Objectives: Dedifferentiated chondrosarcoma presents a very dif cult clinical problem.Long term survival is known to be poor, but a large clinical series has not been analyzed in the era of modern diagnostic and treatment modalities.Methods: A retrospective chart review of all cases of patients presenting with dedifferentiated chondrosarcoma at our institution from 1984-2000 was performed.This was done as an extension to a study published in 1986 prior to the era of modern chemotherapy.Results: There were 42 cases in 25 men and 17 women of average age 56 (range 24-83 years).MSTS grades at presentation were 5 IIA, 27 IIB, and 10 III.Three patients underwent biopsy only, 19 had limb sacri cing, and 20 had limb sparing procedures; surgical margins were intralesional in 3, marginal in 2, and wide in 20, and radical in 14.Twenty-seven patients received adjuvant therapy (22 chemotherapy only, 2 radiotherapy only, 3 combined therapy).Median survival was 8 months; 5-year survival was 7.1%.There was no statistical difference in survival between patients who did and did not receive chemotherapy, had wide versus radical resection, or had limb sparing versus sacri cing procedures.There were no statistically signi cant difference between patients treated prior to 1986 and those subsequently.Conclusions: Despite advances in diagnostic modalities, surgical treatments, and adjuvant therapies, dedifferentiated chondrosarcoma continues to carry a poor prognosis.The use of current adjuvant chemotherapy and its inherent risks and bene ts remains questionable in this population.
To determine the association of MRI features of extra-abdominal desmoid tumours (DTs) with prognosis.MRIs for 90 patients with DT were retrospectively reviewed for imaging features associated with biological behaviour. The primary end point was progression (for lesions managed with chemotherapy, radiation therapy and observation) or recurrence (following surgery). Time to event was studied using univariate and multivariable Cox proportional hazards regression models when accounting for demographic, clinicopathological and imaging variables. Kaplan-Meier plots were used to estimate event-free rate (EFR).Univariate analysis revealed a significant relationship between EFR and treatment, location and compartment of origin [subcutaneous (SC), superficial fascial, intramuscular (IM) and deep fascial/intermuscular]. None of the imaging features commonly associated with biological behaviour of DTs (e.g., shape, enhancement, T2 signal etc.) or surgical margins (in surgical cases) was associated with EFR. Multivariate analysis showed that treatment modality and compartment of origin were independent predictors of EFR. Superficial and deep fascial lesions had a significantly worse EFR as a group [hazard ratio: 3.9; 95% confidence interval (CI): 1.83-8.32; p = 0.0004] than did the SC and IM lesions as a group. 5-year EFR for the fascial lesions was 18% (95% CI: 6-36%), compared with 57% (95% CI: 25-79%) for the SC and IM groups.Intramuscular or SC DTs may be associated with improved prognosis. If validated on multireader and prospective studies, these results can provide for rapid risk stratification at the time of initial MRI.This work has shown that imaging features commonly associated with biological activity of desmoid tumours (e.g. shape, T2 signal and enhancement) do not appear to be associated with prognosis in patients undergoing a variety of treatment modalities. The compartment of origin of the lesion, which can be determined on pre-operative MRI, was shown to be associated with prognosis and can allow for risk stratification in patients with DTs.
Abstract Introduction: Osteosarcoma is the most common primary malignant bone tumor. About 30% of osteosarcoma patients experience relapse and die of their disease. We previously demonstrated that IL-11Rα is overexpressed in primary and metastatic osteosarcoma and plays a role in the development of metastases. Our recent microarray data from KRIB, SJSA1, and LM7 IL-11Rα shRNA cells show decreased expression of several components of polycomb repressive complex 2 (PRC2). EZH2 is the catalytic subunit of PRC2 and blocks transcription of numerous tumor suppressors’ genes. EZH2 has been widely implicated in cancer and inhibition of its catalytic activity has recently emerged as a novel approach to treat cancers. Purpose: To explore the effects and mechanisms of inhibition of EZH2 on osteosarcoma metastasis. Inhibition was tested using GSK126, a novel small-molecule EZH2 inhibitor that competes with methyl group donor S-adenosyl-methionine in a highly selective fashion. Methods: Proliferation assays were performed on a panel of osteosarcoma cell lines subjected to increasing concentrations (0.0625 μm to 20 μm) of GSK126 for 3 days. The effects of IL-11 in PRC1 complex histone H3 methylation (H3K27) were studied by Western blotting. For in vivo experiments, we used an orthotopic metastatic model. Luciferase-labeled SJSA1 osteosarcoma cells were injected into the tibias of 4- to 5-week-old nude mice. After 2 weeks, mice were treated with vehicle or GSK126 three times per week intraperitoneally at 0.1 ml per 20 g of body weight in 20% captisol for 48 days. The tumor-containing legs were amputated when tumor volume reached 2 cm. Primary tumors were measured with calipers, and tumorigenesis and metastasis were evaluated by luciferase imaging. After 4 more weeks of treatment, all the mice were killed and their lungs collected. Immunohistochemical study for EZH2 (1:200, D2C9, Cell Signaling) was performed on tissue microarrays composed of 200 formalin-fixed decalcified human OS specimens: 141 primary and 59 metastatic. Intensity and extent of tumoral labeling were evaluated. Results: EZH2 expression was seen in 79/200 OS specimens (40%) with 54 specimens (27%) with moderate to strong labeling. In the majority of cases, when staining was present, more than 50% of labeling was seen. More metastatic specimens (24/59, 41%) had moderate to strong labeling than primary resection specimens (30/141, 21%). In vitro, SJSA1, HOS and CCH-OS-D osteosarcoma cell lines were sensitive to EZH2 inhibition (IC50= 3.576- 6.450uM). In vivo, mice treated with GSK126 developed significantly fewer osteosarcoma lung metastases than control mice injected with vehicle alone (P<0.01). Conclusion: GSK126, a potent small-molecule EZH2 inhibitor, inhibits the development of osteosarcoma lung metastases in vivo. Thus, GSK126 may be considered as a novel anticancer drug candidate for osteosarcoma. Citation Format: Eswaran Devarajan, Wei-lin Wang, Jen-Wei Tsai, Andrew Futreal, Valerae O. Lewis. Inhibition of EZH2 as a therapeutic strategy for osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5072. doi:10.1158/1538-7445.AM2017-5072
Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%. Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma. A literature search was performed utilizing PubMed. Several recent clinical trials are reviewed in detail, as is innovative research evaluating novel agents and surgical techniques which hold promise. Expert commentary: The outcome for patients with osteosarcoma has not changed in several decades. This plateau in survival rates highlights the need for a novel approach towards research. There remains a great deal of interest in utilizing the very high risk population of recurrent osteosarcoma patients to rapidly and sequentially evaluate novel agents to determine if any of these agents hold promise. Several phase II studies are ongoing or in development that offer hope based on intriguing preclinical data. Furthermore, initiatives in obtaining specimens to further explore the genetic and immunological profile behind osteosarcoma will be essential towards identifying novel pathways and targets to exploit.
Background: Patellar resurfacing after routine arthroplasty remains controversial. Few studies have specifically examined the effect of patellar resurfacing on outcomes after resection of the distal part of the femur and reconstruction with a megaprosthesis. Our objective was to compare the outcomes of megaprosthesis reconstructions of the distal part of the femur with and without patellar resurfacing after resection of a distal femoral tumor. Methods: We retrospectively reviewed the clinical records of patients with a femoral tumor who underwent resection of the distal part of the femur and endoprosthetic reconstruction between 1993 and 2013. We excluded patients who had had extra-articular knee resection, patellectomy, revision, reconstruction with an expandable prosthesis, or a proximal tibial replacement associated with the distal femoral replacement. We compared demographic characteristics, surgical variables, anterior knee pain, range of motion, extensor lag, Insall-Salvati ratio, Insall-Salvati patellar tendon insertion ratio, impingement, patellar degenerative disease, additional patellar procedures, complications, and Musculoskeletal Tumor Society (MSTS) score between the patellar resurfacing and nonresurfacing groups. Results: One hundred and eight patients—sixty without patellar resurfacing and forty-eight with patellar resurfacing—were included in the study. The mean age was 33.9 years (range, twelve to seventy-five years). There were fifty-four men and fifty-four women. The mean duration of follow-up was 4.5 years (range, 0.7 to twenty years). There was no significant difference in anterior knee pain between the groups (p = 0.51). Anterior knee pain did not significantly affect the range of motion, extensor lag, or reoperation or complication rate. Patellar degenerative disease occurred in 48% of the nonresurfaced knees but was not associated with focal pain. Complication rates were similar in the two groups, although peripatellar calcifications were significantly more common in the resurfacing group (19% versus 2%; p = 0.005). There was no significant difference in the mean MSTS score between the nonresurfacing (81%) and resurfacing (71%) groups (p = 0.34). Conclusions: There were no differences in anterior knee pain, range of motion, extensor lag, or MSTS score between the patients with and those without patellar resurfacing. There were no cases of patellar component loosening or revision. In light of the similar outcomes in the two groups, the decision to resurface should be left up to the individual surgeon, who should take into account preoperative peripatellar pain and the status of the patella at the time of resection. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
Local recurrence in Ewing sarcoma is associated with a poor prognosis. The purpose of the study was to determine the factors that predict local recurrence after surgical treatment of the primary tumor.Between 1990 and 2001, 64 patients underwent surgical resection of Ewing sarcoma. Surgical margins were assessed histologically and radiologically. Response to preoperative chemotherapy was determined by detailed specimen mapping. Local recurrence-free survival (LRFS) was calculated by Kaplan-Meier analysis. Multivariate analysis was performed with the Cox proportional hazards model.A number of factors were found to be associated with local recurrence on univariate analysis. Patients with a good response to chemotherapy (> or = 90% tumor necrosis), had superior LRFS at 5 years (86% vs 51%, P = .015). Central site of disease was associated with an increased rate of recurrence. The LRFS at 5 years was 50% for the chest wall, 74% for pelvic/scapular, and 86% for extremity tumors (P = .083). Positive surgical margin was not a strong predictor of recurrence (P = .72). A critical analysis of minimal surgical margin based on preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans also failed to reveal an association between margin and local recurrence. In multivariate analysis, the 2 independent predictors of local recurrence were histological response to chemotherapy and central site of disease.Local recurrence after surgical resection is a complex phenomenon. An important predictive factor is the response to chemotherapy. In the current study, this seems to have the largest impact. Central site of disease may be a second independent predictive factor.
Case: A 72-year-old woman with undifferentiated pleomorphic sarcoma of the thigh received neoadjuvant chemotherapy and radiotherapy. She underwent wide resection and was scheduled for prophylactic fixation of the femur. However, prophylactic fixation was deferred secondary to COVID-19 pandemic. Unfortunately, when stepping out of an elevator, she sustained femur fracture. The fracture was treated with a cemented intercalary endoprosthesis. Three-year follow-up reveals stable fixation without any failure. Conclusion: Postradiation fractures are challenging. Delayed union, nonunion, and infection are associated with internal fixation. To the best of our knowledge, this is the first report of intercalary endoprosthesis used for primary management of radiation-associated femur fracture.
