Bone Cancers
CancerIndex Home - Guide to Internet Resources for Cancer Home > Cancer Types > Bone Cancers

Primary bone tumours are tumours that start in the bone. In contrast, secondary bone cancer is where the cancer started in another part of the body but has then spread to the bones. The most common types of primary bone tumour are osteosarcoma and Ewing's sarcoma, both of which are most frequently diagnosed in children and young adults. Other less common types of bone cancer include: Chondrosarcoma (a cancer arising in cartilage cells, usually found in adults between ages 50-75, though the less common mesenchymal-chondrosarcoma is more frequent in younger patients), Malignant Fibrous Histiocytoma of bone (MFH), Chondoma (a rare low grade malignancy occuring mostly between ages 30 -70), and other rare tumours.

Menu: Bone Cancers

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Chondrosarcoma
Ewing's Sarcoma
Osteosarcoma
Primary Lymphoma of Bone
Bone Metastases (secondary bone cancer)
Bone Cancer FAQ

Information Patients and the Public (8 links)


Information for Health Professionals / Researchers (10 links)

Latest Research Publications

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

Fujiwara-Okada Y, Matsumoto Y, Fukushi J, et al.
Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.
Br J Cancer. 2013; 108(4):836-47 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear.
METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry.
RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients.
CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.


Nakamura T, Grimer RJ, Gaston CL, et al.
The prognostic value of the serum level of C-reactive protein for the survival of patients with a primary sarcoma of bone.
Bone Joint J. 2013; 95-B(3):411-8 [PubMed]
The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing's sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival.


Mounessi FS, Lehrich P, Haverkamp U, et al.
Pelvic Ewing sarcomas. Three-dimensional conformal vs. intensity-modulated radiotherapy.
Strahlenther Onkol. 2013; 189(4):308-14 [PubMed]
PURPOSE: The goal of the present work was to assess the potential advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3D-CRT) planning in pelvic Ewing's sarcoma.
PATIENTS AND METHODS: A total of 8 patients with Ewing sarcoma of the pelvis undergoing radiotherapy were analyzed. Plans for 3D-CRT and IMRT were calculated for each patient. Dose coverage of the planning target volume (PTV), conformity and homogeneity indices, as well as further parameters were evaluated.
RESULTS: The average dose coverage values for PTV were comparable in 3D-CRT and IMRT plans. Both techniques had a PTV coverage of V95 > 98 % in all patients. Whereas the IMRT plans achieved a higher conformity index compared to the 3D-CRT plans (conformity index 0.79 ± 0.12 vs. 0.54 ± 0.19, p = 0.012), the dose distribution across the target volumes was less homogeneous with IMRT planning than with 3D-CRT planning. This difference was statistically significant (homogeneity index 0.11 ± 0.03 vs. 0.07 ± 0.0, p = 0.035). For the bowel, Dmean and D1%, as well as V2 to V60 were reduced in IMRT plans. For the bladder and the rectum, there was no significant difference in Dmean. However, the percentages of volumes receiving at least doses of 30, 40, 45, and 50 Gy (V30 to V50) were lower for the rectum in IMRT plans. The volume of normal tissue receiving at least 2 Gy (V2) was significantly higher in IMRT plans compared with 3D-CRT, whereas at high dose levels (V30) it was significantly lower.
CONCLUSION: Compared to 3D-CRT, IMRT showed significantly better results regarding dose conformity (p = 0.012) and bowel sparing at dose levels above 30 Gy (p = 0.012). Thus, dose escalation in the radiotherapy of pelvic Ewing's sarcoma can be more easily achieved using IMRT.


Yao MS, Chang CM, Chen CL, Chan WP
Synovial chondrosarcoma arising from synovial chondromatosis of the knee.
JBR-BTR. 2012 Nov-Dec; 95(6):360-2 [PubMed]
We report the case of a 51-year-old woman who had suffered from right knee pain and stiffness for 40 years. Her symptoms had gradually worsened over the past 5 years. One year previously, when she first visited our clinic, plain radiographs and CT scan images had revealed synovial chondromatosis over the right knee. At the current admission, follow-up MRI showed synovial masses around the knee and worsening of endosteal cortical scalloping in the patella, femoral condyle, and tibial plateau. After diagnosis on the basis of frozen sections, the patient had total excision of the lesions and total knee athroplasty. Histological examination revealed synovial chondromatosis in the joint cavity and grade 1 chondrosarcoma invasion into the adjacent bone. In long-standing synovial chondromatosis, presentation with aggravated symptoms and deterioration on imaging findings should alert clinicians to the potential for malignant change.


Brusić SK, Pusić M, Cvjetković N, et al.
Osteosarcoma of the mastoid process following radiation therapy of mucoepidermoid carcinoma of the parotid gland--a case report.
Coll Antropol. 2012; 36 Suppl 2:223-5 [PubMed]
Radiation therapy is frequently used method in treatment of the head and neck malignancies. Osteosarcoma is a rare complication of radiation therapy and usually occurs after a long latent period. We report the case of 75-year-old female with osteosarcoma of the mastoid process. Twelve years before presentation she received radiation therapy after total parotidectomy and radical neck dissection in treatment of mucoepidermoid carcinoma of the parotid gland. Diagnostic procedures included contrast-enhanced CT and MRI of the head and neck and HRCT of the temporal bone. The final diagnosis of the low grade osteosarcoma was confirmed by biopsy. Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma.


Ferrari S, Palmerini E, Fabbri N, et al.
Osteosarcoma of the pelvis: a monoinstitutional experience in patients younger than 41 years.
Tumori. 2012; 98(6):702-8 [PubMed]
AIMS AND BACKGROUND: Information is scarce on systemic treatment of pelvic osteosarcoma because most chemotherapy protocols for osteosarcoma include patients with extremity tumors and aged up to 30-40 years.
METHODS: Data on patients <41 years of age with high-grade pelvic osteosarcoma were prospectively collected. Patients received two chemotherapy protocols consisting of methotrexate, cisplatin, doxorubicin (MAP) and standard-dose or high-dose ifosfamide.
RESULTS: Forty patients between 11 and 36 years were included. The most frequent histological subtype was osteoblastic followed by chondroblastic (37.5%). Complete surgical remission was achieved in 65% of patients. Eighteen patients had MAP/standard-dose ifosfamide, 22 MAP/high-dose ifosfamide. Primary chemotherapy was given to 25 patients and 6 (24%) of them had a good histological response. Median follow-up was 32 months (range, 4-134). Five-year overall survival was 27.5%: 33% in localized and 0 in metastatic patients ( P = 0.02); 45% in patients with complete surgical remission and 0 for patients without complete surgical remission (P = 0.001). Local recurrence rate was 46%. In patients with complete surgical remission, 5-year overall survival was 32% with MAP/standard-dose ifosfamide and 59% with MAP/high-dose ifosfamide regimen (P = 0.3).
CONCLUSIONS: Local control is the major issue in the treatment of pelvic osteosarcoma. Poor pathological response and high incidence of chondroblastic variant indicate different characteristics between pelvic and extremity osteosarcoma. Chemotherapy with MAP and high-dose ifosfamide might be beneficial in patients with pelvic osteosarcoma and warrants further investigation.


Gorelik N, Dickson BC, Wunder JS, Bleakney R
Ewing's sarcoma of the patella.
Skeletal Radiol. 2013; 42(5):729-33 [PubMed]
Ewing's sarcoma is a relatively rare malignancy, occurring mainly between 4 and 25 years of age. It usually arises from the pelvis, followed by the femur, tibia, and remainder of both the long bones of the extremities and flat bones of the axial skeleton. To the best of our knowledge, Ewing's sarcoma of the patella has never been reported previously. Patellar tumors occur infrequently and represent an uncommon etiology of anterior knee pain. We describe the rare case of a 41-year-old man who presented with a 3-4 month history of escalating right anterior knee pain and swelling. Imaging demonstrated an aggressive patellar tumor with an adjacent soft tissue mass. The diagnosis of Ewing's sarcoma was confirmed by pathology. Physicians should be aware of atypical locations for Ewing's sarcoma and, conversely, of rare tumors arising in the patella and accounting for anterior knee pain. Early recognition of such malignancies allows prompt initiation of treatment, hence improving prognosis.


Jiang L, Tao C, He A
Prognostic significance of p53 expression in malignant bone tumors: a meta-analysis.
Tumour Biol. 2013; 34(2):1037-43 [PubMed]
Osteosarcoma and Ewing's sarcoma are the two most common primary malignant bone tumors, and findings of prognostic factors are important for clinicians to decide treatment options. High p53 expression has been implicated in tumor development and progression, but studies investigating the prognostic role of p53 overexpression in malignant bone tumors report conflicting findings. We performed a meta-analysis to assess the relationship between p53 overexpression and the survival of malignant bone tumors. A meta-analysis of 13 studies with a total of 703 patients was carried out to evaluate the association between p53 overexpression and overall survival (OS) and disease-free survival (DFS) in patients with malignant bone tumors. The pooled hazard ratio (HR) with its 95 % confidence interval (CI) was used as the effect size estimate. There was no between-study heterogeneity in both OS studies (I (2) = 0.0 %) and DFS studies (I(2) = 0.0 %). Overall, high p53 expression predicted both poor OS (HR 2.13, 95 % CI 1.81-2.52, P < 0.001) and poor DFS (HR 2.06, 95 % CI 1.58-2.69, P < 0.001) in patients with malignant bone tumors. Subgroup analyses by tumor types suggested that p53 expression predicted poor OS in both osteosarcoma patients (HR 2.15, 95 % CI 1.78-2.60, I (2) = 15.2 %, P < 0.001) and Ewing's sarcoma patients (HR 2.09, 95 % CI 1.47-2.97, I(2) = 0.0 %, P < 0.001). Besides, p53 expression also predicted poor DFS in both osteosarcoma patients (HR 2.38, 95 % CI 1.60-3.52, I(2) = 0.0 %, P < 0.001) and Ewing's sarcoma patients (HR 1.83, 95 % CI 1.28-2.63, I(2) = 0.0 %, P = 0.001). Egger's test also did not suggest evidence for publication bias in both OS studies (P = 0.615) and DFS studies (P = 0.258). High p53 expression indicates a poorer prognosis for patients with osteosarcoma and Ewing's sarcoma.


Machado I, Traves V, Cruz J, et al.
Superficial small round-cell tumors with special reference to the Ewing's sarcoma family of tumors and the spectrum of differential diagnosis.
Semin Diagn Pathol. 2013; 30(1):85-94 [PubMed]
Superficial/cutaneous small round-cell tumors comprise a heterogeneous group of neoplasms including sarcoma, carcinoma, melanoma, and lymphomas. Among superficial sarcomas, the Ewing's sarcoma family of tumors (ESFT) represents a poorly understood rare variant, having a behavioral difference characterized by a relative favorable prognosis. Several problems are still to be resolved in superficial ESFT, including the differential diagnosis between ESFT of bone (intraosseous or periosteal) with superficial infiltration and superficial ESFT with bone infiltration, especially in the fingers. Our aim is to review the most common types of small round-cell tumors included in the differential diagnosis of superficial ESFT, analyzing the histopathology, phenotype, and molecular alterations of each entity.


Jianwei Z, Enzhong B, Fan L, et al.
Effects of Kruppel-like factor 6 on osteosarcoma cell biological behavior.
Tumour Biol. 2013; 34(2):1097-105 [PubMed]
Kruppel-like factor 6 (KLF6) is a tumor suppressor gene frequently downregulated in a number of human cancers, including osteosarcoma. However, the role of KLF6 in osteosarcoma remains unclear. This study was aimed at investigating the effects of KLF6 on osteosarcoma cell biological behavior. First, the expression of KLF6 in osteosarcoma cell lines (MG63, SaOS-2, U2OS, and HOS) and a human osteoblastic cell line (hFOB1.19) was detected by Western blotting. Results showed that KLF6 displayed a significant downregulation in osteosarcoma cell lines (MG63, SaOS-2, U2OS, and HOS) compared with human osteoblastic cell line (hFOB1.19). To investigate the role of KLF6 in osteosarcoma cell proliferation, apoptosis, and invasion, we generated human osteosarcoma MG63 cells in which KLF6 was either overexpressed or depleted. The MG63 cell viability, cycle, apoptosis, and invasive ability were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining, propidium iodide (PI) staining, Annexin-V-FITC/PI double staining, and Transwell invasion experiment, respectively. Results showed that the viability, proliferation, and invasive abilities were suppressed, and the apoptosis was enhanced in MG63 cells with overexpression of KLF6. The viability, proliferation, and invasive abilities were improved, and the apoptosis was inhibited in MG63 cells with knockdown of KLF6. At the same time, these molecules, including p21, bcl-2, and MMP-9, associated with the events about cell cycle, apoptosis, and invasion, were detected. Results showed that the expressions of bcl-2 and MMP-9 were downregulated, and the expressions of p21 were upregulated in the MG-63 cells with overexpression of KLF6. Taken together, our results suggested that KLF6 could inhibit proliferation and invasion, and facilitate apoptosis of osteosarcoma cells, which might be a potential target for the treatment of osteosarcoma.


Chou AJ, Gupta R, Bell MD, et al.
Inhaled lipid cisplatin (ILC) in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung.
Pediatr Blood Cancer. 2013; 60(4):580-6 [PubMed]
BACKGROUND: Osteosarcoma treatment failure is most often from the inability to control metastatic disease in the lungs. Encapsulating cisplatin within lipid complexes and delivering the agent via inhalation targets lung metastases with minimal systemic exposure. An open-label, phase Ib/IIa study was performed to characterize the safety and efficacy of inhaled lipid cisplatin (ILC) in recurrent osteosarcoma patients who only had pulmonary metastases.
PROCEDURE: ILC was administered via nebulizer every 2 weeks (=1 cycle). Response was evaluated radiographically every 2 cycles. Cisplatin levels were measured in patients. When possible, metastasectomy was undertaken in patients after 2 cycles.
RESULTS: Nineteen patients were treated. No patients experienced hematologic toxicity, nephrotoxicity or ototoxicity. Nausea/vomiting (≥grade 3) was attributed to study drug in one patient. Respiratory symptoms were observed in 13/19 patients with only one patient experiencing a ≥grade 3 respiratory symptom (not related to study drug). Systemic cisplatin exposure was minimal. Eleven patients had bulky disease, and all progressed prior to cycle 7. Eight patients had all lesions ≤2 cm. One patient had a sustained partial response. An additional two patients had stable disease after 2 cycles, underwent metastasectomy, and remained free from pulmonary recurrence 1 year after initiation of therapy.
CONCLUSIONS: ILC is well tolerated in heavily treated osteosarcoma patients and did not appear to have the typical toxicities associated with intravenous cisplatin. Three of eight patients with less bulky disease had sustained benefit. Further study of ILC is warranted.


Rao-Bindal K, Rao CK, Yu L, Kleinerman ES
Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts.
Pediatr Blood Cancer. 2013; 60(4):575-9 [PubMed]
OBJECTIVE(S): We have previously shown that Fas expression inversely correlates with the metastatic potential of osteosarcoma (OS) to the lung. FasL is constitutively expressed in the lung microenvironment and eliminates Fas(+) OS cells leaving Fas(-) cells to form metastases. Absence of FasL in the lung epithelium or blocking the Fas-signaling pathway interfered with this clearance mechanism allowing Fas(+) cells to remain and form lung metastases. We also demonstrated that while the majority of patient OS lung metastases were Fas(-), 10-20% of the lesions contained Fas(+) cells, suggesting that these cells were not sensitive to FasL-induced apoptosis. The expression of c-FLIP, an inhibitor of the Fas pathway, has been associated with tumor development, progression, and resistance to chemotherapy. We therefore evaluated the expression of c-FLIP in OS patient tumor specimens and human xenograft lung metastases.
METHODS: OS patient tissues, which included both primary and metastatic lesions, were evaluated for the expression of c-FLIP. In addition, tumors from human OS xenografts were examined for c-FLIP expression.
RESULTS: c-FLIP expression was significantly higher in the lung metastases than in the primary tumors.
CONCLUSION(S): c-FLIP may play an important role in the metastatic potential of OS to the lung. Inhibition of c-FLIP may be a future therapeutic target.


Nishio J, Iwasaki H, Takagi S, et al.
Low-grade central osteosarcoma of the metatarsal bone: a clinicopathological, immunohistochemical, cytogenetic and molecular cytogenetic analysis.
Anticancer Res. 2012; 32(12):5429-35 [PubMed]
Low-grade central osteosarcoma (LGCOS) is a very rare low-grade malignant neoplasm that is often confused with a variety of benign fibro-osseous lesions. It rarely involves the small tubular bones of the feet. We present an unusual case of LGCOS arising in the third metatarsal bone of a 16-year-old boy. The radiographic appearance was suggestive of a benign lesion. An open biopsy was performed and the initial diagnosis was fibrous dysplasia. The patient underwent curettage of the lesion and packing of the bony defect with a synthetic bone substitute. Histologically, the curetted specimens consisted of spindle cells admixed with irregular bony trabeculae and osteoid. The spindle cells were fairly uniform with mild atypia, and cellularity varied from low to high. Immunohistochemistry showed that the tumor cells were focally-positive for cyclin-dependent kinase 4 and p53, but negative for murine double minute-2. The MIB-1 labeling index was 36.7% in the highest focus. Cytogenetic analysis exhibited the following clonal karyotypic abnormalities: 48,XY,del(6)(p11),add(8)(q24),add(12)(p11.2),+mar1,+mar-2. Spectral karyotyping demonstrated that marker chromosomes were composed mainly of chromosome 6. Metaphase-based comparative genomic hybridization analysis showed a high-level amplification of 6p12-p21 and gains of 8q21-q24, 10p15, 12q13-q15, and 16q23-q24. Based on these findings, the final diagnosis was revised to LGCOS and the patient was treated with an additional wide excision, followed by reconstruction with a free-vascularized osteocutaneous scapular flap. At 18 months of follow-up, the patient is well with no evidence of local recurrence or distant metastasis. Our case highlights the diagnostic difficulty of this tumor with limited tissue samples and the importance of immunohistochemical and molecular cytogenetic analyses in ambiguous cases.


Tzeng HE, Tsai CH, Chang ZL, et al.
Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma.
Biochem Pharmacol. 2013; 85(4):531-40 [PubMed]
Osteosarcoma is characterized by a high malignant and metastatic potential. Angiogenesis is essential for the caner metastasis. Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the relationship between IL-6 and vascular endothelial growth factor (VEGF) expression in human osteosarcoma is mostly unknown. Here we found that the IL-6 and VEGF expression was correlated with tumor stage and significantly higher than that in normal bone. Incubation of osteosarcoma cells with IL-6 increased VEGF mRNA and protein expression. Pretreatment of cells with IL-6R antibody reduced IL-6-mediated VEGF production. The apoptosis signal-regulating kinase 1 (ASK1)/p38/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced VEGF expression was abolished by the specific inhibitor and siRNA of ASK1, p38, and AP-1 cascades. Importantly, knockdown IL-6 reduced VEGF expression and abolished osteosarcoma conditional medium-mediated angiogenesis. Taken together, these results indicate that IL-6 occurs through ASK1 and p38, which in turn activates AP-1, resulting in the activations of VEGF expression and contributing the angiogenesis of human osteosarcoma cells.


Tan ML, Friedhuber AM, Dass CR
Co-nanoencapsulated doxorubicin and Dz13 control osteosarcoma progression in a murine model.
J Pharm Pharmacol. 2013; 65(1):35-43 [PubMed]
OBJECTIVES: Chitosan is a green (natural, abundant, biodegradable, biocompatible) biopolymer that can be formulated to encapsulate a variety of therapeutic compounds. This study aimed to investigate chitosan nanoparticles (NPs) as a means of improving delivery of the clinically used anti-cancer agent doxorubicin (Dox) and the preclinical lead compound Dz13 oligonucleotide together.
METHODS: A novel chitosan NP system encapsulating Dox and Dz13 was designed, biophysically characterised and tested in a clinically relevant model of the metastasising bone tumour, osteosarcoma (OS).
KEY FINDINGS:  By careful alteration of the concentration of the individual components, a final formulation of Dz13-Dox NPs (DDNPs) was achieved, with high (>91%) loading of both compounds, which consisted of individual 50-nm particles forming aggregates as large as 500 nm, with a large positive ζ-potential. The DDNPs could be stored at various temperatures for a week without loss in activity but were prone to degradation in serum. DDNPs successfully inhibited OS tumour growth more effectively than treatment with NPs of Dz13 and Dox-chitosan, as well as Dox administered intraperitoneally. Apart from inhibiting tumour growth, DDNPs protected the affected bone from substantial destruction by aggressive tumour growth and reduced the incidence of metastasis to the lungs without causing adverse effects in mice.
CONCLUSION: This NP is a promising formulation that could be useful for clinical management of OS.


Matanić D, Kukuljan M, Grgurević E, et al.
Central type of chondrosarcoma with a fulminant course--a case report.
Coll Antropol. 2012; 36(3):1037-40 [PubMed]
Primary chondrosarcoma is a rare malignant tumor. The five types of chondrosarcomas are: central, peripheral, mesenchymal, differentiated and clear cell. The classic chondrosarcomas are central (arising within a bone) or peripheral (arising from the surface of a bone). We describe a patient with central chondrosarcoma of the humerus who underwent surgery and only two weeks later presented with multiple metastases of the lung and small pulmonary tumor embolisms mimicking bilateral pneumonic infiltrates. Therefore, such a fulminant course of central chondrosarcoma, which is not described so far, must be taken into consideration during the treatment of patients with primary chondrosarcoma.


Anninga JK, Picci P, Fiocco M, et al.
Osteosarcoma of the hands and feet: a distinct clinico-pathological subgroup.
Virchows Arch. 2013; 462(1):109-20 [PubMed]
Osteosarcomas of hands or feet are rare, and seemingly these cases differ in presentation and behavior compared to those in usual locations. The clinico-pathological presentation of patients with osteosarcomas of the hand or foot was studied and compared with published cases. Forty osteosarcomas were identified among 4,221 cases, representing 0.95 % of all osteosarcomas. Thirty of these were well documented. Mean age at diagnosis was 43 years (hands) and 36 years (feet) and male-female ratio was 1.2:1 and 2.0:1, respectively. In the hand, 62 % of the osteosarcomas presented in the metacarpals and 23 % in the phalanges, and only two cases occurred in the carpal bones. Distribution in the foot was tarsal bones 56 %, metatarsal bones 33 %, and phalanges 11 %.Of the cases in the hand 54 % were of high grade and of those in the foot 71 %. Survival of osteosarcomas of the hand or foot was 81 %. Only patients with high-grade osteosarcoma died of the disease. Histological grade was the only significant variable related to survival. High-grade osteosarcoma of the hand or feet should be treated similar to those in conventional sites. Osteosarcomas of hands or feet are rare and in a relative high proportion are of low grade. Survival in high-grade cases is comparable to that in conventional sites.


Hauer K, Calzada-Wack J, Steiger K, et al.
DKK2 mediates osteolysis, invasiveness, and metastatic spread in Ewing sarcoma.
Cancer Res. 2013; 73(2):967-77 [PubMed]
Ewing sarcoma, an osteolytic malignancy that mainly affects children and young adults, is characterized by early metastasis to lung and bone. In this study, we identified the pro-metastatic gene DKK2 as a highly overexpressed gene in Ewing sarcoma compared with corresponding normal tissues. Using RNA interference, we showed that DKK2 was critical for malignant cell outgrowth in vitro and in an orthotopic xenograft mouse model in vivo. Analysis of invasion potential in both settings revealed a strong correlation of DKK2 expression to Ewing sarcoma invasiveness that may be mediated by the DKK effector matrix metalloproteinase 1 (MMP1). Furthermore, gene expression analyses established the ability of DKK2 to differentially regulate genes such as CXCR4, PTHrP, RUNX2, and TGFβ1 that are associated with homing, invasion, and growth of cancer cells in bone tissue as well as genes important for osteolysis, including HIF1α, JAG1, IL6, and VEGF. DKK2 promoted bone infiltration and osteolysis in vivo and further analyses defined DKK2 as a key factor in osteotropic malignancy. Interestingly, in Ewing sarcoma cells, DKK2 suppression simultaneously increased the potential for neuronal differentiation while decreasing chondrogenic and osteogenic differentiation. Our results provide strong evidence that DKK2 is a key player in Ewing sarcoma invasion and osteolysis and also in the differential phenotype of Ewing sarcoma cells.


Carter CJ, Ward WG
Osteosarcoma diagnostic delay associated with alendronate-induced pain relief.
J Surg Orthop Adv. 2012; 21(3):165-9 [PubMed]
A 32-year-old man with a painful osteoblastic osteosarcoma of the right hip was initially diagnosed as having Paget's disease of bone. He was treated with alendronate for presumptive Paget's disease. The patient's bone pain was dramatically reduced by the administration of alendronate for 7 months. Following discontinuation of alendronate, his pain promptly recurred, culminating in a more thorough evaluation that led to the correct diagnosis. Despite chemotherapy, the patient succumbed to metastatic osteosarcoma. The main purpose of this publication is to report the potential for pain relief when an osteosarcoma is treated with bisphosphonate medication. Clinicians are advised not to consider an alendronate-associated pain reduction in an osteoblastic lesion as an indicator of an underlying benign process of bone. The evaluation of painful sclerotic bone lesions is briefly reviewed.


Abbas S, Vincourt JB, Habib L, et al.
The cucurbitacins E, D and I: investigation of their cytotoxicity toward human chondrosarcoma SW 1353 cell line and their biotransformation in man liver.
Toxicol Lett. 2013; 216(2-3):189-99 [PubMed]
Cucurbitacins are a class of natural compounds known for their numerous potential pharmacological effects. The purpose of this work was to compare the cytotoxicity of three cucurbitacins I, D, E on the chondrosarcoma SW 1353 cancer cell line and to investigate their biotransformation in man. Cucurbitacins I and D showed a very strong cytotoxicity, which was higher than that of cytochalasin D, used as a drug reference. Almost 100% of the cells were apoptotic as observed by DNA fragmentation (TUNEL assay) after 12 h with cucurbitacins I and D (1 μM) and cucurbitacin E (10 μM). In terms of IC(50) values, cucurbitacins I and E presented a higher toxicity compared to that of cucurbitacin D (MTT assay). Cucurbitacin E was readily hydrolyzed by human hepatic microsomes, leading to cucurbitacin I (K(m) 22 μM, V(max) 571 nmol/mg proteins/min). On the other hand, the three cucurbitacins were hydroxylated at a very low extent, but they were sulfated and glucuronidated. In terms of V(max)/K(m), the cucurbitacin E was the best substrate of UDP-glucuronosyltransferases. This study shows that cucurbitacins I, D and E present a potent cytotoxic activity toward the chondrosarcoma SW 1353 cell line and are metabolized as sulfate and glucuronide conjugates.


Yu M, Wan Y, Zou Q
Reduced mitochondrial DNA copy number in Chinese patients with osteosarcoma.
Transl Res. 2013; 161(3):165-71 [PubMed]
A plethora of somatic mutations and germline variations in mitochondrial DNA (mtDNA) have been increasingly reported in numerous cancer entities including osteosarcoma. However, it remains largely unclear whether mtDNA copy number changes occur during the multistep process of osteosarcoma carcinogenesis. For this purpose, we determined quantitative mtDNA levels in 31 primary osteosarcoma specimens and 5 normal bone tissue samples using a real-time polymerase chain reaction assay. Our data showed that the average mtDNA amount was significantly reduced in osteosarcoma tissues compared with normal bone controls. The copy number of mtDNA was statistically associated with tumor metastasis. There was an approximately 2-fold decrease of mtDNA quantity in tumors with metastasis than that in low-grade tumors without metastasis. Furthermore, change in mtDNA content was linked with somatic mutations in the D-loop regulatory region. Tumors carrying somatic D-loop mutations, at the polycytidine stretch between nucleotide positions 303 and 309 or close to the replication origin sites of the heavy strand, had significantly lowered mtDNA levels in comparison with those without mutations. Taken together, these results provide evidence for the first time that reduced mtDNA content may be critically implicated in the development and/or progression of osteosarcoma. Somatic D-loop mutation is likely one key factor among others leading to altered mtDNA amount in osteosarcoma.


Fayda M, Kebudi R, Dizdar Y, et al.
Spontaneous pneumothorax in children with osteosarcoma: report of three cases and review of the literature.
Acta Chir Belg. 2012 Sep-Oct; 112(5):378-81 [PubMed]
Spontaneous pneumothorax is a rare manifestation of primary lung cancer or metastasis. It is estimated that < 1% of all cases of spontaneous pneumothorax are tumor-associated and metastatic osteogenic or soft-tissue sarcomas are associated most commonly with pneumothorax especially in the setting of cytotoxic chemotherapy or radiotherapy. In this article, we report three pediatric cases with osteosarcoma that developed spontaneous pneumothorax during chemotherapy with a review of the literature. Two of them had lung metastasis at the time of the detection of pneumothorax and the remaining patient was found to have a bronchopleural fistula. SPx is an emergency situation and early diagnosis and management can improve prognosis and quality of life of the patient however the optimal management has yet to be determined.


Bloch O, Parsa AT
Skull base chondrosarcoma: evidence-based treatment paradigms.
Neurosurg Clin N Am. 2013; 24(1):89-96 [PubMed]
Chondrosarcomas are indolent but invasive chondroid malignancies that can form in the skull base. Standard management of chondrosarcoma involves surgical resection and adjuvant radiation therapy. This review evaluates evidence from the literature to assess the importance of the surgical approach and extent of resection on outcomes for patients with skull base chondrosarcoma. Also evaluated is the ability of the multiple modalities of radiation therapy, such as conventional fractionated radiotherapy, proton beam, and stereotactic radiosurgery, to control tumor growth. Finally, emerging therapies for the treatment of skull-base chondrosarcoma are discussed.


Jahangiri A, Jian B, Miller L, et al.
Skull base chordomas: clinical features, prognostic factors, and therapeutics.
Neurosurg Clin N Am. 2013; 24(1):79-88 [PubMed]
Chordomas of the skull base are one of the rarest intracranial malignancies that arise from ectopic remnants of embryonal notochod. The proximity of many chordomas to neurovascular structures makes gross total resection difficult, and the tendency for recurrence leads to the routine use of adjuvant postoperative radiation. Several surgical approaches are used ranging from extensive craniotomies to minimally invasive endonasal endoscopic approaches. In this review, the histopathology and epidemiology, imaging characteristics, surgical approaches, adjuvant therapies, prognostic factors, and molecular biology of chordomas are described.


Abdel MP, Papagelopoulos PJ, Morrey ME, et al.
Malignant proximal fibular tumors: surgical management of 112 cases.
J Bone Joint Surg Am. 2012; 94(22):e165 [PubMed]
BACKGROUND: Malignant tumors of the proximal part of the fibula are rare. We sought to analyze the presenting characteristics, postoperative complications, and local recurrences of malignant tumors in the proximal part of the fibula in a large series of patients.
METHODS: We identified 112 histologically confirmed malignant tumors of the proximal part of the fibula from the time period between 1910 and 2007. The sex ratio was nearly equal (fifty-four male, fifty-eight female). The average age of the patients was 27.6 years, and the average follow-up period was 5.7 years.
RESULTS: Osteosarcoma (44%) was the most common diagnosis. Pain (86%), palpable mass (51%), and peroneal nerve symptoms (12%) were the most common presenting symptoms. One hundred and three (92%) of 112 underwent curative surgical treatment. The two most common procedures were amputation in fifty (45%) of 112 patients and Malawer type-II resection in twenty-four (21%) of 112 patients. Deliberative sacrifice of the peroneal nerve was performed in seventy-four patients (66%). Postoperative complications occurred in fourteen (12.5%) of 112 patients, including wound issues (ten of 112), peroneal nerve palsy despite nerve preservation (two of twenty-nine), and posterior tibial artery thrombosis (two of 112). No long-term knee instability was seen in the fifty-three patients who underwent resection with lateral collateral ligament reconstruction. Fifty-six patients (50%) developed distant metastases and twelve (11%) had local recurrences.
CONCLUSIONS: Osteosarcomas are the most common malignant tumor of the proximal fibula. Complication rates are modest and long-term knee instability was not seen in patients undergoing reconstruction of the lateral collateral ligament. Local recurrence following resection is not uncommon and metastatic dissemination is the main cause of death. This series represents the largest collection of such tumors for which there is extended follow-up and data on surgical complications.


Owens C, Laurence V, Benboubker L, et al.
Phase II study of cisplatin and oral VP16 in patients with refractory or relapsed Ewing sarcoma.
Cancer Chemother Pharmacol. 2013; 71(2):399-404 [PubMed]
BACKGROUND: Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT.
METHODS: Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m(2)/dose for patients <21 years of age and 50 mg/m(2)/dose ≥21 years). VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43 inclusive. A three-stage Fleming statistical design was used for analysis.
RESULTS: Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months.
CONCLUSIONS: Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.


Forest F, David A, Arrufat S, et al.
Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the spectrum of tumors associated with SMARCB1 germline mutations.
Am J Surg Pathol. 2012; 36(12):1892-6 [PubMed]
SMARCB1 germline mutations mainly predispose to rhabdoid tumors. However, less aggressive tumors with a later onset have also been reported in a context of SMARCB1 constitutional mutation-that is, schwannomatosis and meningiomatosis. No other tumor type has formally been observed in such a context thus far. We report on a patient treated for a thoracic malignant rhabdoid tumor at 8 years of age who subsequently developed a mandibular conventional chondrosarcoma at 13 years of age. Both tumors showed a loss of BAF47 expression. The malignant rhabdoid tumor exhibited a large 22q11.2 deletion and an intragenic deletion of SMARCB1 (exons 1 to 3), thus leading to a biallelic inactivation. A 2.8 Mbp deletion encompassing SMARCB1 was found in the germline. This context was a strong incentive to investigate SMARCB1 alterations in the second tumor. As expected, the chondrosarcoma showed the large 22q11.2 deletion but also an additional c.243C>G(p.Tyr18X) premature stop codon in the remaining allele. This report relates for the first time a pediatric conventional chondrosarcoma to the wide family of SMARCB1-deficient tumors. Moreover, we report here the first case of conventional chondrosarcoma arising in a context of constitutional SMARCB1 deletion and, thus, enlarge the spectrum of this tumor predisposition syndrome.


Carozzo S, Schardt D, Narici L, et al.
Electrophysiological monitoring in patients with tumors of the skull base treated by carbon-12 radiation therapy.
Int J Radiat Oncol Biol Phys. 2013; 85(4):978-83 [PubMed]
PURPOSE: To report the results of short-term electrophysiologic monitoring of patients undergoing (12)C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery.
METHODS AND MATERIALS: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision.
RESULTS: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline.
CONCLUSIONS: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may help predict, possible late toxicity.


Neubauer H, Evangelista L, Hassold N, et al.
Diffusion-weighted MRI for detection and differentiation of musculoskeletal tumorous and tumor-like lesions in pediatric patients.
World J Pediatr. 2012; 8(4):342-9 [PubMed]
BACKGROUND: MRI is the diagnostic mainstay for detection and differentiation of musculoskeletal tumors. However, a projection regarding the biological dignity of lesions based on standard MRI sequences remains difficult and uncertain. This study was undertaken to analyse whether diffusion-weighted MRI (DWI) can distinguish between benign and malignant musculoskeletal tumorous and tumor-like lesions in pediatric patients.
METHODS: MR examinations of 44 consecutive pediatric patients (26 girls, mean age 11±6 years) including standard sequences and DWI (b=50/800 s/mm(2)) at 1.5 or 3 Tesla were retrospectively evaluated. The study group contained 10 patients with non-treated malignant tumors and 34 patients with benign lesions. Size, relative signal intensity and apparent diffusion coefficient (ADC, unit ×10(-3) mm(2)/s) were determined in one lesion per patient.
RESULTS: Mean ADC was 0.78±0.45×10(-3) mm(2)/s in patients with malignant tumors and 1.71±0.75 ×10(-3) mm(2)/s in patients with benign lesions (P<0.001). Relative operating characteristics (ROC) analysis showed a sensitivity of 90% and a specificity of 91% for malignancy, based on an ADC cut-off value of ≤1.03. On logistic regression, mean ADC and lesion size accounted for 62% of variability in benign vs. malignant tumors. For malignant tumors, the signal intensity ratio was higher on DWI than on T1w post-contrast images (P<0.002). Two cases of local tumor recurrence were diagnosed by DWI only.
CONCLUSIONS: DWI shows promising results for determination of biological dignity in musculoskeletal tumors. Mean ADC ≤1.03×10(-3) mm(2)/s is a strong indicator of malignancy at the first diagnosis. The use of DWI for early diagnosis of tumor recurrence in comparison with standard MRI sequences should be evaluated in prospective studies.


Niini T, Scheinin I, Lahti L, et al.
Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study.
Cancer Genet. 2012; 205(11):588-93 [PubMed]
Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.


This page last updated: 22nd May 2013
Displaying links verified within last 2 weeks at time of update.

CancerIndex Logo

Home
Site Map
Cancer Types
Treatments
Locations
Glossary
Search

Patients/Public
Health Professionals
Researchers

About

Disclaimer
© 1996-2013