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R. Lor Randall, MD, FACS, discusses the evolving management of desmoid fibromatosis, shares advice on the factors that go into deciding when to treat this disease, and stresses the importance of having a multidisciplinary team involved in the care of these patients.
Desmoid fibromatosis is a rare soft tissue neoplasm that can often be as severe as sarcoma in terms of the problems it can create, according to R. Lor Randall, MD, FACS, who added that in order to manage this disease appropriately, each case should be presented to a multidisciplinary tumor board.
“Surgeons used to be dominant players in the treatment of these tumors; however, [care] has become more multimodal because of unsatisfactory results with surgery alone. Medical and radiation oncologists are now involved,” said Randall, the David Linn Endowed Chair for Orthopaedic Surgery, as well as professor and chair of the Department of Orthopaedic Surgery at the University of California, Davis Health.
“Moreover, just because a patient has a desmoid tumor, doesn't necessarily mean they have a problem or need treatment. Some desmoid tumors will stop growing and won't cause any pain or problems,” added Randall. “However, most [patients] will want treatment because they do not want the bump. We have to be careful that we do not make the problem worse with treatment. Don’t rush to a decision until you have looked at a case from all angles, with all the disciplines weighing in.”
In an interview with OncLive, Randall further discussed the evolving management of desmoid fibromatosis, shared advice on the factors that go into deciding when to treat this disease, and stressed the importance of having a multidisciplinary team involved in the care of these patients.
OncLive: Could you provide an overview of what desmoid fibromatosis is? What are some of the approaches used to treat this disease?
Randall: Desmoid fibromatosis is an interesting disease; I usually refer to it as a nonmalignant malignancy. What I mean by that is, it is in no way, shape, or form a type of cancer. Having said that, from a local situation where the tumor arises, it can be as bad as sarcoma in terms of the problems it creates. Historically, it has [fallen] under the purview of surgical oncology, and specifically orthopedic oncologists; this tumor has always been treated with aggressive surgical management.
We also know that desmoid recurrences are not correlated with margin status; there's still a large number of tumors that recur, even if there is a negative margin tumor resection. Interestingly, in some ways, there are cases where there are positive margins at the time of resection and the tumors don't recur clinically, so they don't grow into a big mass. It’s an enigma wrapped in a mystery in many ways. Several studies have assessed the biology of Wnt signaling pathways.
In the past few years, we got medical oncology on board with this condition. Some exciting agents can be used to help manage these desmoid tumors, although they have their limits. These agents include sulindac (Clinoril), which is a potent non-steroidal anti-inflammatory, and tamoxifen (Nolvadex), which has been shown even independent of estrogen status on the desmoid to sometimes have an effect. There is also imatinib (Gleevec), sorafenib (Nexavar), vinblastine and methotrexate, and pegylated doxorubicin, which all have been used in some form to treat [patients with] aggressive desmoids.
Generally speaking, when we have a patient with a desmoid, we have ensure that they don't carry the adenomatous polyposis coli gene; the vast majority are spontaneous in the extremity. We then bring them before our multidisciplinary tumor board, our sarcoma panel, to talk about all the different treatments and whether treatment is needed.
Could you expand on the role of surgery for these tumors? How has it evolved over the years, and with the newer agents emerging, has it retained a place in the paradigm?
The trouble with this condition is that it can go in many different directions after surgery. When the tumor is resected up front, patients will sometimes get radiation if there's concern about the tumor coming back or if there's a positive margin. Sometimes these tumors will be treated with preoperative radiotherapy. However, in our center along with many others that have a lot of experience, we try to discourage that.
When patients undergo surgery, independent of their margins, we watch them very carefully. If the tumor starts to clinically grow back, historically, they would get additional surgery and/or radiation, essentially duplicating the frontline treatment with another round of the same treatment.
However, more agents have emerged; this is largely due to the fact that so many unfortunate individuals have received the same treatment of surgery plus or minus radiation or even amputation prompting people to pause and consider looking at this more carefully. We have been studying this disease on a biological level, assessing different pathways to see what can be discovered.
Empirically, but also theoretically, the agents that I've already listed have been used in some format to try to control this aggressive, recurrent disease. Since they displayed modest to reasonable efficacy in these patients, we started to ask more questions. We wondered whether we should start using some of these agents first, since surgery has its own set of failures.
We need to have a discussion with patients and their families about how aggressive the treatment should be. No one wants to go through repeated surgeries and repeated treatments with radiation, etc. As such, surgery is actually done much less often now, in 2020, compared with 10 years ago.
How do you decide when to treat a patient versus not? What factors inform that decision?
We need to listen. When we talk with patients about high-grade cancer, we want to try to minimize the risk, but if it’s not metastatic, we need to remove the tumor. We have a dogmatic way of thinking for those patients.
With desmoid tumors, it’s different, more tailored. We tell patients, “OK, this is a large mass, but is it bothering you? Is this mass something that is really interfering with your quality of life (QOL)? If we could get it to shrink a little bit with some medication, would that be satisfactory?” There’s much more of a dialogue with the patient around this because you’re taking about QOL for the disease and the treatment. We have to do a lot more nuanced decision making and listening to the patient’s needs and expectations than when we are dealing with a cancer.
Once the decision has been made to treat a patient, how do you navigate among all the options that are now available?
Treatment is really influenced by the members of the multidisciplinary team. Most medical oncologists on a sarcoma tumor board have a good bit of experience with this. We will usually try and treat patients with either medical therapy but there’s also high-frequency ultrasound, cryotherapy, and other interventional procedures that are not necessarily surgery.
We tell the patient that we're going to bring their case to our tumor board and that we are going to weigh all the pros and cons. We discuss the downside of removing the tumor and weigh that against the downside of waiting. Generally speaking, we will try to recommend a medical therapy first, and that therapy is based on how aggressive the patient wants to be treated. Looking back at the medications I listed before, non-steroidal anti-inflammatories do have their issues, but they are reasonably well tolerated. If the tumor is not bothering a patient too much, maybe they just want to try sulindac for a period of time to see how they do.
The other extreme is, if the tumor is growing quite a bit and it would be very morbid to try and remove it, we might try pegylated doxorubicin or vinblastine and methotrexate as a bit more aggressive treatment. If the tumor is behaving more aggressively, the patient may opt for that, as opposed to something that is more benign, but potentially less efficacious.
Now, to clarify, when I mentioned vinblastine and methotrexate, we're not talking about the dosing that we would use in in some forms of pediatric sarcomas; these are lower doses that are better tolerated.
Is there any ongoing research in this space?
A ton of ongoing research efforts are being made. For example, high-frequency ultrasound is an area of real investigation, as well as cryotherapy. I would encourage patients to reach out to The Desmoid Tumor Research Foundation. In disclosure, I have received funds from them in the past, but I have nothing ongoing. They really are a great resource that could help patients get in touch with other patients and help providers navigate this space as well; they’re very much in tune with the latest thinkers in this condition.
What advice do you have for your colleagues who find themselves caring for these patients?
If these patients present to a surgeon, don’t just perform the surgery; take the case to a multidisciplinary tumor board. Explain to the patient that, while their tumor may end up getting removed, it should first be discussed with medical oncology colleagues that will then bring it to the whole tumor specialty board to ensure that we’re dealing with a desmoid tumor and to go over everything as a group.
If a patient presents to a primary care doctor, they usually are sent to a surgeon. These patients very rarely go to a medical oncologist first because these are masses and the referring provider will usually conclude that the mass will need to be biopsied and removed.
I've been approached by surgeons who have been informed by their patients that, when researching, they came across information about non-surgical management of desmoids, after already being told the mass had to be removed. Slow down. We understand the anxiety around this, but let's ensure that we're not making the treatment worse than the problem itself.