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Emerging Technology in Cancer Treatment: Radiotherapy Modalities

Emerging Technology in Cancer Treatment: Radiotherapy Modalities

ABSTRACT: This is a period of rapid developments in radiotherapy for malignant disease. New methods of targeting tumors with computed tomography (CT) virtual simulation, magnetic resonance imaging (MRI), and positron-emission tomography (PET) fusion provide the clinician with information heretofore unknown. Linear accelerators (linacs) with multileaf collimation (MLC) have replaced lead-alloy blocks. Indeed, new attachments to the linacs allow small, pencil beams of radiation to be emitted as the linac gantry rotates around the patient, conforming to three-dimensional (3D) targets as never before. Planning for these delivery systems now takes the form of “inverse planning,” with CT information used to map targets and the structures to be avoided. In the area of brachytherapy, techniques utilizing the 3D information provided by the new imaging modalities have been perfected. Permanent seed prostate implants and high–dose-rate (HDR) irradiation techniques targeting bronchial, head and neck, biliary, gynecologic, and other anatomic targets are now commonplace radiotherapy tools. CT-guided permanent seed implants are being investigated, and a new method of treating early breast cancer with HDR brachytherapy via a balloon catheter placed in the lumpectomized cavity is coming to the forefront. Newer modalities for the treatment of malignant and benign disease using stereotactic systems and body radiosurgery are being developed. Targeted radionuclides using microspheres that contain radioemitters and other monoclonal antibody systems tagged with radioemitters have been recently approved for use by the Food and Drug Administration.

This is a period of unparalleled
progress in medicine, with astounding
advances in approaches
to the treatment of cancer.
New surgical methods using "stealth"
techniques based on interactive imaging
and endoscopic approaches with
less morbidity are being introduced.
New drug regimens based on novel
biologic processes are rapidly being
incorporated into the armamentarium
of cancer treatment and diagnosis.
With the mapping of the human genome
completed, can genetic attacks
on malignant disease be far behind?

Not Your Father's
Cobalt Treatment Unit

The field of radiation oncology has
undergone no less a renaissance. In
fact, more advances have been made
in radiation oncology in the past 5 to
7 years than in the previous 100+ years
since the discovery of the x-ray and
radiation-emitting nuclides. The separation
and specialization of radiologic
imaging and radiation oncology that
occurred during the 1980s and 1990s
is quickly being reversed. The new
reliance on image guidance to establish
targets for radiotherapy is forcing
radiation oncologists and allied personnel
to become versant in the information
provided by computed tomography
(CT), magnetic resonance imaging
(MRI), and positron-emission
tomography (PET). More and more,
radiologists are entering the therapeutic
venue with procedures such as image-
guided chemoembolization and
radiofrequency-based ablative therapy.[
1] The new targeted radionuclide
therapies-monoclonal antibody-
tagged radionuclides that "seek and
destroy" selective malignant cells-
are being shared by both nuclear radiology
and radiation oncology.

Virtual Simulation

One of the more important recent
advances in radiotherapy has been the
introduction of CT guidance in defining
solid tumor targets and the surrounding
normal tissue systems that
must be excluded from radiotherapy
fields. With conventional x-ray simulators
and planar radiography to image
the treatment portals, bony landmarks
were frequently the only markers
the radiation oncologist had to rely
on in establishing the external linac
beam path to the target. With virtual
CT simulation, a complete CT image
set allows contouring of the target volume
on each axial CT slice along with
normal tissue structures such as the
spinal cord or kidneys and reformatting
of the contoured dataset into coronal,
sagittal, or three-dimensional (3D)
representations with full surface information
marking where the radiation
beams will enter the body.

Figure 1 shows several images from
such a CT-reconstructed dataset. Illustrating
the power of virtual simulation,
the vertex view in this figure could not
be obtained using conventional simulation
techniques because a film could
not be placed in the correct orientation
to obtain this view. This technology
led to the introduction of 3D conformal
radiation therapy (CRT) and
the use of portals that allow radiation
to enter the body from superiorinferior
oblique angles-a capability
that is not available with conventional
imaging methods.

Dose-Volume Histograms
Computer planning systems (which
calculate the dose patterns to targets
so contoured in 3D) had to "keep up"
with the technologic advance afforded
by CT simulation of these targets. Fortunately,
most treatment planning
companies quickly developed software
to import these images to computers
and accurately portray the volume
dose distributions to contoured
targets and normal tissue structures. To
adequately evaluate these 3D plans, a
new graphic technique involving a
"dose-volume histogram" (DVH) allowed
the radiation oncologist and
medical physicist to "see" the effect
of selective beam blocking or small
linac gantry angle changes on partial
volumes being irradiated by the radiation
field portals chosen.[2]

Figure 2 illustrates such a DVH for
a prostate treatment beam arrangement.
The radiation oncologist can now
prescribe, for example, "100% of the
dose to the target while charging the
medical physicist (or dosimetrist) to
calculate the 3D plan to give only 50%
of the dose to 10% or less of the volume
of an adjacent critical structure."
This ability has enhanced the protection
of critical structures to an extent
not previously available.

Multileaf Collimation

Placing lead-alloy blocks on each
field each day of treatment (some
plans called for six to eight individual
fields) would prove taxing to the radiotherapist
charged with daily treatment
for up to 6 weeks-the time
frame for radiotherapy frequently prescribed
to such patients. Again, the
linac manufacturers developed a clever
solution. Instead of the rectangular
collimators that variably blocked the
beams exiting the head of the linac
(along with shaped lead-alloy blocks
further restricting the beam to the target),
the solid tungsten collimators
were "broken up" into individual
leaves that could "slide" against one
another and reproduce the shape of any
of the external blocks used earlier.[3]

Figure 3 is a photo of a modern
linac used in radiotherapy today.
Figure 4 is a view up into the head of
a multileaf collimator-equipped linac
showing the leaves in the required configuration
to treat a particular target.
These leaf positions are set automatically
at the treatment console; they not
only relieve the therapist from hoist-

ing heavy blocks for each field set, but
also allow greater throughput of patients
undergoing radiotherapy, some
using complex portal arrangements.

Computer Verification Systems
At the same time that multileaf collimation
was being developed, another
advance was being made to ensure that
all of the correct parameters associated
with prescribed radiation treatments
were being used for each treatment
fraction. Verify-and-record computer
systems that evaluated all aspects of
the treatment unit (eg, linac, multileaf
collimation shape, patient position,
dose) were developed to electronically
ensure that all parameters were correct
for each treatment delivery.[4] If
any of the parameters were not set
properly, the software would not allow
the radiation beam to be energized.
This represents another level of
patient safety afforded to workers in
the field and enabled the confident use
of more complicated radiation field
arrangements. As with any computerized
control system, however, care
must be taken to input the correct data
initially.[5]

Stereotactic Radiosurgery

The Leksell GammaKnife system
for delivering large, single-fraction
doses to benign lesions was developed
early on to allow neurosurgeons and
radiation oncologists to work together
to control disease entities in the brain
when conventional surgery was contraindicated.[
6] The current version of
this system consists of 201 small cobalt-
60 sources, all pointing to a common
focal point upon which the target
lesion will be placed using a stereotactic
localization frame. Many disease
entities have been treated with this
method, including trigeminal neuralgia,
arteriovenous malformations,
meningiomas, and some metastatic
lesions in the brain.

A version of this technology was
developed for linac-based systems by
adding a "postcollimation" cylindrical
device that could aim the radiation
beam at a target in the brain while the
linac gantry moved in an arc about the
patient.[7] Several oblique arcs are
typically used to "spread" small doses
to normal brain tissue over larger areas
in order to deliver higher doses to
the target. New systems using mini-
multileaf colllimators to treat similar
targets are rapidly coming into vogue.
These systems and their parallel treatment
planning systems can provide
conformal 3D target coverage, while
keeping doses to normal brain tissue
to an acceptable level.[8]

Intensity-Modulated
Radiotherapy

In the early 1990s, Dr. Mark Carol,
a neurosurgeon, had the clever idea
that the large radiation beams being
used in conventional radiotherapy
could be "broken up" into many
smaller beams, each of which could
be opened when an appropriate target
was "in view" or closed when a critical
structure was in the beam's path.[9]
This is a simple description of the first
application of intensity-modulated radiotherapy
(IMRT) using photon
beams. The Nomos Corporation's Peacock
delivery and planning system was
developed to treat solid tumors and
"paint a dose picture," much in the
same way that CT is used to present
"anatomic atlas" axial views of the
inside of the body.

A postcollimation device, termed
the MIMiC, consists of 40 individual
binary collimators (they can be opened
or closed to block the radiation beam),
in two rows of 20 each. Figure 5 depicts
an en face view of the MIMiC
with every other leaf open/closed.
With this system, the tumor target is
treated in axial slices along the body
axis by rotating the gantry in a (usually)
270o arc about the patient. At
each gantry angle, the leaves may be
open or closed depending on the controlling
program of the MIMiC computer.
This computer takes its instructions
from a treatment plan developed
earlier with a separate sophisticated
treatment planning system.

Inverse Planning
In contradistinction to conventional
or 3D planning computer systems that
use "trial and error" to develop the
eventual plan and to a large exent are
dependent on the experience and ability
of the medical physicist or
dosimetrist, the thousands of potential
"opening and closings" of the MIMiC
collimator varying by gantry angle are
impossible to estimate from an a priori
approach. Instead, "inverse planning"
was developed, which involves using
the axial slice CT image data, contouring
targets, and normal tissue structures,
and sending the information to
a robust calculation engine to determine
the MIMiC collimator configuration
at each gantry angle that would
deliver the optimized dose distribution
to the target while keeping the dose to
critical structures at an acceptably low
level. Several iterations of the possible
configurations are calculated until the
system determines the "best" plan
based on criteria selected by the medical
physicist and radiation oncologist.

Figure 6 shows a treatment plan
developed with this inverse planning
technique for a prostate carcinoma.
Note that the system allows for conformation
of the radiation dose around
the anterior rectal wall, a capability not
possible with conventional planning
and delivery systems. This technology
was initially applied to the brain, protecting
the optical chiasm from irradiation
when disease entities such as
glioblastoma multiforme or meningioma
were in close proximity.

Because the high-dose region so
tightly conforms in 3D to the target, a
slight displacement of the high-dose
volume could be dangerous to the patient.
Hence, intricate immobilization
devices had to be developed to ensure
that targets were in the correct place
from day to day. With this system, radiation
oncologists could treat disease

entities like head and neck tumors
while sparing the uninvolved parotid
glands (which frequently produced
xerostomia with conventional methods)
and paraspinal tumors in a wraparound
configuration (which would
not be possible with conventional radiotherapy
methods).

Subsequently, a patented device
was added to the treatment couch that

allowed nonaxial slices to be treated
by this system. This improvement allowed
higher conformality around the
target and made possible the introduction
of intensity-modulated radiosurgery
into the armamentarium of radiation
oncologists.[10]

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