Aims

Myxofibrosarcomas (MFSs) are malignant soft-tissue sarcomas characteristically presenting as painless slowly growing masses in the extremities. Locally infiltrative growth means that the risk of local recurrence is high. We reviewed our experience to make recommendations about resection strategies and the role of the multidisciplinary team in the management of these tumours.

Introduction. Myxofibrosarcoma is described by WHO as comprising of a spectrum of malignant fibroblastic lesions with variably myxoid stoma, pleomorphism and with a distinctively curvilinear vascular pattern. They are reported to be one of the commonest sarcomas of elderly patients. It has previously been reported to have a high rate of locally recurrent disease (50-60%). The aim of the study was to investigate the ROH series of tumours to determine prognostic factors for survival and local recurrence. Methods. Patients were identified from the ROH database who had been treated with a new presentation of myxofibrosarcoma. The size, grade and depth of the tumour at presentation was noted. Those patients who had suffered local or distal disease relapse or died were highlighted. Analysis was undertaken by Kaplan Meier survival curves for univariate and cox regression for multivariate analysis. Results. 90 patients were indentified who had undergone surgery for myxofibrosarcoma. The mean age was 65 years (range 23-93 years) with an equal male to female ratio. They presented deep to fascia in 49 cases (54%) and were most commonly located in the lower extremity in 53 cases (59%) with 32 cases being in the thigh. The maximum dimension at presentation was 9cm (range 0.3 to 42cm). The grade at presentation was high in 41 cases, intermediate in 35 cases and low in 14 cases. The risk of local recurrence was 25% at 5 years and was independent of margin or size. Overall survival was 59% at 5 years with high grade tumours being the only independent prognostic factor for survival at 5 years (HR=10). Conclusion. Myxofibrosarcoma is a tumour that often presents superficially with a high rate of local recurrence. Other studies (Gronchi 2010) have suggested that size and surgical margins were prognostic but this was not seen in our study

Background. Although soft tissue sarcoma (STS) is a rare malignancy, myxofibrosarcoma is a common form diagnosed. Myxofibrosarcoma is complicated by a high local recurrence rate (18–54%) and significant morbidity following treatment, hence management can be challenging. Patients and Methods. Patients treated between 2003–2012 were identified via a database within the histopathology department and case notes were retrospectively assessed. All histology samples were reviewed by a senior histopathologist to ensure a correct diagnosis. Results. 29 patients (12 male, 17 female) with an average age of 61 years (range 19–89 years) underwent surgery at a single centre, with 24 patients receiving adjuvant and two receiving neo-adjuvant radiotherapy. 22 patients had lower limb and 7 had upper limb tumours. 3 were treated for secondary recurrence after having primary surgery elsewhere. 21 patients had Trojani Grade 2 or 3 tumours. All underwent limb-sparing surgery initially but six patients (20.7%) suffered local recurrence after an average follow-up of 28 months and all ultimately required above knee amputation. Four patients developed wound infection, with one requiring VAC therapy. One patient required a flap repair of the forearm. 5-year survival rate was 87.5%. Conclusions. Our results compare favourably against results published so far in the literature with a low local recurrence rate and mortality. Limb-sparing surgery aims to reduce morbidity and disability following treatment but more research is required in adjuvant treatments to further reduce the risk of local recurrence of tumour

Background. Myxofibrosarcomas are malignant soft tissue tumours that often present as painless slowly growing masses in the extremities of older males. Locally infiltrative growth means risks of local recurrence is high. Management emphasises negative surgical margins and adjuvant therapy. The aim of this retrospective case series was to review our experience of this tumour, and make recommendations about a minimum resection margin and how best to utilise the expertise of the multidisciplinary team. Methods. A computerised database identified patients with myxofibrosarcoma surgically treated in our centre between 1997 and 2011. Clinical records were reviewed. Margins were positive if tumour was at or within 1mm of the resection plane. Results. 43 patients (median age 68.6 years; 70% male) were identified. 42 underwent surgery: 26 (62%) by orthopaedics; 9 (21%) by plastics, and 7 (17%) jointly. The lower limb was the most common site (30/43, 70%). Mean tumour size was 5.9cm (range 1.5 to 20cm). 53% had grade III tumours. Of 39 tumours with available data, 21 were superficial fascially-based masses and 18 were deep. 23 (55%) had positive margins. Of these, 9 underwent re-excision, 5 of whom had adjuvant radiotherapy. 13 of the remaining 14 patients had adjuvant radiotherapy. Of the fascially-based tumours, there was microscopic spread beyond the macroscopic mass of between 3–25mm. 3 patients (7%) developed local recurrence at a mean of 25 months (14 to 30 months). 12 (29%) had metastases at a mean of 19 months (range 7 to 48 months). Conclusion. Myxofibrosarcoma poses a number of challenges for sarcoma teams; in particular, high positive margin rates, risks of further surgery and local failure. The infiltrative nature makes it suited to management by multidisciplinary teams. Microscopic tumour can present up to 2.5cm from the macroscopic mass for fascially-based tumours, and teams should plan appropriately

Purpose. Mesenchymal stromal cells (MSCs) are an attractive choice for regenerative medicine. We previously showed that MSCs enhance wound healing in animals after radiotherapy. The effect of MSCs on tumor growth is not well understood. The potential use of MSCs to enhance wound healing after radiotherapy (RT) and resection of soft tissue sarcoma (STS) is dependent on a satisfactory safety profile to ensure that tumor proliferation does not occur and recurrence is not increased. Method. Primary cell lines (human myxofibrosarcoma and undifferentiated sarcoma) derived from sarcoma bearing patients and a commercialized human fibrosarcoma cell line (HT1080) were used. Cell line proliferation assay after co-culture with MSCs was done using flow cytometry (CFSE) and bioluminescence emission (BLI) (using eGFP/Fluc transduced cell lines). Five xenograft models were developed with NOD/SCID gc-null mice (n=164) harbouring primary tissue lines obtained from patients biopsies (myxofibrosarcoma and three pleomorphic undifferentiated sarcoma [PUS A, B and C]) and a a fibrosarcoma cell line previously transduced with eGFP/Fluc. Tumors were passaged to three mouse generations before a tissue line was established and the model was then used. For the fibrosarcoma model, eGFP/Fluc HT1080 were injected under the dorsal skin. When tumors reached 1cm in diameter, they received localized RT and 48hr later were resected. MSCs (n=82) or medium alone (n=82) was injected subcutaneously adjacent to the wound after tumor resection. Histological and in vivo BLI analysis were performed 3 and 12 weeks after surgery. Results. In Vitro Proliferation Assay. For the flow cytometric proliferation assay, there was an increase in the doubling time after five days in the myxofibrosarcoma-MSCs co-culture system (140.4h) compared with controls (55.4 h, p<0.001). No significant differences were found in other cells lines. Lower BLI emission was found in co-cultured myxofibrosarcoma cells at the 3rd and 4th day compared with controls (p<0.01 and p<0.05 respectively). In Vivo Recurrence Assay. For mice bearing the fibrosarcoma cell line, in vivo BLI performed 3 weeks after surgery showed similar emission intensity in MSC-treated mice and controls while histological recurrence was significantly lower in MSC-treated animals (40%) than control (72%, p=0.045). For mice bearing the myxofibrosarcoma tissue line, histological recurrence at 12 weeks was similar in MSCs-treated animals and controls (p=0.44). Mice xenografted with pleomorphic undifferentiated sarcoma A and B did not develop local tumor recurrence after histological analysis, while pleomorphic undifferentiated sarcoma C showed similar recurrence in MSC and medium treated mice (p=0.46). Conclusion. We showed that MSCs decrease the proliferation rate of the myxofibrosarcoma cell line in vitro and have no effect, or even decrease, local recurrence of different STS tissue lines in vivo after RT and resection. Clinical investigation of this approach is warranted

Myxofibrosarcoma (MFS) is the second most common subtype of soft tissue sarcoma (STS) and is associated with a high rate of local recurrence after resection. These tumours frequently present with peri-lesional edema, termed “tumour tails” on staging MRI scans [1]. Tumour tails(TT) may contain satellite neoplastic cells or can represent benign reactive edema. There are no clear radiological features to distinguish malignant from reactive peri-lesional edema which limits accurate surgical planning, resulting in either high rates of inadvertently positive resection margins and local recurrences or overly-aggressive resections which negatively impact function and increase morbidity [2]. The objective of this pilot study was to prospectively study a cohort of MFS patients with TTs in an attempt to identify radiological features that predict which type of edema is malignant and requires resection together with the main tumour mass. Patients diagnosed with MFS on biopsy at an orthopaedic oncology referral centre between January 1-December 31 2018 who also had TTs on staging MRI scans were prospectively recruited for the study. Tumours were treated with wide surgical excision, including the TTs, and (neo)adjuvant radiotherapy as per institutional protocol. Staging MRI scans were reviewed in a blinded fashion by two musculoskeletal radiologists to distinguish malignant from reactive TTs. The main tumour mass underwent standard histological evaluation while the regions encompassing the TTs were photographed and sectioned into grids. Each tissue section was examined histologically for the presence of satellite neoplastic cells based on morphological criteria. Radiological and histological findings were compared. Six patients met the inclusion criteria and underwent analysis. All tumours were located in the extremities and were deep to fascia. Mean age at presentation was 67 years (range 51 – 85), with a male:female ratio of 4:2. All patients received radiotherapy (50 Gy), either pre- (n=4) or post-operatively (n=2) based on multidisciplinary tumor board discussion or enrolment in a prospective clinical trial. Radiologically, TTs were labelled as malignant in four patients (66.7%) and as benign TTs in two others. The tails were recognised to be malignant due to the differing signal characteristics to reactive edema on mixed MRI sequences. The radiological evaluation correlated exactly with histological analysis, as satellite neoplastic cells were identified microscopically in the same four cases in which the TTs were designated to be malignant by MRI (specificity&sensitivity=100%). Surgical resection margins were microscopically positive in 50% of cases in the TTs themselves, and 75% of cases in which TTs were designated as malignant on staging MRI. “The malignant nature of peri-lesional edema in MFS, also known as the TT, was accurately predicted in this small pilot study based on specific radiological features which correlated exactly with histologic identification of isolated tumor cells. These findings validate development of a larger prospective study to recruit additional patients with tumor tails beyond just MFS, in order to more robustly study the correlation between the MRI appearance and histological distribution of satellite sarcoma cells in peri-lesional edema in STS. We are already recruiting to this expanded radiological-histological investigation including evaluation of additional novel MRI sequences

The rate of fracture and subsequent nonunion after radiation therapy for soft-tissue sarcomas and bone tumors has been demonstrated to quite high. There is a paucity of data describing the optimal treatment for these nonunions. Free vascularized fibular grafts (FVFG) have been used successfully in the treatment of large segmental bone defects in the axial and appendicular skeleton, however, their efficacy with respect to treatment of radiated nonunions remains unclear. The purpose of the study was to assess the 1) union rate, 2) clinical outcomes, and 3) complications following FVFG for radiation-induced femoral fracture nonunions. We identified 24 patients who underwent FVFG for the treatment of radiation-induced femoral fracture nonunion between 1991 and 2015. Medical records were reviewed in order to determine oncologic diagnosis, total preoperative radiation dose, type of surgical treatment for the nonunion, clinical outcomes, and postoperative complications. There were 11 males and 13 females, with a mean age of 59 years (range, 29 – 78) and a mean follow-up duration of 61 months (range, 10 – 183 months). Three patients had a history of diabetes mellitus and three were current tobacco users at the time of FVFG. No patient was receiving chemotherapy during recovery from FVFG. Oncologic diagnoses included unspecified soft tissue sarcomas (n = 5), undifferentiated pleomorphic sarcoma (UPS) (n = 3), myxofibrosarcoma (n = 3), liposarcoma (n = 2), Ewing's sarcoma (n = 2), lymphoma (n = 2), hemangiopericytoma, leiomyosarcoma, multiple myeloma, myxoid chondrosarcoma, myxoid liposarcoma, neurofibrosarcoma, and renal cell carcinoma. Mean total radiation dose was 56.3 Gy (range, 39 – 72.5), given at a mean of 10.2 years prior to FVFG. The average FVFG length was 16.4 cm. In addition to FVFG, 13 patients underwent simultaneous autogenous iliac crest bone grafting, nine had other cancellous autografting, one received cancellous allograft, and three were treated with synthetic graft products. The FVFG was fixed as an onlay graft using lag screws in all cases, additional fixation was obtained with an intramedullary nail (n = 19), dynamic compression plate (n = 2), blade plate (n = 2), or lateral locking plate (n = 1). Nineteen (79%) fractures went on to union at a mean of 13.1 months (range, 4.8 – 28.1 months). Musculoskeletal Tumor Society scores improved from eight preoperatively to 22 at latest follow-up (p < 0.0001). Among the five fractures that failed to unite, two were converted to proximal femoral replacements (PFR), two remained stable pseudarthroses, and one was converted to a total hip arthroplasty. A 6th case did unite initially, however, subsequent failure lead to PFR. Seven patients (29%) required a second operative grafting. There were five additional complications including three infections, one wound dehiscence, and one screw fracture. No patient required amputation. Free vascularized fibular grafts are a reliable treatment option for radiation-induced pathologic femoral fracture nonunions, providing a union rate of 79%. Surgeons should remain cognizant, however, of the elevated rate of infectious complications and need for additional operative grafting procedures

Aims

The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients.

Liposarcoma is the most common soft tissue sarcoma accounting for 20% of all mesenchymal malignancies.We report a rare histological variant arising from the dorsum of the foot. A 55 year old lady presented with a slow growing, well defined swelling on the dorsum of the foot. Histological examination following complete excision showed a tumor with zones of dense collagenous tissue containing pleomorphic spindle cells and scattered atypical adipocytes. A diagnosis of spindle cell sarcoma was made and referred to the local Sarcoma unit. Repeat excision and histology confirmed margins free of tumor. Four years after primary excision, patient is well with no evidence of recurrence or metastasis. Spindle cell liposarcoma is a rare variant of well differentiated liposarcoma characterized by prominent spindle cell component. Previously reported cases originated in the subcutaneous tissues of shoulder girdle and upper limb. Main differential diagnoses include benign lesions such as spindle cell lipoma, and diffuse neurofibroma as well as dermatofibrosarcoma pro-tuberans and other malignancies such as sclerosing liposarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumor and fibromyxoid sarcoma. Spindle cell Liposarcomas tend to recur locally and may dedifferentiate with a potential for metastasis. Wide excision and long term follow up looking for recurrence and metastasis is necesssary in these rare variants of liposarcoma especially those arising at atypical sites as in our case

Aims

Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment.

Knee extensor mechanism reconstruction after excision for bone or soft tissue tumors is a challenging procedure. When a resection of the patellar bone-tendon apparatus is required, an omologous graft can be used for its reconstruction to avoid knee arthrodesis and preserve a functional knee. Since 1996 we performed such a procedure in 15 cases in 14 patients. In 4 cases (Group 1) excision and reconstruction involved only the patella and the attached tendons together with the involved soft tissues. In the remaining 11 cases (Group 2) an extrarticular en-bloc knee resection was accomplished and reconstruction was obtained by a megaprosthesis to replace the distal femur and a composite allograft-prosthesis to replace proximal tibia and the extensor apparatus. One of the en-bloc knee resections was performed in a patient who had previously had an isolated extensor apparatus replacement, which was later converted to a complete knee resection and substitution after a local relapse. A free flap (anterolateral thigh) was used in 4 patients. Histotypes were as follows:. Group 1: pleomorphic sarcoma 2, synovial sarcoma 1, myxofibrosarcoma 1. Group 2: osteosarcoma 3 (distal femur 2, proximal tibia 1), Ewing sarcoma 2 (proximal tibia 1, patella 1), giant cell tumor 1 (proximal tibia), chondroblastoma 1 (distal femur) synovial sarcoma 3, pleomorphic sarcoma 1. One patient in group 2 was lost at follow-up after a few months. In the remaining patients follow-up ranged from 7 to 132 months. In Group 1 two local and one distant (groin lymphnodes in one of the two patients affected by local recurrence) relapses occurred, in Group 2 one local and 4 distant relapses (lung) occurred. One of these latter distant relapses affected the patient at the beginning in Group 1 and later converted to Group 2. Besides recurrences, 4 patients in Group 2 were affected by local complications:. one deep infection;. one extended resorption of the tibial allograft, which required a two-stage revision (extensor apparatus allograft could be saved);. one rupture of the patellar tendon allograft after almost 9 years after the first procedure. The ruptured allograft was replaced by an achilles tendon allograft;. one deep vein thrombosis. Active extension was initially obtained in all patients and, when local complications did not occur, it was stable with time. Extension lag ranged from 0 to 30°. Maximum flexion ranged from 80 to 110°. Patients could walk without brace nor aids. Allograft reconstruction after extensor apparatus excision, either alone or combined to a total knee resection, can be an efficacious option in the treatment of sarcomas of the knee

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The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh.

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The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours.

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Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment.

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Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

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Patients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry.

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The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection.

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Iliosacral sarcoma resections have been shown to have high rates of local recurrence (LR) and poor overall survival. There is also no universal classification for the resection of pelvic sarcomas invading the sacrum. This study proposes a novel classification system and analyzes the survival and risk of recurrence, when using this system.

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The existing clinical guidelines do not describe a clear indication for adjuvant radiotherapy (RT) in the treatment of superficial soft tissue sarcomas (STSs). We aimed to determine the efficacy of adjuvant RT for superficial STSs.

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Current literature suggests that survival outcomes and local recurrence rates of primary soft-tissue sarcoma diagnosed in the very elderly age range, (over 90 years), are comparable with those in patients diagnosed under the age of 75 years. Our aim is to quantify these outcomes with a view to rationalizing management and follow-up for very elderly patients.