Novel Surgical Technique Alleviates Adverse Events After Amputation in Patients With Cancer

Thomas J. Scharschmidt, MD, MBOE

Patients with cancer undergoing amputation for their malignancy experience high rates of postamputation secondary to symptomatic neuromas and phantom limb pain, which leads to a lessened use of prosthesis and poor functional outcomes, explained Thomas J. Scharschmidt, MD, MBOE. However, a study evaluating targeted muscle reinnervation (TMR) sought to combat these challenges by transferring the transected peripheral nerves to target muscle motor nerve units, he adds.

In a small study, investigators compared a cohort of patients who underwent TMR with unselected oncologic amputees not treated at The Ohio State University James Wexner Medical Center. At an average follow-up of 14.7 months for the TMR cohort, neuroma symptoms at the amputation site occurred less frequently and with less intensity.

When measured with Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, the mean differences for pain intensity, behavior, and inference for phantom limb pain in the TMR cohort were 5.855 (95% CI, 1.159-10.55; P = .015), 5.896 (95% CI, 0.492-11.30; P = .033), and 7.435 (95% CI, 1.797-13.07; P = .011), respectively. Additionally, the PROMIS pain intensity for residual limb pain was 5.477 (95% CI, 0.528-10.42; P = .031), 6.195 (95% CI, 0.705-11.69; P = .028), and 6.816 (95% CI, 1.438-12.2; P = .014), respectively.

“[This surgical technique] is going to really improve outcomes for amputee patients,” said Scharschmidt. “They're going to have less painful residual limbs, meaning they are going to be more ambulatory and use their prosthetics more. It also leaves the door open for a bioprosthetic that they can learn to power with those reinnervated muscles.”

Beyond amputee advances, the field of tenosynovial giant cell tumor (TGCT) has transformed with the August 2019 approval of pexidartinib (Turalio) as a treatment for patients with TGCT that is associated with severe morbidity or functional limitations and not responsive to improvement with surgery—marking the first drug approved specifically for this disease.

In an interview with OncLive, Scharschmidt, an associate professor and surgical oncologist at The Ohio State University Comprehensive Cancer Center—James, The OSU Wexner Medical Center, discussed the use of TMR for amputee patients with cancer as well as therapeutic advances in sarcoma and TGCT.

OncLive: What research are you excited by in the orthopedic oncology field?

Scharschmidt: It's an exciting time in our field. There is some really innovative research that's going on, both at our institution and within the organization. Big databases have emerged to try to get some answers to some challenging questions. Since sarcoma is such a rare disease, it allows us to get information from a big data set to get meaningful studies out of it. That has been really exciting to see.

At The OSU, a lot of our research is focusing on improving care for amputee patients. We're doing a lot of work to improve outcomes for amputee patients with TMR and some different surgical techniques. We're also doing a lot of research with different clinical trials to improve outcomes for patients with sarcoma.

What are some new surgical techniques in the orthopedic oncology field?

The biggest [surgical technique] that we're developing and continuing to refine is called TMR. The idea behind that is once a patient gets an amputation, whether it's for an oncology problem or for traumatic reasons, the standard technique is to sever the nerves. As a result, those patients can suffer from a lot of postoperative phantom limb pain as well as the development of neuromas, which causes them not to wear their prosthesis as much as they can and they're not happy with their outcome.

A TMR means we're taking those severed nerves and reinnervating them into surrounding muscles in the area—giving those nerves a job to do. We found that it decreases phantom limb pain, neuroma formation, and narcotic use for these patients, and gives them a much better, more functional outcome from their amputation.

How widespread is this surgical technique currently?

We do it in conjunction with our plastic surgery team. It's really catching on as a technique across the country. We're doing a lot of the development at The OSU, along with a few other institutions.

Could you discuss your involvement in the American Academy of Orthopaedic Surgeons Musculoskeletal Tumor Registry?

The OSU is one of the pilot sites for the tumor registry; we are 1 of the 6 pilot states. Sarcoma is such a rare disease that the more you can pull data and experiences, the more you can improve outcomes.

The experience has been good so far. It's very early on in the development and we're working out the kinks with electronic medical records regarding how to capture all of the data that we need. Thus far, there is a lot of enthusiasm around it and it's going to be a great initiative once it gets going.

Moving on to TGCT, what recent advances have occurred in the field?

TGCT used to be called pigmented villonodular synovitis (PVNS). It's this challenging disorder where the lining of the joint goes haywire and causes a lot of pain and disability. The gold standard treatment for TGCT is synovectomy. The recurrence, especially in the diffuse part of the disease, can be up to 50%. It's a very challenging disease.

There has been a new targeted CSF1R agent on the market called pexidartinib—the first FDA-approved drug just for PVNS. Before, we would try different drugs for different [diseases] to see if they would work, but we didn't have anything specifically targeted to PVNS. Early studies suggest about a 40% response rate. Pexidartinib will hopefully improve outcomes for these patients.

Do you have any personal experience using pexidartinib?

At The OSU, we do everything in a team fashion. I take care of the surgical side of things and we work with our medical oncology team. We have a few patients that have been on pexidartinib, with good responses early on.

Are there any agents showing promise in the sarcoma pipeline?

Agents in general are becoming much more targeted. I was involved with a recent multicenter study that was collaborative [effort] between the Children's Oncology Group and the NRG Oncology looking at the targeted agent pazopanib (Votrient) for sarcomas. That study is just wrapping up, but it looks like pazopanib will have a positive effect and response in sarcomas.

Are there any other precision medicine efforts in this field?

Now more than ever, when we see a patient diagnosed with a new sarcoma, we'll send that sarcoma for whole-genome sequencing so we can look for specific mutations or specific targets for targeted chemotherapy or targeted immunotherapy. It's not quite standard of care, but we're doing it in a majority of our patients at The OSU.

Alexander JH, Jordan SW, West JM, et al. Targeted muscle reinnervation reduces the frequency and severity of phantom and residual limb pain in oncologic amputees. Presented at: 2019 Musculoskeletal Tumor Society Annual Meeting; October 2-4, 2019; Portland, OR. Abstract 15.