Charlie Pan, M.D. |
In the research labs of the U-M Department
of Radiation Oncology, the search is on to find ways to kill
more cancer cells with more precision, resulting in fewer side
effects during radiation therapy (RT). Because by definition
radiation’s job is to stop cells from growing or replicating,
and because it does that job so well, there is always a risk
that healthy cells may be exposed during RT. Depending on where
the cancer is, this can lead to complications varying from difficulty
swallowing to urinary dysfunction.
A team of U-M investigators including
Charlie Pan, M.D., and Avraham Eisbruch, M.D., is at the forefront
of one of the newest developments in RT. Called intensity-modulated
radiation therapy, or IMRT, this technique is helping to zero
in on cancer with less impact on nearby healthy organs.
According to Pan, a lecturer in the Department of Radiation
Oncology, the current state-ofthe- science offers tremendous
hope for most patients.“Today, the standard of care
at top centers like Michigan is threedimensional conformal
radiation therapy, or 3DCRT,” he says. “With 3DCRT,
multiple beams surround a defined area with radiation. In
most cases, we can define that area with great precision,
delivering an excellent result.” U-M pioneered this
approach a decade ago, leading the field in a major leap forward
in effectiveness and accuracy.
As Pan points out, though, some patients present particular
challenges.“When tumors are particularly large, cannot
be removed by surgery or are obscured by vital structures,
even the best conventional plan presents too high a risk to
surrounding tissue.” In such cases, an even more precise
method is called for.
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| Intensity-modulated
radiation therapy. A beam of radiation
is segmented into multiple “beamlets,” that vary in intensity.
Higher bars indicate higher doses of radiation. |
IMRT provides that additional precision, offering the ability
to vary the intensity of radiation across the area being treated
by “slicing up” the radiation beam. “Other
methods including 3DCRT deliver the same intensity across
the entire beam,” says Pan.“But by ‘modulating’ the intensity,
IMRT delivers different intensities of radiation within an
individual field – dividing the radiation beam into ‘beamlets,’
each carrying a different dose of radiation as directed by
the treatment plan.” (See image to the left.)
Not only is the delivery of radiation quite different in
IMRT, The process of determining where radiation will go –
and where it won’t – is different too. That process, called
treatment planning, usually begins with a radiation oncologist
writing guidelines to be followed by a dosimetrist, a specially-trained
technician who, aided by a computer, calculates how each beam
will be positioned to administer the proper dosage of radiation.
Several versions of a treatment plan are created, and plans
are refined in consultation with the physician until an acceptable
plan is agreed upon.
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| A
three-dimensional view of a patient’s IMRT targets, as
optimized by the computer. Seven intensity-modulated
beams are directed at a tumor (in the paranasal sinuses),
avoiding vital structures including the eyes. |
IMRT “inverts” the treatment planning approach.The radiation
oncologist and dosimetrist first specify their goals – the
desired dose to the target and the maximum doses acceptable
to neighboring healthy structures.A computer algorithm creates
the treatment plan needed to reach that goal. “By beginning
with our goals and asking the computer to solve the problem,
we end up with a much more precise solution,” Pan explains.“The
computer can evaluate so many more alternative scenarios to
find the best solution that corresponds to our objectives.
Not only can we get closer to our target, but the resultant
dose patterns can be more conformal.” (see image to the
right)
Although still limited mainly to the research lab and clinical
trials, IMRT shows tremendous potential for a wide range of
cancer types. U-M is one of the major centers moving IMRT
forward, with Pan, Eisbruch and others developing clinical
applications for the technology to treat a variety of cancers.
For example, IMRT is currently being used to treat head and
neck cancer patients to preserve their salivary gland function,
and is being tested with prostate cancer patients with the
hope of avoiding urinary side effects.
Treating head and neck cancers while maintaining salivary
function
 |
| Avraham Eisbruch, M.D.,
reviews a patient’s treatment plan. IMRT allows physicians
to administer radiation with more precision, minimizing
the side effects that |
Head and neck cancers such as those in the sinus cavities
frequently involve treatment with radiation therapy, either
to attack tumors or to follow their surgical removal, killing
cancerous cells feared left behind.With standard three-dimensional
RT, a beam of energy is delivered to the entire affected area.
Although this is highly effective in destroying the cancer,
it also results in damage to the salivary glands, diminishing
or halting their ability to produce saliva. This condition,
called xerostomia, might sound like a minor inconvenience, but
it dramatically impacts a patient’s quality of life, altering
his or her ability to taste, chew and swallow.
As an alternative, Avraham
Eisbruch, M.D., associate professor of Radiation Oncology
at U-M, has established the use of IMRT to treat this tumor
type, resulting in a more exact treatment plan. Eisbruch’s
application of IMRT to spare the parotid (saliva) gland has
gained international recognition.
Beyond instituting this treatment technique at Michigan,
Eisbruch’s team has also pioneered a methodology for quantifying
whether and how much the therapy impacts his patients’ quality
of life. In partnership with experts in biostatistics, they
designed a study to measure four quality-of- life factors
before and after treatment: eating, communication, pain and
emotion.
Patients’ answers were combined with measurements taken of
their salivary output before treatment and at three, six and
twelve months after treatment. The results showed that both
xerostomia and quality of life improved significantly over
time during the first year after treatment, which suggests
that IMRT represents a promising alternative for head and
neck cancer patients.
Treating prostate cancer while preserving
urinary function
Learning from the clinical success of IMRT in treating head
and neck cancer, Charlie Pan has begun research to determine
how IMRT might help overcome the side effects associated with
treating prostate cancer. Specifically, he is interested in
addressing urinary dysfunction. Some evidence indicates post-RT
urinary troubles may be caused by radiation impacting the
urethra. As Pan puts it,“the urethra connects the bladder
to the outside world, and it passes through the prostate,
making it difficult to avoid in conventional treatment planning.”
Pan’s research attempts to minimize the dose of radiation
to the urethra during prostate treatment using IMRT.
 |
This IMRT plan
directs beams to focus on the peripheral zone of the
prostate, where the tumor (light purple) is located.
By varying the dose within each beam, the impact is
further minimized to surrounding areas including the
hard-to-avoid urethra (red). |
“The first step is to see into the subanatomy of the urethra,”
explains Pan. “For that, an MRI is needed. Most prostate cancers
are isolated in what’s called the peripheral zone of the prostate.
An MRI ensures there is no obvious cancer in the central or
transitional zone of the prostate, where the urethra passes
through. Once that’s confirmed, we can tell the computer that
the target is the peripheral zone, and tell it to minimize the
dose to the central or transitional zone.That can reduce the
dose to the urethra by about half, depending on the patient.”
(see figure to the right)
Like Eisbruch’s study, Pan’s randomized clinical trial– currently
enrolling patients – also includes a measurement of quality
of life before, during and after treatment. “We’re looking
for improvement in the urinary-related side effects that frequently
bother prostate cancer patients. Obtaining these measurements
is critical.
“When you step back and look at the big picture,” Pan continues,
“every treatment plan begins with trying to treat a target
while avoiding organs at risk (OAR). What IMRT allows us to
do is either escalate the dose to the target while maintaining
the same amount of radiation to the OAR, or keep the target
at the same dose while decreasing the dose received by the
OAR. We’re looking for that optimal balance.”
To learn more about clinical trials in Radiation Oncology
at the U-M Comprehensive Cancer Center, call the Cancer AnswerLine
at 800- 865-1125.
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