ago that the storehouse of data on nuclear science and radiation
transport that Lawrence Livermore was developing would one day be
applied to cancer treatment? In the early 1990s, Livermore researchers
began combining that huge database with Monte Carlo statistical
techniques to create PEREGRINE, a new tool for analyzing and planning
radiation treatment for tumors. Approved for use by the U.S. Food
and Drug Administration last September, PEREGRINEnamed for
the patron saint of cancer patientsis beginning to find its
way into hospitals and clinics.
In July 1999, Livermore licensed
the PEREGRINE technology to the NOMOS Corporation of Sewickley,
Pennsylvania, to commercialize it. NOMOS has been developing advanced
radiation therapy solutions in the fight against cancer since the
early 1990s and is a leader in the new field of inverse planning
for radiation treatment. NOMOS is very innovative, according
to physicist Rosemary Walling, program manager for PEREGRINE at
PEREGRINE is equally innovative.
While several dose calculation systems dot the radiation planning
landscape, PEREGRINE is the first to exploit the mathematical power
of Monte Carlo statistics (see S&TR, October
Takes Aim a Cancer Tumors, and May
Improving Radiation Treatment for Cancer). It took the computing
revolution of the 1980s and 1990s to make Monte Carlo fast enough
for use by clinicians.
When patients receive radiation
therapy, they are bombarded by billions to trillions of particles.
PEREGRINE Monte Carlo radiation transport algorithms determine the
dose deposited in the patient by following the path of representative
particles as they travel through the body. The probabilistic laws
of modern physics prevent scientists from knowing the exact fate
of each particle, but they do allow scientists to predict a distribution
of how these particles, and their daughter products, interact in
matter. By sampling millions of the trillions of particles that
enter the body and recording the energy deposited by each as it
travels through the body, PEREGRINEs Monte Carlo statistical
method develops an accurate representation of the dose distribution.
The Livermore team and NOMOS
worked together to prepare all necessary documents for FDA approval.
NOMOS submitted the application to the FDA in October 1999 and got
the good news not quite a year later.
Former Secretary of Energy
Bill Richardson announced FDA approval at NOMOS headquarters on
October 6, 2000. PEREGRINE could change the way cancer is
treated in America, he said. This technology was developed
through advances resulting from nuclear weapons research and with
the multidisciplinary scientific expertise of a Department of Energy
national laboratory. This is an excellent example of turning swords
resulting from some of the PEREGRINE measurements taken by the
staff at the University of California at San Francisco. They
demonstrate how effectively PEREGRINE can handle different materials
and shapes: (a) heterogeneities in the lung, (b) a steel prosthesis,
and (c) a partial transmission block to protect healthy tissue
during radiation treatment.
of the biggest pieces of documentation that went to the FDA was
a set of clinical measurements prepared in conjunction with cancer
researchers at the University of California at San Francisco (UCSF).
These measurements were important for verifying PEREGRINEs
accuracy as a treatment tool. In radiation therapy, the goal is
to maximize the radiation dose that hits the tumor while minimizing
the dose to surrounding, healthy tissue. No clinical trials were
performed for FDA approval. Rather, clinicians at UCSF used their
accelerators (which create the radiation beam) to take measurements
in water phantoms using various beam directions and
angles as well as the many types of modifiers that are used to change
the shape of the beam to match the needs of a particular tumor.
UCSF also took measurements
with layers of various materials above and in the water phantom.
PEREGRINE is unique in being the only dose calculation code that
can examine radiation activity where different kinds of materials,
such as bone, soft tissue, and air (in our lungs), meet. NOMOS staff
took measurements in solid phantoms to duplicate bone and other
The NOMOS submission to
FDA requested what is known as 510(k) approval. A 510(k) is a premarketing
notification demonstrating that the device to be marketed is as
safe and effective as another legally marketed device. In the submission,
PEREGRINE was compared to other radiation treatment dose calculation
systems. What makes it work as well as it doesMonte Carlo
mathematicsis significantly different from the means of calculating
dose in other systems, but its end use as a planning tool for todays
clinics is substantially the same.
PEREGRINEs dose calculation
capability will be used with a radiation treatment planning system.
A radiation oncologist, medical physicist, radiation therapist,
or dosimetrist will use the two together to design a series of radiation
treatments that can be reviewed by the patients physician
prior to treatment. PEREGRINE is being used with CORVUS, an inverse
planning system created and marketed by NOMOS.
The City of Hope Cancer Center
in Los Angeles was the first customer to purchase PEREGRINE, and
UCSF, Livermores long-time collaborator, was the first to
take delivery. Numerous other hospitals, including one in Belgium,
are beginning the commissioning process. The first patients to benefit
from PEREGRINE will likely begin to receive treatment this summer.
Medical physicist Christine
Hartmann-Siantar is program leader for PEREGRINE at Livermore. She
says, Our goal has always been to get what is known as ubiquitous
distribution of PEREGRINE. We want to see it in as many clinics
as possible, from university centers to community hospitals. This
way, every patient will have access to the most accurate radiation
dose calculation method.
The Livermore team is now
working with NOMOS to add more types of accelerators and more accelerator
radiation energy levels to PEREGRINEs database. They are also
continuing to work with UCSF, expanding PEREGRINEs capabilities
to include electron radiation treatment. Treatment with photons
is the most commonly used because photons can travel deep into the
body. Electrons are useful for tumors close to the surface because
electrons deposit their energy within a few centimeters of the skin.
The PEREGRINE team has also
begun a quality assurance project with UCSF to examine the photon
radiation dose that exits the body on the side away from the beams.
Known as portal imaging, it could be used to check where a small
dose goes before the full dose is administered. Portal imaging would
also be an excellent tool for periodic use as the full series of
treatments are given to assure that the dose being received is the
one the radiation oncologist planned.
Hartmann-Siantar joined the
Laboratory in 1993 with the goal of applying Livermores nuclear
data and computational know-how to radiation treatment. I
got a chance to work with some of the best computer scientists,
engineers, and physicists in the Laboratory, she says. Without
them, PEREGRINE never would have happened.
PEREGRINE team members have
won many awards for their work. Hartmann-Siantar added another in
February 2000 as one of four first-ever recipients of the Edward
Teller Fellowship Award. Working with the team, she is using the
fellowship to study how radiation damages DNA. At the time of the
award, Hartmann-Siantar said, I am very excited to have an
opportunity to push new frontiers in science. She and her
team have already pushed a few, and they arent stopping yet.
cancer treatment, Monte Carlo mathematics, PEREGRINE, U.S. Food
and Drug Administration.
information contact Rosemary Walling (925) 422-4104 (firstname.lastname@example.org).