Radiosurgery: becoming the treatment of choice for spinal metastases
"T4 popped up, came out of nowhere, in August 2016," explained Theresa Barrett, 45, T4's former owner. She's been dealing with breast cancer since 2009. She knows the lingo.
"We found it on a PET scan, and confirmed it with an MRI," she said. "It was big and painful, more painful than big." It wasn't as big as T7, but the pain was much worse. "It's fair to say: excruciating." Within three months, it had doubled in size.
The T in T4, as well as T7, is short for thoracic. T4 is the fourth thoracic vertebra – part of the middle spine, counting down from the base of the neck – and T7 is the seventh.
There was no T4 issue when Barrett was first diagnosed with breast cancer, almost eight years ago. Her disease at that time was stage-one. She and her doctors, at another hospital, were aggressive. They chose to remove both breasts, followed by chemotherapy and five years of estrogen-blocking treatment.
In 2010, she transferred her care to the University of Chicago Medicine. In 2013, her doctors found a new lump, under her right arm. They removed the lump as well as all the nearby lymph nodes, and followed up with six weeks of radiation therapy to the area.
Two weeks later, she felt a new pain, this time in her back. That was the onset of T7. Her cancer had metastasized, moved from her breast to one of the bones of her spine. Shortly thereafter, T8 appeared. Surgery wasn't an option. Instead, she went through more radiation, plus additional chemo, followed by more hormone therapy.
"Some things work; some don't," Barrett said." The tumor kept growing, slow but persistent. Then, three years later, without warning, T4, the one that really hurt, emerged. "That's when my doctors introduced me to Dr. Pitroda."
Sean P. Pitroda, MD, an assistant professor of radiation and cellular oncology and a researcher in the University of Chicago's Ludwig Center for Metastasis Research, is the new guy. He joined the faculty last July, but he already knew the institution. He trained at Pritzker, the University of Chicago's medical school, and did his residency at UChicago Medicine. Then the department sent him to Memorial Sloan-Kettering Cancer Center in New York, for seasoning.
At Sloan-Kettering, he worked with Dr. Yoshiya Yamada, a pioneer of spinal radiosurgery, an emerging technique that is becoming a standard of care for tumors that invade the spine. This approach is currently available at only a limited number of U.S. medical centers.
More than 90 percent of spine tumors are metastatic. They begin somewhere else. Then a small number of cells break loose from the original tumor, enter the blood stream and travel to the spine. Once they establish a beachhead, "they can cause severe, debilitating pain and paralysis," Pitroda said. "Spine mets require aggressive management."
In Barrett's case that meant radiosurgery, an effort to apply high doses of radiation with the precision of microsurgery – but no incision. The process begins with a myelogram, an injection of dye into the thecal sac, a tube that encases the spinal cord. This enables the team to map out the precise location of the spinal cord as it passes through the affected vertebra, and thus avoid exposing the sensitive, easily damaged cord to radiation. It can be difficult to avoid; sometimes the tumor is bumping up against or wrapped around the spinal cord. They share a small, inflexible space.
"Radiosurgery is currently the best way to treat this, to deliver a very high dose to a really small area," Pitroda explained. "Our first patient received one of the highest single doses ever used in our clinic."
A typical radiation therapy dose is about two gray (the absorption of one joule of radiation energy per kilogram of matter). This is given five days a week for five weeks, for a total of 50 gray. The first spinal radiosurgery patient cared for at the University of Chicago received 24 gray in one dose.
"Fewer treatments with a much higher dose can trigger a different mechanism," Pitroda explained. Smaller doses target tumor cells, primarily damaging their DNA. The bigger doses can have the same effect, but they are also thought to damage the blood vessels that feed the tumor. They may also activate an immune response to fight off tumor cells.
Although the high-dose approach is more difficult for the treatment team, it is more convenient for patients. High-dose patients have fewer sessions, one to three, doses, occasionally as many as five, compared to five standard therapy treatments a week, for four to five weeks.
These high intensity treatments, however, take longer, from 60 to 90 minutes, compared to the customary 10 to 15 minute visit for standard therapy. The physician team – which includes neurosurgeon Edwin Ramos and interventional radiologist Seon-Kyu Lee has to devote much more time to planning each case.
"With high doses, we have to be ultra careful," Pitroda said. Just planning a case takes about a week. One treatment session involves multiple measurements and beam adjustments, fine tuning the entire process, plus support from additional technologies to make sure the beams are following the plan, hitting only tumor tissue. The margin of error is less than one millimeter.
During therapy, the radiation beam is modulated by 120 tiny collimators, thin metal leaves that are programmed to guide the radiation beams, each a few millimeters wide. They move "like little fingers, in and out to shape the beam in a complex way that leads to maximum tumor-cell kill," Pitroda said. "That, and lots of planning, is how we administer high doses to the tumor while preventing the beams from hitting healthy structures, such as the spinal cord."
"With such high doses," he added, "there's so much that could go wrong. So we have to design a near-perfect plan. That's all worked out, tested and retested before we bring in the patient and turn the machines on."
Patient preparation was also "a little intense," Barrett recalled. The team took out some spinal fluid and replaced it with a dye that shows up on a CT scan. "To my surprise," she said, "that was the worst part."
"Dr Pitroda told me all about the procedure, that I was perfect, a text-book candidate, that I would respond well and that we should give it a go, just to get rid of the pain."
By then, however, she had been dealing with cancer for years. "I knew too much," Barrett said. "I was thinking this is just another thing that sounds good but won't work."
At least the process was smooth. "I couldn't have been in better hands," Barrett said. "These guys knew their stuff. They explained every step. Patients never get tired of explanations."
She completed all three treatments in December, 2016. Then she had to wait three months for the swelling to go away. "I chose not to get excited," she recalled. "It's just another procedure."
Her wait ended March 11. "The images of T4 from the previous August showed this horrible thing," she said. By November, it had doubled in size. By early December it was "starting to wrap around my spinal cord. I thought, there's no way they could have gotten all of this." But a PET scan, and then an MRI, showed no evidence of metastatic disease at T4.
This was "a turning point," Barrett said, "the first time that I've had such great news. With this disease, it's rare to smile when you get results."
Barrett still has metastatic disease. The T7 and T8 tumors continue to grow and new ones could emerge at any time. "Although T7/T8 doesn't hurt in the same way, it's much bigger than T4," she said. The T7 tumor was previously treated with standard radiation therapy, with limited benefit, but she and Pitroda are reconsidering it. Maybe the tightly focused higher dose could bring the desired effect.
Meanwhile, with the worst of her pain gone, Barrett has been spending time with her family and can once again take Jack, her neglected Labrador retriever, out for short walks.
"He's not well trained on a leash," she said, and she tires easily, so she takes him for multiple short outings. Sometimes she feels bad for him, an energetic young dog who needs to romp. But she hasn't run, with or without a dog, since her diagnosis in 2009. "I can't do that," she said, but in early May they were strolling through the neighborhood and Jack started to pick up the pace.
"I don't know what came over me," Barrett said, "but I started running with him, so he went faster and faster. We only ran maybe a city block, past six or seven houses. Finally, I was laughing so hard I had to stop. I could not believe I was running, painlessly. I could not imagine trying that in December. I could barely walk."
Such victories are never fully detected by CT or PET or MRI scans, or even witnessed. "They are measured in these little moments that mostly nobody sees," Barrett said. "But there I am, on a Wednesday afternoon, running down the street with my dog."