Sydney Stern on advancing treatment and advocacy in TGCT

Dr Sydney Stern discusses how advances in CSF1-targeted therapies are reshaping care for tenosynovial giant cell tumour (TGCT), while highlighting the ongoing need for multidisciplinary management, earlier specialist referral, and patient-driven research initiatives.

The impact on patients diagnosed with TGCT can be profound. It is characterized by high recurrence rates, chronic symptoms, and frequent delays in specialist care. Although it is a benign tumor, diffuse TGCT often requires complex multidisciplinary management similar to that used in sarcoma care. In this interview, Dr Sydney Stern (Head of TGCT Support Programs) discusses the evolving treatment landscape, the promise of targeted therapies, and the role of patient advocacy in improving outcomes for people living with this rare tumour.

How would you define TGCT, and what distinguishes it biologically and clinically from other benign or inflammatory joint disorders?

TGCT is a benign, yet locally aggressive neoplasm arising from the tendon sheath, bursa, or synovium. TGCT has two clinically distinguishable subtypes: localized and diffuse. Both subtypes of TGCT are characterized by a chromosomal translocation leading to overexpression of colony stimulating factor-1 (CSF-1). This aberrant protein leads to recruitment of tumor-promoting macrophages and tumor growth.

What characteristics do TGCTs share with malignant tumours like sarcoma, and are the treatment pathways similar?

TGCT has a clinically variable presentation, spanning from asymptomatic to severely debilitating. While biologically benign, diffuse TGCT is highly recurrent, difficult to treat, and can lead to significant burden on patients emotional, social, economic, and physical well-being. Similar to sarcomas, TGCT (particularly diffuse TGCT) requires multidisciplinary specialized oncology care to avoid under or over-treatment.

What are the current standard-of-care treatment approaches for TGCT, and how do you decide between strategies such as active surveillance, surgery, and systemic therapies in clinical practice?

For asymptomatic patients with diffuse or localized TGCT, active surveillance is often the preferred approach. However, for symptomatic patients with TGCT, the frontline treatment has historically been surgery. However, diffuse TGCT is often not amenable to complete macroscopic resection and recurrence risk is high. For symptomatic patients not amenable to surgery, with recurrent and/or diffuse symptomatic TGCT, or symptomatic patients that prefer alternatives to surgery, systemic therapies are often available. In the USA, two systemic therapies (pexidartinib and vimseltinib) are approved by the FDA.

What are the biggest challenges and clinical unmet needs in treating and advancing research in TGCT?

Patients with TGCT often have inadequate management of their disease, with patients primarily being treated by orthopedic sports surgeons. Referral to multidisciplinary oncology teams makes up only a minority of the treatment teams in real-world patient communities. Often, patients have several surgeries before consulting a multidisciplinary oncology team (on average three surgeries for diffuse TGCT patients).¹ Improper management of TGCT contributes to disability and the emotional, physical, and financial burden.

What are the most exciting recent research advances and developments in this field?

CSF1/CSF1 receptor signaling axis was a landmark treatment target that has transformed care in TGCT. There are two approved systemic therapies, pexidartinib (2019) and vimseltinib (2025), and several others are in the pipeline. These provide an effective alternative to surgery in patients unlikely to benefit, a subgroup of patients that previously had no other options besides symptomatic management. TGCT Support has also published several analyses that attempt to address the burden of TGCT in an observational registry, the first and largest of its kind.

Can you tell us about the mission of the TGCT Support, particularly in improving awareness, research, and patient support in this rare disease space?

The mission of TGCT Support is to enhance treatment options and quality of life for patients living with TGCT through patient-powered research, education, empowerment, and global advocacy efforts. We do this through creating programs for patients such as support groups, tumor boards, consensus guidelines, webinars, patient conferences, one-on-one outreach, and consultations for expert opinions. We support clinicians by fostering the development of geographically relevant consensus guidelines and continuing medical education curriculums. We support both the community of clinicians and patients by leading and participating in global research projects such as our global patient registry.

References

1. Stern S, McKenzie PF, Bernthal N.  Localized and diffuse tenosynovial giant cell tumor: real-world results from a patient observational registry. Future Oncol. 2025;21:1501-10. doi: 10.1080/14796694.2025.2488635.