According to the National Cancer Institute, as many as 170,000 cancer patients are diagnosed with intracranial metastatic disease every year in the U.S., and up to 80 percent of them have more than one lesion (tumor). Determining the best treatment for patients is something a physician must do on a case-by-case basis, in many scenarios, however, stereotactic radiosurgery (SRS) is an excellent option.

Given the various offerings from Varian, Elekta, Accuray, and BrainLab, how does a physician decide which device will deliver the right treatment modality for their patients? And how does a facility decide which radiation device is right for their cancer center? HealthCare Business News reached out to physicians and manufacturers alike to assess the options, and, spoiler alert: there is no one-size-fits-all answer.

Recent history
Although not everyone agrees on the best solutions available for SRS, the consensus is that Elekta’s Gamma Knife has historically set the standard. It was invented and developed exclusively for brain treatment. Catherine Gilmore-Lawless, vice president of clinical intelligence at Elekta, tells us that more than 900,000 patients have received Gamma Knife treatment on one of more than 300 systems in use worldwide. She says those figures account for 75 percent of the world’s total stereotactic radiosurgery procedures.

However, there are limitations to the Gamma Knife. Most notably, it is restricted to treating brain lesions and utilizes a stereotactic head frame to achieve immobilization and accuracy of the treatment. Securing the head frame to the skull is uncomfortable and means radiosurgery must (almost always) be performed in a single fraction.

Other devices, such as Accuray’s CyberKnife and TomoTherapy, and the latest linear accelerators, including BrainLab’s Novalis, Varian’s Edge and TrueBeam, and Elekta’s Versa HD, utilize image guidance and motion sensing to stay on target while treating brain lesions as well as tumors located in other parts of the body. Eliminating the head frame also means that those platforms can treat in multiple fractions if the patient’s needs call for it.

So, one may make the assumption that the Gamma Knife set the stage for stereotactic surgery and then new equipment came and improved on every aspect of its innovations. That’s not exactly the case. Dr. Lijun Ma, a physicist from the UCSF radiation oncology department, has all of those options at his disposal, however, he and his colleagues continue to exclusively use Gamma Knife when treating the brain.


Small target precision
Ma, who has nearly 20 years of experience performing SRS, says the latest version of Gamma Knife (Perfexion) retains an advantage over other platforms with regard to dosimetry and accuracy. He also points to the vast amounts of published data on Gamma Knife SRS as an invaluable resource in utilizing the tool responsibly and to its highest potential.

Ma participated in a study published online earlier this year entitled, Variable Dose Interplay Effects Across Radiosurgical Apparatus in Treating Multiple Brain Metastases, which evaluated the use of Gamma Knife, Novalis, TrueBeam, and CyberKnife at six different clinics to better understand how well each modality spares healthy tissue from radiation. Their findings indicate that treatment by the Gamma Knife did the best job at sparing normal tissue, however, it requires the longest beam-on time (the amount of time that the radiation beam is transmitting radiation to the patient).

“From a physics point of view, the head frame does several important things that people need to know,” says Ma, “Once you target the lesion, it’s easy to be very precise.” He says that the body movements that an image guided platform has to account for—rotational shifts, breathing, sweating, even gravity itself—are infinitely complex and can result in reduced accuracy of the treatment.

When radiation is off-target, it subjects normal tissue to radiation, which can lead to various side effects of varying complexity. For example, when treating trigeminal neuralgia, which affects the fifth cranial nerve, there is precious little room for missing the target.

“You want to zap a little nerve, (1mm by 7mm), with a high dose such as 80 gray,” says Ma, “You better do that with something that can deliver the dose precisely.” Ma says that Gamma Knife is more focused than other platforms and has sharper dose falloff. “The dosimetry using X-ray comes from electrons hitting the target,” says Ma, “Those modalities tend to deliver a factor 2 to 3 times higher in the normal tissue dose, or the skirting dose, than does the Gamma Knife.”

“For other tumors you can make the argument saying those things are tolerable, however, the entire backbone of doing radiosurgery is to be precise,” says Ma. So, for whatever temporary discomfort it implies, he believes the Gamma Knife and its head frame yield better outcomes, especially for the most complex brain cancer cases.

Considerations for throughput and versatility
Alliance Oncology, a technology agnostic and comprehensive network of radiosurgical programs, has Gamma Knifes installed in two of their 29 partnering radiation therapy centers. They also partner with hospitals using modalities from the other major stereotactic manufacturers.

Cindy Winker, senior vice-president of operations at Alliance Oncology, says that a patient’s individual needs dictate the choice in both the technology and method of radiation. “As more long-term data accrues for SRS treatment delivered with different devices, physicians are able to select the platform and proper type of radiation based on factors such as type of lesion, size and proximity to critical anatomy,” she says.

Dr. Salim Siddiqui, a radiation oncologist at Henry Ford Hospital, uses Varian linear accelerators for intracranial treatments. His hospital has performed more than 4,000 stereotactic procedures throughout the body, and their brain treatments are typically performed in a single fraction, despite the option of multi-fraction.

In March of this year, Henry Ford Hospital installed a Varian Edge linear accelerator. Siddiqui says they chose the Edge because it is more efficient and offers the same accuracy as other platforms while having the versatility to treat the entire body. Other key benefits include the 2.5mm multi-leaf collimator and a robotic couch that assists in properly positioning the patient. Those features allow for better dosimetry (dose accuracy to the tumor) and faster delivery.

With the Edge, there is also the option to extend into additional fractions when necessary. “You balance treating the target against the organ at risk,” says Siddiqui, “If you’re going to or above the tolerance of that organ then you move to three fractions. If you still can’t do it then you move to five.” With the Edge, he says they only reach three fractions in less than 10 percent of their treatments.

“When you compare Gamma Knife to linac, it was not robust enough for our stereotactic needs,” says Siddiqui, whose hospital has treated over 1,000 spine cases radiosurgically. Varian’s RapidArc (volumetric modulated arc therapy), and cone beam CT imaging capabilities make it a state of the art option for treating extracranial lesions as well as those in the brain.

“With the Edge, some spine treatments using Varian’s RapidArc planning and the higher dose rates have beam-on times of approximately 3 minutes — that makes a big difference for the spine patients suffering a great deal of pain,” says Siddiqui.

Raymond Schulz, radiosurgery manager at Varian Medical Systems, points to the efficiency of Varian’s latest linacs, (Edge and TrueBeam) as the primary feature that distinguishes them from comparable platforms. “Recent studies have shown that we are as precise, or more precise, and dosimetrically equivalent to other platforms,” says Schulz, “But we have substantial efficiency benefits.”

One such study is entitled, Comparison of Plan Quality and Delivery Time between Volumetric Arc Therapy (RapidArc) and Gamma Knife Radiosurgery for Multiple Cranial Metastases, and was published online and in the October 2014 issue of the journal, Neurosurgery. That study, conducted at the University of Alabama, illustrates drastically reduced treatment times for the latest VMAT-capable linear accelerators.

The study also indicates equivalent conformity and moderate iso-dose spill between Gamma Knife, Novalis, and TrueBeam. However, it is noteworthy that the Gamma Knife in the study is a Leksell Model C, which is an older model than the current Perfexion.

The capability to deliver 2400 monitor units per minute means giving a dose 3 to 6 times higher than competing technologies, says Schulz. In the case of Henry Ford Hospital, the combination of throughput, accuracy, whole-body versatility, and positive clinical outcomes with Varian’s Edge has been invaluable to their practice.

With the brain in mind
Like Gamma Knife, the CyberKnife was designed for treating intracranial lesions. David Schaal, senior director of clinical publications at Accuray says, “From the start, John Adler, the inventor of CyberKnife, wanted to design a device that would be able to deliver many beams of radiation from multiple non-coplanar angles around the patient, but without a head frame.”

He says the company achieved that goal with the implementation of their robotic, motion-sensing system. To get a better understanding of the CyberKnife’s capabilities we spoke to a physician from Stanford Health Care, where they have a Varian TrueBeam linac as well as two CyberKnifes, and perform stereotactic radiosurgery in an average of 2.5 fractions.

In favoring X-rays over gamma rays, Dr. Steven Chang, a neurosurgeon at Stanford Health Care, points to the evolution of the machinery. “A lot of radiation oncology machines now use image guided tracking,” says
Chang, “It has sort of become a de facto standard for radiation delivery compared to older methods using rigid immobilization.”

Chang believes that for treating certain indications, some radiation delivery devices do not have sufficient accuracy. “The primary two machines that have an established long term track record regarding sub-millimeter accuracy are Gamma Knife and CyberKnife,” says Chang, who also points to trigeminal neuralgia as a disease that should specifically be treated with those platforms.

Chang says that with CyberKnife you have many of the benefits that are associated with linacs: you can treat the entire body, you can break up treatment into multiple fractions, and you can treat infants who have soft skulls. In weighing the benefits of CyberKnife over Gamma Knife, Chang says it’s in the lack of head frame and the option to treat the entire body.

It’s not the car, it’s the driver
When analyzing the differences between these modalities it’s easy to lose sight of the big picture. “In terms of outcomes, if you used the same doses and had the same target, whether you treat on the Edge, Novalis, CyberKnife, or Gamma Knife, your outcomes should basically be the same,” says Siddiqui, who emphasizes that all these cutting edge modalities can universally outperform anything from just a few years ago.

What matters most of all is the experience of the team performing the procedures, and their level of knowledge and expertise with the system they use. “If you imagine a racecar, you can have the best car but you need the best driver and the best pit crew to make it work,” says Siddiqui, “Good technology has to be in great hands.”

Chang takes the car analogy a step further saying, “If you give a NASCAR driver a Honda and give you or me a Ferrari, the NASCAR driver would still beat us.” Meaning the experience of the team goes a long way, and for patients, it’s important to choose facilities that practice a high volume of the treatment technique that they are seeking.

Ma, from UCSF, warns that patients looking at treatment options should be mindful of the studies they are presented with and make sure the information is not being provided with a particular manufacturer’s interests in mind. “You have to look at academic and multi-institutional studies,” says Ma. “Were the physicians involved experienced and were the modalities equivalent and state-of-the-art?”

Economic factors will also inform a hospital’s choice of modality. Each machine has something special that sets it apart from the others and, if they had the space and the budget, there is no reason a hospital would not elect to have all of them at their disposal. Winker, with Alliance Oncology, emphasizes the role of the physician in selecting the best course of treatment for each individual patient. “Our hospital and physician partners are integral in the choice of equipment,” she says, however, the palliative and curative needs of the center’s patients are the ultimate deciding factors.

A recent partnership between the American Association of Neurological Surgeons (AANS) and the American Society for Radiation Oncology (ASTRO) should yield even more insight into maximizing positive outcomes in SRS. The two groups are building a national registry that will log data from 30 diverse, high-volume, stereotactic radiosurgery centers for a three-year time period. The data from this registry will be aggregated and analyzed in order to ensure safe, high-quality care and to help define treatment guidelines.