Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study.

BACKGROUND: Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a mono-articular, soft-tissue tumor. Although it can behave locally aggressively, D-TGCT is a non-malignant disease. This is the first study describing the natural course of D-TGCT and evaluating active surveillance as possible treatment strategy. METHODS: This retrospective, multicenter study included therapy naïve patients with D-TGCT from eight sarcoma centers worldwide between 2000 and 2019. Patients initially managed by active surveillance following their first consultation were eligible. Data regarding the radiological and clinical course and subsequent treatments were collected. RESULTS: Sixty-one patients with primary D-TGCT were initially managed by active surveillance. Fifty-nine patients had an MRI performed around first consultation: D-TGCT was located intra-articular in most patients (n = 56; 95 %) and extra-articular in 14 cases (24 %). At baseline, osteoarthritis was observed in 13 patients (22 %) on MRI. Most of the patients' reported symptoms: pain (n = 43; 70 %), swelling (n = 33; 54 %). Eight patients (13 %) were asymptomatic. Follow-up data were available for 58 patients; the median follow-up was 28 months. Twenty-one patients (36 %) had radiological progression after 21 months (median). Eight of 45 patients (18 %) without osteoarthritis at baseline developed osteoarthritis during follow-up. Thirty-seven patients (64 %) did not clinically deteriorate during follow-up. Finally, eighteen patients (31 %) required a subsequent treatment. CONCLUSION: Active surveillance can be considered adequate for selected therapy naïve D-TGCT patients. Although follow-up data was limited, almost two-thirds of the patients remained progression-free, and 69 % did not need treatment during the follow-up period. However, one-fifth of patients developed secondary osteoarthritis. Prospective studies on active surveillance are warranted.

The Prognostic Relevance of MRI Characteristics in Myxofibrosarcoma Patients Treated with Neoadjuvant Radiotherapy.

To improve local control, neoadjuvant radiotherapy (nRT) followed by surgery is the standard of care in myxofibrosarcoma (MFS) because of its infiltrative growth pattern. Nevertheless, local recurrence rates are high. Data on prognostic factors for poor clinical outcomes are lacking. This retrospective study thus investigates the prognostic relevance of magnetic resonance imaging (MRI) characteristics before and after nRT in 40 MFS patients, as well as their association with disease-free survival (DFS) and overall survival (OS). A vascular pedicle, defined as extra-tumoral vessels at the tumor periphery, was observed in 12 patients (30.0%) pre-nRT and remained present post-nRT in all cases. Patients with a vascular pedicle had worse DFS (HR 5.85; 95% CI 1.56-21.90; p = 0.009) and OS (HR 9.58; 95% CI 1.91-48.00; p = 0.006). An infiltrative growth pattern, referred to as a tail sign, was observed in 22 patients (55.0%) pre-nRT and in 19 patients (47.5%) post-nRT, and was associated with worse DFS post-nRT (HR 6.99; 95% CI 1.39-35.35; p = 0.019). The percentage of tumor necrosis estimated by MRI was increased post-nRT, but was not associated with survival outcomes. The presence of a tail sign or vascular pedicle on MRI could support the identification of patients at risk for poor clinical outcomes after nRT.

One-Stage Synovectomies Result in Improved Short-Term Outcomes Compared to Two-Stage Synovectomies of Diffuse-Type Tenosynovial Giant Cell Tumor (D-TGCT) of the Knee: A Multicenter, Retrospective, Cohort Study.

Diffuse-type tenosynovial giant cell tumors' (D-TGCTs) intra- and extra-articular expansion about the knee often necessitates an anterior and posterior surgical approach to facilitate an extensive synovectomy. There is no consensus on whether two-sided synovectomies should be performed in one or two stages. This retrospective study included 191 D-TGCT patients from nine sarcoma centers worldwide to compare the postoperative short-term outcomes between both treatments. Secondary outcomes were rates of radiological progression and subsequent treatments. Between 2000 and 2020, 117 patients underwent one-stage and 74 patients underwent two-stage synovectomies. The maximum range of motion achieved within one year postoperatively was similar (flexion 123-120°, p = 0.109; extension 0°, p = 0.093). Patients undergoing two-stage synovectomies stayed longer in the hospital (6 vs. 4 days, p < 0.0001). Complications occurred more often after two-stage synovectomies, although this was not statistically different (36% vs. 24%, p = 0.095). Patients treated with two-stage synovectomies exhibited more radiological progression and required subsequent treatments more often than patients treated with one-stage synovectomies (52% vs. 37%, p = 0.036) (54% vs. 34%, p = 0.007). In conclusion, D-TGCT of the knee requiring two-side synovectomies should be treated by one-stage synovectomies if feasible, since patients achieve a similar range of motion, do not have more complications, but stay for a shorter time in the hospital.

The route to diagnosis of sarcoma patients: Results from an interview study in the Netherlands and the United Kingdom.

INTRODUCTION: Sarcomas are rare tumours. Early diagnosis is challenging, but important for local control and potentially survival and quality of life(QoL). We investigated (1)the route to diagnosis (RtD) experienced by sarcoma patients, including factors contributing to the length of the RtD from patients' perspective; (2)the impact of the RtD on QoL and care satisfaction; and (3)differences in aims 1-2 between English and Dutch patients. METHODS: Fifteen sarcoma patients from The Royal Marsden Hospital, United Kingdom, and Radboud University Medical Centre, The Netherlands, were interviewed, exploring RtD experiences. Interviews were analysed according to qualitative content analysis. RESULTS: The main themes were: patient interval, diagnostic interval, reflection on the RtD and recommendations for improvement. Patient interval was long if symptoms were attributed as benign, did not interfere with daily life or were expected to cease. An incorrect working diagnosis, ineffective process of additional investigations, long referral times and lack of a lead clinician lengthened the diagnostic interval. Long waiting times, false reassurance and inadequate information provision led to dissatisfaction and a high emotional burden. Factors for improvement included increasing awareness of patients and healthcare providers, empowering patients, and having a lead clinician. CONCLUSION: The RtD of sarcoma patients is complex. Increasing awareness of patients and healthcare providers may contribute to shorten the RtD.

Radiologic follow-up of untreated enchondroma and atypical cartilaginous tumors in the long bones.

BACKGROUND AND OBJECTIVES: Both enchondroma and atypical cartilaginous tumors (ACT) are not considered malignant, so inactive and asymptomatic tumors might not need surgery. To the best of our knowledge, this is the first study that has been done to evaluate the natural course of conservative-treated enchondroma and ACT in the long bones. METHODS: For this retrospective study, we analyzed the results of patients in whom we refrained from surgery and only regularly performed radiological follow-up of the tumor. Minimal follow-up after initial diagnosis was 24 months. RESULTS: Forty-nine patients were included in this study. Eight out of forty-nine cases received surgical treatment during follow-up of the tumor. The reasons for this surgery were radiologic growth of the tumor in two cases, pain in one case, patient request in three cases, another indication for surgery in the same limb in two cases. CONCLUSION: In this small series of conservatively treated enchondroma and ACT, only 6% of the patients had a medical indication for surgery. This study shows that indication for surgery should be discussed more thoroughly. Based on our results, we would recommend annual radiologic follow-up for asymptomatic enchondroma or ACT in the long bones, irrespective of tumor size. J. Surg. Oncol. 2016;114:987-991. © 2016 Wiley Periodicals, Inc.

Maturation toward neuronal tissue in a Ewing sarcoma of bone after chemotherapy.

BACKGROUND: Ewing sarcoma is the second most common bone tumor, occurring mainly in children and young adults. It shows a typical primitive, small round cell morphology and a characteristic fusion oncogene involving EWSR1 and members of the ETS family in most of the cases. Neuronal maturation after chemotherapy is a rare phenomenon and we herein describe such an exceptional case. CASE PRESENTATION: An 8-year old boy was diagnosed with a Ewing sarcoma in the left femur. On biopsy the morphology was typical and there was an EWSR1-FLI1 gene fusion. He underwent neo-adjuvant chemotherapy and resection of the tumor. On microscopic evaluation, part of the tumor showed ganglioneuroblastoma-like differentiation with expression of neuronal markers. The continued presence of EWSR1 rearrangement in both the blue round cell component and the ganglioneuroblastoma-like component was shown by FISH analysis. CONCLUSIONS: In conclusion, this case describes the possibility of a Ewing sarcoma to differentiate into a ganglioneuroblastoma-like lesion after neo-adjuvant chemotherapy treatment; the prognostic value of this phenomenon remains questionable.

IGF signaling pathway analysis of osteosarcomas reveals the prognostic value of pAKT localization.

AIM: The aim of this study was to examine the expression of the IGF signaling pathway components in osteosarcoma samples before and after chemotherapy with special emphasis on their prognostic value. MATERIALS & METHODS: Tumor material and follow-up data of 58 osteosarcoma patients were analyzed. Immunohistochemical staining was carried out to identify proteins related to the IGF pathway. Changes in protein expression during treatment, correlations between proteins and subsequent influence on survival were tested. RESULTS: Proteins of the IGF signaling system are widely expressed in osteosarcoma samples. We demonstrate a change in expression of intracellular pathway proteins after chemotherapy. Remarkably, cytoplasmic pAKT, but not nuclear pAKT, is associated with poor survival. CONCLUSION: IGF pathway proteins seem to be widely activated in osteosarcoma, but their expression changes after chemotherapy. This has implications for the timing of both measuring target expression and pathway interference. Our observations on the prognostic value of cytoplasmic pAKT warrant further investigation while considering the introduction of AKT inhibitors for osteosarcoma treatment.

F-18 FDG PET/CT as a crucial guide toward optimal treatment planning in a case of postirradiation sarcoma 10 years after primary bone lymphoma of the pelvis.

Ten years after chemoradiation for primary lymphoma of the left pelvic bone, a 38-year-old man presented with a 4-month history of gradually increasing pain in his left upper leg and thigh. Initial radiographs and contrast-enhanced magnetic resonance imaging were consistent with recurrent lymphoma, infection, or postirradiation sarcoma. Subsequent F-18 fluorodeoxyglucose positron emission tomography/computed tomography demonstrated a focal area of F-18 fluorodeoxyglucose-avidity within the previously irradiated bone consistent with tumor and the location was confirmed by advanced magnetic resonance imaging techniques and histopathology, thus optimizing treatment planning.

The stability of impacted morsellized bone grafts in a metal cage under dynamic loaded conditions: an in vitro reconstruction of a segmental diaphyseal bone defect.

INTRODUCTION: Reconstructions of segmental diaphyseal bone defects with massive allografts are related to complications like nonunion and fractures. A reconstruction of these defects with a cage filled with an impacted morsellized bone graft could be an alternative. The bone graft in these cages should ideally be loaded to prevent resorption. Loading of morsellized bone grafts however can cause instability. The goal of this study was to assess the stability of an impacted morsellized bone graft in a cage under dynamic loaded conditions in an in vitro reconstruction of a segmental diaphyseal bone defect. The second goal was to assess the influence of cage type, washing of the graft and bone-cage fit. MATERIALS AND METHODS: Two different cage types were filled with impacted morsellized bone graft. The grafts were used washed and unwashed and in variable bone-cage fit conditions. We recorded the bone graft deformation in the cage under dynamic loaded conditions. RESULTS: Stability appeared to be not very sensitive to the cage type and whether the bone chips were washed or not. However, quality of the fit of the cage with the bone segment was an important parameter and should be optimized during surgery. CONCLUSIONS: Morsellized impacted bone graft in a cage is stable in dynamic loaded conditions in an in vitro reconstruction of a segmental diaphyseal bone defect. We believe that this method of reconstruction is a promising alternative for the reconstruction of large diaphyseal bone defects and should be tested relative to its biological merits in animal experiments.

Cryosurgery in aggressive, benign, and low-grade malignant bone tumours.

Cryosurgery is a method of treatment for various tumours that induces tissue necrosis with ablative intent. It is used in benign, aggressive, and low-grade malignant bone tumours such as chondrosarcoma grade 1. We describe the history of the technique and the issues associated with cryobiology, as well as the indications, technique, complications, and results of cryosurgery. At the University Medical Centre Nijmegen, Netherlands, 302 tumours have been treated by use of cryosurgery with at least 2 years' follow-up. 96-100% of patients were cured-the response depended on tumour type. Comparison of functional results with data from studies shows that these results concur with other studies on cryosurgery, and are at least equal to results of marginal excision and mostly better than those of wide excisions of grade 1 chondrosarcomas. Thus from an oncological point of view, cryosurgery combined with intralesional excision is equal to marginal excision.

Limb salvage in musculoskeletal oncology.

Since the early 1970s, substantial progress in dealing with musculoskeletal tumours has been made, with improvements in surgical skills, radiology, chemotherapy, pathology, and radiotherapy. Nowadays, 70-85% of all malignant tumours are treated by limb salvage, without compromising the oncological result. After many years, the functional result that may be achieved with a limb-saving procedure is becoming clear. Limb salvage has cosmetic advantages, but whether the quality of life of these patients is superior to that of those who undergo amputation is unclear. The non-oncological complication rate is much higher after limb salvage than after amputation, and consequently additional surgery is necessary. In the future, the co-operating disciplines should strive for better survival of these patients, for which the development of new chemotherapeutic drugs is especially needed.