Pathologic Fractures Linked With Poor Outcomes in Osteosarcoma, Ewing Sarcoma

For patients with osteosarcoma or Ewing sarcoma who develop pathologic fractures, the prognosis remains poor; however, there is still the possibility for limb salvage therapy, R. Lor Randall, MD, explained.

“For medical oncologists, what they need to know is if they are managing a patient with a bone sarcoma, there is still a role for limb salvage surgery,” Randall said. “They absolutely must get aggressive chemotherapy still. Their prognosis is worse, but they need systemic therapy, they need to be seen by an orthopedic oncologist who can at least do up-front provisional fixation of the fracture, and there still may be a role for limb salvage surgery.”

Existing literature have demonstrated how pathologic fractures impact prognosis in patient with osteosarcoma and Ewing sarcoma.^1-4

In an interview with OncLive^®, Randall, who is the David Linn Endowed Chair for Orthopaedic Surgery and professor and chair of the Department of Orthopaedic Surgery, University of California Davis Health, discussed how pathologic fractures can determine outcomes for these patients and the potential for limb salvage therapy.

OncLive^®: What is the impact of pathologic fractures on the outcome or prognosis of patients, particularly pediatric patients, with bone sarcomas?

Randall: On our sarcoma service at UC Davis, we recently took care of a [young patient], who unfortunately, sustained the pathologic fracture of their femur to what they thought was a bone cyst. A very well-intended orthopedic surgeon did an open reduction, internal fixation and fixed the fracture. However, it turned out that this fracture was caused by osteosarcoma.

Historically, when someone has fractured through a primary bone sarcoma, it has been a relative indication to do ablative surgery, because you can imagine that the fracture is like a cracked egg. The tumor is usually contained in the egg, but if you break the egg and the poisonous yolk, and egg white gets out all over the place, you have a problem and it's harder to clean up. The same can be said in an extremity.

When you have this tumor through a pathologic fracture, it spills into the whole compartment and beyond contaminates [into] neurovascular structures. You have this contaminated area, and then it's much harder to do limb salvage surgery. The question also becomes: how do these patients do ontologically, not just in terms of their local control, but how they do systemically or from their oncologic status?

We learned early on that doing ablative surgery or amputations on these kids didn't necessarily do them any much better than if we didn't do ablative surgery on them—meaning they usually died of systemic relapse at a predictable rate. Therefore, [researchers thought that perhaps they] shouldn't be doing these surgeries. Perhaps we should even try to do limb salvage in these pathologic fractures. There is a shifting of thinking.

There have been a variety of studies over the years. In this [pediatric case] I mentioned, we [discussed it in our] monthly journal club; we thought it would be an interesting topic to review recent literature on and see if there's been any new findings. Unfortunately, the data now are about the same as the data 20 years ago, but the bottom line is that prognostically patients with bone sarcomas with sustained pathologic fractures have a worse overall survival and worse disease-free survival compared with those who do not sustain fracture. There is also a small increase in local recurrence in patients who undergo limb salvage in the setting of pathologic fracture compared with those without pathologic fracture. However, that margin is not nearly so dramatic as the overall survival.

What can we conclude from this?

It's fair to say that patients with sustained pathologic fractures from their bone sarcomas probably have a more aggressive tumor because it's eroding the bone and causing more mechanical weakness, so the tumor is in a more aggressive state and, therefore, when they fracture, they are likely to be prognostically In a worst category because of the nature of their tumor. That could be one inference.

The other could be that these patients who come in with pathologic fractures also may be presenting later, meaning these may be a cohort of patients who for whatever reason, whether it's socioeconomic or what have you, they're not [coming in to get treated]. Because these tumors tend to be painful, they're not showing up or not getting evaluated, or maybe the doctors aren't looking at looking at this seriously because they present with a dull ache in their leg. For whatever reason, these patients with pathologic fractures may be presenting in a more advanced state—not necessarily a more aggressive biology, but just a more advanced state. Therefore, because their tumor has probably been around longer and hasn't seen systemic treatment, they're more likely for relapse.

The third point with this is there is still not an absolute indication to do ablative surgery in patients who have a pathologic fracture of an osteosarcoma. Local control rates are indeed a little bit worse with pathologic fracture than comparable non-pathologic fracture cases, but not so substantially that they should undergo ablative surgery given that their overall prognosis remains so poor. The surgeon with his or her experience needs to use discretion in managing the local control of patients with pathologic fractures for bone sarcomas. 

What are the typical ways that you would approach treatment for these more advanced patients?

It really depends on a variety of things. When they present with a pathologic fracture, we'll get an MRI, which is a difficult task, particularly [for young patients]. We look at the fracture, we look at the extent of the contamination, where the hematoma is, and we will then usually do some sort of provisional stabilization. Sometimes if the child is young enough, that can be a spica cast. However, in an adult, a young adult, or a teenager, they will often need some sort of surgical fixation that can sometimes be an external fixator, where you put pins above and below on the bone and attach it with a rod on the outside.

Sometimes we'll go in and do what we call provisional fixation with a limited approach to the bone to go in, bring the bone together, but then put on a shorter plate than we would normally put on a bone. The idea there is that you're staying still within the contaminated area where the tumor is. If you put on a long plate that goes above the tumor or below the tumor, then you're spreading the tumor further geographically or anatomically.

In talking up front with the patient with a pathologic fracture, the message is: there's still a good chance we can save your limb. From a cancer standpoint, the overall prognosis is a bit worse, but we do save patients with these pathologic fractures nonetheless with aggressive chemotherapy.

The 2 types of sarcomas we're really talking about are osteosarcoma and Ewing sarcoma. All the things that I've highlighted are much more much more straightforward in assessing an osteosarcoma because there's no role for radiation. With Ewing sarcoma, radiation does play a role, and so that may affect decisions around radiation and surgery combinations to manage the primary tumor in the setting of a pathologic fracture.

Whereas, with an osteosarcoma fracture or no fracture, it's just surgery. Another way of putting that is for patients with Ewing sarcoma, if they have a non-pathologic fracture, almost invariably, it will be surgery—sometimes radiation—but invariably surgery. When you have a pathologic fracture, and you're going for limb salvage, there's probably going to be surgery and radiation, because you have this wide field of contamination.

Outside of Ewing sarcoma and osteosarcoma, is this an issue among other sarcoma subtypes?

The other one that I haven't spoken about yet is chondrosarcoma, and that's a big one for medical oncologists because that's almost exclusively an adult sarcoma. A lot of patients with an advanced chondrosarcoma are elderly patients who have a pathologic fracture through very high-grade, differentiated chondrosarcoma.

Now, these patients have an abysmal prognosis, and often they're too frail to receive systemic chemotherapy. A medical oncologist, if they are in a busy sarcoma program, will probably see at least 1 or 2 of these a year. The question becomes: Is there a role for chemotherapy? Is there a role for a wide resection for these pathologic fractures? Or should these factors just be stabilized because many of these patients die within a couple of years?

What next steps can we take from this research?

The message for now is: Pathologic fracture is not necessarily an indication for amputation, but the overall prognosis is worse. It would be nice to obviously get to these patients before they fracture, again, whether it's the biology or the duration. If someone has any sense of fullness, or mass effect in an extremity with pain that's not associated with activity, they should immediately get an x-ray or radiograph.

Another message to the medical oncologist is: we know that patients who have pathologic fractures from metastatic carcinoma to bone, when they fracture, they do less well also. One of the things for the medical oncologist would be to have a low threshold, whether you have a patient with a carcinoma, or someone who might have a sarcoma who has a low threshold for getting a radiograph. It's a very important message. You could just send them to the radiology suite, they could just get the report, but don't [ignore] the pain.

Now, in terms of next steps for research, there's not much research that can be done here. Raising awareness through things like we're doing here is the way to prevent these pathologic fractures from happening. Then, we just need to do better with the patients who don't fracture.

References

1. Salunke AA, Chen Y, Tan JH, Khin LW, Luhaindran ME. Does a pathological fracture affect the prognosis in patients with osteosarcoma of the extremities? A systematic review and meta-analysis. Bone & Joint Journal. 2014;96-B(10):1396-1403. doi:10.1302/0301-620X.96B10.34370.
2. Scully SP, Ghert MA, Zurakowski D, Thompson Jr RC, Gebhardt MC. Pathologic fracture in osteosarcoma. J Bone Joint Surg Am. 2002;84-A(1):49-57.
3. Schlegel M, Zeumer M, Prodinger PM, et al. Impact of pathological fractures on the prognosis of primary malignant bone sarcoma in children and adults: a single-center retrospective study of 205 patients. Oncology. 2018;94(6):354-362. doi:10.1159/000487142
4. Ruggieri P, Mavrogenis, Casadei R, et al. Protocol of surgical treatment of long bone pathological fractures. Injury. 2010 Nov;41(11):1161-1167. doi:10.1016/j.injury.2010.09.018