Current Systemic Treatment Options for Tenosynovial Giant Cell Tumor/Pigmented Villonodular Synovitis: Targeting the CSF1/CSF1R Axis

  • Mehdi Brahmi
  • Armelle Vinceneux
  • Philippe A. CassierEmail author
Sarcoma (SH Okuno, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Sarcoma

Opinion statement

Adequate surgical resection remains the treatment of choice for tenosyovial giant cell tumor (TGCT). However, diffuse type TGCT (D-TGCT) is more difficult to resect and has a higher rate of recurrence (up to 50 %), which is often multiple. D-TGCT is rarely lethal and only rare cases of metastases have been described. Nevertheless, patients might have a significant decline in their quality of life due to multiple operations, which may sometimes result in a partial loss of function of the affected joint and may also be associated with perioperative morbidity and secondary arthrosis. As of today, no systemic treatment is approved for this rare disease. The aims of systemic therapy in the context of a non-lethal tumor are to reduce surgical morbidity and to preserve function and patient quality of life. Because TGCT is associated with characteristic cytogenetic abnormalities resulting in the overexpression of CSF1, systemic therapies targeting the CSF1/CSF1R axis (imatinib, nilotinib, emactuzumab, and PLX3397) have been tested in patients with locally advanced or relapsed D-TGCT. The more recent and more specific CSF1R inhibitors have shown a very interesting clinical activity with acceptable toxicity in early phase trials. These results will need to be confirmed in larger, ideally randomized, trials. But the high rate of clinical and functional improvement seen in some patients with advanced D-TGCT, often after multiple operations, suggests that these inhibitors will likely have a role in the management of patients with an inoperable disease; the definition of “inoperable TGCT” still requires refinement to reach a consensus. Another point that will need to be addressed is that of “the optimal duration of therapy” for these patients. Indeed, we and others have observed often prolonged clinical benefit and symptomatic relief even after treatment was stopped, with both monoclonal antibodies and tyrosine kinase inhibitors. Responses were observed very early on with emactuzumab and PLX3397, and patients experienced significant symptom improvement within a few weeks of starting therapy (2–4 weeks). Another possible application of CSF1R inhibitors could be used either as a preoperative or postoperative therapy for patients with operable TGCT. However, we currently lack sufficient follow-up to adequately address these questions which will each require specific trial designs. Overall, the striking clinical activity of CSF1R specific inhibitors in TGCT has created great enthusiasm among clinicians, and further development of these agents is clearly medically needed. Nevertheless, further investigations are necessary to validate those treatments and assess how to best incorporate them among other treatment modalities into the overall therapeutic strategy for a given patient.


Tenosynovial giant cell tumor Pigmented villonodular synovitis Systemic therapy Imatinib Colony-stimulating factor 1 Colony-stimulating factor 1 receptor Anti-TNF-alpha Imatinib Nilotinib Emactuzumab PLX3397 



Mehdi Brahmi and Armelle Vinceneux contributed equally to this work.

Compliance with Ethical Standards

Conflict of Interest

Mehdi Brahmi declares that he has no conflict of interest.

Armelle Vinceneux declares that she has no conflict of interest.

Philippe A. Cassier has received research funding through grants from Roche and Novartis, as well as non-financial research support from Plexxikon, and has also received compensation from Roche and Novartis for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mehdi Brahmi
    • 1
  • Armelle Vinceneux
    • 1
    • 2
  • Philippe A. Cassier
    • 1
    Email author
  1. 1.Department of Medical OncologyCentre Léon BérardLyonFrance
  2. 2.Department of Medical OncologyCentre Hospitalier Universitaire BretonneauToursFrance

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