The diffuse-type tenosynovial giant cell tumor (dt-TGCT) patient journey: a prospective multicenter study

Abstract

Background Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm arising from the synovium of joints, bursae, and tendon sheaths affecting small and large joints. It represents a wide spectrum ranging from minimally symptomatic to massively debilitating. Most findings to date are mainly from small, retrospective case series, and thus the morbidity and actual impact of this rare disease remain to be elucidated. This study prospectively explores the management of TGCT in tertiary sarcoma centers. Methods The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study involving 12 tertiary sarcoma centers in 7 European countries, and 2 US sites. This study enrolled for 2 years all consecutive ≥ 18 years old patients, with histologically diagnosed primary or recurrent cases of diffuse-type TGCT. Patient demographic and clinical characteristics were collected at baseline and every 6 months for 24 months. Quality of life questionnaires (PROMIS-PF and EQ-5D) were also administered at the same time-points. Here we report baseline patient characteristics. Results 166 patients were enrolled between November 2016 and March 2019. Baseline characteristics were: mean age 44 years (mean age at disease onset: 39 years), 139/166 (83.7%) had prior treatment, 71/166 patients (42.8%) had ≥ 1 recurrence after treatment of their primary tumor, 76/136 (55.9%) visited a medical specialist ≥ 5 times, 66/116 (56.9%) missed work in the 24 months prior to baseline, and 17/166 (11.6%) changed employment status or retired prematurely due to disease burden. Prior treatment consisted of surgery (i.e., arthroscopic, open synovectomy) (128/166; 77.1%) and systemic treatments (52/166; 31.3%) with imatinib (19/52; 36.5%) or pexidartinib (27/52; 51.9%). Treatment strategies at baseline visits consisted mainly of watchful waiting (81/166; 48.8%), surgery (41/166; 24.7%), or targeted systemic therapy (37/166; 22.3%). Patients indicated for treatment reported more impairment compared to patients indicated for watchful waiting: worst stiffness NRS 5.16/3.44, worst pain NRS 6.13/5.03, PROMIS-PF 39.48/43.85, and EQ-5D VAS 66.54/71.85. Conclusion This study confirms that diffuse-type TGCT can highly impact quality of life. A prospective observational registry in rare disease is feasible and can be a tool to collect curated-population reflective data in orphan diseases. Name of registry: Tenosynovial Giant Cell Tumors (TGCT) Observational Platform Project (TOPP). Trial registration number: NCT02948088. Date of registration: 10 October 2016. URL of Trial registry record: https://clinicaltrials.gov/ct2/show/NCT02948088?term=NCT02948088&draw=2.

Pexidartinib in the Management of Advanced Tenosynovial Giant Cell Tumor: Focus on Patient Selection and Special Considerations

“…OncoTargets and Therapy 2022:15 54 systemic treatment was indicated. 7 However, the percentage of severe cases (instances of extra-and intra-articular disease with magnetic resonance imaging [MRI]-confiirmed involvement of multiple muscles or ligaments) 13 in this group was similar to that in the other cohorts, suggesting that clinical grade of the disease does not necessarily correlate with level of impairment. Thus, disease severity may not be a sufficient indicator of optimal treatment modality on its own, but rather should be considered in the context of the patient's symptomatology at presentation.…”

“…These patterns were demonstrated in the TGCT Observational Platform Project (TOPP), a recent multinational, multicenter prospective observational study in which the "watchful monitoring" approach was assigned primarily to patients with diffuse TGCT who had undergone only surgery prior to enrollment. 7 At baseline, the watchful monitoring cohort in TOPP had lower pain and interference scores, lower frequency of painkiller use, and higher quality of life than patients for whom surgical or https://doi.org/10.2147/OTT.S345878…”

“…Case reviews found that patients treated with RSO after surgery experienced a recurrence rate of 23-44%, compared with the 44-72% rate observed in patients treated with surgery only. 7,13,16,17,21,22 • Overall response rate: 65%…”

“…Most of the cohorts in published trials had a mean age in the 40s and were predominantly female. 7 Patients in the ENLIVEN study all had pain and stiffness scores of at least 4 on the relevant numeric rating scales. 12 Of note, the majority of the ENLIVEN patients had TGCT of the knee and ankle.…”

“…2 Diffuse TGCT typically impacts larger joints-most commonly the knee, hip, and ankle-and constitutes 10-20% of TGCT cases. 2,7,8 Significantly more common is localized TGCT, which accounts for 80-90% of all TGCT cases and is most frequently observed in the tendon sheaths of radial three digits. 1,8 For TGCT of the hand, patients will commonly observe an initially painless mass that eventually grows and painfully impinges on surrounding anatomy.…”