Ewings sarcoma (EWS) is the second most common primary malignancy of bone. Five-year survival ranges between 50 and 70% for patients who present with localized disease. EWS occurs in both axial and appendicular locations. The prognostic importance of anatomic location (axial vs. appendicular) is unclear. The purpose of this study is to report a single institution experience in the management of patients with EWS, and to investigate anatomic location as a prognostic factor. After ethics board approval, we searched our prospective sarcoma database for all EWS patients treated between 1989 and 2007. Sixty-seven patients with adequate follow-up were identified and records were reviewed. Axial bone EWS was defined as originating from the spine, sacrum, pelvis, scapula, clavicle, or rib cage. Appendicular bone EWS was defined as disease from any bone in the extremities. Axial soft tissue EWS was defined as originating in the head, neck, or torso. Appendicular soft tissue EWS originated from the extremeties. Sixty-six (99%) patients received chemotherapy. Definitive local treatment was by surgical resection whenever possible (n=44). Radiation therapy (RT) was used for unresectable lesions (n=10) or to treat positive margins (n=10). The primary outcome measure was overall survival (OS) measured from the date of diagnosis to the date of death or last follow-up and estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Besides anatomic location, the variables of tumor size, metastases at diagnosis, treatment with radiation, and surgical margins were studied.Purpose
Method
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. 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.Purpose
Method
The main predictors in the literature of local control for patients operated on for a soft tissue sarcoma are age, local presentation status, depth, grade, size, surgical margins and radiation. However, due to the competing effect of death (patients who die are withdrawn from the risk of local recurrence), the influence of these predictors on the cumulative probabilities may have been misinterpreted so far. The objective of the study was to interpret the influence of known predictors of local recurrence in a competing risks setting. This single center study included 1519 patients operated on for a localized soft tissue sarcoma of the extremity or trunk. Cox models were used to estimate the cause specific hazard of known predictors on local recurrence. Cumulative incidences were estimated in a competing risks scenario.Purpose
Method
The focus of current management of soft tissue sarcoma on limb preservation often necessitates that patients undergo multimodal treatment, including both surgery and external beam radiotherapy. Pathologic fracture is a serious, late complication of radiotherapy. In patients who have also undergone wide excision of soft tissue sarcoma, nonunion rates of 80–90% persist despite optimal internal fixationMany sequelae of the treatments for soft tissue sarcoma exhibit the potential to perpetuate failure of bony union. Limb salvage surgery is associated with extensive periosteal excision, disruption of vascular supply and eradication of local osteoprogenitor cells. External beam radiotherapy leads to obliterative endarteritis, decreased osteoblast proliferation and reduction in bone matrix production. We hypothesize that the combination of radiotherapy and surgical periosteal stripping leads to greater impairment in the fracture repair process than either intervention alone will produce. We developed a method for creating a reproducible, low energy, simple femoral fracture in an animal model designed to proceed to nonunion. Female Wistar, retired breeder rats were separated into four treatment groups of 18 animals each: control, radiotherapy, surgery and combination radiotherapy and surgery. Animals were then further randomized to temporal end-points of 21, 28 and 35 days post-fracture. Designated animals first underwent external beam radiotherapy, followed by surgical stripping of the periosteum three weeks later and femoral fracture with fixation after another three weeks. Animals were sacrificed at their randomly assigned end-points.Purpose
Method
Fibromatosis is a disorder characterised by a spectrum of biological behaviour from relative indolence to aggressive local infiltration. With aimed to describe the pre and post-operative functional status of these patients managed with surgery and analyse the effect of radiotherapy on functional outcome. 43 patients were analysed in the upper and lower limb fibromatosis database in which functional data was available pre-op and at a minimum of two years post-op. Any plantar, palmer, chest or abdominal lesion was excluded as were hormonal or chemotherapy treated patients.Introduction
Methods
Fibromatosis represent a highly heterogeneous group of tumours in growth pattern, location and management. Our aim was to describe the demographics of the patient population who had undergone surgical resection and to identify predictors of local recurrence. Any lesion that was infiltrating the chest or abdominal cavity was excluded. Patients were also not included if they had a plantar or palmar lesions or had received hormonal or chemotherapy. 67 men and 88 women aged from 16 to 77 with a median age of 39 were analyzed. 121 patients had no prior resective operative intervention. 34 patients had undergone an attempted resection procedure at another unit of which 30 had locally recurred. 3 were located in the abdominal wall, 5 chest wall, 15 paraspinal, 56 lower and 76 upper limb. 40 patients did not receive XRT, 18 in the post-operative period and 97 in the pre-operative period. 67 operations produced margin negative resection, 85 were positive and 3 in which the margin status was unknown. Follow-up ranged from 1 day post op to 23.3 years. 23 patients had a local recurrence. Following subsequent re-resections, the total number of patients who were alive with evidence of disease was 16. 6 pts had deceased. 149 were alive with no evidence of disease. No factors were found to be statistically significant for predicting local recurrence, including the use of radiation (0.06) and margin status (0.81). Although radiation, given either pre or post-operatively did trend towards preventing local recurrence (HR 0.40; 95% CI 0.15 to 1.06; p = 0.06). The retention of critical structures whilst resecting fibromatosis continues to be an appropriate management strategy, as local recurrence rates seem to be independent of margin status. Although not statistically significant, the use of XRT did tend towards reducing local recurrence.Conclusions
Many authors believe that size, histological grade and depth are the best predictors of outcome in soft tissue sarcoma. Enneking’s surgical staging system included compartmental status, and was intended to guide surgical intervention as well as provide prognostic information. Advances in surgical and radiotherapy techniques may mean that extracompartmental status is no longer a poor prognostic factor. We compared a group of popliteal fossa sarcomas with a group from the posterior thigh, and found that although the former group required more extensive surgery to obtain wide margins, their functional and survival outcomes were similar. No single staging system has been generally accepted for extremity soft tissue sarcoma, although histologic grade, size and depth are widely accepted as prognostic indicators. Enneking outlined a surgical staging system which used compartmental status as a predictor of outcome. However, surgical reconstruction and adjuvant radiotherapy have advanced considerably. We wanted to know if a tumour arising in the popliteal fossa still had poorer survival or functional outcome in the light of these advances. We identified twenty-three patients who had sarcomas of the popliteal fossa and forty-six patients who had sarcomas of the nearby posterior thigh compartment. Popliteal sarcomas were not of a different size or more likely to present with metastasis. Popliteal tumours more frequently required reconstructive techniques such as local or free tissue transfer and skin grafting than posterior thigh tumours (39.1% v 4.3% respectively). Popliteal tumours were also more likely to undergo a dissection or reconstruction of the major neurovascular structures of the lower limb (30.4% v 0% respectively). There was no difference in local or systemic recurrence rates between the groups. TESS and MSTS 1987 functional scores also showed no difference between the groups. We conclude that popliteal fossa sarcomas require a greater level of surgical intervention to follow sound principles of sarcoma resection and achieve reconstruction of the ensuing soft tissue defect. However, if these principles are followed in a planned multidisciplinary setting, then survival and functional results similar to the posterior thigh can be expected.
Forty-six patients with an uncemented proximal tibial endoprosthesis were reviewed following resection of a proximal tibial tumor. The mean age was thirty-four years and the majority were male. The most common malignant diagnosis was osteosarcoma. Oncologic and functional analysis was performed on these cases. At latest follow-up thirty of the patients remain alive with no evidence of disease and eleven had died. The most common complication was deep infection (7/46). Only six patients had mechanical prosthesis related complications. At latest follow up the average TESS score was 76.3 and MSTS score 75.5 with an average extensor lag of 6.5o. To review the oncologic and functional results of a series of forty-six uncemented proximal tibia tumour replacements. A retrospective review of our prospectively collected database revealed forty-six patients with an uncemented proximal tibial replacement following tumour excision. The data was analysed with respect to patient demographics, operative and prosthetic complications. Oncologic diagnosis and results and functional results were also reviewed. The average age of the forty-six patients was thirty-four years (14–73) with thirty-three males and thirteen females. The most common diagnosis was osteosarcoma. There were four cases of benign GCT. At an average follow-up of 85.8 months (11–170), thirty were alive with no evidence of disease while eleven patients had died of their disease. Four patients were alive with evidence of disease at latest follow-up and one patient had died of unrelated causes. The most common operative complication was infection (9/46) with seven of these being deep infections requiring prosthesis removal, followed by mechanical problems including stem fracture (3/46) and bushing failure (3/46) also requiring operative intervention. Functional assessment revealed an average extensor lag of 6.5o with an average ROM of 83.6o, average TESS scores of 76.3 and MSTS 93 scores of 75.5. Large series of uncemented proximal tibial endoprostheses are uncommon in the literature. In our series there is a low rate of aseptic loosening at an average seven year follow-up, but this is offset by problems including infection and prosthetic fracture. Overall the functional and oncologic results remain satisfactory.
The unusual phenomenon of histological grade change in locally recurrent soft tissue sarcomas is examined by retrospective review of a large sarcoma database. Increased histological grade was found to occur in 20% of recurrent tumours. Several possible factors predisposing to grade change were examined, and only the histologic diagnosis of myxoid malignant fibrous histiocytoma was found to be significant. Despite increased histologic grade, these tumours do not appear to have a worse prognosis in terms of developing systemic disease. Soft tissue sarcomas (STS) have a reported local recurrence rate of between five and thirty percent. Recurrent tumours are often similar histologically to the initial tumour, however they are occasionally of higher histological grade than the original lesion. Factors that predispose to this change in grade are not known. We sought to identify the frequency at which locally recurrent STS demonstrate a change in histological grade, and to investigate the possible factors leading to this change. We also investigate whether a change in grade is associated with a poorer prognosis. We identified one hundred and seventy-three patients who developed locally recurrent STS, one hundred and twenty-four of which met inclusion criteria and who will form the basis of this study. Ninety-two patients (74%) had no change in histological grade, twenty-four (19%) demonstrated an increase in histological grade and eight (7%) a decreased histological grade. Univariate analysis of time to local recurrence, histological diagnosis and use of radiotherapy and chemotherapy did not reveal significant differences between the groups who did and did not undergo change in grade. When the diagnosis of myxoid MFH was looked at separately, there was a higher proportion in the group that developed increased histological grade. Development of a change in grade was not associated with a poorer survival rate. Increase in histological grade occurs in approximately 20% of locally recurrent STS, but this phenomenon is not associated with a poorer prognosis than if the grade remains the same. A histological diagnosis of myxoid MFH predicts for an increase in histological grade.
Two hundred and forty-one patients with extremity osteosarcoma presented to our institution between 1989 and August 2002, thirty-six of whom had a pathologic fracture. There were twenty-five limb salvage surgeries and ten primary amputations, with three limb salvage surgeries requiring secondary amputations. One patient had an unresectable tumor and was treated palliatively. At mean follow-up of 96.9 months there was one local recurrence and eighteen patients were alive without disease in the pathologic fracture group. There was no survival difference between the pathologic fracture group with no metastases at presentation and the non-pathologic fracture group with no metastases (119.4 months vs 134.3 months, log rank 0.83, p=0.36). To examine the outcome of osteosarcoma patients that present with a pathologic fracture as compared to those patients without a pathologic fracture. There was no significant difference in the rate of amputation vs limb salvage surgery in osteosarcoma patients that presented with a pathologic fracture as compared to those without. There was no difference in the two groups’ disease-free and overall survival, for those patients that presented without metastatic disease. Presentation with a pathologic fracture in osteosarcoma does not preclude limb salvage surgery and is not a prognostic indicator for decreased survival. Retrospective review of all patients presenting to our institution with extremity osteosarcoma between 1989 and August 2002. There were two hundred and forty-one patients with extremity osteosarcoma, thirty-six of whom presented with a pathologic fracture. In the pathologic fracture group, there were nineteen males and seventeen females. Twenty-five were treated with limb salvage surgery, ten required a primary amputation and one was unre-sectable. Three limb salvage surgery patients required a secondary amputation. Sevenpatients presented with metastatic disease. Twenty-eight of the thirty-six patients received (neo) adjuvant chemotherapy. At last follow-up, eighteen patients were alive no evidence of disease (51.4%), three were alive with disease, eleven were dead of disease and three were deceased from other causes. There was one local recurrence (2.8%). Mean overall survival was 119.4 months (0–147.1) for patients with a pathologic fracture and no metastasis at presentation and 134.3 months (0–172.5) for patients with no pathologic fracture and no metastasis (log rank 0.83, p=0.36).
In this paper, a retrospective review was undertaken of a large musculoskeletal tumour database to identify patients who presented with tumours of the foot and ankle. Soft tissue tumours occurred more frequently than bone tumours, and were also more frequently malignant than bone tumours. In contrast to the more recent trend towards limb-preserving surgery in other anatomic areas, malignant tumours of the foot and ankle were frequently unresectable and were treated with amputation. Although the majority of extremity tumours that present to the orthopaedic surgeon are found in the proximal limbs or around the knee, tumours of the ankle and foot are also relatively common. The purpose of this study is to identify the frequency with which benign and malignant bone and soft tissue tumours occur in the foot and ankle and the oncologic and surgical outcomes of these patients. A retrospective review of a large musculoskeletal tumor database in a tertiary referral center from the years 1986–2002 was undertaken. For oncologic outcomes, a minimum two-year follow up was considered. A total of one hundred and sixteen bone and one hundred and seventy-one soft tissue tumours were identified. Seventy-seven bone tumours were benign and thirty-nine were malignant. Sixty-six soft tissue tumours were benign and one hundred and five were malignant. The most common benign bone tumour was giant cell tumour and osteosarcoma was the most common malignancy. Malignant fibrous histiocytoma was common in the distal leg but synovial sarcoma and clear cell sarcoma were more common in the foot. Twenty patients with bone malignancies (51%) and twenty-four with soft tissue sarcomas (23%) had amputation as definitive surgical management. Death from metastases occurred in 25% of patients with bone malignancies and 10% of soft tissue sarcomas. At this center, the majority of bone tumours treated are benign but the majority of soft tissue tumours are malignant. Limb salvage is often not possible and amputation for local tumour control is necessary far more often than in other anatomic sites.
Lymph node metastasis in soft tissue sarcoma is considered to be a rare event (1.6–8.2%), From 1986 to 2001 1066 patients with extremity soft tissue sarcoma were treated surgically (+/− adjuvant therapy) at our institution. Thirty-nine patients (3.6%) were identified with lymph node metastasis, most common histological subtypes were: Epitheliod sarcoma (3/15), rhabdomyosarcoma (4/21), clear cell sarcoma (2/18), and angiosarcoma (2/18). Comparing expected five- year survivorship, we found that surprisingly in this study, extremity soft tissue sarcoma patients initially presenting with lymph node metastases had survival comparable to patients with high grade soft tissue sarcoma and no metastases. To determine the outcome in patients with soft tissue sarcoma (STS) of the limbs that presented with lymph node metastasis (LNM) at diagnosis or developed them after it, comparing to all STS of limbs population that was treated at our center. LNM in soft tissue sarcoma is considered to be a rare event (1.6–8.2%) with a devastating effect on the outcome,our study represent one of the largest reported cohorts, and suggest that agressive approach to LNM might contribute to survivorship. Thirty-nine patients (3.6%) were identified with LNM along their course of disease Thirteen patients presented with both lymphatic and systemic disease while twenty-six had isolated LNM at time of diagnosis. The mean follow-up from diagnosis of the primary tumor was 46.3 months (range zero to one hundred and forty-eight), and from diagnosis of lymph node involvement was 29.9 months (range zero to one hundred and twenty). Expected five year survival in patients initially presenting with LNM was comparable to patients with high grade soft tissue sarcoma and no metastases. From Jan’ 1986 to Dec’ 2001 1066 patients with extremity STS were treated at our institution. Fifteen patients presented with LNM at time of first diagnosis, and twenty-four subsequently developed LNM after it. Linear regression analysis and Kaplan-meier curves were used to compare expected survivorship in all patients with STS of limbs. Comparing expected five- year survivorship, we found that Surprisingly in this study, extremity STS patients initially presenting with LNM had survival comparable to patients with high grade soft tissue sarcoma and no metastases.