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SRI Magazine 2016

SRI Magazine 2016

A new kind of radiotherapy kills brain tumours with pinpoint precision

Researchers say it will only get better once they add MRI to the mix

In 2010, just before her daughter’s fifth birthday, Annie Parker was diagnosed with breast cancer. The battery of treatments she received—chemotherapy, radiation and mastectomy—seemed to be working. Early in 2014, however, she was beset with excruciating back pain.

Parker had spinal metastasis—the disease had spread to her vertebrae. (Bone is the most common site of secondary breast cancer; malignant cells stray to areas such as the spine, ribs, skull and pelvis via the blood and lymphatic system.) The tumour had put such pressure on her spinal cord that she had emergency surgery to remove it. Her husband feared she’d never walk again, but there was a silver lining.

“She came in with very limited disease,” says Dr. Arjun Sahgal, a clinician-scientist at Sunnybrook Research Institute (SRI) and deputy chief of radiation oncology at Sunnybrook’s Odette Cancer Centre. “I treated her with postoperative stereotactic ablative radiation, and she’s been perfectly controlled for years. She’s an example of somebody who would otherwise have been told, ‘You’re going to die. Let’s use palliative radiotherapy.’ But we took an aggressive approach, and we treated her for cure. As time goes on, we’ll know whether she’s truly cured, but for now nothing else has come up,” he says, smiling.

Fortunately, Parker was a good candidate for this fairly new therapy, which uses advanced 3-D imaging to deliver higher-than-normal doses of radiation to the target. Conventional radiotherapy is given in small doses over many weeks. In contrast, the high-dose, focally delivered ablative radiation used in stereotactic radiotherapy allows for fewer treatment sessions. It’s usually limited to patients with small, well-defined cancers, including those of the lung, liver, spine, abdomen and prostate. Sunnybrook is an academic leader in spine stereotactic body radiotherapy and one of the few institutions developing the postoperative indication used to treat Parker. Saghal notes doctors perform the procedure on about 200 patients annually, making the hospital one of the largest single-site practices in the world.

When performed on the brain, it’s called stereotactic radiosurgery. At Sunnybrook, stereotactic radiosurgery is performed on as many suitable patients as possible—about 500 yearly—to spare them the negative effects of whole-brain radiation. These include seizures, memory loss and extreme fatigue. As evidence in support of focal radiation in the brain mounts, Sahgal is training clinicians from other Canadian centres in how to use it.

His passion (obsession, one could argue) is to understand fully when it is best to treat with stereotactic radiation and how to deliver it more effectively.

“[For] the last seven years, all our research has been on safety and developing the technique, learning what our outcomes are, the adverse effects [and] how to manage those effects. We’ve advanced the field to where we have good patient selection,” says Sahgal.

His research shows cause for optimism. In 2015, he published a review of Phase 3 trials involving patients with fewer than five metastatic brain tumours. He found that patients aged 50 years and younger treated with only stereotactic radiosurgery had better survival rates than those treated with radiosurgery and whole-brain radiation. The results provide strong evidence of the benefit of stereotactic radiosurgery for younger patients with limited disease.

The cancer ablation therapy program at Sunnybrook, of which Sahgal is director, is conducting practice-changing research into treatment of central nervous system (CNS) cancers. At its core is a partnership with Elekta, a company that is investing in its brain radiosurgery device, known as a gamma knife, and magnetic resonance (MR) linear accelerator technologies. In all, three systems, including Elekta’s, will be installed by autumn 2016. [See sidebar.]

The technologies integrate MR imaging into the therapy systems. “It’s not only going to improve our ability to be accurate in terms of how to target the tumour, but it also allows real-time [tumour response] assessment using high-field-strength MRI for the first time,” says Sahgal.

Hunks of Steel

By 2016’s end, the Odette Cancer Centre (OCC) will be the first in Canada to offer radiation therapy guided by real-time imaging. Here’s how.

Gamma Knife Icon
The Icon uses real-time computed tomography to home in on brain lesions. The system, which weighs about 20 tonnes, will enable treatment of more patients, including those with up to 30 brain tumours. Bonus: instead of screwing a metal frame into patients’ heads to keep them still during treatment, patients will don a custom-fitted mask.

Magnetic Resonance Linear Accelerator (MR-linac)
Currently, doctors use pretreatment scans to estimate a tumour’s location during therapy. The MR-linac will enable doctors to see the tumour during treatment for precise delivery. Applying the dose more accurately reduces the size of the safety margins around the tumour, thereby minimizing exposure of healthy tissue. They will even be able to zero in on moving targets, such as pancreatic tumours. Installation won’t be easy; the massive system will be delivered via a hole in the ceiling with a diagonal nearly four metres long.

Magnetic Resonance-Guided Brachytherapy
Brachytherapy is the placement of radioactive substances in or near tumours. The OCC treats about 300 patients with brachytherapy annually. It is the largest single-institution program of its kind in North America. In the summer of 2016, the centre will install an MR imaging machine in its brachytherapy suite. For the first time, doctors will be able to monitor the effects of radiation on the tumour—at a cellular level—at the moment it is delivered.

Sunnybrook is the only Canadian centre within a seven-member global consortium that has partnered with Elekta to optimize use of the MR linear accelerator technology.
As the lead centre for CNS trials, one order of business will be a randomized study comparing radiosurgery with whole-brain radiation plus radiosurgery in patients who have between 10 and 20 metastatic brain tumours.

“This is at the real forefront because you need the technology to deliver the radiosurgery, and there is a question as to whether more therapy in this indication is better,” says Sahgal, who adds the study is about two years away.

Before it can begin, researchers must develop more efficient therapy planning strategies. Sahgal notes treating patients with more than 10 brain tumours is extremely complex; the sheer number of lesions makes it difficult for doctors to distinguish between tumours that have already been treated and those that are new. He is working with Dr. Anne Martel, a senior scientist at SRI, to develop software that uses image segmentation to identify new lesions automatically.

Sahgal points out such advances are a team effort. The program fosters collaboration among oncologists, medical physicists, radiologists and imaging scientists at SRI to validate the advantages of MR-guided radiotherapy. He notes another example: a project with Dr. Greg Stanisz, a physicist at SRI, on functional imaging to measure therapy response. “At any time, about one-third of our department is working on the MR [linear accelerator] and gamma knife in some way or another,” he says.

His next focus will be to develop the first-in-human trial using the MR linear accelerator to treat glioblastoma, the most common and aggressive primary brain cancer. This is a major challenge, as the technology has not been used on patients.

His ultimate goal is to be able to roll out new radiation applications to more patients so that they, like Parker, can have options. Parker’s journey highlights the promise of stereotactic spine radiotherapy; even so, Sahgal says further proof is needed before it can be made widely available. In addition to his research on the brain, he is the lead investigator of a national trial comparing stereotactic body radiotherapy with conventional radiation in patients with painful spine tumours. “It’s an important study to ensure that we’re not just using new technology indiscriminately and believing in it without evidence.”

Parker describes her health as “excellent.” On the snowy February morning on which we chat, she has shoveled the driveway of her home in Ajax. The road to recovery has been gradual, but not painful, she says. She is grateful for the care she received at Sunnybrook, the effects of which differed markedly from the conventional radiation she had the first time around. “I had five weeks of radiation for breast cancer. I was tired. I could fall asleep anywhere. I had four [sessions] with [Dr. Sahgal], and it’s like I went for coffee.”

Her lifestyle is that of a busy stay-at-home parent. She also goes to the gym three times a week. “If you saw me, you’d never think I was ever sick.”

Sahgal’s research is funded by Elekta, the Federal Agency for Economic Development for Southern Ontario, and Ontario Ministry of Research and Innovation.