John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses surgical improvements in tenosynovial giant cell tumor (TGCT).

Surgery remains a mainstay in the treatment of patients with TGCT, says Abraham. Moreover, improved techniques have made surgery a more tolerable option for patients. 

For example, patients with diffuse TGCT of the knee require front and back synovectomies, Abraham says. This surgery requires making incisions in the front and back of the knee, opening the joint up on both sides, and removing the damaged synovium. 

However, critical nerves, blood vessels, and lymphatic vessels are located at the back of the knee, so the procedure is associated with significant complications, including nerve injury, lymphatic disruption, swelling, range of motion limitations, and lymphatic leakage, Abraham says.

Historically, the front and back procedures were spaced apart to mitigate major complications, explains Abraham. However, improved surgical techniques now allow both sides of the operation to be completed on the same day with limited swelling, concludes Abraham.

Videos

John A. Abraham, MD, FACS, discusses surgical improvements in tenosynovial giant cell tumor.  



Dr. Abraham on Surgical Improvements in TGCT 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses remaining questions with pexidartinib (Turalio) in tenosynovial giant cell tumor (TGCT).

In August 2019, the FDA approved pexidartinib for the treatment of adult patients with symptomatic TGCT that is associated with severe morbidity or function limitations and not responsive to improvement with surgery. 

The regulatory decision marked the first approval in TGCT. As such, the question of how to best utilize the agent in practice remains to be seen, Abraham says. 

For example, it may be best to give pexidartinib to all patients with TGCT for 3 months prior to surgery, similar to what is done with neoadjuvant chemotherapy, says Abraham. Alternatively, giving pexidartinib for 6 months after surgery may be an optimal way of decreasing the rate of recurrence. 

Another option is to use the agent preoperatively and perform surgery in patients who progress on pexidartinib, explains Abraham.

Ongoing research efforts are aimed at navigating these questions and optimizing the use of pexidartinib in patients with TGCT, concludes Abraham.

John A. Abraham, MD, FACS, discusses remaining questions with pexidartinib in tenosynovial giant cell tumor.  



Dr. Abraham on Remaining Questions With Pexidartinib in TGCT 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses the clinical utility of pexidartinib (Turalio) in tenosynovial giant cell tumor (TGCT). 

In August 2019, the FDA approved pexidartinib for the treatment of adult patients with symptomatic TGCT that is associated with severe morbidity or function limitations and is not responsive to improvement with surgery.

Monoclonal antibodies and small molecule inhibitors were evaluated in TGCT prior to the approval of pexidartinib, says Abraham. 

The phase 3 ENLIVEN trial, which served as the basis for the regulatory decision, demonstrated a 38% overall response rate, reduction in disease volume, and significant symptom improvement with pexidartinib, Abraham explains. 

However, pexidartinib is not without adverse effects, so patients should be selected based on whether the potential benefits associated with the agent outweigh the risks, Abraham says.

Moreover, although surgery remains the mainstay frontline option, pexidartinib should be considered in patients who are not candidates for surgery, have extensive disease, or have undergone multiple surgeries, concludes Abraham.

John A. Abraham, MD, FACS, discusses the clinical utility of pexidartinib in tenosynovial giant cell tumor.   



Dr. Abraham on the Clinical Utility of Pexidartinib in TGCT 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses the surgical management of patients with tenosynovial giant cell tumor (TGCT).

Surgical intervention is dependent on what joint the disease is located in, Abraham says. Ultimately, the goal of surgery is to rid the patient of the diseased synovium, while leaving an adequate amount healthy tissue. 

Diseased synovium tissue has a purplish discoloration due to hemosiderin pigmentation that deposits from the significant amount of bleeding associated with TGCT, Abraham explains. As such, identifying what tissues needs to be removed during surgery is relatively straightforward. 

The surgical techniques employed are dependent on the site of disease, but are always specialized and extensive, Abraham says. Some examples include anterior and posterior operations of the knee, surgical dislocation of the hip or shoulder, and opening an ankle joint to see the full extent of disease.

As these are specialized procedures, it is important that patients are operated on by orthopedic surgeons who are familiar with and comfortable performing these surgeries, concludes Abraham.

John A. Abraham, MD, FACS, discusses the surgical management of patients with tenosynovial giant cell tumor.  



Dr. Abraham on the Surgical Management of TGCT 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses future research efforts in tenosynovial giant cell tumor (TGCT).

Ongoing clinical trials are evaluating monoclonal antibodies and small molecule inhibitors as potential treatments for patients with TGCT, Abraham says.

 for patients with symptomatic TGCT, a benchmark in terms of systemic therapy has been established in this space, explains Abraham. 

As such, investigational agents will have to demonstrate additional benefit compared with pexidartinib, which is associated with an overall response rate of approximately 38%. 

Alternatively, as pexidartinib is associated with some toxicities, developing an agent with a lower toxicity profile would be beneficial for patients with TGCT, concludes Abraham.

John A. Abraham, MD, FACS, discusses future research efforts in tenosynovial giant cell tumor.  



Dr. Abraham on Future Research in TGCT 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses key considerations regarding the management of tenosynovial giant cell tumor (TGCT).

Though rare, TGCT is a disease that should be kept in mind for patients who present with symptoms such as knee pain, Abraham says.

Diagnosing TGCT is typically based on symptoms and imaging, explains Abraham. As such, relying on a patient’s history, physical, and imaging is preferred to performing broad molecular panels for nondescript symptoms.

If a patient has TGCT, surgery remains the standard treatment, Abraham says. Additionally, patients may not need to see a medical oncologist upon diagnosis, but rather may be referred to a surgeon who can perform TGCT-related surgery. 

Beyond surgery, the recent approval of pexidartinib (Turalio) offers an oral treatment option for patients with symptomatic TGCT that is associated with severe morbidity or functional limitations and not responsive to improvement with surgery, concludes Abraham. 

John A. Abraham, MD, FACS, discusses key considerations regarding the management of tenosynovial giant cell tumor. 



Dr. Abraham on Key Considerations in the Management of TGCT 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses potential symptoms of tenosynovial giant cell tumor (TGCT).

TGCT can occur within or outside any joint. Therefore, the symptoms of TGCT are based on where the disease occurs, says Abraham.

The synovium of the affected joint will become thick and friable, causing it to break apart, says Abraham. Moreover, as the synovium breaks down, significant bleeding into the affected area can lead to swelling, irritation, and pain.

Joint swelling can result in loss of range of motion and stiffness, explains Abraham. While these symptoms are typically intermittent, they can come on suddenly and without incidental damage to the joint.

Additionally, chronic symptoms such as the disease eroding into the bone are often experienced by patients with TGCT and can cause long-term pain , concludes Abraham.

John A. Abraham, MD, FACS, discusses potential symptoms of tenosynovial giant cell tumor.

John A. Abraham, MD, FACS

Articles