Transcript Lecture 22 - biologyofcancer.org

Lecture 22
Radiobiological aspects of alternative
dose delivery system
Lecture 22
Ahmed Group
Protons
High LET sources
BNCT
Stereotactic radiosurgery/radiotherapy,
IMRT, IORT: Dose distribution and dose
heterogeneity
Lecture 22
Ahmed Group
Alternative Radiation Modalities
The early recognition that X-rays could produce local tumor control
in some patients and not in others led to the notion that other forms
of ionizing radiations might be superior.
In the case of neutrons, they give up their energy to produce
recoil protons, alpha-particles, and heavier nuclear fragments.
Consequently, their biologic properties differ from those of X-rays:
reduced OER, little or no repair of sublethal damage, and less
variation of sensitivity through the cell cycle.
Protons have radiobiologic properties similar to those of X-rays;
Negative π-mesons and heavy ions were introduced with the hope
of combining the radiobiologic advantages attributed to neutrons
with the dose distribution advantage characteristic of protons.
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Alternative Radiation Modalities
Neutrons - superior to X-rays in a limited number of situations,
specifically for prostate cancer, salivary gland tumors, and
possibly soft-tissue sarcomas;
Protons - used for treatment of uveal melanoma and tumors such
as chordomas-they are located close to spinal cord and benefit from
the localized dose distribution. The wider use of protons for broadbeam radiotherapy is being tested now.
Negative π-mesons and heavy ions have been used to treat hundreds
of patients, but the trials have never been completed to prove their
superiority over conventional X-rays.
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Fast Neutrons
The first clinical use of neutrons
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Alternative Radiation Modalities
Fast Neutrons. Practical sources
The only practical source
of neutrons for clinical
radiotherapy is a cyclotron.
Cyclotron is an electric
device capable of accelerating
positively charged particles,
such as protons or deuterons,
to an energy of millions of
volts
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Alternative Radiation
Modalities
Fast Neutrons
More recently, cyclotrons to
produce neutrons have been
built using the p+
Be reaction.
The cyclotron can be small
enough to be installed in a hospital.
Neutron spectra produced by the
two processes are shown
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Percentage Depth Doses for Neutron Beams
An essential factor in the choice of a neutron beam for clinical use
is its ability to penetrate to a sufficient depth.
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Current Efforts with Neutrons
Emphasis is being placed on two factors:
• First, subgroups of patients with specific types of tumors
that may benefit from neutrons must be found.
• Second, different fractionation patterns will be tried
for neutrons.
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Current efforts with neutrons
Emphasis will be placed on slowly growing tumors, in view of
the observation of Breuer and Batterman that neutron RBE,
measured from pulmonary metastases in patients, increases
as tumor volume doubling time increases
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Protons
Protons are attractive for radiotherapy because of their physical
dose distribution. The RBE of protons is undistinguishable from
that of 250-kV X-rays, which means that they are 10 to 15% more
effective than cobalt-60 gamma-rays or megavoltage X-rays
generated by a linear accelerator.
The OER for protons is undistinguishable from that for X-rays,
namely about 2.5 to 3.
These biologic properties are consistent with the physical
characteristics of high-energy proton beams; they are
sparsely ionizing.
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Ahmed Group
Protons
The dose deposited by a
beam of monoenergetic
protons increases slowly
with depth, but reaches a
sharp maximum near the
end of the particle’s range
in the Bragg peak.
Proton beams ranging in
energy from 150 to 200
MeV are of interest in
radiotherapy because this
corresponds to a range in
tissue of 16 to 26 cm.
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Ahmed Group
Protons
The way the
Bragg peak can
be spread out to
encompass a tumor
of realistic size is
shown.
The spread-out
Bragg peak can be
made narrower or
broader as
necessary
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Protons
Many researchers consider protons to be the treatment of choice for
choroidal melanoma.
Protons have found a small but important place in the treatment of
ocular tumors and also some specialized tumors close to the spinal cord
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Ahmed Group
Protons
Current proton therapy facilities worldwide, light- and heavy-chargedparticle facilities, and the number of patients treated
Lecture 22
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Protons
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Protons
Most of the protons machines were built initially for physics
research and were located in physics laboratories.
Lecture 22
Ahmed Group
Protons
High LET sources
BNCT
Stereotactic radiosurgery/radiotherapy,
IMRT, IORT: Dose distribution and dose
heterogeneity
Lecture 22
Ahmed Group
Boron Neutron-Capture Therapy
(BNCT)
The basic idea behind boron neutron-capture therapy (BNCT) is
elegant in its simplicity.
The idea is to deliver to the cancer patient a boron-containing
drug that is taken up only in tumor cells and then to expose the
patient to a beam of low-energy (thermal) neutrons that themselves
produce little radiobiologic effect but that interact with the boron
to produce short-range, densely ionizing alpha-particles.
Thus, the tumor is intensely irradiated, but the normal tissues
are spared.
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Boron Neutron-Capture Therapy
(BNCT)
There are two problems inherent in this idea:
1. What is a “magic” drug that distinguish malignant cells
from normal cells?
2. The low-energy neutrons necessary for BNCT are poorly
penetrating in tissue
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Boron Neutron-Capture Therapy
(BNCT)
Boron compounds
For BNCT to be successful, the compounds used should have
high specificity for malignant cells, with low concentrations
in adjacent normal tissues and in blood.
The two classes of compounds have been proposed:
1. Low-molecular weight agents that simulate chemical precursors
required for tumor cell proliferation, can traverse cell membrane
and be retained intracellularly.Two boron compounds, the
BSH and BPA, have been identified and used to treat brain tumors.
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Boron Neutron-Capture Therapy
(BNCT)
Boron compounds
2. High molecular-weight agents such as monoclonal
antibodies and bispecific antibodies.
These are highly specofoc, but very small amounts reach
brain tumors following systemic administration.
Boron-containing conjugates of epidermal growth factor, the
receptor for which is overexpressed on some tumors,
also have been developed.
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Neutron Sources for BNCT
During fission within the core of a nuclear reactor, neutrons
are “born” that have a wide range of energies. Neutron beams
can be extracted from the reactor.
Current interest in the United States focuses on the use of
epithermal neutron beams (1-10,000 eV), which have a greater
than thermal neutrons (0.025 eV) depth of penetration.
These neutrons do not themselves interact with the boron
but are degraded to become thermal neutrons in the tissue
by collisions with hydrogen atoms.
The need for a nuclear reactor as a source for neutrons
is a serious limitation and would preclude BNCT facilities
in densely populated urban areas.
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Lecture 22
Protons
High LET sources
BNCT
Stereotactic radiosurgery/radiotherapy,
IMRT, IORT: Dose distribution and dose
heterogeneity
Ahmed Group
Stereotactic radiosurgery/radiotherapy
Lecture 22
Ahmed Group
Stereotactic radiosurgery/radiotherapy
What is stereotactic radiosurgery? Stereotactic radiosurgery is a
medical procedure that utilizes very accurately targeted, large “killing”
doses of radiation. This noninvasive “operation”has proven to be an
effective alternative to surgery or conventional radiation for treating
many small tumors and a few other select medical disorders.
Standard stereotactic techniques rely on a rigid metal frame fixed to a
patient’s skull for head immobilization and target localization.
However, such frame-based systems have numerous limitations,
including:
1)
restricting
treatment
to
the
brain,
2) limiting the possible angles which radiation could be delivered,
3) causing considerable discomfort for the patient.
In contrast to the standard frame-based radiosurgical instruments,
the CyberKnife uses noninvasive image-guided localization, and a
robotic delivery system. This combination of technologies enables
the CyberKnife to overcome the limitations of older frame-based
radiosurgery such as the Gamma Knife and LINAC.
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Stereotactic radiosurgery/radiotherapy
What is image-guided CyberKnife radiosurgery?
The present design of the CyberKnife derives from the original
concept of a frameless alternative to frame-based radiosurgery.
The CyberKnife consists of three key components:
1) an advanced, lightweight linear accelerator (LINAC) (this device
is used to produce a high energy (6MV) "killing beam" of radiation),
2) a robot which can point the linear accelerator from a wide variety
of angles, and
3) several x-ray cameras (imaging devices) that are combined with
powerful software to track patient position. The cameras obtain
frequent pictures of the patient during treatment, and use this
information to target the radiation beam emitted by the linear
accelerator. The robot is instrumental in precisely aiming this
device. When a patient moves during treatment, the change in position
is detected by the cameras, and the robot compensates by re-targeting
the linear accelerator before administering the radiation beam.
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Stereotactic radio-surgery/radiotherapy
This process of continually checking and correcting ensures
accurate radiation targeting throughout treatment.
In summary, the CyberKnife replaces the stereotactic head frame
with a patient-friendly image-guided localization system.
This technology has the added benefit of enabling the
CyberKnife to be used for radiosurgical applications outside
the brain and for staged radiosurgery. It is difficult if not
impossible to perform these other procedures with standard
frame-based radiosurgical systems
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Stereotactic radio-surgery/radio-therapy
Performance characteristics for gamma knife
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Stereotactic radio-surgery/radio-therapy
Test of the
gamma-knife
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Stereotactic Radiosurgery involves a radiation
treatment procedure designed to treat small intracranial
tumors. The radiation is produced by a linear accelerator
that is collimated (focused) to create a small beam size
and directed towards the center of the the treatment
field. The tumor's location is pinpointed in the
intracranial space using a stereotactic method that
accesses diagnostic images (CT scans) and markers to
allow a positioning frame to be mounted on the patient's
head for reference when treatment is started.
Radiation treatment beams are directed to the target by
rotation of the therapy machine through various arcs
around the patient's head.
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Example. The Novalis Shaped Beam Surgery system
represents cutting-edge technology for the delivery of highly
precise radiation treatments within the brain as well as other
areas of the body. The Novalis system will allow a
multidisciplinary group of medical specialists to showcase the
latest innovation in stereotactic radiosurgery. The Novalis
system features an image-guided localization technique to allow
radiation oncologists to pinpoint tumors with sub-millimeter
accuracy and to position patients automatically and with a
higher degree of precision. The Novalis system is able to
precisely contour the shape of a tumor from any angle and
achieves a more consistent superior dose
distribution. Radiosurgery is a proven alternative for many
indications in the brain, head and neck and spine. The Novalis
system represents an advancement that will allow neurosurgery,
surgical and radiation oncology teams a wider ranger of
applications for radiosurgery throughout the body.
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The Novalis system
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The Novalis
system
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The Novalis
system
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IMRT
The development of Intensity Modulated radiation Therapy
(IMRT), tomography, and proton/light-ion beams results in
greatly improved dose distributions, with more limited
doses to normal tissues for comparable tumor doses. This
suggests the attractive possibility of increasing the dose per
fraction, since the need to spare late responding normal
tissues by fractionation is reduced, because of the lower
dose to these tissues
Lecture 22
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Photons IMRT
A typical dose distribution that can be obtained with IMRT
(intensity-modulated proton therapy) compared with intensitymodulated photon therapy is shown on the next slide.
It is striking that with protons, the dose can be confined to the
target volume, with much less irradiation of normal structures.
With photons, a large fraction of the lungs are exposed to low
doses of radiation.
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Dose distribution obtained with Photons
IMRT compared with Protons IMRT
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Carbon Ion Radiotherapy
There is a sufficient
renaissance of interest
in heavy-ion
radiotherapy, in
particular, on highenergy carbon ions.
Depth-Dose Profiles
The depth at which
the Bragg peak occurs
depends on the energy
of carbon ions
Lecture 22
Ahmed Group
Carbon Ion Radiotherapy
RBE considerations
For carbon ions RBE increases
toward the end of the particle
range. The rapid change of RBE
with depth is shown
Lecture 22
Ahmed Group