Ask anyone you meet at Varian Medical Systems to describe Thanos Etmektzoglou's work ethic, and inevitably they'll tell you he runs marathons.
Funny thing is, he doesn't. Not anymore. He hurt himself running a few years ago, and since then he has cut down his routine to an average of two or three miles, three or four times a week.
But the aura of a marathoner clings to him like the sweat on a runner's brow.
"It's an example of how tirelessly he works," says Pete Coronado, Varian's manager of software and electronic engineering.
"It shows he sets high goals and works hard to achieve them," adds Varian medical physicist Calvin Huntzinger.
"It describes his focus and his persistence," insists Craig Van Antwerp, delivery-system scientist at the company.
Etmektzoglou says he'll get back to running marathons eventually. Whether he does or not, he is a marathoner in spirit. It took an Olympic-size effort to meld together the physics and engineering behind Varian's pioneering cancer-treatment technology known as Intensity-Modulated Radiation Therapy (IMRT) and capture it in the control software that makes the technology work. That's what he did, and it's those efforts that earned him the Design News Special Achievement Award, the first software engineer to win the honor.
It was no easy task to reconcile different disciplines while developing the control system. Among the challenges were synchronization of beam and microwave power; handling the limitations of dose-measurement subsystems; operation of the beam servo system; and the discrete nature of radiation pulses.
Etmektzoglou's key role in development of the technology, acknowledged by mechanical engineers, electronics engineers, and physicists alike, shows the emerging prominence of software engineering in motion control and other technologies today.
IMRT is based in large part on a sophisticated, precise, computer-controlled motion control system that evaluates millions of possible X-ray-beam arrangements, creates a treatment plan, and delivers radiation doses directly to a tumor, not to adjacent non-cancerous cells. It includes an array of custom motors, encoders, controllers, and lead screws, as well as magnets, materials, and other technologies, all tied together by software. Working with engineers designing the individual components of the system, Etmektzoglou wrote the Dynamic Beam Delivery control system that makes the precise delivery of radiation doses possible, and the program that converts treatment plans into electronic instructions for controlling the system. "Thanos' concepts drove everything in the development of IMRT," says Tim Guertin, executive vice president of Varian's Oncology Systems Division. "He turned our technology into a programmable machine."
Deliverer: Appearing like a cell phone on steroids, Varian's Clinac linear accelerator sends precise beams of radiation to kill tumors. The patient lies on a table under the beam.
Understanding the tradeoffs with each of these technologies and the software was key, says Varian Chief Engineer Stan Mansfield. Only someone with Etmektzoglou's deep background in physics could have pulled it off, he and others say.
"Thanos worked easily with the mechanical and electronics designers, figuring out what hardware mechanisms were needed and defining the software protocol without changing the electronics," says Coronado. Adds Guertin, "He solved problems senior management didn't even know we had."
Varian's SmartBeam IMRT technology is a form of so-called 3D conformal therapy intended to eliminate—or minimize—one of the biggest problems with radiation treatment for cancer: damage to non-cancerous cells. The radiation that kills cancerous cells also kills healthy tissue. But perhaps the biggest benefit of IMRT is in its potential to increase cure rates because of the larger dose rate it allows. There are 3,700 Varian Clinac® medical linear accelerators in use worldwide at some of the most prestigious hospitals and medical clinics on the planet, such as the Memorial Sloan-Kettering Cancer Center in New York and University of Texas M.D. Anderson Cancer Center in Houston. Across the globe, more than a million cancer patients are treated with Clinac machines each year. That means about 100,000 times a day a radiotherapist somewhere executes the control program Etmektzoglou developed to drive all elements of the technology and deliver a lethal blow to cancer cells.
"IMRT lets us distribute (radiation) doses that were previously impossible, and opens up some extraordinary possibilities," says Ted Lawrence, MD and professor of radiation oncology at the University of Michigan.
Here, in the simplest of terms, is how IMRT works:
The Clinac is a massive, 35,000-lb linear accelerator that looks like a cell phone on steroids. It generates X-ray radiation by accelerating electrons to near the speed of light and then crashing them into a piece of tungsten to create a beam of photons or X-rays with energies that reach up to 20 million electron volts.
This X-ray beam is channeled through a multi-leaf collimator, which uses up to 120 tungsten bars, or "leaves" to shape it and thus distribute a precise dose of cancer-killing radiation within the tumor site. Engineers chose tungsten for the 400-lb collimator because of its density. Lead, they felt, is too soft and not dense enough for this application.
Sub-fractional-horsepower motors and encoders attached to the leaves move the individual bars simultaneously so that they jointly form an aperture that closely approximates the shape of the tumor. The continuous movement of the leaves and aperture creates what Varian calls a "sliding-window." This computer-controlled coordination of leaf movement paired with precise throttling of the beam intensity creates more precise dose distributions.
The tumor-shaped pattern of tungsten leaves collimates the X-rays into pencil-thin beamlets directed at the tumor.
Separate controllers rotate the 18,000-lb gantry of the Clinac into different positions so the radiation hits the tumor from different angles, enveloping it in a crossfire in the area where the beams intersect with one another.
The tumor shape of the X-ray beams maximizes the radiation dose on the cancerous cell while minimizing collateral damage to nearby healthy tissue.
The result: more cancer-killing radiation where it's needed, less where it could be harmful.
That simplified description, of course, omits several details important to the treatment plan, such as the CT (computed tomography) and PET (positron emission tomography) scans that image the tumor and surrounding anatomy, the automotive-GPS-like computer mapping of the best X-ray beam shapes and exposure times, and the respiratory-gating system that synchronizes the treatment with the patient's breathing cycle to account for movement of the tumor during inhalation and exhalation.
It's a tour de force of engineering, but does it help patients?
Herman Kattlove, a retired medical oncologist now with the American Cancer Society, says that while he knows of no formal head-to-head studies of 3D conformal therapy, radiologists who have used it say it's better than other forms of treatment that don't concentrate the beam. While that may seem a lukewarm endorsement, others in the field speak more enthusiastically of the technology.
"IMRT has taken us to another level of care for our patients," says Richard Emery, chief medical physicist and director of radiation services at St. Vincent's.
Patrick Swift, MD and medical director for radiation oncology at the Alta Bates Comprehensive Cancer Center in Berkeley, CA, has been using Varian's IMRT technology since October 2001 on patients with prostate, head, and neck cancer. Now he wants to use it to treat brain tumors in children. "Treating certain pediatric brain tumors with IMRT could lower the risk of deafness," he asserts.
Beam Shaper: Varian's multi-leaf collimator shapes radiation beams with 120 computer-controlled leaves, or tungsten bars.
A Penchant for Science
The 42-year-old Etmektzoglou, quiet, unassuming, and more prone to explaining things by drawing on a white board or piece of paper than using words, came to be a soldier in the cancer war by coincidence. The son of a Greek electromechanical engineer and his Italian wife, he was born in Athens, relocated to Italy with his parents, then returned with them to Greece while in grade school. He liked science, so when it came time for college he studied physics, then came to the U.S., where he attended Washington State University and earned an MSEE in computer engineering and an MS in computer science.
Though he always enjoyed building things, he decided he didn't want to follow in his father's engineering footsteps. His physics studies satisfied his scientific curiosity, but eventually computer science proved a bigger magnet for him. "In physics, you work hard to get to the frontier of knowledge, but there aren't many doors open," he says. "In computer science, everything is new."
The opportunity to manipulate physics with computers and software is what attracted him to Varian when he finished graduate school in 1987. The company's preeminence as the leading supplier of radiotherapy and X-ray systems was a nice plus, but it wasn't until later that his personal commitment to the company's products began to hinge on their life-saving potential. "That came after I began to meet face to face with the technicians and physicians who use IMRT and heard them tell of how it helps them help patients," he says. He has yet to meet any of the patients treated with IMRT, but through his contacts with medical professionals he has come to know their stories.
George Rugtiv, a retired surgeon in Northern California, was treated for prostate cancer. And Elizabeth Czekanski, a nurse in Pittsburgh, who had uterine cancer. IMRT wiped out the cancers in all of them. "It's exhilarating to know that," he says.
Nailing the Basics
Etmektzoglou's first achievement at Varian—and the one that became the basis for his work on the multi-leaf collimator control in the company's current IMRT machines—was developing the Dynamic Beam Delivery Tool Box. It's the underlying software engine that automates both the delivery of the radiation dose along with the simultaneous movement of the Clinac. The Dynamic Wedge, as it was called, was the first clinical product based on that concept, It was a vast improvement over the previous technology, which required technicians to manually adjust the lead blocks between treatments.
Medical physicists in the company had been looking for a way to replace that manual system, and explained their goals to Etmektzoglou. "He developed a program that buries the kinematics into the control system," says Huntzinger. "When I described the physics to him, he knew just what I wanted." Huntzinger says Etmektzoglou is the smartest person at Varian in terms of raw intellect. "He went beyond the bits and bytes and often provided us easier ways to do things in physics."
Open and shut case: The multi-leaf collimator consists of up to 120 tungsten bars, or leaves, that are driven by sub-fractional horsepower motors into different positions to approximate the shape of the tumor. X-ray beams directed onto the tumor are shaped by the collimator.
For example, after the Dynamic Wedge had been in the field for awhile, clinicians decided they wanted something simpler. Varian responded with the Enhanced Dynamic Wedge, which simulated a wedge-shaped radiation dose distribution using a linear attenuation coefficent model. "X-rays interact with water and tissue in a certain way," Huntzinger says. "Thanos showed us that a linear-attenuation coefficient approach would produce the wedge-shaped dose distribution better than a more complex way. His background in physics was critical."
So is his marathoner-like focus and perseverance. "He knows that things aren't always easy and that solutions don't come overnight," says control systems engineering manager Coronado. "It took years to perfect the multi-leaf collimator concept before we delivered the first prototype to Memorial Sloan-Kettering."
From all accounts, Etmektzoglou is that rare individual who is both a people person and a private person, a detail guy who sees the big picture, a brainstormer who can spend hours in his cubicle thinking and making notes before tapping a keyboard. Observes Coronado, he is a clever thinker and a team player, meticulous and methodical, who, like most software pros, likes to work alone late at night the closer a product gets to the release date.
He'll spend hours in that cubicle thinking through a problem, devise a possible solution, then move to a testing lab loaded with computers, small multi-leaf collimators, and simulators and try out his solution. "Thanos grasps the nuances of a technical problem, brings all the pieces together, and keeps everyone on track," says Van Antwerp, who worked closely with him on development of IMRT technology. And, he is always prepared.
As an example, Van Antwerp recalls a recent meeting of an International Electrotechnical Commission task force on procedures for developing IMRT specifications. He and Etmektzoglou are members of the task force. "Before the meeting, Thanos e-mailed everyone his concepts for conveying graphically how all the elements of IMRT interrelate, and asked for comments," Van Antwerp says. "He knew the limits of words and the benefits of graphics to explain all the contributing factors, and his ideas set the tone." In any meeting, Van Antwerp says, others may be more vocal but Etmektzoglou exerts the most influence.
But, we are not canonizing a saint here. Guertin also says that Etmektzoglou has a stubborn streak. "He has strong views and he can dig in his heels."
If he's not a saint, neither is he the typical nerd. Fluent in Greek and Italian, and somewhat fluent in Spanish, he likes to listen to ethnic music as well as classical. He enjoys reading philosophy and general non-fiction, and he barely watches television at all, though he does like fixing TVs. He doesn't wear a pocket protector.
He does have projects outside of work. His current obsession: building a solar-power de-vice for powering light bulbs and small electrical devices or charging batteries he brings along on camping trips. "I like to tent, and I like to be energy independent," he says.
And he likes to keep learning. "Curiosity is what makes me tick," he says. "Science and engineering takes over your life." Unlike long-distance running, they don't cause muscle strain.