Precision Dosing a Reality with Intensity Modulated RT

BOSTON--Advances in three fields--imaging, medical physics, and computertechnology--have led to the development of a radiation therapy modalitythat may represent a significant breakthrough in cancer treatment.

"Intensity modulated radiation therapy (IMRT) is the most sophisticatedform of computer-delivered radiation therapy currently available,"said David E. Wazer, MD, director of the Radiation Oncology Center of theNew England Medical Center, which has pioneered the technique.

Mark J. Engler, PhD, physicist-in-chief at the Radiation Oncology Center,said that the technique is not just an improvement on state-of-the-artradiation therapy technology, but rather offers a complete change in theway in which radiation therapy is administered. Dr. Engler headed one ofthe first physics teams responsible for making IMRT a reality.

IMRT is a three-dimensional conformal radiation treatment that usesa powerful computer model to plan therapy and a multileaf intensity-modulatedcollimator to deliver highly focused radiation doses with minimal damageto surrounding tissue (see images ).

In an interview with Oncology News International, Dr. Engler said that,in effect, all radiation therapy is conformal. "Obviously, from thetime the first physicians aimed an x-ray tube at a cancer, they wantedthe dose to conform to the target." But unlike conventional 3D-conformalradiation therapy (3D-CRT), IMRT treatment decisions are based on complexmathematical models, resulting in a level of precision previously unattainable,Dr. Engler said.

A Brief History of IMRT

When Mark Carol, MD, first envisioned dose optimization using a computer-controlledintensity-modulating multileaf collimator, the year was 1975, and computertechnology could not meet the needs of the idea.

In 1989, London physicist Steve Webb, PhD, published a paper applyingcomplex mathematical principles to radiation oncology, and, in 1992, Dr.Carol began working on a prototype IMRT system, based on Dr. Webb's article.

He named the system Peacock, from the fan of peacock feathers that symbolizethe multifaceted beam patterns utilized in IMRT.

In 1996, Dr. Mark Engler and his colleague Jen-San Tsai, PhD, definedthe international safety standards for IMRT in two papers presented atASTRO. The FDA gave final clearance to the Peacock hardware in 1994 andthe planning software in 1995. It is made by NOMOS Corp. (Sewickley, Penn),founded by Dr. Carol.

The Planning Phase

For treatment planning with IMRT, a series of 40 to 80 CT images areobtained and sent to the planning computer where radiation oncology personneldelineate targets and sensitive surrounding normal tissues. The clinicianthen determines the optimal dosage for the tumor site and the maximum tolerateddosages for the surrounding normal organs and tissues. This allows fora radiation prescription that expresses the relative importance of sparingdifferent normal tissues.

"In a prostate cancer patient, for example, the physician can tellthe computer the maximum tolerated dose for the rectum, the bladder, theheads of the femurs, and so forth," Dr. Engler said. "In a braintumor patient, the system forces the physician to quantify the relativeimportance of, say, the auditory nerve versus the optic nerve."

Once all the data are entered, the IMRT software simulates the radiationphysics for the desired doses, using mathematical models to search forthe plan that best satisfies the physician's multifaceted prescription.The plan typically includes "an astronomical number of beam patterns,providing dynamic, optimized, intensity-modulated 3D radiation therapy,"Dr. Engler said.

The data for the optimal plan are then transferred to a disk, whichis inserted into the MIMic collimator controller on the accelerator fordelivery of the treatment plan. (The MIMic--multileaf intensity-modulatedcollimator--is part of the Peacock IMRT system, manufactured by NOMOS Corporation.)

As the MIMic rotates around the patient, it constantly measures thebeam angle and adjusts the small vanes that shape the beam. Thus, the fieldshape and intensity of the beam are continuously varied so as to mold theradiation beam to the target and modulate the intensity of the radiationacross the target.

In contrast, with conventional 3D-CRT, Dr. Engler said "you'reaiming at a silhouette of the target, and you're treating normal tissuesin front of and behind that silhouette in a somewhat arbitrary fashion.IMRT technology is aimed at minimizing the dose to these tissues in frontof and behind the target in a very systematic manner with intensity modulatation."

The conformity of the dose distribution to the target using IMRT isshown in the images , in which a setof colored lines represents the actual radiation dose that was deliveredwith IMRT.

Typically, the prescription dose (shown by the innermost overlappingred-yellow lines around the tumor) is about 85% of the maximum dose, fallingoff to 55% of maximum at the outermost blue-black line. "The wholepoint of this system is that it creates a very sharp fall off of dose rightaround the target," Dr. Engler said.

Clinical Results

While IMRT is currently being used primarily on head and neck tumors,in the near future, refinements in immobilization and imaging techniquesshould allow its use to treat cancers in almost any location, includingthe breast and lung.

"We are already seeing dramatic outcomes in patients with headand neck tumors," Dr. Wazer said."One patient with a brain tumor wrapped around the optical nerve wouldhave been blinded as a result of the tumor. Using IMRT, we were able todramatically reduce the size of the tumor and preserve the person's eyesightwithout damaging the optical nerve with radiation."

Dr. Wazer has submitted the results of preliminary clinical trials usingIMRT for presentation at the annual ASTRO meeting this fall. Nine otherAmerican sites are involved in IMRT clinical trials, but the RadiationOncology Center has treated about one quarter of the more than 360 IMRTpatients in the United States.

Dr. Engler noted that many of the initial brain cancer patients weretreated under investigational device exemptions and protocols with criteriathat resulted in "extremely sick patients who did not have other options."Nonetheless, he said, one of the preliminary observations is that withIMRT most of these patients have not needed repeat surgery for aggressivebrain tumors.

He said that prostate cancers are now being treated using IMRT, and"the system is allowing us to cut down the dos-ages to the rectumand bladder by about 50%." Several years of follow-up will be necessaryto determine if the technique does indeed produce fewer complications.

National research groups, including RTOG, have drafted dose escalationprotocols to be used with IMRT in prostate cancer patients, he added.