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Chondrosarcoma

radiograph of pelvic chronrosarcoma Chondrosarcoma is a type of cancer that forms in bone cartilage. The most frequent primary sites are the pelvis, shoulder, ribs, or at the ends of the arms and legs. Chondrosarcoma can occur at any age but is more common in people older than 40 years.

Mesenchymal chondrosarcoma is aggressive variant of chondrosarcoma, which tend to occur in younger people.

Extraskeletal chondrosarcoma is a rare type of chondrosarcomadoes, which forms in the soft tissues, rather than bone cartilage.

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Information for Patients and the Public
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Latest Research Publications
Mesenchymal Chondrosarcoma
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Molecular Genetics of Chondrosarcoma

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  • PubMed search for publications about Chondrosarcoma - Limit search to: [Reviews]

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    MeSH term: Chondrosarcoma
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Polychronidou G, Karavasilis V, Pollack SM, et al.
Novel therapeutic approaches in chondrosarcoma.
Future Oncol. 2017; 13(7):637-648 [PubMed] Related Publications
Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

Huang Y, Wan G, Tao J
C1q/TNF-related protein-3 exerts the chondroprotective effects in IL-1β-treated SW1353 cells by regulating the FGFR1 signaling.
Biomed Pharmacother. 2017; 85:41-46 [PubMed] Related Publications
Cartilage degeneration is known as a major cause of osteoarthritis (OA). C1q/TNF-related protein-3 (CTRP3) is an adipokine relative to chondrogenesis in vitro. However, its effect on cartilage degeneration in OA remains unclearly. In the present study, SW1353 cells were treated with IL-1β to imitate the microenvironment of OA for vitro research. Then, an obvious down-regulation of CTRP3 were validated in IL-1β-treated SW1353 cells. In addition, CTRP3 overexpression significantly attenuated the decrease in cell proliferation and increase in cell apoptosis triggered by IL-1β. Moreover, CTRP3 up-regulation significantly inhibited the expression of FGFR1, but with slight decrease in FGFR3 levels. Further analysis corroborated that FGFR1 overexpression markedly ameliorated the pro-proliferation and anti-apoptotic effects of CTRP3 elevation in cells upon IL-1β. Down-regulation of FGFR1 attenuated the increase in Ras-GTP expression caused by IL-1β stimulation. Moreover, EGFR1 elevation also abated the inhibitory effect of CTRP3 on Ras expression and the CRTP3-induced activation of PI3K/AKT in cells upon IL-1β. Furthermore, Ras inhibitor manumycin A antagonized the decrease in phosphorylation of PI3K and Akt caused by IL-1β treatment. Both Manumycin A and PI3K/Akt agonist FGF-1 attenuated the inhibitory effect of IL-1β on cell growth. Together, this research suggested that CTRP3 might protect chondrocytes against IL-1β-induced injury by suppressing the FGFR1- Ras/PI3K/Akt signaling-mediated growth inhibitory pathway, indicating a potential agent against osteoarthritis.

Verdegaal SH, van Rijswijk CS, Brouwers HF, et al.
MRI appearances of atypical cartilaginous tumour/grade I chondrosarcoma after treatment by curettage, phenolisation and allografting: recommendations for follow-up.
Bone Joint J. 2016; 98-B(12):1674-1681 [PubMed] Related Publications
AIMS: The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma.
PATIENTS AND METHODS: We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence.
RESULTS: In 14 patients (18.6%) a second procedure was undertaken after a mean period of 59 months (8 to 114). Radio frequency ablation (RFA) was used in lesions of < 10 mm and curettage, phenolisation and bone grafting for those ≥ 10 mm. Only six of these (8% of total) had a histologically-proven recurrence. No increase in tumour grade was seen at time of recurrence.
CONCLUSION: Based on this study, we have been able to classify the post-operative MRI appearances into four groups. These groups differ in follow-up, and have a different risk of recurrence of the lesion. Follow-up and treatment vary for the patients in each group. We present a flow diagram for the appropriate and safe follow-up for this specific group of patients. Cite this article: Bone Joint J 2016;98-B:1674-81.

De Amorim Bernstein K, Liebsch N, Chen YL, et al.
Clinical outcomes for patients after surgery and radiation therapy for mesenchymal chondrosarcomas.
J Surg Oncol. 2016; 114(8):982-986 [PubMed] Related Publications
INTRODUCTION: We report the outcome of 23 patients with mesenchymal chondrosarcomas treated with surgery and radiation therapy +/- chemotherapy. The intent of the project was to review the impact of patient and treatment variables on treatment outcome, in particular with regard to extent of surgery and radiation dose.
PATIENTS AND METHODS: Twenty-three patients with mesenchymal chondrosarcomas were treated with surgery and radiation therapy (min. dose 44 Gy; max. dose 78 Gy; median dose 60 Gy; mean dose 61 Gy).
RESULTS: The median survival for the entire cohort of patients was 21.65 years (95% confidence interval ± 4.25). The 5- and 10-year OS was 78.6%. Median disease-free survival for the 23 patients was 7.2 years. Disease-free survival (DFS) at 3 and 5 years was 70.7% and 57.8%, respectively. The local control rate at 5 and 10 years was 89.5% (95%CI 64.1-97.3%). Only three patients experienced local failure, three patients had regional failure, and eight developed distant metastases.
CONCLUSIONS: In this cohort of patients local tumor control was high when using a combination of surgery and radiation. There was not a clear relationship between radiation dose and local tumor control. J. Surg. Oncol. 2016;114:982-986. © 2016 Wiley Periodicals, Inc.

De Amorim Bernstein K, DeLaney T
Chordomas and chondrosarcomas-The role of radiation therapy.
J Surg Oncol. 2016; 114(5):564-569 [PubMed] Related Publications
Achieving negative surgical margins can be challenging for skull base and spinal/paraspinal sarcomas. Data shows that pre- or post-operative radiation therapy improves local control. Delivery of sufficient dose of radiation can be difficult because of the proximity to normal organs/tissues that are sensitive to radiation therapy and therefore dose-limiting. A comprehensive literature search was conducted using PubMed search engine. The scarcity of prospective, randomized data limits the ability to generate definitive treatment recommendations. J. Surg. Oncol. 2016;114:564-569. © 2016 Wiley Periodicals, Inc.

Kang Y, Yuan W, Ding X, Wang G
Chondrosarcoma of the para-acetabulum: correlation of imaging features with histopathological grade.
Radiol Med. 2016; 121(12):897-904 [PubMed] Related Publications
OBJECTIVE: To evaluate the computed tomography (CT) and magnetic resonance (MR) imaging features of para-acetabular chondrosarcoma (CS) and assess the difference between low-grade CS (LGCS) and high-grade CS (HGCS).
MATERIALS AND METHODS: Thirty-one patients with histopathologically confirmed central para-acetabular CSs (6 LGCS and 25 HGCS) were retrospectively reviewed. Image features were evaluated for the following: cortical destruction, tumor border and pattern, calcification mode, soft-tissue mass, density/signal intensity, peritumoral edema, acetabular (cartilage) destruction, diffuse signal changes in acetabulum, mass inside hip joint, femoral head involvement, enhancement manifestations and the maximum length of the tumor. These image features between LGCS and HGCS were also assessed.
RESULTS: The most common CT and/or MR findings included cortical destruction, punctate, ring-and-arc and linear calcification, soft-tissue mass, lobulated border, high signal intensity with low signal septa on T2-weighted image, peritumoral edema, hip joint infiltration, peripheral and septal enhancement on post-enhanced MR image. Statistical analysis showed that the image features, such as cortical destruction, soft-tissue mass, hip joint infiltration and tumor size were significantly different between LGCS and HGCS (p < 0.05).
CONCLUSION: The characteristic radiological features of para-acetabular CSs are osteolytic lesions with cortical destruction, soft-tissue mass, lobulated border, calcification, and high signal intensity with low signal septa on T2-weighted MR image, peripheral and septal enhancement on post-enhanced MR image. Cortical destruction, soft-tissue mass, hip joint infiltration and tumor size can differentiate HGCS from LGCS.

Xu X, Tang X, Guo W, et al.
TCF-1 participates in the occurrence of dedifferentiated chondrosarcoma.
Tumour Biol. 2016; 37(10):14129-14140 [PubMed] Free Access to Full Article Related Publications
The present study demonstrated that T cell factor 1 (TCF-1) protein, a component of the canonical Wnt/β-catenin signaling pathway, can regulate the expression of runt-related transcription factor 2 (runx2) gene and Sry-related HMG box 9 (sox9) gene, which may participate in the differentiation of chondrosarcoma. Dedifferentiated chondrosarcoma (DDCS) is a special variant of conventional chondrosarcoma (CCS), associated with poor survival and high metastasis rate. However, little is known about the mechanism of its occurrence; thus, no effective treatment is available except surgery. Earlier, high expression of runx2 and low expression of sox9 were found in DDCS compared with CCS. Using Western blot to detect clinical tissue samples (including 8 CCS samples and 8 DDCS samples) and immunohistochemistry to detect 85 different-grade chondrosarcoma specimens, a high expression of TCF-1 in DDCS tissues was found compared with CCS tissues. This difference in expression was related to patients' prognosis. Results of luciferase, chromatin immunoprecipitation, and gel electrophoresis mobility shift assays demonstrated that TCF-1 protein could bind to the promoter of runx2 gene directly and sox9 gene indirectly. Hence, it could regulate expression of runx2 gene positively and sox9 gene negatively. Furthermore, in vitro and in vivo experiments showed that TCF-1 protein was closely related to the phenotype and aggressiveness of chondrosarcoma. In conclusion, this study proved that TCF-1 participates in the dedifferentiation of DDCS, which may be mediated by runx2 gene and sox9 gene. Also, TCF-1 can be of important prognostic value and a promising therapeutic target for DDCS patients.

Shao R, Lao IW, Wang L, et al.
Clinicopathologic and radiologic features of extraskeletal myxoid chondrosarcoma: a retrospective study of 40 Chinese cases with literature review.
Ann Diagn Pathol. 2016; 23:14-20 [PubMed] Related Publications
The aim of this study is to describe the clinicopathologic and radiologic features of 40 cases of extraskeletal myxoid chondrosarcoma (EMC) from China. There were 25 males and 15 females (sex ratio, 1.7:1). Apart from an adolescent, all patients were adults with a median age of 49years. Twenty-four tumors (60%) occurred in the lower limb and limb girdles, especially the thigh, followed by the upper limb and limb girdles (20%) and trunk (10%). Other less commonly involved locations included the head and neck, sacrococcygeal region, and perineum. Tumors ranged in size from 1.5 to 19cm (mean, 7cm). By radiology, they appeared as hypoattenuated or isoattenuated masses on computed tomography with hyperintense signal on T2-weighted magnetic resonance imaging. Intralesional hypointense septa were present in most cases. Of the 40 tumors, 30 belonged to the classic subtype, whereas 9 cases were cellular, and 1 case had a rhabdoid phenotype. Tumor cells showed variable expression of synaptophysin (36%), S-100 protein (29%), epithelial membrane antigen (11%), and neuron-specific enolase (7%). Ki-67 index was remarkably higher in the cellular variant (mean, 30%). EWSR1-related rearrangement was detected in 12 of 14 cases tested by fluorescence in situ hybridization using break-apart probes. The overall 5- and 7-year survival was 71% and 60%, respectively. Awareness of the imaging features may help pathologists in the diagnosis of EMC. Fluorescence in situ hybridization also serves as a useful diagnostic tool for EMC, especially in the distinction from its mimics.

Andolfi M, Vaccarili M, Crisci R, Puma F
Management of tracheal chondrosarcoma almost completely obstructing the airway: a case report.
J Cardiothorac Surg. 2016; 11(1):101 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary malignant tracheal tumors account for only 0.2 % of all malignancies of the respiratory tract. Tracheal chondrosarcoma is a rare condition and only 17 cases have been described in the literature from 1965 to date. Herein we report the very unusual case of a patient with a tracheal chondrosarcoma, electively treated by curative surgery despite the virtually complete obstruction of the airway.
CASE PRESENTATION: We present the case of a 79-year old Caucasian man with long-lasting wheezing misdiagnosed as asthma and affected by a tracheal chondrosarcoma almost completely obstructing the airway. Videobronchoscopy and imaging investigations revealed a well-circumscribed mass arising from the cartilaginous rings of the cervical trachea with a posterior residual respiratory space of about 1 mm. Because of the mobility and flaccidity of the uninvolved pars membranacea, the tiny respiratory space slightly expanded during inspiration and expiration allowing the patient to be treated without an essential emergency procedure. Standard tracheal intubation was impossible. Rigid bronchoscopy enabled placement of a small tracheal tube distally to the tumor. Successful cervical tracheal resection and reconstruction was then performed, achieving complete tumor excision. Histologically, the mass was characterized as a low-grade tracheal chondrosarcoma. Videobronchoscopy performed 9 months after surgery showed a wide, well healed tracheal anastomosis. Ten months after surgery, the patient is alive and disease free.
CONCLUSION: Complete surgical resection is the treatment of choice for tracheal chondrosarcoma. Rigid bronchoscopy is an essential tool for diagnostic and therapeutic purposes. It allows the palliative maneuvers for obstruction relief but also, in resectable patients, the intraoperative safe and straightforward management of the obstructed airway.

Zhou HW, Wang J, Liu Y, Zhang HM
Recurrent chondrosarcoma of the larynx: A case report and literature review.
Medicine (Baltimore). 2016; 95(27):e4118 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Laryngeal chondrosarcoma (LCS) is a rare laryngeal tumor that most commonly originates from the cricoid cartilage. The current trend for treatment of low-grade LCS is function-sparing surgical option with negative margins.
CASE SUMMARY: We reported here a case of a 63-year-old male patient with a 3-month history of progressive hoarseness and throat pain. The patient had undergone surgical resection of a laryngeal mass 2 years prior. A supracricoid partial laryngectomy was performed this time. Histological examination supported the diagnosis of low-grade chondrosarcoma. Three years later, the radiological and clinical findings showed no evidence of recurrence.
CONCLUSION: Currently, total laryngectomy is preferred for patients with recurrent low-grade LCS. However, the literature review and our case suggest that a second function-preserving procedure may be a reasonable choice for recurrent LCS.

Xiao JR, Huang WD, Yang XH, et al.
En Bloc Resection of Primary Malignant Bone Tumor in the Cervical Spine Based on 3-Dimensional Printing Technology.
Orthop Surg. 2016; 8(2):171-8 [PubMed] Related Publications
OBJECTIVE: To investigate the feasibility and safety of en bloc resection of cervical primary malignant bone tumors by a combined anterior and posterior approach based on a three-dimensional (3-D) printing model.
METHODS: Five patients with primary malignant bone tumors of the cervical spine underwent en bloc resection via a one-stage combined anteroposterior approach in our hospital from March 2013 to June 2014. They comprised three men and two women of mean age 47.2 years (range, 26-67 years). Three of the tumors were chondrosarcomas and two chordomas. Preoperative 3-D printing models were created by 3-D printing technology. Sagittal en bloc resections were planned based on these models and successfully performed. A 360° reconstruction was performed by spinal instrumentation in all cases. Surgical margins, perioperative complications, local control rate and survival rate were assessed.
RESULTS: All patients underwent en bloc excision via a combined posterior and anterior approach in one stage. Mean operative time and estimated blood loss were 465 minutes and 1290 mL, respectively. Mean follow-up was 21 months. Wide surgical margins were achieved in two patients and marginal resection in three; these three patients underwent postoperative adjuvant radiation therapy. One vertebral artery was ligated and sacrificed in each of three patients. Nerve root involved by tumor was sacrificed in three patients with preoperative upper extremity weakness. One patient (Case 3) had significant transient radiculopathy with paresis postoperatively. Another (Case 4) with C 4 and C 5 chordoma had respiratory difficulties and pneumonia after surgery postoperatively. He recovered completely after 2 weeks' management with a tracheotomy tube and antibiotics in the intensive care unit. No cerebrovascular complications and wound infection were observed. No local recurrence or instrumentation failure were detected during follow-up.
CONCLUSION: Though technically challenging, it is feasible and safe to perform en bloc resection of cervical primary bone tumors. This is the most effective means of managing cervical spine tumors. Preoperative 3-D printing modelling enables better anatomical understanding of the relationship between the tumor and cervical spine and can assist in planning the surgical procedure.

Dolinaj V, Milošev S, Janjević D
LARYNGEAL CHONDROSARCOMA: SUCCESSFUL USE OF VIDEO LARYNGOSCOPE IN ANTICIPATED DIFFICULT AIRWAY MANAGEMENT.
Acta Clin Croat. 2016; 55 Suppl 1:108-11 [PubMed] Related Publications
Laryngeal chondrosarcoma is a rare mesenchymal tumor, most frequently affecting cricoid cartilage. The objective of this report is to present successful video laryngoscope usage in a patient with anticipated difficult airway who refused awake fiberoptic endotracheal intubation (AFOI). A 59-year-old male patient was admitted in our hospital due to difficulty breathing and swallowing. On clinical examination performed by ENT surgeon, preoperative endoscopic airway examination (PEAE) could not be performed properly due to the patient's uncooperativeness. Computed tomography revealed a spherical tumor that obstructed the subglottic area almost entirely. Due to the narrowed airway, the first choice for the anticipated difficult airway management was AFOI, which the patient refused. Consequently, we decided to perform endotracheal intubation with indirect laryngoscope using a C-MAC video laryngoscope (Karl Storz, Tuttlingen, Germany). Reinforced endotracheal tube (6.0 mm internal diameter) was placed gently between the tumor mass and the posterior wall of the trachea in the first attempt. Confirmation of endotracheal intubation was done by capnography. In a patient with subglottic area chondrosarcoma refusing PEAE and AFOI, video laryngoscope is a particularly helpful device for difficult airway management when difficult airway is anticipated.

Kumari I, Ahmed M, Akhter Y
Multifaceted impact of trichothecene metabolites on plant-microbe interactions and human health.
Appl Microbiol Biotechnol. 2016; 100(13):5759-71 [PubMed] Related Publications
Fungi present in rhizosphere produce trichothecene metabolites which are small in size and amphipathic in nature and some of them may cross cell membranes passively. Hypocreaceae family of rhizosphere fungi produce trichothecene molecules, however it is not a mandatory characteristic of all genera. Some of these molecules are also reported as growth adjuvant, while others are reported as deleterious for the plant growth. In this review, we are exploring the roles of these compounds during plant-microbe interactions. The three-way interaction among the plants, symbiotic microbial agents (fungi and bacteria), and the pathogenic microbes (bacteria, fungi) or multicellular pathogens like nematodes involving these compounds may only help us to understand better the complex processes happening in the microcosm of rhizosphere. These metabolites may further modulate the activity of different proteins involved in the cell signalling events of defence-related response in plants. That may induce the defence system against pathogens and growth promoting gene expression in plants, while in animal cells, these molecules have reported biochemical and pharmacological effects such as inducing oxidative stress, cell-cycle arrest and apoptosis, and may be involved in maintenance of membrane integrity. The biochemistry, chemical structures and specific functional group-mediated activity of these compounds have not been studied in details yet. Few of these molecules are also recently reported as novel anti-cancer agent against human chondrosarcoma cells.

Indelicato DJ, Rotondo RL, Begosh-Mayne D, et al.
A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine.
Int J Radiat Oncol Biol Phys. 2016; 95(1):297-303 [PubMed] Related Publications
PURPOSE: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine.
METHODS AND MATERIALS: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated.
RESULTS: The mean follow-up time was 3.7 years (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1).
CONCLUSION: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by treating patients at the time of initial diagnosis. The impact of age is a novel finding of this study.

Song J, Wang X, Zhu J, Liu J
Rapamycin causes growth arrest and inhibition of invasion in human chondrosarcoma cells.
J BUON. 2016 Jan-Feb; 21(1):244-51 [PubMed] Related Publications
PURPOSE: Chondrosarcoma is a highly malignant tumor that is characterized by a potent capacity to invade locally and cause distant metastasis and notable for its lack of response to conventional chemotherapy or radiotherapy. Rapamycin, the inhibitor of mammalian target of rapamycin (mTOR), is a valuable drug with diverse clinical applications and regulates many cellular processes. However, the effects of rapamycin on cell growth and invasion of human chondrosarcoma cells are not well known.
METHODS: We determined the effect of rapamycin on cell proliferation, cell cycle arrest and invasion by using MTS, flow cytometry and invasion assays in two human chondrosarcoma cell lines, SW1353 and JJ012. Cell cycle regulatory and invasion-related genes' expression analysis was performed by quantitative RT-PCR (qRT-PCR). We also evaluated the effect of rapamycin on tumor growth by using mice xenograph models.
RESULTS: Rapamycin significantly inhibited the cell proliferation, induced cell cycle arrest and decreased the invasion ability of human chondrosarcoma cells. Meanwhile, rapamycin modulated the cell cycle regulatory and invasion-related genes' expression. Furthermore, the tumor growth of mice xenograph models with human chondrosarcoma cells was significantly inhibited by rapamycin.
CONCLUSIONS: These results provided further insight into the role of rapamycin in chondrosarcoma. Therefore, rapamycin targeted therapy may be a potential treatment strategy for chondrosarcoma.

Lu Y, Li F, Xu T, Sun J
miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A.
Oncol Res. 2016; 23(4):155-63 [PubMed] Related Publications
Chondrosarcoma (CHS) is the second most common malignant bone sarcoma with increased risk of invasion and metastasis. However, the regulatory mechanisms of CHS tumorigenesis remain unknown. Here we investigated the novel role of miR-497 in regulating chondrosarcoma cell growth and cell cycle arrest. RT-PCR analysis showed that the expression of miR-497 is aberrantly downregulated in human chondrosarcoma samples and cells. After transfection with miR-497 mimic or antagomir, the proliferation and apoptosis of JJ012 and OUMS-27 chondrosarcoma cells were determined by CCK-8 assay and flow cytometric analysis, respectively. Results showed that the proliferation capacity of JJ012 and OUMS-27 cells was significantly decreased by miR-497 overexpression but increased by miR-497 repression. Apoptosis in both cell types was remarkably enhanced by miR-497 mimic but inhibited by miR-497 antagomir. By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells. Further studies indicated that miR-497 modulates the growth of chondrosarcoma cells by targeting Cdc25A, in which the cell cycle inhibitor p21 is involved through a p53-independent pathway. In conclusion, we demonstrated that miR-497 represents a potential tumor suppressor in human chondrosarcoma that regulates the growth of chondrosarcoma cells by targeting Cdc25A. This may provide a novel therapeutic target for chondrosarcoma.

Tang XY, Zheng W, Ding M, et al.
miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism.
Drug Des Devel Ther. 2016; 10:571-83 [PubMed] Free Access to Full Article Related Publications
Chondrosarcoma is the second most common type of primary bone malignancy in the United States after osteosarcoma. Surgical resections of these tumors are the only effective treatment to chondrosarcoma patients due to their resistance to conventional chemo- and radiotherapy. In this study, miR-125b was found to perform its tumor-suppressor function to inhibit glucose metabolism via the direct targeting of oncogene, ErbB2. We report miR-125b was downregulated in both chondrosarcoma patient samples and cell lines. The total 20 Asian chondrosarcoma patients showed significantly downregulated miR-125b expression compared with normal tissues. Meanwhile, miR-125 was downregulated in chondrosarcoma cells and doxorubicin resistant cells. Overexpression of miR-125 enhanced the sensitivity of both parental and doxorubicin resistant cells to doxorubicin through direct targeting on the ErbB2-mediated upregulation of glycolysis in chondrosarcoma cells. Moreover, restoration of the expression of ErbB2 and glucose metabolic enzymes in miR-125 pretransfected cells recovered the susceptibility to doxorubicin. Our study will provide a novel aspect on the overcoming chemoresistance in human chondrosarcoma cells and may help in the development of therapeutic strategies for the treatments of patients.

Shooshtarizadeh T, Nazeri A, Zare-Mirzaie A, Movahedinia S
Expression of insulin-like growth factor II mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma.
Pathol Res Pract. 2016; 212(4):335-9 [PubMed] Related Publications
Atypical cartilaginous tumor and enchondroma are similar in histopathologic aspects. Although the clinical course, radiologic and pathologic examinations enable distinction in most cases, difficulties are still encountered by the pathologists. There is no known biomarker to help make a distinction between benign and malignant cartilaginous tumors. Insulin-like growth factor II mRNA binding protein (IMP3) is a member of an oncofetal family of proteins that is expressed in different human malignancies and rapidly emerging as a prognostic and diagnostic marker in surgical pathology. In this study, IMP3 expression was examined by immunohistochemistry in 36 enchondromas and 42 chondrosarcomas of different histologic grades. The results showed that all 36 cases of enchondroma were negative for IMP3, while it was overexpressed in 15 of 42 chondrosarcomas (36%) (P<0.01). Significant higher levels of IMP3 were detected in grade III chondrosarcomas (6 of 7; 85.7%) when compared to low-grade tumors (6 of 19; 31.5% in grade II and 3 of 16; 18.7% in Atypical Cartilaginous Tumor). We proved statistically significant difference in IMP3 expression between enchondromas and ACTs (P=0.025). Our study clearly demonstrated differentiation-dependent expression of IMP3 in chondrosarcoma, and suggests IMP3 as a novel marker for differentiating problematic cases of enchondroma from well-differentiated chondrosarcomas. To our knowledge, this study is the first study to clarify expression of IMP-3 in chondromas and chondrosarcomas.

McCarthy C, Anderson WJ, Vlychou M, et al.
Primary synovial chondromatosis: a reassessment of malignant potential in 155 cases.
Skeletal Radiol. 2016; 45(6):755-62 [PubMed] Related Publications
OBJECTIVE: Primary synovial chondromatosis (PSC) is a rare disorder characterised by cartilage formation in synovium-lined joints, tendon sheaths and bursae. It is thought that PSC cartilage arises from the proliferation of mesenchymal cells, which exhibit cartilaginous metaplasia in subintimal connective tissue. There are reports of transformation of PSC to chondrosarcoma, although the precise incidence and nature of this complication is uncertain. In this study we carried out a retrospective review PSC to determine the incidence of sarcomatous change in this condition, in addition to the clinical, radiological and pathological features that characterise this complication
MATERIALS AND METHODS: We reviewed 155 cases of PSC and identified 4 cases (3 in the hip joint; 1 in the elbow joint) of aggressive behaviour and chondrosarcoma-like histology.
RESULTS: Radiologically, these cases were all reported as showing features consistent with PSC and aggressive extra-articular soft tissue/bone involvement. Histologically, in addition to typical features of PSC, there was morphological evidence of peri-articular soft tissue and, in 2 cases, bone involvement by an infiltrating cartilaginous tumour. These tumours all behaved as locally aggressive neoplasms and did not give rise to metastasis.
CONCLUSION: Our findings show that chondrosarcoma arises infrequently in PSC (approximately 2.5 %), and that this complication occurs most commonly in the hip joint (approximately 11 % of cases of hip PSC). These tumours behaved mainly as low-grade, locally aggressive tumours analogous to atypical cartilaginous tumour of bone/grade 1 chondrosarcoma of bone.

Dierselhuis EF, Gerbers JG, Ploegmakers JJ, et al.
Local Treatment with Adjuvant Therapy for Central Atypical Cartilaginous Tumors in the Long Bones: Analysis of Outcome and Complications in One Hundred and Eight Patients with a Minimum Follow-up of Two Years.
J Bone Joint Surg Am. 2016; 98(4):303-13 [PubMed] Related Publications
BACKGROUND: A central atypical cartilaginous tumor (ACT)--formerly known as chondrosarcoma grade 1 (CS1)--is a tumor of intermediate-type malignancy, often treated with surgery. The extent of surgery remains controversial, as some advocate resection and others favor local treatment by curettage. Because of the low prevalence of ACT/CS1, the available data are limited and generally not uniform. The purpose of this study was to present the outcome for a large cohort of patients with ACT/CS1 in the long bones who were treated with curettage and adjuvant phenolization and followed for a minimum of two years according to national guidelines.
METHODS: A retrospective study was designed to analyze data from 108 patients treated for central ACT/CS1 in the long bones between 2006 and 2012. All patients were treated with curettage and adjuvant phenolization, and defects were filled with polymethylmethacrylate, bone graft, or bone substitutes. The primary end point was local recurrence or residual tumor. Secondary end points included the type and rate of complications and reoperations.
RESULTS: All patients were free from local recurrence at a mean follow-up of 48.7 months (range, 24.3 to 97.5 months). Residual tumor was suspected in five patients, leading to a 95.4% disease-free survival rate. A fracture occurred in eleven patients (10.2%). Other complications were osseous penetration during the surgery (two patients), wound infection (one patient), arthrofibrosis (one patient), and skin necrosis (one patient). Tumor volume was related neither to the risk of fracture nor to the occurrence of residual tumor.
CONCLUSIONS: In our experience, curettage of ACT/CS1 in the long bones with adjuvant phenolization is safe, even with large tumors of up to 100 cm(3). Most worrisome is the risk of fracture, which occurred in 10.2% of our patients. Considering the relatively mild behavior of ACT/CS1, less aggressive treatment, by observation or by minimally invasive surgery, could be the next step that should be evaluated prospectively.

Aviel-Ronen S, Zadok O, Vituri A, et al.
α-methylacyl-CoA racemase (AMACR) expression in chordomas differentiates them from chondrosarcomas.
Sci Rep. 2016; 6:21277 [PubMed] Free Access to Full Article Related Publications
AIMS: Chordomas and chondrosarcomas are malignant mesenchymal tumours with overlapping morphological and immunohistochemical (IHC) characteristics. Our aim was to evaluate the IHC expression of α-methylacyl-CoA racemase (AMACR/P504S), β-catenin and E-cadherin in chordomas relative to chondrosarcomas and assess the utility of these markers for differential diagnosis.
METHODS: Archival sections of 18 chordomas, 19 chondrosarcomas and 10 mature cartilage samples were immunostained and scored for AMACR, β-catenin and E-cadherin and the relative differential capacity of each marker was calculated. In addition, AMACR mRNA level was assessed in 5 chordomas by RT-PCR and evaluated by comparative CT method.
RESULTS: AMACR and β-catenin stained 88.9% and 94.1% of the chordomas respectively, 21.1% and 10.5% of the chondrosarcomas correspondingly and none of the mature cartilage samples. E-cadherin stained positively 82.4% of the chordomas, 36.8% of the chondrosarcomas and 42.9% of the mature cartilage cases. Both AMACR and β-catenin showed statistically significant difference between chordomas and chondrosarcomas (p < 0.001 for both), unlike E-cadherin. AMACR was detected at the mRNA level.
CONCLUSIONS: AMACR is expressed in most of the chordomas but only in a minority of chondrosarcomas. AMACR may serve as IHC marker of chordoma with differentiating ability comparable to that of β-catenin.

Hobusch GM, Tiefenboeck TM, Patsch J, et al.
Do Patients After Chondrosarcoma Treatment Have Age-appropriate Bone Mineral Density in the Long Term?
Clin Orthop Relat Res. 2016; 474(6):1508-15 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: In long-term survivors of osteosarcoma and Ewing sarcoma treated with the addition of radio- and chemotherapy, low bone mineral density (BMD) and fractures have been observed, presumably resulting from these adjuvants. Because patients with chondrosarcoma usually are not treated with conventional adjuvant treatment, observation of low BMD in patients with chondrosarcoma presumably would be the result of other mechanisms. However, BMD in patients with a history of chondrosarcoma has not been well characterized.
QUESTIONS/PURPOSES: The aim of our study was to address the following questions: (1) Do long-term survivors of chondrosarcoma have normal BMD and, if not, which factors contribute to low BMD? (2) Is there a greater risk of fracture and does the Fracture Risk Assessment Tool (FRAX(®)) score reflect fracture likelihood?
METHODS: All known patients with a history of chondrosarcoma treated at our institution before 2006 were identified. Of 127 patients believed to be alive at the time of this study, 30 agreed to participate in this study (11 females, 19 males; mean age at surgery, 39 ± 12 years; mean followup, 12 ± 5 years). With the data available, the 30 participants were not different from the 97 nonparticipants in terms of age, sex, BMI, tumor grade, tumor location (axial versus appendicular, lower extremity versus elsewhere), and use of any treatment known to influence osteopenia (chemotherapy, lower extremity surgery). BMD was measured and history of fractures was assessed using a questionnaire. The patients´ BMD measurements in this study were sex- and age-matched with a normative sex- and age-categorized reference population reported by Kudlacek et al. Associations were tested by univariate regressions and ANOVAs of all measures of BMD and eligible oncologic and demographic factors.
RESULTS: Eighteen of 30 (60%) patients had a pathologic BMD according to the WHO dual-energy x-ray absorptiometry definition, 15 (50%) had osteopenia, and three (10%) had osteoporosis. T-scores in the study cohort were lower than reference values for the femur neck (mean difference, 0.64; 95% CI, 0.27-1.01; p < 0.0015), but not for the spine (mean difference, 0.39; 95% CI, -0.06 to 0.84; p = 0.09). Thirteen patients (45%) reported a history of fractures not distinguishing between low and high impact. The incidence of fractures was 2.8 greater than expected from a comparison with a published microcensus survey of the Austrian population. No effect of the FRAX(®) score on fracture risk could be identified (p = 0.057).
CONCLUSIONS: Long-term survivors of chondrosarcoma appear to be at greater risk for having low BMD develop than the healthy population. Although these results are preliminary and based on a very small sampling of patients, if they can be confirmed in larger studies, BMD assessment by dual-energy x-ray absorptiometry might be considered as these patients are followed posttreatment by sarcoma care units. The reasons for low BMD still must be elucidated.
LEVEL OF EVIDENCE: Level IV, prognostic study.

Feuvret L, Bracci S, Calugaru V, et al.
Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study.
Int J Radiat Oncol Biol Phys. 2016; 95(1):312-21 [PubMed] Related Publications
PURPOSE: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS).
METHODS AND MATERIALS: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively.
RESULTS: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS.
CONCLUSIONS: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

Bakyalakshmi K, Jayachandran S, Sureshkumar M
Primary juxtacortical chondrosarcoma of mandibular symphysis: Unique and rare case report.
J Cancer Res Ther. 2015 Oct-Dec; 11(4):1025 [PubMed] Related Publications
Juxtacortical chondrosarcoma (JC) is a rare, malignant, cartilage-forming tumor arising from the external bone surface. It mainly involves long bones and very rarely involves maxillofacial skeleton. Chondrosarcoma in general accounts for about 10-20% of all bone neoplasm, of which only 1-3% is involved in maxillofacial skeleton. So far only two cases of JC have been reported in mandible. In this article we report a rare case of JC in a 49-year-old male primarily involving symphysis of mandible. This is the third case of JC in mandible and first of its kind to be reported in mandibular symphysis region is concerned. Literature relevant to its clinical, radiological features, and prognosis is analyzed.

Danışman M, Mermerkaya MU, Bekmez Ş, et al.
Reconstruction of periacetabular tumours with saddle prosthesis or custom-made prosthesis, functional results and complications.
Hip Int. 2016; 26(2):e14-8 [PubMed] Related Publications
Reconstruction after resection of pelvic tumours is a major challenge. We report the outcomes and complications of 7 patients who underwent limb salvage following type II or type II, III pelvic resection and reconstruction using a saddle prosthesis or custom-made hemipelvic prosthesis. In our opinion, reconstruction using custom-made prostheses is better than placement of saddle prostheses because of a lower risk of complications and improved functional outcomes.

Ruamrungsri N, Siengdee P, Sringarm K, et al.
In vitro cytotoxic screening of 31 crude extracts of Thai herbs on a chondrosarcoma cell line and primary chondrocytes and apoptotic effects of selected extracts.
In Vitro Cell Dev Biol Anim. 2016; 52(4):434-44 [PubMed] Related Publications
Thirty-one dichloromethane and methanol crude extracts of 16 herb species used in Thai traditional folk medicine were studied for their cytotoxic activities on the SW 1353 chondrosarcoma cell line and primary chondrocytes. Methyl thiazolyl tetrazolium (MTT) cell viability assay and flow cytometric method were used as screening tools for cytotoxicity testing. The half maximal inhibitory concentration (IC50) was measured and reported for each crude extract. Apoptosis, necrosis, and cell viability were measured by flow cytometry at IC50. Two out of 31 herbal extracts, methanol extracts of Paris polyphylla var. chinensis and Ficus thailandica C.C. Berg & S. Gardner, showed potent anticancer activity. They demonstrated high apoptosis induction activity in SW 1353 cells but had less effect on percentage of viability and necrosis of normal chondrocyte cells. Cytotoxic screening and apoptosis assays suggest the potential anticancer activity of some plants used in Thai traditional medicine and provide information concerning their direct effects.

Fisher CG, Versteeg AL, Dea N, et al.
Surgical Management of Spinal Chondrosarcomas.
Spine (Phila Pa 1976). 2016; 41(8):678-85 [PubMed] Related Publications
STUDY DESIGN: An ambispective cohort study.
OBJECTIVE: The aim of this study was to determine whether the application of the Enneking classification in the management of spinal chondrosarcomas influences local recurrence and survival.
SUMMARY OF BACKGROUND DATA: Primary spinal chondrosarcomas are rare. Best available evidence is based on small case series, thus making it difficult to determine optimal management and risk factors for local recurrence and survival.
METHODS: The AOSpine Knowledge Forum Tumor developed a multicenter ambispective database of surgically treated patients with spinal chondrosarcoma. Patient data pertaining to demographics, diagnosis, treatment, cross-sectional survival, and local recurrence were collected. Tumors were classified according to the Enneking classification. Patients were divided into two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). They were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation, and otherwise, they were categorized as EI.
RESULTS: Between 1987 and 2011, 111 patients (37 female; 74 male) received surgical treatment for a primary spinal chondrosarcoma at a mean age of 47.4 ± 15.8 years. Patients were followed for a median period of 3.1 years (range = 203 d-18.7 yrs). Median survival for the entire cohort was 8.4 years postoperative. After 10 years postoperative, 36 (32%) patients died and 37 (35%) patients suffered a local recurrence. Twenty-three of these 37 patients who suffered a local recurrence died. Sixty (58%) patients received an EA procedure while 44 (42%) received an EI procedure. EI patients had a higher hazard ratio for local recurrence than those who received an EA procedure (P = 0.052). Local recurrence was strongly associated with chondrosarcoma-related death (risk ratio = 3.6, P < 0.010).
CONCLUSION: This is the largest multicenter cohort of spinal chondrosarcomas. EA surgical management appeared to correlate with a decreased risk of local recurrence, yet no relationship with survival was found. Where possible, surgeons should strive to achieve EA margins to minimize the risk of local recurrence.
LEVEL OF EVIDENCE: 4.

Rekhi B, Joshi S, Panchwagh Y, et al.
Clinicopathological features of five unusual cases of intraosseous myoepithelial carcinomas, mimicking conventional primary bone tumours, including EWSR1 rearrangement in one case.
APMIS. 2016; 124(4):278-90 [PubMed] Related Publications
Primary intraosseous myoepithelial tumours, including carcinomas are rare tumours. The concept of histopathological spectrum of these tumours is evolving. We describe clinicopathological and immunohistochemical features of five myoepithelial carcinomas, including molecular cytogenetic results in one case. There were five male patients within age-range of 8-40 years (median = 26). Four tumours occurred in the long bones, including two tumours, each, in the femur and fibula, respectively, while a single tumour occurred in the proximal phalanges. Tumour size (n = 3 cases) varied from 5.6 to 8.6 cm. On radiological imaging, most tumours appeared as expansile, lytic and destructive lesions. Two tumours appeared as sclerotic lesions. Two cases were referred with diagnoses of chondrosarcomas and a single case was referred with two different diagnoses, including an adamantinoma and an osteosarcoma. Histopathological examination in all these cases showed multinodular tumours comprising mostly polygonal cells, exhibiting moderate nuclear atypia and interspersed mitotic figures within a stroma containing variable amount of myxoid, chondroid, hyalinised and osteoid-like material. Three tumours revealed prominent squamous differentiation. By immunohistochemistry, tumour cells were positive for EMA (5/5), pan CK (AE1/AE3) (3/3), CK5/6 (4/4), CK MNF116 (1/1), S100 protein (5/5) and GFAP (3/5). The first tumour revealed EWSR1 rearrangement. The first patient, 10 months after tumour resection and a simultaneous lung metastatectomy, is free-of-disease (FOD). The second patient, 11 months after tumour resection is FOD. The third and fourth patients underwent wide resections and are on follow-up. The fifth patient underwent resections, including a lung metastatectomy. Primary intraosseous myoepithelial carcinomas are rare and mimic conventional primary bone tumours. Some primary intraosseous myoepithelial carcinomas display EWSR1 rearrangement. Squamous differentiation may be considered as an addition to their evolving histopathological spectrum. Immunohistochemical stains constitute as a necessary tool for arriving at the correct diagnosis in such cases, which has treatment implications. Surgical resection remains the treatment mainstay.

Awad M, Gogos AJ, Kaye AH
Skull base chondrosarcoma.
J Clin Neurosci. 2016; 24:1-5 [PubMed] Related Publications
Intracranial chondrosarcoma are rare tumours, accounting for approximately one in 1000 intracranial neoplasms. Although more common in the axial or appendicular skeleton, intracranial tumours present a challenging surgical and oncological problem. Chondrosarcoma have a predilection for the skull base and although commonly slow growing, Grade II and III lesions do occur. We present two illustrative patients from the Royal Melbourne Hospital, Australia, demonstrating dramatically differing presentation and clinical outcome and the diagnostic difficulties that may arise. A review of the literature regarding skull base chondrosarcoma is presented. We summarise the clinical, radiological and histological features. The evidence for surgical resection, radiotherapy and chemotherapy is presented and critically evaluated. Based on the available evidence, we advocate maximal safe resection, followed by radiotherapy for Grade II and III tumours. There is no current role for chemotherapy. Radical excision should not be attempted at the expense of neurological function.

Kamal AF, Husodo K, Prabowo Y, Hutagalung EU
Correlation between survival and tumour characteristics in patients with chondrosarcoma.
J Orthop Surg (Hong Kong). 2015; 23(3):365-9 [PubMed] Related Publications
PURPOSE: To evaluate the correlation between survival and tumour characteristics in 23 patients with chondrosarcoma.
METHODS: Records of 15 men and 8 women aged 14 to 66 (mean, 37) years who were diagnosed with primary (n=19) or secondary (n=4) chondrosarcoma of the axial skeleton (n=8), proximal extremity (n=9), or distal extremity (n=6) were reviewed. The tumour diameter was <10 cm in 4 patients, 10-19 cm in 12, and 20-30 cm in 7. The tumour involved the intramedullary in 17 and the periosteum in 6 patients; tumour extension was intracompartmental in 5 and extracompartmental in 18 patients. The Evans histological grade for the tumours was grade 1 in 6 patients, grade 2 in 10, and grade 3 in 7. The mean tumour size was 12.3 cm for grade 1 tumours, 18.2 cm for grade 2 tumours, and 18.3 cm for grade 3 tumours. 13 patients had no metastasis and 3 of 10 patients with grade 2 tumours and all 7 patients with grade 3 tumours had metastasis to the lung at presentation. 17 patients underwent surgery, one underwent adjuvant treatment only, and 5 declined treatment.
RESULTS: The mean follow-up period for the 23 patients was 3.1 years (range, 3 weeks to 9 years). The 5-year survival rate was 43% overall, 83.3% for grade 1 tumours, 50% for grade 2 tumours, and 0% for grade 3 tumours. The median survival duration was 20 (95% confidence interval, 11-29) months. Two patients had local recurrence and 16 did not, and the 5 patients who declined treatment died. Survival correlated with Evans histological grading (p=0.004), the presence of metastasis at presentation (p=0.026) and local recurrence (p=0.004).
CONCLUSION: The survival rate was lower in patients with higher Evan grading, metastasis, or local recurrence.

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