Surgical outcomes of patients with diffuse-type tenosynovial giant-cell tumours: an international, retrospective, cohort study

Mastboom, Monique J L; Palmerini, Emanuela; Verspoor, Floortje G M; Rueten‐Budde, Anja J.; Stacchiotti, Silvia; Staals, Eric L.; Schaap, Gerard R.; Jutte, Paul C.; Aston, Will; Gelderblom, Hans; Leithner, Andreas; Dammerer, Dietmar; Takeuchi, Akihiko; Thio, Quirina C. B. S.; Niu, Xiaohui; Wunder, Jay S.; Sande, Michiel A.J. van de

doi:10.1016/s1470-2045(19)30100-7

Cited by 83 publications

(121 citation statements)

References 28 publications

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“…Our results con rm that surgery was the mainstay of treatment (75%), which is consistent with other studies [13,16,29]. Furthermore, all patients with recurrent dt-TGCT disease had surgery, often combined with other treatment modalities (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…TOPP represents the largest prospective, international, multi-center disease registry for dt-TGCT, being able to include 166 patients in slightly more than 2 years, and shows that conducting collaborative observational studies for rare tumor is feasible. Current literature is largely focused on the oncological outcomes of this often chronic disease [15,16,17,18,19,20,21,22]. Data derived from this registry made it possible for the rst time to describe the dt-TGCT patient journey and treatment decisions around disease onset and diagnosis of dt-TGCT patients.…”

Section: Discussionmentioning

confidence: 99%

“…The primary form of care for TGCT is complete surgical removal of abnormal tissue, performed arthroscopically, open or combined, often requiring multiple incisions to access the disease thoroughly. However, there is a high risk for recurrence, especially in dt-TGCT, due to invasive growth both in and outside the joint [13,16,28,29]. Synovectomies are generally relatively invasive, with a high recurrence rate and repetitive surgery causing signi cant impairment [16].…”

Section: Discussionmentioning

confidence: 99%

“…However, there is a high risk for recurrence, especially in dt-TGCT, due to invasive growth both in and outside the joint [13,16,28,29]. Synovectomies are generally relatively invasive, with a high recurrence rate and repetitive surgery causing signi cant impairment [16]. Multimodality treatments (e.g., external beam radiotherapy and radiosynoviorthesis) have been performed in an attempt to reduce the recurrence rate in dt-TGCT, leading to varied reported outcomes [17,18,19].…”

Section: Discussionmentioning

confidence: 99%

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

Bernthal¹,

Spierenburg²,

Healey³

et al. 2020

Preprint

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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. The majority of 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 explores prospectively the real-world management of TGCT.Methods: The TGCT Observational Platform Project (TOPP) 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, and 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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Bernthal¹,

Spierenburg²,

Healey³

et al. 2020

Preprint

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“…Constitutively high levels of CSF1 lead to massive recruitment of macrophages, primarily in the synovium and tendon sheath of young adults. Both the TKI PLX3397, also called pexidartinib [260,261], and the CSF1R-blocking antibody RG7155, also called emactuzumab [246,262], achieved important responses and high rates of sustained remissions in patients with dTGCT [263], which are otherwise treated with surgery. The U.S. Food and Drug Administration (FDA) has recently approved PLX3397 for the treatment of symptomatic dTGCT.…”

Section: Clinical Trials With Macrophage-targeting Agentsmentioning

confidence: 99%

Biology and therapeutic targeting of tumour‐associated macrophages

Beltraminelli

Palma

2020

The Journal of Pathology

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Macrophages sustain tumour progression by facilitating angiogenesis, promoting immunosuppression, and enhancing cancer cell invasion and metastasis. They also modulate tumour response to anti-cancer therapy in pre-clinical models. This knowledge has motivated the development of agents that target tumour-associated macrophages (TAMs), some of which have been investigated in early clinical trials. Here, we provide a comprehensive overview of the biology and therapeutic targeting of TAMs, highlighting opportunities, setbacks, and new challenges that have emerged after a decade of intense translational and clinical research into these multifaceted immune cells.

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Long‐term outcomes of pexidartinib in tenosynovial giant cell tumors

Gelderblom

Wagner

Tap

et al. 2020

Cancer

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BACKGROUND: The objective of this study was to report on the long-term effects of pexidartinib on tenosynovial giant cell tumor (TGCT). METHODS: This was a pooled analysis encompassing 3 pexidartinib-treated TGCT cohorts: 1) a phase 1 extension study (NCT01004861; 1000 mg/d; n = 39), 2) ENLIVEN patients randomized to pexidartinib (1000 mg/d for 2 weeks and then 800 mg/d; n = 61), and 3) ENLIVEN crossover patients (NCT02371369; 800 mg/d; n = 30). Eligible patients were 18 years old or older and had a histologically confirmed TGCT that was unresectable and symptomatic. Efficacy endpoints included the best overall response (complete or partial response) and the duration of response (DOR) by the Response Evaluation Criteria in Solid Tumors (RECIST) and the tumor volume score (TVS). The safety assessment included the frequency of treatment-emergent adverse events (TEAEs) and hepatic laboratory abnormalities (aminotransferase elevations and mixed/cholestatic hepatotoxicity). The data cutoff was May 31, 2019. Results: One hundred thirty patients with TGCT received pexidartinib (median treatment duration, 19 months; range, 1 to 76+ months); 54 (42%) remained on treatment at the end of the analysis (26 months after initial data cut of March 2017). The RECIST overall response rate (ORR) was 60%; the TVS ORR was 65%. The median times to response were 3.4 (RECIST) and 2.8 months (TVS), with 48 of the responding patients (62%) achieving a RECIST partial response by 6 months and with 72 (92%) doing so by 18 months. The median DOR was reached for TVS (46.8 months). Reported TEAEs were mostly low-grade, with hair color changes being most frequent (75%). Most liver abnormalities (92%) were aminotransferase elevations; 4 patients (3%) experienced mixed/cholestatic hepatotoxicity (all within the first 2 months of treatment), which was reversible in all cases (recovery spanned 1-7 months). Conclusions: This study demonstrates the prolonged efficacy and tolerability of long-term pexidartinib treatment for TGCT. Cancer 2020;0:1-10.

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Surgical outcomes of patients with diffuse-type tenosynovial giant-cell tumours: an international, retrospective, cohort study

Cited by 83 publications

References 28 publications

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

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

Biology and therapeutic targeting of tumour‐associated macrophages

Long‐term outcomes of pexidartinib in tenosynovial giant cell tumors

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