Fracture risk after intralesional curettage of atypical cartilaginous tumors.

INTRODUCTION: The need for curettage of atypical cartilaginous tumors (ACT) is under debate. Curretage results in defects that weaken the bone potentially leading to fractures. The purpose of this study was to retrospectively determine postoperative fracture risk after curettage of chondroid tumors, including patient-specific characteristics that could influence fracture risk. METHODS: A total of 297 adult patients who underwent curettage of an ACT followed by phenolisation and augmentation were retrospectively evaluated. Explanatory variables were, sex, age, tumor size, location, augmentation type, and plate fixation. The presence of a postoperative fracture was radiologically diagnosed. Included patients had at least 90 days of follow-up. RESULTS: A total of 183 females (62%) were included and 114 males (38%), with an overall median follow-up of 3.2 years (IQR 1.6-5.2). Mean diameter of the lesions was 4.5 (SD 2.8) cm. Patients received augmentation with allograft bone (n = 259, 87%), PMMA (n = 11, 3.7%), or did not receive augmentation (n = 27, 9.1%). Overall fracture risk was 6%. Male sex (p = 0.021) and lesion size larger than 3.8 cm (p < 0.010) were risk factors for postoperative fracture. INTERPRETATION: Curettage of ACT results in an overall fracture risk of 6%, which is increased for males with larger lesions.

The effect of surgery in tenosynovial giant cell tumours as measured by patient-reported outcomes on quality of life and joint function.

AIMS: The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment. PATIENTS AND METHODS: This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years. RESULTS: A total of 206 TGCT patients, 108 localized- and 98 diffuse-type, were analyzed. Median age at diagnosis of localized- and diffuse-type was 41 years (interquartile range (IQR) 29 to 49) and 37 years (IQR 27 to 47), respectively. SF-36 analyses showed statistically significant and clinically relevant deteriorated preoperative and immediate postoperative scores compared with general Dutch population means, depending on subscale and TGCT subtype. After three to six months of follow-up, these scores improved to general population means and continued to be fairly stable over the following years. VAS scores, for both subtypes, showed no statistically significant or clinically relevant differences pre- or postoperatively. In diffuse-type patients, the improvement in median WOMAC score was statistically significant and clinically relevant preoperatively versus six to 24 months postoperatively, and remained up to five years' follow-up. CONCLUSION: Patients with TGCT report a better HRQoL and joint function after surgery. Pain scores, which vary hugely between patients and in patients over time, did not improve. A disease-specific PROM would help to decipher the impact of TGCT on patients' daily life and functioning in more detail. Cite this article: Bone Joint J 2019;101-B:272-280.

Surgical Treatment of Localized-Type Tenosynovial Giant Cell Tumors of Large Joints: A Study Based on a Multicenter-Pooled Database of 31 International Sarcoma Centers.

BACKGROUND: Localized-type tenosynovial giant cell tumor (TGCT) is a rare, neoplastic disease with only limited data supporting treatment protocols. We describe treatment protocols and evaluate their oncological outcome, complications, and functional results in a large multicenter cohort of patients. A secondary study aim was to identify factors associated with local recurrence after surgical treatment. METHODS: Patients with histologically proven localized TGCT of a large joint were included if they had been treated between 1990 and 2017 in 1 of 31 tertiary sarcoma centers. Of 941 patients with localized TGCT, 62% were female. The median age at initial treatment was 39 years, and the median duration of follow-up was 34 months. Sixty-seven percent of the tumors affected the knee, and the primary treatment at the tertiary center was 1-stage open resection in 73% of the patients. Proposed factors for predicting a first local recurrence after treatment in the tertiary center were tested in a univariate analysis, and those that demonstrated significance were subsequently included in a multivariate analysis. RESULTS: The localized TGCT recurred in 12% of all cases, with local-recurrence-free rates at 3, 5, and 10 years of 88%, 83%, and 79%, respectively. The strongest factor for predicting recurrent disease was a prior recurrence (p < 0.001). Surgical treatment decreased pain and swelling in 71% and 85% of the patients, respectively, and such treatment was associated with complications in 4% of the patients. Univariate and multivariate analyses of the patients who had not undergone therapy previously yielded positive associations between local recurrence and a tumor size of ≥5 cm versus <5 cm (hazard ratio [HR] = 2.50; 95% confidence interval [CI] = 1.32 to 4.74; p = 0.005). Arthroscopy (versus open surgery) was significantly associated with tumor recurrence in the univariate analysis (p = 0.04) but not in the multivariate analysis (p = 0.056). CONCLUSIONS: Factors associated with recurrence after resection of localized-type TGCT were larger tumor size and initial treatment with arthroscopy. Relatively low complication rates and good functional outcomes warrant an open approach with complete resection when possible to reduce recurrence rates in high-risk patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Long-term efficacy of imatinib mesylate in patients with advanced Tenosynovial Giant Cell Tumor.

Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1-80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1-2 (89%). Five patients experienced grade 3-4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments.

Treatments of tenosynovial giant cell tumours of the temperomandibular joint: a report of three cases and a review of literature.

Tenosynovial giant cell tumours (TGCTs) are benign lesions affecting synovial joints. The classified subtypes are localized and diffuse. They seldom occur in the temporomandibular joint (TMJ). The aim of this study is to report on three new cases and to review the literature. One patient had surgical debulking with adjuvant external beam radiation therapy (EBRT). After 1year of follow-up, no evidence of disease was presented. The second patient was misdiagnosed and treated with denosumab. Debulking with adjuvant EBRT followed. Ten months postoperatively, no disease progression was seen. The third patient received systemic nilotinib and remained stable for over 5years. The literature review included 106 cases of which 95 had diffuse subtype. Most patients, had surgical excision. Thirteen (14%) patients received adjuvant EBRT. Eleven (14%) recurrences were identified. After 1-, 5- and 10 years of follow-up, an overall progression-free survival (PFS) of 99% (95% confidence interval (CI) 0.96-1), 80% (95% CI 0.68-0.94), 67% (95% CI 0.51-0.90) was calculated, respectively. Treatments for diffuse-TGCT-TMJ should be individualized depending on age, severity of symptoms, extent of disease and progression, expected mutilation of surgical interference, and current systemic treatment options. In stable disease a 'wait and see' policy, is a viable option. Additional treatments should be reserved for symptomatic, irresectable tumours or residual disease after surgical treatment with persistent complaints.

Severity classification of Tenosynovial Giant Cell Tumours on MR imaging.

AIM: Current development of novel systemic agents requires identification and monitoring of extensive Tenosynovial Giant Cell Tumours (TGCT). This study defines TGCT extension on MR imaging to classify severity. METHODS: In part one, six MR parameters were defined by field-experts to assess disease extension on MR images: type of TGCT, articular involvement, cartilage-covered bone invasion, and involvement of muscular/tendinous tissue, ligaments or neurovascular structures. Inter- and intra-rater agreement were calculated using 118 TGCT MR scans. In part two, the previously defined MR parameters were evaluated in 174 consecutive, not previously used, MR-scans. TGCT severity classification was established based on highest to lowest Hazard Ratios (HR) on first recurrence. RESULTS: In part one, all MR parameters showed good inter- and intra-rater agreement (Kappa≥0.66). In part two, cartilage-covered bone invasion and neurovascular involvement were rarely appreciated (<13%) and therefore excluded for additional analyses. Univariate analyses for recurrent disease yielded positive associations for type of TGCT HR12.84(95%CI4.60-35.81), articular involvement HR6.00(95%CI2.14-16.80), muscular/tendinous tissue involvement HR3.50(95%CI1.75-7.01) and ligament-involvement HR4.59(95%CI2.23-9.46). With these, a TGCT severity classification was constructed with four distinct severity-stages. Recurrence free survival at 4 years (log rank p < 0.0001) was 94% in mild localized (n56, 1 recurrence), 88% in severe localized (n31, 3 recurrences), 59% in moderate diffuse (n32, 12 recurrences) and 36% in severe diffuse (n55, 33 recurrences). CONCLUSION: The proposed TGCT severity classification informs physicians and patients on disease extent and risk for recurrence after surgical treatment. Definition of the most severe subgroup attributes to a universal identification of eligible patients for systemic therapy or trials for novel agents.

Cryosurgery as Additional Treatment in Tenosynovial Giant Cell Tumors.

Introduction. Tenosynovial giant cell tumors (TGCT) emerge from the synovium and can behave aggressively. Surgical resection is the standard treatment. However, up to half of the patients with diffuse type show recurrences. Several additional treatments have been applied to reduce recurrences; none of these treatments was proven to be superior to surgical resection solely. This article describes the results of additional cryosurgery to surgical resection. Materials and Methods. We retrospectively evaluated 141 TGCT patients, between 1999 and 2007. Twelve patients had additional cryosurgery. The knee (n = 8), hip (n = 2), ankle (n = 1), and elbow (n = 1) were affected. Primary outcome variables were treatment indications, recurrences, and complications. Results. Indications for additional cryosurgery were extended disease, bone involvement, and locations that are difficult to surgically get disease-free such as cruciate ligaments. Five patients had recurrent disease, all of which had prior treatments. None of the primary treated patients had recurrent disease. One patient had a deep infection. Discussion. Cryosurgery may serve as an additional treatment for diffuse TCGT in selected cases. However, because of the small number of patients and the heterogeneous group we could not prove an advantage of additional cryosurgery over surgical resection only. Cryosurgery should be considered for further evaluation in a prospective study. If there is any effect it would be helpful, especially in patients with multiple TGCT recurrences.