This report originally appeared in the October 2009 issue of DOTmed Business News

According to the American Cancer Society, almost 1.5 million new cases of cancer are expected to be diagnosed in the U.S. this year, and over half a million Americans are expected to die of cancer. That's more than 1,500 people per day, which makes it one of the leading causes of death in the country - second only to heart disease. The silver lining - or beam in this case - is that a growing number of treatments are available to combat the disease. Linear particle accelerators and simulators have shaped-up to be among the most powerful systems for delivering precise radiation therapy and radiosurgery.

Like many medical equipment markets today, the linear accelerator segment of the industry is stretched-thin due to economic pressures and recent changes to Centers for Medicare and Medicaid Services (CMS) reimbursement practices. Some experts believe another 50% cut in reimbursement may be yet to come. Still, new techniques are delivering increasingly targeted and more aggressive radiation therapies in fewer sessions, resulting in some remarkable improvements in cancer outcomes.




Linear accelerators, or linacs, are essentially external beam radiation therapy systems that use microwave technology to produce electron and/or photon beams powerful enough to damage or destroy tissues. The majority of radiotherapy procedures carried out by linear accelerators are for the curative, therapeutic or palliative treatment of cancer and this technology has the ability to home in on a wide variety of malignancies throughout the body, whether on the skin, breast, prostate, deep inside the brain, or now, with respiratory gating, the hard-to-pin-down lungs and liver.

It's all in the application

In the current market, a new linear accelerator can cost anywhere from $1.5 to $3 million. Linacs are used primarily in a limited but critical handful of applications. Intensity modulated radiation therapy (IMRT) is the new gold standard of radiation therapy and involves using beams of varying energies that can deliver very specific radiation doses to targeted lesions in the actual shape of the tumor - this is thanks to the modern multi-leaf collimator (MLC). The MLC uses radiation-blocking "leaves" that can be programmed to make the beam conform to the shape of the tumor. The high-end systems are precise to within a couple of millimeters.

IMRT has been advancing for about ten years now, in part due to the assistance of image guided radiation therapy (IGRT), which ensures that the patient remains in the exact position they were in during simulation for the entire course of actual treatment, which may be "fractionated" over several days or weeks. IGRT has been in development for three or four years. Proper positioning obtained by IGRT is sparing more healthy tissues and increasing the therapeutic value of treatment more than ever before. IGRT is made possible with onboard image-guidance systems that are integrated into the linear accelerator - either 2-D portal imaging or 3-D cone-beam CT systems. Now there are even "4-D" imaging systems built in that can mimic fluoroscopic imaging. This kind of IGRT helps account for patient respiration and registers the motion of lung cancer tumors and liver tumors, which move with the diaphragm.

Varian is the market-leading manufacturer of linear accelerators. Corey Zankowski, Varian's senior director of oncology product management, says that modern IMRT is making it possible to move therapy into the realm of stereotactic radiosurgery (SRS) for some forms of cancer.

SRS and stereotactic body radiation therapy (SBRT) have revolutionized the way ionizing radiation is used to treat and cure cancer. Rather than delivering radiation over the course of several sessions, stereotactic procedures ensure highly accurate beam positioning in three-dimensional space and involve higher electron and photon energies and much higher absorbed radiation dose, which is measured in grays.

Today's linear accelerators offer spectrums of photon and electron beam strengths, measured in megavoltage units, or MV. Different cancers call for different beam strengths depending upon the tumor type, location and stage of disease.




"We treat some disease sites with photons and others with electrons," says Brent Evans, linac product manager for Siemens' Oncology Care Systems. "When you deliver electron radiation and it hits the skin, it scatters. Electrons don't penetrate deep into the skin, but it's great for treating skin cancer and melanomas. We also use electrons with some TBI - total body irradiation, which is sometimes used before chemo to keep the white blood cells low or before a bone marrow procedure."

Most of the other disease sites and 90% of cancer treatments employ photons, says Evans. "Some energy spectrums on your photon beam go up as high as 23 MV. Six is an IMRT beam and you might treat the breast with 10 or 15 MV. With the liver it could be an 18 MV beam." The higher energy and absorbed radiation dose is permissible because far less healthy tissue is affected and risk of toxicity is lower with IMRT and stereotactic procedures.

"Radiotherapy typically delivers 2 gray fractions, so every day the patient comes in and receives 2 grays of [radiation] dose," says Zankowski. "That setup involves image guidance, positioning of the patient and then the treatment occurs in about a 15-minute time slot. When you're doing stereotactic applications you're giving very high doses in a single fraction or very few fractions, which can take 20 minutes to several hours...One of the trends we've been seeing over the past three to five years is that a lot of what was standard radiotherapy is starting to migrate toward hypofractionated radiotherapy so that instead of seeing the same patient 30 to 45 times and delivering small doses each time, these regimens are starting to become more and more compressed and in some instances it's as extreme as doing it all in five fractions."

Significant success rates with IMRT and IGRT

Dr. David Parda is chairman of the West Penn Allegheny Health System Radiation Oncology Network. Allegheny General Hospital's Radiation Oncology Department is among several rising stars in the field and one of the larger programs in the American College of Radiology. Allegheny offers a dedicated radiation oncology residency program and provides tertiary care for 300 patients a day throughout the network. Dr. Parda estimates that the lifetime incidence of life-threatening cancer is one in two for men and one in three for women, which makes cancer-fighting technologies like linear accelerators all the more relevant. According to recent data, advanced and highly personalized therapies delivered by linear accelerators have led to some staggering cure rates and a dive in toxicity levels.

"For lung cancer treatment - if you have a 2 cm lung nodule that is non-small cell lung cancer and if you treat it with conventional radiation treatment techniques you are able to eradicate that local tumor anywhere from 15% to 30% of the time," says Dr. Parda. "If you use stereotactic radiosurgery and radiotherapy approaches, eradicating the tumor has been shown to occur 90% of the time." Dr. Parda stated that dose escalation procedures combined with IMRT and IGRT showed cure rates also at or exceeding 90% for prostate cancer patients.

The most common toxicity is rectal toxicity, which is currently on the order of about 1% to 2% for colorectal cancer patients receiving treatment, says Dr. Parda. This rate has plummeted in recent years from previous toxicity ranges of 20% to 30%.

"Improved dosing and targeting of radiation has increased tumor control probability and decreased normal tissue complication probability - that is what we call the therapeutic ratio," says Dr. Parda. "This has resulted in improved cure rates, organ preservation, functional outcome, cosmetic outcome, quality of life and palliation."

Adaptive radiation therapy

The next big thing in linear accelerator therapy is adaptive radiation therapy (ART), which is dynamic adaptation of treatment as the tumor changes during the course of therapy.

"Adaptive radiation therapy is a function of adapting the radiation dose on a regular basis," says Dr. Parda. "Since the tumor that you're treating changes in size and shape over time, the question is whether you need to modify the radiation on day 10 compared to day one."

Another foreseeable advancement in the technology is real-time image guidance. It may be the ultimate vision, but we're not quite there yet.

"As it stands, the cone-beam CT scans are taken right before the treatments," says Dr. Parda. "The whole reason that we're interested in MV CT is that we are using the actual treatment beam to generate the image. There currently is no real-time imaging solution where you are making real-time adjustments in position and dose, but that is essentially the incremental direction of adaptive radiation therapy."

The hierarchy of radiation therapy systems

The linear accelerator is just one of many modalities in external beam radiation therapy and surgery. The Gamma Knife, manufactured by Elekta, is dedicated to intracranial radiosurgery. Although it is still a very viable technology, the advancements in linear accelerators are somewhat overshadowing that modality, says Dr. Parda.

"We have better manipulation of variables associated with dosing and radiation now and that makes linacs more precise and individualized for delivering radiation," Dr. Parda explains. "That's why most major radiation centers are moving away from Gamma Knife technology and toward the linear accelerator based technology."

Other more experimental modalities, like proton therapy systems, can cost a radiation oncology facility $100 million or more, but because the entrance and exit dose is far less, there is a great advantage for pediatric applications. Even more astounding are carbon ion systems, which are debuting at $300 million, says Dr. Parda.

For OEMs, new unit sales dip but upgrades buoy revenue

Historically, there's been a 3% annual growth in linear accelerator units sold. This year, there's been a decent downturn in new units sold - about a 15% decline, but revenue is only down 1% due to upgrading, says Evans.

"Basically, what this means to us is customers are upgrading their existing machines rather than opting to purchase new linear accelerators," he says.

As far as the most advanced systems go, Varian offers the Novalis Tx, a radiosurgery platform based on Varian's Trilogy linear accelerator and a suite of additional technologies for image guidance, motion management and treatment planning. About 18 months ago, Varian introduced Rapid-Arc radiotherapy, an IMRT technology that shapes the dose distribution as it is delivered with one or more arcs, or rotations, around the patient. The accelerator delivers up to 10 grays per minute for "very fast, high-dose treatment." Varian's MLC is a 120 tungsten-leaf collimator that can shape the beam to 2.5 mm and the Trilogy offers both 2-D and 3-D KV onboard image guidance.

"Varian accelerators-Trilogy, Novalis Tx, and Clinic iX models have everything you need for the radiotherapy market," says Zankowski.

Elekta is also a major manufacturer of linear accelerators and offers the Infinity, which provides a therapy called VMAT, or volumetric modulated arc therapy, a similar IMRT technique.

"The beam stays on and you rotate the gantry around the patient in a continuous motion," says Timothy Prosser, director of Elekta's Radiation Oncology Business. "That allows you to spread the dose out a lot more at the target. This has been a very recent innovation. It's just now starting to catch on within the last one or two years."

The Infinity features VolumeView, a 3-D cone-beam imaging system for IGRT. Elekta also offers the Axesse linear accelerator, a dedicated stereotactic system for both radiosurgery and radiation therapy.

Siemens launched the Artiste linear accelerator last year. This is the system used at Dr. Parda's practice at Allegheny General Hospital. The Artiste features the fastest MLC on the market, with 160 leaves - 80 on each side, says Evans. It delivers up to 23 MV photon therapy and onboard imaging includes 3-D cone-beam imaging.

What's new in radiation therapy simulators

Before therapy gets underway, oncologists must first conduct treatment planning with a simulator, which provides all the essential information about the tumor. Up until recently, this was done using a traditional radiographic simulator, but in recent years, most radiation oncology practices have moved into using CT simulators. Dr. Parda's practice uses a Siemens 40-slice 4-D CT simulator.

Many larger tertiary and research facilities are now using MRI and PET/CT simulators, as well. "That is the next wave - that is exactly what people are looking at. You have CT for structures, MR for soft tissues and PET for biological information," says Zankowski. Software packages can co-register or fuse those images.




Philips Healthcare does not manufacture linear accelerators, but that doesn't stop them from dominating the CT simulator market. "Philips has really maintained a good position in the oncology market," says Rene Velasquez, product manager for Philips Healthcare.

Used and refurbished market thin but holding

Economic pressures and cuts in reimbursement are not only affecting the OEMs. Fewer new-unit sales mean fewer used systems being turned out for inventory.

"In general, like most other refurbished equipment businesses and medical device businesses right now, we're experiencing some decline because of cuts in reimbursement and uncertainties in the health care market," says Greg Bare, vice president of Radiation Oncology Systems, Inc. (ROS), but the service business is up and more customers are looking for any means of cost-savings.

ROS offers used Varian, Siemens and Elekta linear accelerators. Bare estimates that independent service contracts are running about 20% to 30% less than OEM contracts and a used or refurbished linear accelerator could cost about 40% to 60% off a brand new unit. ROS also offers GE and some Siemens simulators.

Tony Richardson, director of business development for Oncology Services International (OSI), says that the company is faring well, but buyers are definitely being more conservative in their used purchases.

"In the last 12 months, our unit volumes have remained steady despite a rapid slowdown in the sales of new equipment. However, the sales of more expensive (newer high specification) equipment are definitely slower with more buyers attracted to IMRT capable units which are somewhat older and offering maximum reimbursement at a lower acquisition price point," says Richardson.

Kenneth Wolff, CEO of RS&A, a southeast regional linear accelerator parts, sales and service organization, says that he is seeing a healthy increase in revenue - about a 15% increase over prior years, but more from the service side than used equipment sales. RS&A services Varian, Elekta and Siemens linacs at the company's 10,000 square foot facility with two linacs in house for testing. RS&A also offers a range of parts, which account for about 10% of the company's business. Available parts include L3's magnetrons, thyrotrons and klystrons - all vacuum tube technologies used to power the linear accelerator beam.

"Our parts division has really just gotten off the ground," says Wolff. "We are actually the exclusive dealer for L-3 Electron Devices."

Most sought-after systems in the used market

"[The] Varian 21EX, with dynamic MLC and aS500 electronic portal imagers are the most sought after models, which reflects the market leadership for new machines," notes Richardson, who sees fewer calls for Siemens and slightly more demand for Elekta systems. "Of course, customers ask for IGRT equipped technology, but so far, onboard KV imaging equipped units are too new to justify replacement, so supply is non-existent." Richards adds that during the past five years the resale market has seen an increased demand for multi-leaf collimator equipped units. Justification for that feature can be found in the revenues made possible by IMRT procedures.

As far as simulators go, sales of used or refurbished traditional radiographic simulators are faltering. "That has been a declining market for sometime now," says Wolff.

Accelerating sales overseas

Both manufacturers and independent service organizations are enjoying strong sales in international markets.

"Overseas markets in certain countries, such as some of those in South America, are buoyant. However, many developing markets in Asia are excluding importation of pre-owned medical equipment, perhaps due to bad experiences from unscrupulous sellers of unmaintainable equipment in other modalities," remarks Richardson.

Stewart Farber, president of Farber Medical Solutions, LLC, a linear accelerator brokering company, has experienced a 50% increase in used unit sales this year, with the majority of that business involving deinstallation in the U.S. and export to various international markets.

"Elekta Precise and Elekta Synergy units have been the highest priced and the most recent models that I've been able to broker this year," says Farber. "Both of those went to centers in and around Moscow."

To get more of a look at what the future holds for linear accelerators, drop by the 51st Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), scheduled to be held in Chicago Nov. 1-5.

"There's probably going to be some interesting things going on at ASTRO - their main focus is linear accelerators," says Prosser. "All of us keep our little secrets until then."

A lot goes into deinstalling and installing a linear accelerator. To prove it, one company filmed the entire process and posted the video online (don't worry - they present it in a sped-up format). Read more and watch the video here: http://www.dotmed.com/news/story/10264