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 .

Keywords: Arthroscopy; Diagnosis; Diffuse TGCT; Patient journey; Surgery; Synovectomy; Systemic therapies; TOPP registry.

Fig. 1

A typical timeline of dt-TGCT in a single TOPP patient. The disease had its onset in an 18-year-old patient who was forced to stop exercising and in need of physical therapy due to dt-TGCT-related complaints. Several recurrences occurred despite multimodality treatment, leading to secondary gonarthrosis at the age of 25

Fig. 2

This figure represents the general patient journey of patients with dt-TGCT. Non-specific symptoms and disease unawareness results in several visits to different healthcare practitioners and unnecessary or excessive treatment in first and second line before referral to an orthopedic or sarcoma oncologist

Fig. 3

This flowchart gives a schematic overview of the treatment types patients received prior to TOPP, according to tumor status: primary diagnosis or recurrent disease. In addition, the cohort is stratified into 2 patient groups according to treatment plan at baseline: watchful waiting and indicated treatment at baseline. Possibly important factors in treatment decision making are shown per subgroup