Dr. William Chu (photograph by Doug Nicholson)
Warming a tumour makes it more receptive to radiation or chemo treatment, and a Sunnybrook team is perfecting the technique with real-time monitoring
After five years of treatment for colorectal cancer – a regimen that included chemotherapy, radiation and surgery to remove the cancerous tumour and numerous lymph nodes – Keith Binette seemed to be on the road to recovery.
But last year he received bad news from his doctor: His levels of carcinoembryonic antigen (a protein in the blood that indicates the presence of certain cancers) had shot up again.
“It was considered too high risk to do a proper biopsy, but they were 99 per cent sure that it was lymph node cancer recurrence,” recalls Keith, a 55-year-old Toronto entrepreneur who runs a security services firm. “Because of the location of the tumour in my pelvis – it’s too close to the nerves – it was also too high risk to do surgery.”
Keith’s doctors at Sunnybrook suggested attacking the new growth with a combination of chemotherapy and radiotherapy. They also proposed something else: a new approach currently being studied at Sunnybrook that would bolster this treatment by heating the tumour with ultrasound, delivered with the guidance of real-time magnetic resonance (MR) mapping.
“Heating makes cells more sensitive – and receptive – to radiotherapy and chemotherapy,” says Kullervo Hynynen, a senior scientist at Sunnybrook Research Institute. “With radiotherapy, studies have shown that you can have roughly twice as many patients having complete response to treatment than they would have without heating.”
Also known as hyperthermia, this practice of heating tumours to increase their responsiveness to treatment isn’t new. Since at least the 1990s, heat from sources such as ultrasound, radiofrequency and microwave has been applied to many types of cancers, says Hynynen.
What is novel with Sunnybrook’s approach is the marriage of heat and real-time MR guidance. Using a specially designed magnetic resonance imaging (MRI) table with a built-in ultrasound machine – developed and built by the Dutch technology company Philips, with added expertise from Sunnybrook – heat is delivered while a high-definition MR image of the tumour site is being captured. By comparison, traditional hyperthermial applications typically use MR imaging before and after heat is delivered.
“MRI has been used for some time to guide therapies, but it has not been used to date with focused ultrasound to treat through prolonged heating at lower temperatures,” says Hynynen.
Real-time MR imaging during hyperthermia allows for a more precise and longer delivery of heat to the tumour. Instead of blasting the tumour with high-intensity heat at levels of up to 60 C for just a few minutes at a time, Sunnybrook’s approach is to warm the tumour continuously from 10 minutes to up to 30, at a temperature between 40 C and 43 C.
Another advantage to the use of MR-guided ultrasound? Dr. Chu says the technology gives doctors the ability to deposit heat more deeply into the body, instead of being restricted to the superficial tissue level. “With other studies to date, you did not have the technology to actually see where the tumour was,” says Dr. Chu. “With our high-definition MR partnered on the same platform as the ultrasound delivery system, we can monitor and deliver heat to targets at specific depths.”
The MR images also give a visual reading of the temperature at the target site. Without this MR guidance, doctors would have to use temperature probes – essentially needles that are inserted repeatedly into the skin during hyperthermia – to ensure the target area isn’t overheated.
“MR-guided delivery of focused ultrasound is a non-invasive procedure – everything goes through the skin, nothing goes through the body,” says Hynynen. Dr Chu adds: “For patients, a non-invasive procedure is best, minimizing any risk.”
Sunnybrook recently launched the first phase of a feasibility study of its MR-guided ultrasound technology. Dr. Chu says the hospital has chosen to focus the study on patients with recurrent rectal cancers that cannot be treated surgically because the tumours are located deep in the pelvis, close to delicate structures such as nerves, blood vessels and muscles.
For these patients, the only option left is usually radiation with chemotherapy to reduce the tumour or at least prevent it from growing and spreading. But only about one in five patients sees successful outcomes from this approach, says Dr. Chu. By the time most patients get to the recurrent stage of rectal cancer, they can only receive lower doses of radiation.
Adding MR-guided heat could boost their chances of success, he adds. “We know that heat enhances tumour responses to chemo and radiation. We hope to move this technology soon to clinical settings – it really makes sense for those patients who have no other option but chemotherapy and radiation.”
The MR-guided hyperthermia study, which will initially involve 10 rectal cancer patients with recurring tumours, is expected to last about two years. If the trial yields good patient responses, then the next step will be to use the technology on patients with newly diagnosed rectal cancer, says Dr. Chu. Sunnybrook is also exploring other applications of the technology, for head, neck and bone tumours, he adds.
Keith is grateful to have been given the opportunity last November to try the MR-guided ultrasound to enhance treatment of his rectal cancer. Last December, he came in for an MRI and a CT scan. The images showed that his cancer had shrunk since his last treatment. “The tumour is slowly but surely shrinking, which is kind of exactly what the doctors expected,” says Keith. “It’s a slow-growing cancer, so it will be a slow-reducing cancer.”
While it’s too early to make definitive conclusions about the treatment, Keith says that it’s “so far, so good.” Today, he’s back to work at his company, just north of Toronto. He and his girlfriend got engaged just recently, and they’re both looking forward to his recovery.
“I feel as normal as I can be,” says Keith. “I’m really satisfied, and very grateful, for the work they’ve done on me at Sunnybrook.”
Hyperthermia in action
Sunnybrook’s latest device against cancer is a magnetic resonance imaging (MRI) table with an integrated ultrasound source. This equipment − developed and built by Philips in the Netherlands − is a powerful machine that captures and renders images in high resolution.
During a hyperthermia procedure for recurrent rectal cancer, patients lie down on the MRI table with their buttocks supported by a donut-shaped cushion. This cushion is positioned over a glass surface. Underneath this glass is a transducer that concentrates sound waves and sends them into the patient’s body, right through the skin.
These ultrasound waves, which can pass deep into the body, heat the rectal tumour. Patients remain alert during this procedure and are asked to let the medical team know if the heat starts to cause discomfort.
What makes this technology unique is its ability to let doctors see what’s happening inside the body as the tumour is heated. The MRI images, which appear in real-time, are temperature-sensitive, with variations in temperatures depicted by different colours: red areas are hottest, yellow means warm and blue areas are cool.
“That’s the biggest advance from old hyperthermia treatments,” says Dr. William Chu, a radiation oncologist and clinician investigator at Sunnybrook. “This machine allows us to do true deep-tissue tumour heating, not just to a surface but to a three-dimensional mass in the body, with the ability to precisely monitor temperature and to regulate changes as we need to.”
The MRI table was designed originally to treat uterine fibroids. In 2014, Health Canada approved the use of the table for clinical trials focused on rectal cancers. Sunnybrook treated its first patient in the study last November and plans to sign up a total of 10 patients over two years.
“We worked closely together with Philips on pre-clinical development and testing to get the equipment up to a level suitable for testing on rectal cancer patients,” says Dr. Chu. “It’s definitely unique, this combination of MRI and ultrasound.”