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