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Taking Aim at Cancer

Terence S. Herman, MD
Chairman, Department of Radiation Oncology

Chair Terence S. Herman, M.D., doesn't pinch himself to prove the exciting transformation under way at the Department of Radiation Oncology is really happening, but well he might. The changes are that rapid and significant.

First came plans to move radiation oncology services from a new but disjointed building to the Stephenson Cancer Center in 2010. The program will occupy a 25,000-square-foot area on the bottom floor of the institute, convenient both for patients and physicians.

Second was the arrival of the latest in conventional radiation equipment, a new medical linear accelerator called the Trilogy that delivers higher doses of radiation to cancers more precisely. This accelerator is equipped with all the bells and whistles, including CT, that allow Herman and his colleagues to locate and target tumors more accurately each day of treatment.

Third was the icing on the cake: the announcement that OU Cancer Institute (OUCI) will boast the latest-generation proton beam system, one that uses a smaller and much more efficient synchrocyclotron to produce cancer-killing proton "bullets." This equipment will allow physicians to deposit a far bigger dose of killing power within a tumor while sparing more of the surrounding normal tissues, minimizing side effects while increasing tumor control rates.

As Herman remarked when the proton center was announced, "When I came a year ago to head the department, I was promised they would bring the most advanced techniques to Oklahoma. Today is the validation of that pledge."

Only a few years old, and after taking a few faltering baby steps, the Department of Radiation Oncology is at full stride. Herman gives all the credit to the department's "midwives," Carl R. Bogardus Jr., M.D., and Elizabeth J. Syzek, M.D.

Both former members of the faculty, they agreed to leave their successful private practices and return to OUHSC when Executive Dean M. Dewayne Andrews, M.D., asked them to help him create a new Department of Radiation Oncology. Andrews pulled radiation oncology from the Department of Radiological Sciences and made it a separate department as part of the plan for developing the OU Cancer Institute.

For Herman, "being asked to head this new department by Dr. Andrews represented a very unusual opportunity to build a truly exceptional academic department, because the faculty was already quite strong with the return of Drs. Bogardus and Syzek and the presence ofSalahuddin Ahmad, Ph.D., the department's head of physics and a nationally recognized academic medical physicist. We were also very fortunate that we were able to attract Chih-Yao (Roger) Cheng, Ph.D., a very talented young medical physicist from the University of Texas - San Antonio program."

When Herman arrived, about 70 patients were being treated daily. That number quickly rose to about 125 and is expected to rise further with the addition of two more experienced radiation oncologists, Spencer Thompson, M.D., and Ozer Algan, M.D.

In addition, radiation biologists Muayyad Al-Ubaidi, Ph.D., and Natarajan Aravindan, Ph.D. joined the team to research new techniques and help train residents.

Because of these unusually strong factors, the Accreditation Council for Graduate Medical Education approved a residency program for the new department after only the first request. The department took its first resident in July of 2007.

In radiation oncology, it's all about finding the right spot in the body to "hit," then hitting that spot day after day. "When you are using precise radiation, you need precise imaging to guide therapists in positioning the patient daily," Herman said.

Asking how this is possible prompts a tutorial on the world of ultra-high-tech gadgetry, all designed to increase damage to the tumor and reduce collateral damage to surrounding tissue. One of these is the computer-assisted program called intensity modulated radiation therapy, or IMRT.

With IMRT, the physician precisely maps the tumor in three dimensions using a special CT scan often coupled (fused) with other imaging techniques. The IMRT program then determines the optimum directions of literally hundreds of ultra small "pencil" beams to accomplish the delivery of the prescripted energy level to the tumor and surrounding normal tissue. The resulting distribution of dose can be made to conform closely to the shape of the tumor.

"A standard linear accelerator produces a large cone-shaped beam, and the energy deposition is difficult to make conform to tumor shapes," Herman explained. "The IMRT systems use special micro-beams created by a multi-leaf collimator placed between the patient and the machine."

These collimators break up the cone of radiation into many, much smaller beams by using 1 centimeter or smaller blocking doors, which open or close in about 0.1 seconds. The computer determines how it fires those micro-beams to treat the tumor shape to the dose the oncologist specifies - while optimally avoiding depositing dose in normal tissue.

"Today's computer can come up with a solution that's ‘randomly optimized', [a system] that's an offshoot of the ‘Star Wars' missile defense program. The computer goes from one solution to a better solution to a better solution in microseconds, just as occurs when a computer directs a speeding missile to hit another speeding missile," Herman said.

Fast, modern computers require only about half an hour to reach the optimized random solution that not long ago required 24 hours of computer time.

Moreover, the department's new accelerator has a micro collimator with doors only 3 millimeters in size, "so we can treat even smaller tumors very precisely."

To deliver these ultra-precise treatments, it is important that the patient be in the correct, pre-planned position and remain perfectly still during treatment. But human beings can't hold completely still, and they have no control over whether their tumors might have moved internally between treatments.

This is where new movement-restraining devices and imageguided radiation therapy, or IGRT, come in.

CT images are taken just before treatment to identify, in real time, any changes in the location of the tumor that may have resulted from a variety of causes, including weight loss or bowel or bladder volume changes. These changes are adjusted for each day.

A method called respiratory gating also is used to account for breathing. "If the tumor is in the lung, it is moving around as you breathe," Herman said. "We use computer control to fire the radiation only during a very precisely determined part of the cycle of breathing, so that every time the machine is on, the tumor will be in the center of the field. This allows the radiation oncologist to decrease the safety margin around the tumor. The smaller the margin, the less the lung function that is sacrificed."

For small tumors and those located adjacent to critical and sensitive tissues, "we CT them every day" to ensure accuracy.

The new proton unit also will be equipped with CT, but here similarities end.

Traditional radiation therapy uses linear accelerators to produce photons, which are packets of uncharged energy in the form of X-rays that ionize DNA (removed electrons from critical DNA atoms), destroying tumor cells.

Conventional radiation equipment deposits the therapy dose along the entire energy beam path to the tumor - and beyond it, damaging normal tissues.

In contrast, protons (which are positively charged) enter the body through skin and tissue, hit the tumor and then stop entirely at a distance determined by the energy of acceleration.

Collateral damage to normal tissues is markedly decreased. The advantages are obvious when the target tumor is adjacent to critical structures - the eye, brain, base of the skull or the spinal cord.

The real advantage of proton therapy lies in its dose-depositing characteristics. With conventional external beam radiation therapy, the photon beam delivers its peak radiation dose shortly after entering the body and diminishes gradually as it travels through the tumor and exits the body. With proton therapy, the dose of radiation deposited increases gradually before suddenly rising to a peak and then dropping to zero. The maximum dose is known as the "Bragg Peak," which occurs just before the proton particle stops. The proton beam can be modulated so that a series of Bragg Peaks create a dose pattern that fully conforms to the tumor volume.

The dose drops from 100 percent to zero over a distance of about a 16th of an inch, a distance critical for the 250 to 300 patients with brain tumors, prostate cancer and tumors adjacent to critical organs whom Herman expects to treat annually once the proton equipment is operational.

Herman was trained in medical oncology at the University of Arizona, after which he completed a special NIH fellowship in anticancer drug pharmacology. He trained in radiation oncology at Stanford University after a five year academic career as a medical oncologist.

Herman has always maintained his interest in medical oncology; in fact, he still attends for the Department of Medicine.

Not surprisingly, his research interests concern the interactions between anticancer drugs and radiation therapy, and his knowledge of both fields has resulted in his recieving several NIH laboratory-based grants to study those interactions.

"We know that the energy deposited by therapeutic radiation causes DNA damage and cell death. We also know that various chemicals can increase or decrease the cell death associated with this level of DNA damage, thus either sensitizing cancer cells to or protecting normal cells from the effects of ionizing radiation," Herman said.

While Herman has a long history of studying these interactions, he has always studied chemicals with photon irradiation because he never had access to a proton beam. This will change when the new proton equipment arrives, and the study of biological interactions with the proton beam becomes the core of the department's research efforts in both laboratory and clinic.

"We will have a nearly unique opportunity to study sensitizing and protecting chemicals with proton irradiation when the proton beam comes on line." Herman said. "This should provide a strong research direction with great potential for improving the treatment outcomes for the people of Oklahoma."