ
development, and can produce side effects such as undesired lung diseases. With proton
therapy, the risk of growth abnormality is reduced from 100% to 20%.
•
It is estimated that more than 50% of cancer patients will receive radiation therapies during the
course of their treatment.
•
Today, the key indications for PT represent up to 30% of all cancers treated in conventional
radiation therapy.
•
This corresponds to more than 700.000 potential patients per year for proton therapy.
•
When it comes to treatment options, patients naturally seek the best possible cancer
treatment.
•
However, to date less than 1% of them have benefited from proton therapy given the limited
number of centers equipped with appropriate equipment.
•
Today, the potential of patients being treated with proton therapy is huge, however the access
is limited. This is why IBA is dedicated to making proton therapy more available to patients, as
well as more affordable to healthcare systems.
•
IBA has designed and installed the majority of clinically operating proton therapy centers in the
world with 12 proton therapy centers treating patients and 11 more in various stages of
development.
•
Benefiting from more than 25 years of experience, IBA is developing proton therapy systems
that are smaller, more affordable, easier to install and easier to operate.
Sources :
World Health Organization, http://www.who.int/cancer/en/index.html, visited on May 2012.
OncoLink, http://www.oncolink.org/treatment/article.cfm?id=322&s=27&c=5, visited on April 2012.
Particle Therapy Cooperative Group (PTCOG), http://ptcog.web.psi.ch/, visited on April 2012.
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•
With IBA, protons are possible for more patients worldwide.
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