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Improving Radiation Therapy

Charline Pan, MD
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.

graph of beam intensity
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.

image of head receiving IMRT
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, MD
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.

IMRT used on prostate tumor
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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