Individualized Care Informs Treatment Modality Choices in Pelvic and Sacral Ewing Carcinoma

The distinctions between surgery and radiation in the treatment of nonmetastatic pelvic and sacral Ewing carcinoma are highly nuanced, according to R. Lor Randall, MD, FACS. Deciding which modality to use, he said, requires a multidisciplinary approach.

In data recently published online in the Journal of Surgical Oncology, Randall and his coauthors determined there is little difference in overall survival (OS) for surgery vs radiation.¹ As such, combined treatment options may rise to the foreground in this setting.

“Our study’s conclusions don’t indicate that either surgery or radiation is potentially [more] acceptable,” he said. “However, there might be a role for combined treatment, particularly in cases with extraosseous components, as suggested by data from the National Cancer Database [NCDB].”

In an interview with OncLive^®, Randall, The David Linn Endowed Chair for Orthopaedic Surgery, chair of the Department of Orthopaedic Surgery, and a professor in the Department of Orthopaedic Surgery at University of California Davis Health, discussed the similar benefits offered by radiation and surgery, improved surgical techniques, concerns with morbidity with each approach, and the next steps surgeons and radiation therapists can take to increase patient survival.

OncLive^®: You were a coauthor on a study investigating the effects of local treatment modalities on survival in nonmetastatic pelvic and sacral Ewing sarcoma. What was the focus of this study?

Randall: We asked the age-old question: What is the optimal local control for Ewing sarcoma of the pelvis and sacrum? Ewing sarcoma is the second-most common form of bone cancer in children and young adults. It is also a tumor that, unlike many sarcomas, is particularly radiosensitive but also can be managed for local control purposes with surgery.

Surgery has become the mainstay of treatment for many of the appendicular lesions, but for areas in the spine, pelvis, and sacrum, the controversy rages on about optimal local control. For the spine itself, because of the spinal cord that’s higher up and the nerve roots that are further down, surgery has become a central management modality, reserved for issues such as cord compression.

When you get down to the sacrum and the pelvis, treatment is controversial. Historically, [sarcomas in those areas have] been treated with radiation. But more recently, surgery has come into the fore with advanced imaging and surgical techniques, enabling more precise resections and decreasing morbidity.

Many people have argued whether surgery is as good as radiation therapy. Many papers have shown that surgery is better than radiation therapy for managing primary pelvic and sacral Ewing sarcoma. However, [these recommendations carry] a selection bias, meaning that smaller tumors tend to get the surgery and those that are more locally advanced, albeit not metastatic, will get radiation. [It’s a point of contention, but many physicians believe that sarcomas that are] more locally advanced portend a worse prognosis. Many parts of the world use a combined modality approach, with lower-dose radiation therapy up front followed by a more strategic surgical resection.

What we decided to do was to step back and look at the [National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)] database, as well as the NCDB from the American College of Surgeons, to see what we could learn from these [institutions] and if they could shed any light on the subject. We looked at both the SEER database and the NCDB for primary nonmetastatic cases of the pelvis and sacrum, not including the mobile spine.

A total of 235 cases from the SEER database and 285 cases from the NCDB were able to be analyzed, all with localized Ewing sarcoma in the bone. We found no statistical difference in disease-specific survival for any of the local treatment modalities in the SEER database. Similarly, in the NCDB, we didn’t see much improvement [with 1 modality over the other].

However, we pointed out that with extraosseous nonmetastatic disease, there might be an improved disease-specific survival that we were able to see in the NCDB. The NCDB records disease-specific survival and the SEER only records OS. We were able to use the NCDB to tease out that added piece of information about disease-specific survival. What’s also nice about the NCDB is that it can give us some demographics such as insurance status, which didn’t prove to be statistically significant in this group. Nonetheless, this was one of the largest combinations of the NCDB and SEER databases.

Could you elaborate on what improved surgical techniques look like in this setting?

It is remarkable what we can do now surgically, with the digital technology that we have. We can use fuse images with computed tomography scans and magnetic resonance imaging to preoperatively see the tumor in 3 dimensions and define its intimate structural relationships ahead [of surgery] in ways we’ve never been able to before.

Importantly, we can also use real-time technology to plan our cuts ahead [of surgery] and use prefabricated, 3D-printed cutting guides to do these resections which obviate the need for techniques like navigation. We can also build custom implants that can fit like a jigsaw piece into the puzzle from where we resect the tumors. This has revolutionized our ability to expeditiously remove the tumor with minimal morbidity and then also replace the anatomy where needed.

Where does morbidity most often appear in surgery and radiation when treating Ewing sarcoma, and how can this issue be mitigated with both approaches?

The early morbidity tends to be seen with surgery. That is being minimized by the aforementioned technologies, but long-term radiation can have major sequelae. There can be issues such as pathologic fractures of the acetabulum or the structural portions of the pelvis, or nerve root damage from the radiation in the areas of the sacrum and the sciatic nerve. But those tend to be later sequelae.

The other issue is that with radiation therapy, we’re not resecting the tumor; we’re leaving it in situ. When there’s evolution of the imaging through time, the tumor, while it may be necrotic, tends to change as the body’s immune system infiltrates and resorbs some of it. Changing enhancement patterns in the tumor bed leads to anxiety about whether there’s a viable tumor there.

What is your message for treating physicians who are deciding between surgery and radiation therapy for these patients?

For the medical oncology community, the key is to get both the surgeons and the radiation therapists to discuss the merits of each approach. Considerations include the age of the patient, whether they’re skeletally mature, or whether they have fertility issues associated with radiation. There’s much to be discussed around this topic.

Ultimately, in terms of OS, there isn’t any difference between the 2 modalities. But in terms of disease-specific survival, there is a suggestion that surgery may be better. There may be some bias there, because some of those [surgically resected] tumors may be smaller, but surgery certainly should be entertained. If a patient is going to local control, we want to make sure the surgeons are at the table at the tumor board to weigh in on whether the morbidity of surgery is worth it.

Is there any ongoing or planned research about Ewing sarcoma treatment modalities that could potentially provide additional insight into this decision?

Through the cooperative groups, we are trying to look at potentially developing a randomized trial where we could talk about [the possibility of] preoperative radiation in patients who are going to undergo surgical resection to see if there are ways that we can [use cytoreduction on the tumor] and improve outcomes. That could be in the form of different doses or regimens of radiation. Right now, however, it’s important that we move on from the either/or philosophy and start thinking about combined modality treatment.

Reference

1. Jawad MU, Pollock BH, Zeitlinger LN, et al. Impact of local treatment modality on overall- and disease-specific survival for nonmetastatic pelvic and sacral Ewing sarcoma. J Surg Oncol. Published online May 18, 2022. doi:10.1002/jso.26922