Diffuse Tenosynovial Giant Cell Tumor Research Articles

Invasion Patterns and Long-Term Clinical Outcomes of Diffuse Tenosynovial Giant Cell Tumor of the Ankle Joint.

The invasion patterns and long-term outcomes ofdiffuse tenosynovial giant cell tumor (D-TSGCT) of the ankle joint remain unclear. Seven patients who visited our department between 2011 and 2023 and were diagnosed withD-TSGCT of the ankle joint by contrast-enhanced MRI and a pathological diagnosis were included. The invasion patterns of ankle D-TSGCT on MRI were investigated. The recurrence rate and clinical symptoms were examined in five patients followed up for more than seven years after total resection. In seven patients (1 male/6 females, mean age 37.0±16.6 years, range 15-57 years) with D-TSGCT of the ankle joint, contrast-enhanced MRI at the initial presentation showed invasion within the ankle joint, extending along the tendon sheath, within the talocalcaneal joint, and in the tarsal sinus in 100% of cases, around the deltoid ligament in 86%, within the plantar surface in 43%, invasion of the interosseous membrane in 57%, around the Achilles tendon in 29%, and scalloping on the talocrural joint in 43%. The mean time from mass awareness to the first visit was 51.9±80.0 months (range 1-240 months). Gross total resection, defined as the removal of all tumors as gauged by MRI, was initially performed on 6/7 patients. One patient underwent partial resection of only the anterior part of the tumor. Of the six cases in which gross total resection was performed, 5 had long-term follow-up of more than seven years post-operatively, and one case is still only one year post-operatively. The long-term results offive patients followed for more than seven years after total resection were as follows: a mean follow-up period of 125 months (range 89-171 months), a 100% recurrence rate, a mean time to recurrence of 27.5±19.2 months (range 7-60 months), and a 16% reoperation rate. In the last follow-up, osteoarthritic changes were observed radiographically in 2/5 patients (40%), both of whom had scalloping of the talocrural joint on MRI at the time of the initial diagnosis. Four of the five patients (80%) had no clinical symptoms in the last follow-up. Ankle D-TSGCT presents with a strong local infiltrative pattern inside and outside the ankle joint along the tendon sheath, radical resection may be difficult, and the recurrence rate may be higher than previously reported. On the other hand, there are many cases that remain free of clinical symptoms in the long term after recurrence, and surgical indications for ankle D-TSGCT need to consider function preservation as well as recurrence rates.

Diffuse Tenosynovial Giant Cell Tumor of the Wrist with Joint Destruction and Invasion

Abstract A 54-year-old man took antitubercular drugs for 1 year for right wrist pain, swelling, and restriction of movements, with no improvements. Magnetic resonance imaging wrist reported multiple nodules and soft-tissue mass with intraosseous erosions involving carpal bones, distal radius, and ulna. Resection of the mass, excision of the distal ulna, and wrist arthrodesis were done. The histopathology confirmed a diffuse tenosynovial giant cell tumor (TSGCT). No postoperative radiotherapy or systemic therapies were given. The patient remained symptom-free at 2 years of follow-up. Diffuse TSGCT with joint destruction and invasion of the wrist is rare. Therefore, a high index of suspicion is required before considering the most common infective etiologies in the wrist.

Bone SPECT/CT in Advanced Diffuse Tenosynovial Giant Cell Tumor of the Wrist.

Tenosynovial giant cell tumor, previously known as pigmented villonodular synovitis, is a benign low-grade fibrohistiocytic proliferation with hemosiderin deposits in synovial joints. Mostly affecting the knee, it can also manifest in other synovial joints, infrequently also in the wrist. Tenosynovial giant cell tumor typically causes intense radionuclide uptake in all phases in planar bone scintigraphy, making a differentiation from other bone tumors or osteomyelitis difficult, especially in cases associated with extensive bone destruction. We present a case of an unusually advanced and extended tenosynovial giant cell tumor of the wrist in bone scintigraphy, SPECT/CT, radiograph, and MRI.

A phase 2, open-label, adaptive, dose-ranging study with long-term extension to evaluate the safety, tolerability, efficacy, and pharmacokinetics of intra-articular AMB-05X injections in patients with tenosynovial giant cell tumor.

TPS11585 Background: CSF1R is a clinically validated target for Tenosynovial Giant Cell Tumor (TGCT). CSF1 is overexpressed in TGCT and, via action at the colony-stimulating factor 1 receptor (CSF1R), leads to the proliferation of synovial-like mononuclear cells and recruitment of multinucleate giant cells, foam cells, siderophages, and inflammatory cells, which compose the bulk of the neoplasm. Although nonmetastatic in nature, TGCT can develop into locally destructive lesions that cause significant local tissue injury, loss of joint function, and impaired quality of life. When complete resection is achievable without significant morbidity, the standard of care for patients with TGCT is surgical resection. Recurrence after surgery occurs in up to 30% of patients with localized TGCT and 83% of patients with diffuse TGCT ( Mastboom 2019, Patel 2017). Repeat surgeries may be necessary but often leads to further morbidity, complications, and reduced function of affected joints. A safe, effective, and convenient pharmacotherapy is a desirable addition to the therapeutic armamentarium for TGCT. AMB-05X is a potent and selective anti-CSF1R monoclonal antibody in development for local treatment of TGCT. Intra-articular (IA) injection of AMB-05X enables high drug concentration at the tumor site while minimizing systemic exposure and toxicity. A proof-of-concept study of IA AMB-05X for TGCT found clinically meaningful improvement in objective response rate, functional (pain, stiffness, range of motion) and quality of life measures after 12 weeks of therapy with no serious and a low number of adverse events associated with targeting CSF1R. This phase 2 study aims to establish the optimal dosing regimen and local administration of AMB-05X and confirm the efficacy and safety of 24 weeks and longer treatment. Methods: AMB-051-07 (NCT05349643) is an open-label, multicenter, phase 2 study of AMB-05X in patients with TGCT. The trial is being conducted at multiple sites in North America, Europe, and Australia. The dosing schedule includes an injection interval of every 4 weeks and longer, including an extended dosing period. Adult patients with histologically confirmed symptomatic TGCT with one joint involvement whether surgically amenable or non-amenable with measurable disease and adequate organ function are being enrolled. After the initial cohort of patients with TGCT of the knee, other joints may be enrolled pending evaluation by the DMC. The primary study outcome measures are objective response rate (ORR) per RECIST v1.1 by central radiology review and safety. Secondary outcome measures include ORR per modified RECIST and Tumor Volume Score, duration of response, time to response, PRO/QOL (including range of motion, stiffness, pain), pharmacodynamics and pharmacokinetics. Clinical trial information: NCT05349643 .

Image findings of tendon sheaths affected by diffuse tenosynovial giant cell tumors of the skull base.

This study investigated radiographic images and the differential diagnosis of intracranial diffuse tenosynovial giant cell tumor (D-TGCT) in order to better understand the disease and improve the rate of preoperative diagnosis. Images and clinical data of patients with D-TGCT were retrospectively analyzed. Routine Computer Tomography (CT), routine Magnetic Resonance Imaging (MRI), and contrast-enhanced MRI were performed for nine cases. Susceptibility-weighted imaging (SWI) was also performed for one case. We reviewed nine patients (6 males and 3 females) aged between 24 and 64 years, with a mean age of 47.33 ± 14.92 years. The most frequent complaints were hearing loss (5/9, 55.6%), pain (4/9, 44%), masticatory symptoms (2/9, 22.2%), and mass (4/9, 44.4%), with a mean duration of 22 ± 21.43 months. All cases were centered on the base of the skull, and showed hyper-density soft-tissue mass with osteolytic bone destruction on CT. The tumor signal mainly showed iso-intensity or hypo-intensity on T1WI compared with that in the brain parenchyma in all patients. On T2WI, nine lesions mainly showed hypo-intensity. Among these nine lesions, three displayed cystic region showing hyper-intensity on T2WI and hypo-intensity on T1WI (Figure 2A, 2B) in the lesion. Nine lesions showed hypo-intensity on DWI sequences. SWI images presented low signal in two cases, showing the "flowering effect". Nine patients showed heterogeneous enhancement, and two patients had meningeal thickening. Intracranial D-TGCT is extremely rare, but must be differentiated from other tumors. Osteolytic bone destruction in the area of the skull base with hyper-density soft-tissue mass and hypo-intensity on T2WI images are indicative of D-TGCT.

Effectiveness of arthroscopic excision based on the distribution of the tenosynovial giant cell tumor around knee joint

BackgroundThe mainstay treatment for tenosynovial giant cell tumor (TGCT) is open excision. However, open excision is associated with the risk of stiffness, infection, neurovascular injury, and prolonged hospital stay and rehabilitation. The purpose of this study was to evaluate the efficacy of arthroscopic excision of tenosynovial giant cell tumor (TGCT) of the knee joint, including the diffuse type of TGCT. MethodsPatients who underwent arthroscopic excision of TGCT between April 2014 and November 2020 were retrospectively analyzed. TGCT lesions were divided into 12 distributions (nine intra- and three extra-articular lesions). The distribution of TGCT lesions, portals used, degree of excision, recurrence, and magnetic resonance imaging (MRI) scans were evaluated. The prevalence of intra-articular lesions in diffuse TGCT was also analyzed to validate the existence of a connection between intra- and extra-articular lesions. ResultsTwenty-nine patients were included in the study. Fifteen patients (52%) had localized TGCT, and 14 patients (48%) had diffuse TGCT. The recurrence rates for localized, and diffuse TGCT were 0%, and 7%, respectively. Intra-articular posteromedial (i-PM), intra-articular posterolateral (i-PL), and extra-articular posterolateral (e-PL) lesions were found in all patients with diffuse TGCT. The prevalence rates of i-PM and i-PL lesions among e-PL lesions were both 100% (p = 0.026 and p < 0.001, respectively). Diffuse TGCT lesions were managed with posterolateral capsulotomy and viewed from the trans-septal portal. ConclusionsArthroscopic excision of TGCT was effective in both localized and diffuse TGCT. However, diffuse TGCT was associated with posterior and extra-articular lesions. Therefore, technical modification such as posterior, trans-septal portal, and capsulotomy were required. Study designRetrospective case series; level Ⅳ.

Midterm outcomes of 18 patients with primary intra-articular diffuse tenosynovial giant cell tumor (TGCT) of the knee treated with complete arthroscopic synovectomy and postoperative low-dose radiotherapy at a mean follow-up of 68months.

To evaluate the long-term clinical outcome of the treatment of complete arthroscopic synovectomy combined with low-dose external radiotherapy in the knee affected by primary intra-articular diffuse tenosynovial giant cell tumor (TGCT). From May 2009 to January 2016, 18 patients with intra-articular diffuse TGCT underwent complete arthroscopic synovectomy and low-dose external-beam radiotherapy in Zhongnan Hospital were enrolled in this retrospective study. The preoperative symptoms of patients, the complications during or after the arthroscopic procedure and the recurrence were collected and recorded. Each patient was evaluated before treatment and at the follow-up visit. Efficacy evaluation criteria were based on Ogilvie-Harris score, and the evaluation of the functional ability of knee was based on the International Knee Documentation Committee (IKDC) Score. The mean time from symptom onset to surgery was 9.1 ± 5.8months (range from 3 to 29months). The most frequent preoperative symptoms were joint effusion (100%), diffuse non-specific knee pain (66.7%), and a decreased range of motion (83.3%). Mean follow-up time was 68.0 ± 18.1months (range from 35 to 120months). The mean evaluation score according to the Ogilvie-Harris criteria before treatment was 3.19 ± 0.74, which corresponded to a rating of "poor". The mean score after treatment was 8.79 ± 1.57, rated as "good". The Ogilvie-Harris score was significantly increased after treatment (P = 0.003). The IKDC score of all patients increased significantly from 37.1 ± 3.8 before treatment to 83.9 ± 11.3 after treatment. The IKDC score was obviously increased after treatment (P = 0.001). No recurrence was noted at final follow-up. There were no complications during or after the arthroscopic procedure. The outcome of this study proved that complete arthroscopic synovectomy combined with low-dose external radiotherapy was appropriate for treating primary intra-articular diffuse TGCT of the knee joint. It could be safely and reliably used with minimal complications, fast postoperative recovery and satisfactory control of recurrence rates.

Giant Cell Tumor of Bone Versus Tenosynovial Giant Cell Tumor - Similarities and Differences.

Giant cell tumor of bone (GCTB) and tenosynovial giant cell tumor (TGCT) share misleadingly similar names, soft texture and brown color macroscopically, osteoclast-like multinucleated giant cells microscopically and localisation in the musculoskeletal system. However, these two tumor types are biologically and clinically two distinct entities with different natural courses of progression and considerably different modes of surgical and medical treatment. In this article, we provide a detailed update on the similarities and the differences between both tumor types.GCTB is a locally aggressive osteolytic bone tumor, commonly seen in patients in their third decade of life. It usually occurs as a solitary lesion in the meta-epiphyseal region of long bones. It can be diagnosed using plain radiographic imaging, CT radiography or MRI to estimate the tumor extent, soft tissue and joint involvement. GCTB is usually treated with intralesional excision by curettage. Systemically, it can be treated with bisphosphonates and denosumab or radiotherapy.TGCT is a rare, slowly progressing tumor of synovial tissue, affecting the joint, tendon sheath or bursa, mostly seen in middle-aged patients. TGCT is usually not visible on radiographs and MRI is mostly used to enable assessment of potential bone involvement and distinguishing between two TGCT types. Localised TGCT is mostly treated with marginal surgical resection, while diffuse TGCT is optimally treated with total synovectomy and is more difficult to remove. Additionally, radiotherapy, intraarticular injection of radioactive isotopes, anti-TNF-α antibodies and targeted medications may be used.

Chondroid tenosynovial giant cell tumor of the temporomandibular joint presenting as a deep-lobe parotid tumor

Tenosynovial giant cell tumor (TGCT) is a rare benign craniofacial soft-tissue tumor characterized by overgrowth of the synovial tissue, tendon sheath, bursa, and joint structure. It is classified into two types, diffuse and localized TGCT, and has rarely been reported in the temporomandibular joint. The etiology of TGCT is unknown, and the management of TGCT varies depending on the tumor location and treatment-related morbidity. Here, we describe the case of a 47-year-old man who presented with a complaint of a right parotid mass that had slowly increased over 2 months and was associated with ear fullness. Initially, the lesion was painless, but pain during chewing without any limitation of the jaw movement developed subsequently. The patient was diagnosed with diffuse TGCT with chondroid metaplasia.

Updates on the Treatment of Tenosynovial Giant Cell Tumor.

Tenosynovial giant cell tumor (TGCT) is a rare inflammatory disorder affecting the joint synovium, bursae, and tendon sheaths that causes non-specific and often insidious joint discomfort. The application of systemic chemotherapy has been limited due to poor and unsustained disease responses. Surgery with or without adjuvant radiation is the primary treatment modality for TGCT. With its locally destructive nature and increased recurrence, multiple surgical interventions become necessary throughout the course of the disease, leading to disfigurement, decreased quality of life, and increased mortality. However, owing to recent evidence demonstrating the overexpression of colony-stimulating factor 1 (CSF-1) in TGCT, selective tyrosine kinase inhibitors targeting CSF-1 receptors are being developed. Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.

A New Simple and Practical Clinical Classification for Tenosynovial Giant Cell Tumors of the Knee.

ObjectiveTo propose a simple and practical clinical classification for tenosynovial giant cell tumor (TGCT) of the knee.MethodsA retrospective study was conducted to verify the value and significance of this clinical classification. TGCT growth patterns, knee joint capsule, and bone erosion were applied to establish this novel clinical classification. Seventy‐eight patients who underwent surgery for TGCT from 2008 to 2016 were identified. This novel clinical classification was retrospectively applied to patients' existing classification, and patients with different TGCT types were statistically compared to verify the significance of the clinical classification.ResultsThe clinical classification included three types and four subtypes. Type 1: localized TGCT, Subtype 1a: localized intra‐articular TGCT, Subtype 1b: localized extra‐articular TGCT. Type 2: diffuse TGCT, Subtype 2a: diffuse intra‐articular TGCT with bone normal, Subtype 2b: diffuse intra‐articular TGCT with bone destruction. Type 3: diffuse TGCT across the knee joint capsule. The mean follow‐up time for the 78 patients was 59.6 months. Twenty‐one patients were in Subtype 1a, four were Subtype 1b, 38 were Subtype 2a, seven were Subtype 2b, and eight were Type 3. Oncological results and surgical complications differed significantly (P = 0.000, P = 0.000). The mean Musculoskeletal Tumor Society functional scores differed significantly at 27.8 for Type 1 patients, 22.9 for Type 2 patients, and 17.0 for Type 3 patients (P = 0.000).ConclusionsThis clinical classification can be easily used to evaluate TGCT of all knees prior to surgery or other treatments and can help determine surgical options.

Treatment, recurrence rates and follow-up of Tenosynovial Giant Cell Tumor (TGCT) of the foot and ankle-A systematic review and meta-analysis.

The tenosynovial giant cell tumor (TGCT) is a usually benign lesion which arises from the synovium. It affects joints, tendon sheaths and bursae. The clinical course is often unpredictable, and local recurrences frequently occur. The aim of this study was to describe different treatment options, surgical complications, and to develop a follow-up regime based on a systematic literature review and meta-analysis of foot and ankle lesions. 1284 studies published between 01/1966 and 06/2021 were identified. 25 met the inclusion criteria, with a total of 382 patients. Of these, 212 patients had a diffuse (dTGCT) and 170 a localized (lTGCT) TGCT. Patients with a dTGCT had a mean age of 36.6±8.2 years, and 55% were female. The overall complication rate was 24% in dTGCT, irrespective of the therapeutic procedure; the mean follow-up was 37.9±27.4 months with a recurrence rate of 21%, and recurrences occurred between 3 and 144 months, the vast majority (86%) within the first 5 years following intervention. Patients with a lTGCT had a mean age of 31.2±5.7 years, and 53% were female. Complications occurred in 12%. The mean follow-up was 51.1±24.6 months, the recurrence rate was 7%, and recurrence occurred between 1 and 244 months after intervention. Diffuse TGCTs of the foot and ankle region have a remarkable recurrence rate irrespective of therapeutic procedures, and most lesions reoccurred within 5, with more than half of these in the first 2 years. The lTGCTs are well treatable lesions, with a low recurrence and a moderate complication rate. Based on these findings, we propose a follow-up regime for the dTGCT including a clinical survey and MR imaging 3 months after surgical intervention (baseline), followed by twice-yearly intervals for the first 2 years, yearly intervals up to the fifth year, and further individual follow-up due to the fact that recurrences can even occur for years later. For the lTGCT a clinical survey and MRT is proposed after 3-6 months after intervention (baseline), followed by annual clinical examination for 3 years, and in case of symptoms MR-imaging. Larger prospective multi-center studies are necessary to confirm these results and recommendations.

1821P Safety and preliminary efficacy of vimseltinib in tenosynovial giant cell tumor (TGCT)

Diffuse TGCT is a rare, locally aggressive neoplasm, where overexpression of colony-stimulating factor 1 (CSF1) drives recruitment of macrophages leading to local inflammation and joint destruction. Vimseltinib (DCC-3014) is an oral, highly selective, switch-control kinase inhibitor of CSF1 receptor (CSF1R). We report the safety and efficacy of patients (pts) with TGCT in the phase 1 arm of the phase 1/2 study (NCT03069469).

Malignant Diffuse Tenosynovial Giant Cell Tumor: Case Report and Review of the Literature

Abstract Diffuse-type tenosynovial giant cell tumor (TGCT) is a neoplasm that exhibits infiltrative growth, tends to recur locally, and is often located within a joint. We describe a challenging diagnosis and clinical course of a 14-year-old girl with malignant diffuse TGCT, highlighting the difficulty of acquiring a representative biopsy. The patient presented with a painful foot mass, which was diagnosed initially through open biopsy as chronic osteomyelitis. Because her pain persisted, additional open biopsies were performed 1 and 2.5 years after the initial biopsy, which also showed features of benign TGCT. At age 16 years, she underwent marginal resection but developed local recurrence with metastatic disease 1 year later. Core needle biopsy of the foot mass again confirmed diffuse TGCT and showed no evidence of atypical or malignant features. Malignant features were confirmed only through excisional biopsy of chest wall metastasis. The patient started chemotherapy and underwent below-the-knee amputation at age 17 years. Amputation specimen showed malignant diffuse TGCT. She died of disease progression approximately 1 year later. Metastasis of diffuse TGCT with benign histology is challenging to diagnose. Previous studies have also found that benign diffuse TGCT can transform into an aggressive, malignant tumor. This case highlights that biopsy sampling can be challenging in histologically heterogeneous tumors. Initial evaluation by a multidisciplinary team, as well as image-guided biopsy techniques, may increase diagnostic accuracy of the biopsy.

PRO26 Economic Burden in Tenosynovial GIANT Cell Tumor (TGCT) Patients in Europe: An Observational Disease Registry

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm of joints and tendon sheaths. The aim was to estimate the economic burden that TGCT causes across several European countries. The TGCT Platform Project (TOPP) is an observational prospective study conducted in several countries (Austria, Germany, Italy, the Netherlands, UK, France and Spain) on adult patients with a histologically confirmed diagnosis of diffuse TGCT, enrolled between November 2016 and March 2019. Patients were followed for two years, however, two time-points were considered: baseline (information recorded related to the prior 12 months) and 12 months follow-up. The entire societal impact was considered in this study; we evaluated the impact not only healthcare costs (hospitalizations, medical visits, surgery and radiotherapy), but also non-healthcare costs (social services and informal care) and productivity losses associated with the disease (reference year: 2019). 146 patients with TGCT were enrolled, although 137 fulfilled the inclusion criteria. Mean age was 44.5 years and 62% were female. The annual average total costs associated with TGCT were 4,866€ in the 12 months before baseline and 5,160€ after 12 months of follow-up. The annual average healthcare costs associated with TGCT were 4,620€ before baseline (94.1% of the total cost); 66.5% and 18% attributed to surgery and outpatient visits, respectively. At follow-up, mean healthcare costs amounted to 5,094€ (98.7% of the total cost), with surgery representing 70% of total costs. Productivity losses represented, on average, 5% of the total costs before baseline and 1.3% at follow-up. Wide differences were observed between countries, with Germany reaching the higher mean total costs per person with TGCT at both time periods. This study demonstrates the considerably high healthcare costs among patients with TGCT in TOPP registry. Costs increased 12 months after the first TGCT claim, with three quarters of the costs covering surgery.

Magnetic resonance imaging features of intra-articular tenosynovial giant cell tumor in children.

Magnetic resonance imaging (MRI) plays a critical role in disease characterization of intra-articular tenosynovial giant cell tumor. To characterize the MRI features of intra-articular tenosynovial giant cell tumor in children with respect to disease subtype and anatomical location. This retrospective study included children with tenosynovial giant cell tumor who underwent preoperative MRI between January 2006 and May 2020. Two radiologists reviewed each examination to determine disease subtype, signal intensities and the presence of an effusion, osseous changes, chondromalacia, juxtacapsular disease and concomitant joint involvement. Fisher exact, Mann-Whitney U, and Kruskal-Wallis H tests were used to compare findings between subtypes and locations. Twenty-four children (16 girls, 8 boys; mean age: 13.1±3.8years) with 19 knee and 5 ankle-hindfoot tenosynovial giant cell tumor had either diffuse (n=15) or localized (n=9) disease. An effusion (P=0.004) was significantly more common with diffuse than localized disease. There was no significant difference in MRI signal (P-range: 0.09-1) or other imaging findings (P-range: 0.12-0.67) between subtypes. Children with knee involvement were significantly more likely to present with diffuse disease while those with ankle-hindfoot involvement all presented with focal disease (P=0.004). Juxtacapsular (n=4) and concomitant proximal tibiofibular joint involvement (n=5) were observed with diffuse disease in the knee. Erosions (P=0.01) were significantly more common in the ankle than in the knee. In our study, diffuse tenosynovial giant cell tumor was more common than localized disease, particularly in the knee where juxtacapsular and concomitant proximal tibiofibular joint disease can occur.

Management of Tenosynovial Giant Cell Tumor: A Neoplastic and Inflammatory Disease.

Background:Patients with diffuse tenosynovial giant cell tumor (TGCT) face a high risk of recurrence, progression, and disability. This systematic review assesses the recent evidence of surgical, adjuvant, and systemic treatments for TGCT.Methods:We searched PubMed and Ovid with the terms “Giant cell tumor of tendon sheath” OR “pigmented villonodular synovitis” OR “tenosynovial giant cell” AND “treatment” OR “surgery.” Inclusion criteria: published 2013 to present; prospective or retrospective design; English language; > 20 patients with histopathological confirmed diagnosis of TGCT; and ≥ 1 efficacy and/or safety outcome from surgery, systemic drug therapy, or adjuvant 90yttrium radiosynoviorthesis.Results:Of the 434 studies identified, 25 met the inclusion criteria. Of 11 studies in patients with disease in the knee, nine examined surgical treatment approaches, and two evaluated adjuvant 90yttrium radiosynoviorthesis. Of 11 studies in patients with mixed sites of disease, six assessed surgical treatment approaches, and five evaluated systemic drug therapies. Three studies assessed surgery in patients with TGCT in the hand, hip, and ankle or foot.Discussion:The high rates of recurrence and risks associated with surgery emphasize the need for novel treatments in patients with symptomatic, advanced TGCT. Systemic therapy may be valuable as part of a multidisciplinary approach.

Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor.

Tenosynovial giant cell tumor is a rare proliferative tumor that arises from the synovium, bursae, or tendon sheaths due to an overproduction of colony-stimulating factor 1. Historically, treatment options for patients with local or diffuse tenosynovial giant cell tumor have been limited to surgical interventions. However, for some patients, surgical resection could worsen functional limitations and/or morbidity. In August 2019, the FDA approved pexidartinib (TURALIO™, Daiichi Sankyo), the first systemic treatment option for adult patients with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations that were not amenable to improvement with surgery. Pexidartinib is an oral tyrosine kinase inhibitor with selective inhibition of colony-stimulating factor 1 receptor and is the first systemic therapy to show significant improvement in overall response rates when compared with placebo. Clinicians using pexidartinib should monitor for liver-related adverse events, which may require treatment interruption, dose reduction, or treatment discontinuation. Pexidartinib provides a novel non-surgical treatment option for patients with tenosynovial giant cell tumor that may significantly improve patients’ overall response, range of motion, physical function, tumor volume, and stiffness.

Pexidartinib for the treatment of adult symptomatic patients with tenosynovial giant cell tumors

ABSTRACT Introduction Tenosynovial giant cell tumor (TGCT) is a benign mesenchymal tumor arising from the synovium of tendon sheats and joints, driven by colony-stimulating factor 1 (CSF1) over-expression. Standard treatment is surgery, but local recurrences are frequent, especially in diffuse TGCT subtype, rarely cured with surgery. When TGCT becomes a chronic condition, which may severely compromise joint function and quality of life, patients may need a systemic therapy. Areas covered: We reviewed the drugs on clinical development in TGCT, focusing on the pharmacodynamics, pharmacokinetics, efficacy, and toxicity profile of pexidartinib, the first drug approved in the US for TGCT, and on the open questions about its optimal use in clinical practice. Expert opinion CSFR1 inhibitors have opened a new avenue for treatment of TGCT patients. Pexidartinib is the first-in-class FDA approved agent for symptomatic locally advanced TGCT, based on a phase III study where pexidartinib showed high anti-tumor activity, improved patient symptoms, and functional outcome. A few cases of potentially life-threatening hepatic toxicity were observed. TGCT patients candidate to pexidartinib need to be carefully selected by the multidisciplinary board of center of expertise, balancing the expected risk-benefit ratio. Close monitoring of liver function and adequate education on the approved indication is warranted.

Patient journey and quality of life (QOL) among diffuse-type TGCT in the U.S.

e23565 Background: Diffuse Tenosynovial Giant Cell Tumor (d-TGCT) is a rare, locally aggressive neoplasm of joint and tendon sheath synovia, which may severely affect patients (pts) QOL due to pain, limited joint function and destruction of bone and local tissues. This study analyzes real-world data to describe d-TGCT pt journey and QOL in the US. Methods: The TGCT Observational Platform Project (TOPP), the first non-interventional prospective disease registry, enrolled d-TGCT pts at 10 Western European (EU) and 2 US sarcoma centers from Nov 2016 to Mar 2019, with prospective follow-up of 24 mo. Pts demographics, disease history and ongoing medical treatment and pt-reported outcomes (PROs) (pain, stiffness, PROMIS Physical Function [PF] and EQ-5D) were collected at baseline and every 6 mo during follow-up periods. Descriptive analyses from baseline compared US pts with Western EU pts (Table). Results: Of 166 d-TGCT pts, 30 were enrolled in the US. Mean age was 40.6 ± 12.82 y, with 63.3% female and 66.7% with tumor in knee. Median time from first symptom to diagnosis was 12 mo (range; 0–153). 28 pts (93.3%) had surgery, 4 pts (13.3%) had tyrosine kinase inhibitors (TKI), no pts had radiotherapy. 18 pts (60%) experienced &gt;1 locoregional recurrence. Median Pain Severity Score (PSS) and Pain Interference Score (PIS) were 2.8 and 3.0, respectively. Median PROMIS PF Score was 39.8. Mean EQ-5D index score and visual analogue scale (VAS) were 0.73 ±0.229 and 75.5 ±13.31, respectively. Compared with Western EU pts, US pts reported similar PROs and QOL, were younger, had shorter delay in diagnosis, and lower use of systemic therapy or radiotherapy (Table). Conclusions: d-TGCT affects a relatively young population in the US, similar to Western EU, resulting in serious impairment in daily activities and QOL. Shorter diagnostic delay and less frequent use of non–surgical approach was observed in the US. [Table: see text]