Alan Sag, MD, performs an imaging-guided cryoablation procedure to conduct a biopsy and to relieve pain.
Alan Sag, MD, performs an imaging-guided cryoablation procedure to conduct a biopsy and to relieve pain. (photo by Shawn Rocco)

When Confronting Bone Metastasis, It Takes a Team

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Alan Sag, MD, reassures Pam Kohl ahead of her cryoablation procedure
DEEP FREEZE: Duke interventional radiologist Alan Sag, MD, reassures Pam Kohl ahead of her cryoablation procedure on January 27, 2020. “I have my ice skates ready,” Kohl joked.

Pam Kohl, 68, has been living with metastatic breast cancer for more than three years.

Kohl, who’s well-known locally for her longtime leadership of the N.C. Triangle to the Coast Affiliate of the Susan G. Komen Foundation, was first diagnosed with stage 1 breast cancer in 2009.

After a lumpectomy, radiation, and five years of endocrine therapy, she was declared cancer-free.

But two years on, in Oct. 2016, a new tumor in the same breast was discovered. Following a mastectomy, PET scan and biopsy, she learned, on January 31, 2017, that the new cancer had already metastasized to two lymph nodes near her lungs.

Already taking endocrine therapy for the recurrence, she was then prescribed a relatively new oral targeted chemo therapy (Ibrance).

Kohl’s DCI oncologist and Komen Scholar Kimberly Blackwell, MD, explained that the Ibrance could potentially slow the progression of her cancer for the next 18 to 26 months. Essentially, she was given about two years to live — a day she'll never forget.

Provided the two tumors remained stable and no new tumors appeared in a year’s time, the plan was, Blackwell said, “to radiate the hell out of them.” When that year was up, in early 2018, Blackwell had left Duke, and Kohl was now under the care of breast oncologist Jeremy Force, DO, and radiation oncologist Rachel Blitzblau, MD, PhD.

“It was a slow, not-real-smart cancer, so we decided “Let’s go get ‘em,”” shared Kohl, confident in her treatment team.

The radiation worked. For about another year, with her cancer stable, she went about her business — educating the community about breast cancer prevention and treatment and raising funds for research. She was living well. Then, a setback. Over the 2018 holidays, a tumor emerged in her left hip.

Blog_BrianBrigman 2.jpeg
ALL FOR ONE: “The goal of our multidisciplinary team is to find the right treatment at the right time, for patients with metastatic disease to bone,” said Duke Cancer Institute orthopedic oncologist Brian Brigman, MD.

Matrix Model

More than half of those people living with metastatic cancer — often referred to as metavivors or forever fighters — have cancer that’s spread to their bone; most typically having originated in the breast, prostate, lung, kidney or thyroid. Myeloma, a cancer of bone marrow cells, typically presents with destructive tumors in bone as well.

In 2012 it was estimated that there were about 330,000 people living with metastatic disease to the bone. (Clin Epidem 2015 (7): 335-345.)

Bone metastasis is painful and notoriously difficult to treat.

Bones are made of a network of fibrous tissue called matrix. Calcium and other minerals attach to this matrix; giving the bone its strength and hardness. Osteoblasts form new bone, while osteoclasts, dissolve old bone. That is when these two kinds of cells are working correctly.

When cancer cells infiltrate the bone, they interfere with this process; causing damage. Bone may be broken down without new bone being made — weakening the bone, causing lytic lesions. Or new bone might be made without the old bone breaking down first — causing blastic lesions.

As a result, bones may break or fracture with a fall or during everyday activities. At the same time, cancer cells cause calcium to be released from the bones into the bloodstream causing dangerously high blood calcium levels.

“Not everybody who has bone metastasis needs treatment, but many of them do,” explained orthopedic surgical oncologist Brian Brigman, MD, PhD. “We’re thoughtful about which treatment we choose when a patient presents with a metastatic lesion in their bone. Do they need a minimally invasive procedure or a big operation? And will that procedure prevent that issue from being a problem for the rest of that patient’s life. As patients grow older, as patients live longer, that’s becoming more challenging to predict.”

Last month, Brigman joined fellow orthopedic surgical oncologists William Eward, MD, DVM, Julia Visgauss, MD, interventional radiologist Alan Sag, MD radiation oncologist Nicole Larrier, MD, MS, and orthopedic oncology nurse practitioner Pam Pennigar, MSN, FNP, in launching a Bone Metastasis Clinic to meet these treatment challenges.

The clinic (on floor 00 of Duke Cancer Center Durham) focuses exclusively on caring for patients whose primary cancer has spread to their arms, legs or pelvis. (Those with metastasis to the spine are seen by DCI's brain and spine metastasis team, of which Sag is also a member.)

Brigman said he and colleagues were already consulting on about 30 to 50 bone metastasis patient cases a month, but they were often “curbside consults” by email or phone.

“An important part of evaluating these patients is meeting them, examining them, and seeing how much pain they’re having,” said Brigman. “With the new clinic, we can more easily triage the patient to the right specialist, depending on the kind of treatment that would be in the patient’s best interest.”

Alan Sag, MD / interventional radiologist
CT and imaging technologist Caitlin Rutledge, RT (R) (CT)
CT and imaging technologist Caitlin Rutledge, RT (R) (CT), monitors, in real-time, the targeting of a pelvic tumor for biopsy and cryoablation.

Damage Control

The prescribed systemic therapies (targeted therapy, chemotherapy, immunotherapy, and/or hormone therapy) that bone metastasis patients are already taking to treat their primary cancer may or may not stall growth in the bone.

Most patients with bone metastasis, Brigman said, are treated intravenously with drugs, such as denosumab, zoledronic acid, or pamidronate to reduce pain and damage to bone, lower the risk of breaks, and reduce high blood calcium levels.

Bone metastasis patients may also benefit from radiation therapy (high-energy x-rays) and or radiopharmaceuticals (drugs with radioactive elements) — both of which kill or slow the growth of cancer cells and relieve pain.

A complimentary option, explained Sag, is image-guided bone tumor ablation, whereby cold (cryoablation) or heat (energy) is deposited into the tumor using special probes through 3 mm incisions. If desired, a biopsy of the bone tumor can be obtained through the same access incision at the same session. These are typically outpatient procedures.

Also, at the same session, the bone can be strengthened or stabilized by injecting bone cement or glue (also called cement augmentation, cementoplasty, or in the spine, kyphoplasty), if needed. If cryoablation is performed, it can also freeze the painful nerves in the vicinity of tumors, allowing extended durations of pain relief up to six months, at which point the cryoablation can be repeated. These modalities are safe in areas that have been previously treated with surgery and radiation.

Interventional radiology, said Sag, can also help enable some surgical options. A procedure called embolization, when performed the day before surgery, can reduce tumor bleeding during surgery and speed the intra-operative course. (This is a process through which the blood vessels to the bone tumor are accessed using a microcatheter — approximately 1 mm in diameter — and particles are delivered to block the blood supply to the bone tumor.)

Kidney cancer and lung cancer that’s metastasized to the bone — typically more aggressive tumors — are more likely than breast or prostate cancer patients to need and benefit from surgery.

“We do operate on people with breast cancer or prostate cancer, but the percentage of those patients that need surgery is much lower,” said Brigman.

A common way for an orthopedic surgeon to treat patients (not cure the cancer) has been to use a metal rod (intermedullary nailing) to strengthen the bone, prevent fracture, and reduce pain, he said, but there’s an increasing number of these patients “outliving their reconstruction.”

“As these patients live longer, the disease will continue to grow and destroy much larger parts of the bone and make it such that the reconstruction fails and they need another surgery,” explained Brigman, who published on this, with Eward, about a year ago. “This problem is only going to get worse.”

There’s a higher likelihood now, he said — in cases of kidney cancer that’s spread to the bone, for example — that Duke surgeons will resect the tumor and reconstruct the bone with a prosthesis rather than stabilize it with a rod.

“Resection, of course, is a much bigger operation,” said Brigman. “If the patient were to die of that disease within a few years, we wouldn’t put them through such a big operation. But now, if the patient is expected to live a lot longer, it’s worth considering these interventions even if the recovery path is more difficult than with less invasive procedures.”

Interventional radiologist Alan Sag, MD
PERSONALIZED: Interventional radiologist Alan Sag, MD, demonstrates what the frozen probe (above) would look like once inside the tumor in the bone: “The probe is inserted into the tumor and, at the push of a button, creates an ice ball around itself, destroying the tumor cells in the freeze zone. We can adjust the size of the ice ball to each patient’s particular tumor size and location, so it is a tailored, personalized treatment.”

Frozen in Time

Pam Kohl, for one, has already benefited from the collaborative efforts of an array of specialists in the bone metastasis space.

In late 2018, after the tumor in her left hip was diagnosed, her care team decided the best course was SBRT (stereotactic ablative radiotherapy), which trains several precisely focused radiation beams on the tumor. Her cancer was stable for another year.

When, this past December 2019, a tumor in her lower mammary lymph node appeared, SBRT was called for again.

A new strategy was considered when, in January 2020, a second tumor emerged in her left hip — making it Kohl’s fifth tumor over the span of three years and the second one to the bone. This time Kohl’s core care team brought Sag into the conversation. Kohl’s tumor (small at 1cm), he explained, was the perfect size for cryoablation.

Guided by CT, he’d make a 3mm incision through the skin into the bone, drilling straight into the tumor where he’d extract bits of the tumor for biopsy to see if Kohl’s cancer had mutated yet, and if so, if there was a drug available to target that mutation (either approved or in clinical trials).

Then, still guided by CT, he’d insert a probe, which, once inside the tumor, would make just the right size and right temperature ice ball (-40 °C ) that would, within seconds, shatter the tumor cells and tear apart the tumor DNA. The body would clean up what was left of the debris. The whole session would take about an hour-and-a-half.

“Cryoablation technology has gotten smaller, safer and gentler on patients,” said Sag, who specializes in treating bone and spine metastasis. “The big wins with cryo are you can do it while the patient’s awake, you don’t have to stop chemotherapy, and you can get a biopsy at the same session. It can also be combined with surgery and radiation. It doesn’t delay any other treatment and it can be repeated. If something comes back or if there’s another tumor adjacent, you can always go back and refreeze.”

Kohl was intrigued by this “new” option more commonly used to treat kidney, lung, and liver lesions, but increasingly, she learned, a technology that was also being deployed in the bone.

Over the past couple years, she’s openly shared her cancer journey with DCI, WRAL-TV’s Debra Morgan, and the local breast cancer community. She even agreed to having her cryoablation and biopsy procedure filmed for TV. WATCH: Pam's Story: Treating Tumors with Ice to Buy Time

She was awake and talking the whole time. Afterwards, she felt bruised, but required no painkillers and felt no nausea or fatigue. She even stayed up late that night to watch the Carolina game.

When I was first diagnosed three years ago, I was told no surgery, no radiation, none of that kind of thing with metastatic breast cancer unless it’s palliative, to relieve pain,” said Kohl. “But it’s three years later and I am doing really well on my first line of therapy. My tumor markers are low and overall I feel pretty well. A lot of us are living longer and well on systemic therapies. Rethinking “metastatic,” being aggressive with it, doesn’t mean that we’re curing it. I’m going to get additional tumors. But these kinds of interventions, early on in stage 4, may help prolong my life. We don’t have the data, but I’m so thrilled, just grateful that I am fortunate enough to be in the Triangle where there’s the best care available to folks and where I can be a partner in deciding how to proceed and be part of the data.”

In January, Kohl transitioned from leading the N.C. Triangle to the Coast Affiliate of the Susan G. Komen Foundation to leading the charge for a new affiliate initiative — her brainchild — designed to fast-track collaborative bench-to-bedside research in MBC by Duke and University of North Carolina at Chapel Hill researchers.

For Kohl, and thousands like her, the answers can’t come soon enough.

This page was reviewed on 02/26/2020