Status of Ion Beam Therapy in 2002
J. M. Sisterson
Northeast Proton Therapy Center, Massachusetts General Hospital
Boston, Massachusetts
Abstract. Dose distributions produced by using proton and ion beams in radiation therapy conform closely to the target
volume maximizing the sparing of adjacent normal tissues and sensitive structures. Worldwide, through 2001, over
30,000 patients have been treated with proton beams and over 3,500 with ion beams. In 2002, there are 21 operating
proton therapy facilities, including several hospital-based dedicated facilities. Seven of these facilities are limited to
treating eye tumors only. Carbon ions are available at two facilities in Japan and one in Germany. All existing centers
use either a cyclotron or a synchrotron and several facilities have one gantry or more to provide beams at any angle to the
patient. For several treatment sites, there are good long-term follow-up results, increasing the interest worldwide in
having proton or ion beams more readily available. As a result many new facilities are under construction or being
planned and some existing facilities are being upgraded.
INTRODUCTION
R. R. Wilson in 1946 [1] first suggested that the
physical properties of proton and ion beams could be
used to advantage in radiation therapy. Dose
distributions that conform closely to the target volume
can be achieved. Thus, the optimal dose to the tumor
can be delivered, while sparing adjacent normal tissue
and sensitive structures as much as possible. Using
intensity modulated proton or ion beams will lead to
further improvements in the dose distribution [2].
Proton beams have a radiobiological effectiveness
(RBE) that is similar to X-rays. A RBE of 1.1 is used
clinically but experiments have shown that near the end
of range the maximum RBE is ~1.3 [3]. Ion beams
have a higher variable RBE which must be included in
treatment planning [4]. All currently operating ion
beam facilities use carbon ions but heavier ions have
been used in the past [5].
The first clinical use of proton beams was in 1954 at
the University of California, Berkeley. Helium ions
were used at this facility from 1957 – 1992. The second
program using proton beams began in 1957 at the
former synchrocyclotron at the Gustav Werner Institute
(now the The Svedberg Laboratory), Uppsala
University, Sweden.
In the 1960s, proton therapy centers opened in
Russia and the USA. In 1961, the clinical program at
the Harvard Cyclotron Laboratory (HCL) began and
9115 patients were treated before HCL closed in
2002. Patients at HCL were treated in collaboration
with departments at Massachusetts General Hospital
(MGH) and Massachusetts Eye and Ear Infirmary. All
clinical programs at HCL were completely transferred
to the Northeast Proton Therapy Center (NPTC),
located on the MGH campus, by April 2002.
Proton therapy facilities opened in Russia and
Japan in the 1970s. During this period, many of the
techniques to produce clinically useful beams were
developed including passive scattering techniques [6]
and beam scanning [7]. Since 1980 there are has been
a steady increase in the number of proton therapy
facilities worldwide, particularly in Europe and Japan.
Only one proton therapy facility is located in the
Southern Hemisphere. The first heavy ion program,
using ions heavier than helium, began at the
University of California, Berkeley in 1975.
The first dedicated proton therapy facility designed
specifically for the hospital setting opened in 1990 at
Loma Linda University Medical Center (LLUMC),
California. Now in 2002, there are five such facilities
operating. Two of these hospital-based facilities, at
Proton Medical Research Center, University of
CP680, Application of Accelerators in Research and Industry: 17th Int'l. Conference, edited by J. L. Duggan and I. L. Morgan
© 2003 American Institute of Physics 0-7354-0149-7/03/$20.00
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Tsukuba, Japan and NPTC/MGH replace long-running
existing programs at accelerator facilities originally
designed for physics research.
From 1954 - July 2002, over 32,000 patients were
treated with proton beams. The number of patients
treated in a given year has increased steadily over the
years as is shown in Figure 1. This trend should
continue – and the number of patients treated each year
may increase dramatically – once the several proton
therapy facilities under construction or planned are
completed.
Radiological Sciences (NIRS), Chiba, Japan and in
1997 the first patient was treated with carbon ions at
Gesellschaft
fur
Schwerionforschung
(GSI),
Darmstadt, Germany. In 2002, the first patients were
treated with carbon ion beams at the Hyogo Ion Beam
Medical Facility, Harima Science Garden City,
Hyogo, Japan, to become the third operating carbon
ion facility. From 1975 - July 2002, 3808 patients
have been treated with carbon or heavier ions. The
cumulative patient totals are shown in Figure 2 for
patients treated since 1994.
OPERATING FACILITIES
Annual Patient Totals
3000
Patients treated/year
2500
Annual patient total
Europe
North America
Southern Hemisphere
Russia
Japan
The first accelerator specifically designed to
provide proton beams in the hospital setting began
operation in 1990. Before that time, almost all proton
and ion beam therapy facilities used accelerators
designed for physics research and adapted for medical
use. In a few cases, low-energy accelerators,
originally designed to provide beams for neutron
therapy, were adapted to provide proton beams in the
clinical setting. The accelerators used at the 19
operating facilities in 2001 (the two programs at PSI,
which use different accelerators, are considered
separately) are summarized in Table 1. At seven
facilities, only relatively superficial tumors – such as
ocular tumors – could be treated because of the
relatively low maximum proton energy available.
2000
1500
1000
500
1980
1985
1990
1995
2000
2005
Year
FIGURE 1. Patients treated per year with proton therapy
TABLE 1: Accelerators used in 2001
Type of Accelerator
Number
Total number of accelerators
19
Patients treated w ith carbon ions
1400
Cumulative annual patient totals
1200
1000
800
600
Synchrotron
Cyclotron
Synchrocyclotron
4
11
4
Maximum energy ~70 MeV
7
Hospital based
5
3
2
400
200
0
1992
1994
1996
1998
2000
2002
Year
FIGURE 2. Cumulative totals for patients treated with
carbon ions.
The clinical heavy ion program at the University of
California, Berkeley closed in 1992 after >400 patients
were treated with ion beams heavier than helium. Two
new carbon ion facilities began operation in the 1990s.
In 1994, the first patient was treated at Heavy-Ion
Medical Accelerator (HIMAC), National Institute for
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At most facilities where clinical programs have to
share beam time with experimental physics programs,
the beam time available for patient treatment is
limited. This results in both the total number of
patients and the clinical sites that can be treated being
compromised. The annual patient loads at proton
therapy facilities from 1990 – 2001 are summarized in
Table 2. The data in this table show both the increase
in the number of operating facilities over this eleven
year period and the increase in patient throughput at
several facilities. In 2001, a milestone was reached
when over 1000 patients a year were treated at
LLUMC. In Table 2, the patient statistics from the
two clinical programs at the Paul Scherrer Insititute
(PSI), in Switzerland are combined.
TABLE 2. Proton therapy annual patient load*
Patient load
Number of facilities
Patients/year
1990
1995
2001
0 –10
3
3
3
11 – 50
2
3
4
51 – 100
2
3
5
101 –200
2
3
1
201 – 300
1
1
2
301 – 400
1
2
401 – 500
1
1001 - 1100
1
Total facilities
10
15
18
*the programs at PSI are considered as one facility
Almost all proton and heavy ion therapy facilities
use passive scattering techniques, range modulation
and patient compensating devices to produce the large
volume uniform beams required. Beam scanning is
used on a routine basis at only a few proton and ion
facilities but is under development at several
institutions. Beam scanning is essential to fully
implement intensity modulated proton therapy. Another
important development for both proton and ion beam
therapy was the development of gantries, which allow
the delivery of the beam at any angle to the patient.
Several institutions now use gantries routinely for
patient treatments.
CLINICAL RESULTS
Proton Therapy
For patients treated with proton beams there are
good follow-up data for selected treatment sites. These
sites include choroidal melanoma, chordoma and
chondrosarcomas of the skull base, arteriovenous
malformations and prostate cancer. A good review of
the clinical results is given in [8]. A few patients have
follow-ups of over 20 years.
There are three general categories of patient treatments:
1.
Radiosurgery. Treatment of intracranial targets
usually in one or at most two sessions.
2.
Eye tumors. These tumors are relatively
superficial, so that all operating facilities can
potentially treat these tumors. Uveal
melanomas are treated with four or five
fractions.
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3.
Fractionated therapy. Fractionated therapy is
used to treat a variety of diagnoses and
clinical sites located in all parts of the body.
The number of fractions depends on the
diagnosis. For example at HCL/MGH, over
the last two years of operation, the average
number of proton fractions per patient was 25
and the maximum was 48 for patients treated
in this program.
The clinical sites treated using proton beams varies
from center to center. In some cases, particularly those
located at physics research accelerators, the types of
patient treatment are constrained by the limited beam
time available. At other centers, only relatively
superficial lesions can be treated. The needs of the
local community and cancer demographics also
influence the choice of patient treatments.
To summarize the worldwide proton and ion beam
therapy clinical experience, data has been collected
from all facilities operating in 2001. From this
information, the percent of patients treated/year for
selected sites can be estimated as a percent of the total
number of patients treated in that particular year.
These numbers should be regarded as reasonable
estimates only and not absolute numbers.
Table 3 summarizes the clinical data for selected
treatment sites for 1990 – 2001, the last year for
which statistics are available. As Table 3 shows, over
three times as many patients were treated with proton
beams in 2001 than were treated in 1990.
TABLE 3. Patient statistics for selected treatment sites
Year
1990
1995
1999
2001
Total # of patients
866
1847
2562
2770
%
%
%
%
Uveal melanoma
47
42
34
33
Macular Degeneration
0
3
9
5
Other eye patients
2
3
4
3
Total eye patients
49
47
47
41
Prostate
1
17
19
All sites chordoma &
4
5
5
chondrosarcoma
AVM
11*
5
3
Meningioma
1
2
3
Lung
1
0.2
2
Liver
1
1
2
*Does not include data from ITEP, Moscow
25
5
3
3
2
2
As new proton therapy centers became operational
in the 1980s, there was a period of time when the
treatment of eye patients accounted for over 50% of
all patients treated in a given year. Since that time,
this percentage has been decreasing and in 2001, the
treatment of eye tumors accounted for ~41% of all
patients treated. This decrease reflects the opening of
the dedicated hospital based proton therapy facilities
with the capability of treating all parts of the body.
throughput. Many of these challenges have been met
but some still remain to be solved by the community
involved in the design and development of proton and
ion beam facilities.
Carbon Ion Therapy
For patients treated recently with carbon ions, the
longest follow-up is 7 - 8 years. A good review of the
experience at HIMAC, where >1100 patients have been
treated since 1994, is given in [9].
The year 2000 is the most recent year for which
annual patient data is available. 227 patients were
treated with carbon ions at HIMAC and GSI with the
following patient distribution for the major sites: lung
20%; prostate 14%; head and neck 13%; base of skull
11%; bone/soft tissue 11%; liver 10%.
ACKNOWLEDGMENTS
The data presented here are based on information
provided to me by representatives of all operating
proton and ion beam therapy facilities. This
information was essential to the preparation of this
paper. I thank them all for taking the time and effort to
provide me with the information that I needed to
present this status report.
REFERENCES
FUTURE FACILITIES
1.
Wilson R. R., Radiology 45, 487-491 (1946).
The successful development of accelerators
designed specifically for the hospital environment has
led to many new hospital-based facilities starting to
treat patients, being constructed, or in the final design
stage. Some of these new hospital-based facilities
replace existing programs using physics research
accelerators. Patient treatment capabilities are also
being added at some existing research accelerator
centers. Within the next five years a conservative
estimate might be that at least 10 new proton therapy
centers will be completed and in operation throughout
the world.
2.
Lomax A., et al., Med. Phys. 28, 317-324 (2001).
3.
Robertson J. B., et al., Cancer 35, 1664-77 (1975).
4.
Wambersie A., Strahlenther. Onkol. 175 Suppl. 2, 3943 (1999).
5.
Alonso J. R., “Review of ion beam therapy: present and
future” in Proc. of European Particle Accelerator
Conference EPAC 2000, Vienna, Austria, June 25-30,
2000, pp 235-239.
6.
Chu W. T., et al., Rev. Sci. Instr. 64, 2055-2122 (1993).
7.
Pedroni E., et al., Strahlenther. Onkol. 175 Suppl. 2,
18-20 (1999).
8.
Spiro I. J. et al., “Proton beam radiation therapy” in
Cancer: Principles and Practice of Oncology, 6th
edition, edited by V. T. Vita, S. Hellamann, S. A.
Rosenberg, Philadelphia: Lippincott, Williams &
Wilkins, 2001, pp. 3229.
9.
Tsujii H., et al., “Experiences of carbon ion
radiotherapy at NIRS” in Progress in Radio-Oncology
VII, edited by H. D. Kogelnik, P. Lukas, and F.
Sedlmayer, Bologna, Monduzzi Editore S.p.A, 2002,
pp. 393-405.
CONCLUSIONS
Proton and ion beam radiation therapies were
originally developed at accelerators designed and used
for physics research and adapted for medical use. In
most cases these accelerators were located at some
distance from the collaborating hospital. The success of
these programs has resulted in the development of
accelerators designed specifically to operate in a
hospital setting and the building of dedicated facilities
located within the hospital. Thus accelerators that are
compact, reliable, use power efficiently and simple to
maintain and operate, plus gantries to deliver the beam
at any angle to the patient were developed. It is a
challenge to bring these concepts from the design stage
to one where the beam delivery system can operate
easily and reliably in a busy clinic with a large patient
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