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PubMed2003

Neoadjuvant chemotherapy for osteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcome.

PURPOSE: The aim of this study was to compare the results in terms of histologic response to primary chemotherapy of two sequential studies in osteosarcoma patients preoperatively treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, given at different doses. PATIENTS AND METHODS: Between January 1993 and March 1995, 171 patients with osteosarcoma of the extremity were treated according to a protocol of neoadjuvant chemotherapy with preoperative methotrexate, cisplatin, doxorubicin, and ifosfamide. From April 1995 to December 1999, 196 osteosarcoma patients were preoperatively treated with the same drugs at higher doses. Postoperatively, patients received the same treatment in both studies used, but poor responders (tumor necrosis <95%) had more cycles of treatment than good responders. RESULTS: Comparing the two chemotherapy regimens, there were no significant differences in terms of good histologic response to chemotherapy (69% vs. 62%), 5-year event-free survival (60% vs. 65%), 5-year overall survival (74% vs. 80%), and rate of local recurrence (6% vs. 4%). The 5-year event-free survival was significantly related to the serum level of alkaline phosphatase before treatment (77% for patients with normal values vs. 46% for patients with high values) and the degree of histologic response to preoperative chemotherapy (69% for good responders vs. 54% for poor responders). CONCLUSIONS: Increasing the doses of preoperative chemotherapy does not improve the rate of good histologic response and survival in osteosarcoma of the extremity. The degree of necrosis induced by preoperative treatment probably reflects an innate sensitivity to chemotherapy, which is not altered by increasing drug doses.

Adolescent↗
PubMed2004

The incidence and prognosis of osteosarcoma skip metastases.

The poor prognosis for patients with osteosarcoma skip metastases has been established in the literature; however, most of the data in the literature concerning osteosarcoma skip metastases were collected before routine use of magnetic resonance imaging and before the use of modern multiagent chemotherapy regimens. This retrospective multiinstitutional study was done to evaluate the efficacy of magnetic resonance imaging to detect skip metastases and to evaluate the prognosis for these patients when treated with modern multiagent chemotherapy protocols. In a group of 155 patients who were younger than 26 years when diagnosed and treated for high-grade osteosarcoma of the long bones, 10 (6.5%) patients with skip metastases were identified. Eight of the 10 lesions were detected on pretreatment magnetic resonance imaging scans and two were detected only from the surgical pathology specimens. Five patients had concomitant pulmonary metastases at presentation and five patients had no other known site of diseases. All 10 patients died, with an average survival of 32.5 months (range 11-71 months). The five patients with only skip metastases at presentation survived an average of 27.2 months (range 15-44 months). Despite advances in the treatment of patients with osteosarcomas, those with skip metastases continue to have a poor prognosis, and they should be counseled regarding the limitations of current therapies.

Adolescent↗
PubMed2006

Outcome of postradiation osteosarcoma does not correlate with chemotherapy response.

UNLABELLED: Postradiation osteosarcoma is a rare tumor with a historically poor prognosis. Recent reports concerning the prognosis of the disease have been conflicting. We ascertained the long-term outcome of patients with this disease treated in the era of contemporary chemotherapy. Twenty-seven patients diagnosed with postradiation osteosarcoma and treated with chemotherapy and surgical resection from 1980-2003 were identified. Demographics, anatomic location, stage, chemo- therapy, necrosis rate, recurrence and metastatic rates were recorded; Kaplan-Meier survival rates were estimated. The median age was 54 years (range, 12-86 years). Nineteen patients were female and eight patients were male. Median followup was 39.2 months (range, 0-218 months). Twenty-two patients received induction chemotherapy for a mean of four cycles (range, 2-6 cycles). Mean tumor necrosis was 63.5%. Seven patients had 90% necrosis; four of these patients died of their disease. The mean survival was 23 months, and the 5-year disease free survival estimate was 27.2%. Histologic response to chemotherapy did not correlate with survival. Patients who had a latency of greater than 10 years after radiation had a better prognosis. Unlike conventional osteosarcoma, response to chemotherapy (necrosis) did not have prognostic significance. Current chemotherapy regimens fail to impact survival in postradiation osteosarcoma. LEVEL OF EVIDENCE: Therapeutic study, level IV (retrospective comparative study).

Adolescent↗
PubMed2007

Fibular osteosarcomas: contaminated margins may not impact survival.

The fibula is an expendable bone which when affected by primary malignancy may simplify treatment and improve outcome. This concept was questioned previously in a study showing a high rate of inadequate margins at surgical resection. We asked whether margin status and other dependent variables affect survival. We analyzed the charts of 36 patients with fibular osteosarcomas treated from 1919 to 2000. We estimated survival by the Kaplan-Meier method and the prognostic significance of dependent variables, especially marginal status, with univariate association using Cox proportional hazard regression. The survival of patients with fibular osteosarcomas was limited, with a median survival of 5 years 4 months after diagnosis. At 5 years, 16 patients died of their disease. Sixteen patients were still alive at 10 years followup. The margin status at surgery was not associated with survival. A higher tumor grade at diagnosis, surgical treatment with above-knee amputation, and occurrence of metastasis were associated with poorer long-term survival. The survival of patients with fibular osteosarcomas was not better than with osteosarcomas arising in other locations. A marginal resection surprisingly did not impact on overall survival, although we had a limited dataset and heterogeneous treatment protocols.

Adolescent↗
PubMed2005

Ligation and partial excision of the cauda equina as part of a wide resection of vertebral osteosarcoma: a case report and description of surgical technique.

STUDY DESIGN: A case report. OBJECTIVES: To describe the unique challenges and novel surgical approach to treatment of vertebral osteosarcoma involving the dura as a margin. SUMMARY OF BACKGROUND DATA: Osteosarcoma of the vertebral column is a rare, malignant osseous tumor, carrying a poor prognosis. Currently, best available evidence supports that optimal surgical treatment entails wide excision of the tumor. Intentionally compromising neurologic function in order to ensure resection of the tumor with wide surgical margins can pose a difficult dilemma for the surgeon and patient. We describe here the first reported case, to our knowledge, of wide surgical resection of a vertebral osteosarcoma, including ligation and resection of part of the cauda equina and conus medullaris. METHODS: The clinical and radiographic presentations of a patient with osteosarcoma of L2 are presented. The challenges of surgical treatment of a primary malignant tumor of the spine, involving the dura as a margin, are discussed. The ultimate surgical technique employed to achieve wide surgical margins is described in detail. RESULTS: Four-year follow-up shows the patient is doing well, ambulating in a wheelchair, with no clinical or radiologic evidence of active disease or back or neuropathic pain and solid bony fusion. CONCLUSION: Currently, there is sufficient evidence to support the premise that the best chance for cure in sarcomas of the spine can be afforded through en bloc resection with negative margins. Neurologic forfeit in resection of spinal tumors, however, is usually at the root level, and this is the only case where such dramatic neurologic sacrifice was carried out. Although it is still early, the surgical and medical goals have been met, but most importantly, the patient's foremost goal of survival has been accomplished.

Adult↗
PubMed2006

Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

STUDY DESIGN: Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. OBJECTIVES: To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. SUMMARY OF BACKGROUND DATA: To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. METHODS: The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. RESULTS: En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. CONCLUSION: En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

Adult↗
PubMed2004

Primary pelvic telangiectatic osteosarcoma metastatic to both orbits.

We report a case of a 23-year-old man with primary pelvic telangiectatic osteosarcoma metastatic to both orbits. The patient had proptosis with optic neuropathies and intermittent third nerve palsies. His disease was unresponsive to chemotherapy or radiotherapy, and extensive craniofacial involvement precluded surgical resection. The patient died of his disease. Telangiectatic osteosarcoma, a rare variant of osteosarcoma that is distinguished by blood-filled cystic spaces, may metastasize to the orbit and skull base. Because telangiectatic osteosarcoma may radiographically resemble other benign and malignant lesions, biopsy is essential for accurate diagnosis that will ultimately dictate clinical therapy. However, patients with this disease have a poor prognosis.

Adult↗
PubMed2005

Osteosarcomas of the larynx.

OBJECTIVES/HYPOTHESIS: The objective was to review the etiology, presentation, treatment, and prognosis in patients with osteosarcoma of the larynx using an illustrative case example. STUDY DESIGN: Case report and literature review. METHODS: A case is reported, and a review of all available published cases of osteosarcoma of the larynx is presented. RESULTS: Osteosarcoma of the larynx may be a difficult clinical diagnosis. To be able to reach the correct diagnosis, a high index of suspicion and due diligence in obtaining deep biopsy specimens are important. Treatment is primarily surgical. Outcomes for this disease are generally poor, with most patients dying of the disease as a result of pulmonary metastasis. CONCLUSION: Osteosarcoma of the larynx is a rare entity, with only 14 cases reported to date. Pathological confirmation of osteoid is required for diagnosis. It is likely that aggressive surgical intervention directed at complete tumor extirpation is the treatment of choice, although long-term prognosis is poor.

Aged↗
PubMed2005

Clinicopathologic features, treatment, and prognosis of postirradiation osteosarcoma in patients with nasopharyngeal cancer.

OBJECTIVES: Postirradiation osteosarcoma (PIOS) arising after radiation of nasopharyngeal cancer (NPC) is rare and seldom reported. In this article, we report its clinicopathologic features, outcome, and prognostic factors. STUDY DESIGN: Retrospective cohort study. METHODS: Fifteen patients with NPC were determined to have PIOS after reviewing 426 patients with osteogenic sarcomas. Their clinical records, image and pathologic slides, and follow-up data after treatment were collected to perform analysis. RESULTS: The incidence rate of PIOS in NPC was approximately 0.037% (15/40,719), which occupied approximately 3.5% (15/426) among all kinds of osteogenic sarcomas. The latent time of PIOS after irradiation for NPC ranged from 4 to 27 years, with a mean of 13.3 years. The location where PIOS arose included 33.3% (5/15) from maxilla, 46.7% (7/15) from mandible, and 20% (3/15) from a mixture of nasal cavity and paranasal sinuses. Radiologically, soft tissue mass, bone destruction, and tumor new bone formation were the main characteristics. Pathologic subtypes included 53.3% (8/15) of fibroblastic osteosarcoma, 33.3% (5/15) of chondroblastic osteosarcoma, and 13.3% (2/15) of mixed type osteosarcoma. Of 15 patients with PIOS, 12 patients were treated with curative intent, and the remaining 3 patients with palliative intent. For 12 patients who had undertaken ablative surgery, 1 patient had residual tumor, and 6 patients had tumor recurrence. The survival time after treatment for all patients ranged from 7 to 41 months, with a mean of 18 months. Kaplan-Meier estimates of 1 year and 2 year survival rates were 60% and 24%, respectively. Statistical analysis showed that sex and tumor bone formation are significant prognostic factors. CONCLUSIONS: PIOS in NPC is a highly malignant disease with poorer prognosis than in other sites. Surgery combined with pre- and postoperative chemotherapy might be an effective way to improve survival.

Adolescent↗
PubMed1998

Association of loss of heterozygosity at the p53 locus with chemoresistance in osteosarcomas.

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite sensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 (p53) and 13q14 (Rb) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss (P < 0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.

Adolescent↗
PubMed1999

Inhibition of spontaneous rat osteosarcoma lung metastasis by 3S-[4-(N-hydroxyamino)-2R-isobutylsuccinyl]amino-1-methoxy-3,4-dihydroc arbostyril, a novel matrix metalloproteinase inhibitor.

In the present experiment, we examined the effects of OPB-3206, 3S-[4-(N-hydroxyamino)-2R-isobutylsuccinyl]amino-1-methoxy-3,4- dihydrocarbostyril, a novel metalloproteinase inhibitor, on the growth and metastasis of transplantable osteosarcomas (spontaneous osteosarcoma, selected lung metastatic lesions; S-SLM), which were previously established in rats. OPB-3206 inhibited the activities of interstitial collagenase, gelatinases A and B, and stromelysin in vitro. After oral administration to rats, its serum concentration peaked at 40 min and the drug was no longer detectable at 8 h. When OPB-3206 was orally administered at 0%, 0.1% and 0.4% in the diet for 4 weeks, starting 7 days after subcutaneous transplantation of osteosarcomas to male Fischer 344 rats, numbers of lung metastatic nodules were significantly reduced by the highest dose, while the growth of subcutaneous tumors was not affected. Zymographic analysis showed the presence of pro matrix metalloproteinase (proMMP)-2, proMMP-9 and MMP-9 activities in S-SLM. In animals fed 0.4% OPB-3206, the activity of proMMP-9 was increased, but that for MMP-9 had become undetectable. The results thus suggest that OPB-3206 selectively inhibits lung metastasis of rat transplantable osteosarcomas by inhibiting MMP-9 activation.

Administration, Oral↗
PubMed1989

Thrombospondin is synthesized and secreted by human osteoblasts and osteosarcoma cells. A model to study the different effects of thrombospondin in cell adhesion.

In this study we have shown by both immunofluorescence and immunoprecipitation techniques that human osteoblasts and osteosarcoma cells synthesize and secrete thrombospondin, a 450-kDa glycoprotein initially found in platelets. Immunofluorescence with a mouse monoclonal antibody to human platelet thrombospondin yielded specific granular staining within the cytoplasm of human osteoblasts. SDS/polyacrylamide gel electrophoresis analysis of immunoprecipitates obtained with polyclonal and monoclonal anti-thrombospondin antibodies allows the identification of thrombospondin in the cellular lysates and the culture media of biosynthetically labelled osteoblasts and osteosarcoma cells. Kinetic and dose/response studies of osteoblasts and of two osteosarcoma cell lines (MG-63, SaOs-2) were performed to assess the ability of these cells to adhere to thrombospondin and type-I collagen. Thrombospondin promoted the attachment of human osteoblasts whereas it inhibited the adhesion of MG-63 and SaOs-2 cells, both when it was directly adsorbed to plastic and when it was bound to type-I collagen. Therefore osteoblasts and osteosarcoma cells may be valuable tools to study the role of thrombospondin in cell adhesion.

Animals↗
PubMed1992

Three human osteosarcoma cell lines exhibiting different phenotypic expressions.

to elucidate the differences in histological features and biological behavior of osteosarcomas, three human osteoblastic-type osteosarcomas were studied in vitro and in nude mice. The secretory processing and extracellular fiber formation of type I collagen proved to be the most important factor in bone formation in the osteosarcomas. Alkaline phosphatase also seemed to be important. However, we were unable to find any particular protooncogene abnormalities which could have been implicated in the occurrence or biological behavior of these osteosarcomas.

Alkaline Phosphatase↗
PubMed1990

Immunohistochemical analysis of bone morphogenetic protein (BMP) in osteosarcoma.

The monoclonal antibody against bovine bone morphogenetic protein (bBMP-McAb) was first used for demonstration of bone morphogenetic protein (BMP) in osteosarcoma. The avidin-biotin complex method (ABC) demonstrated that of the 18 osteosarcomas, 15 stained positive, while all 6 fibrosarcomas were negative. The results showed that BMP mainly exists in the tumor cell plasma and some tumor-like bone tissues. Using this staining method, we can not only differentiate osteosarcoma from fibrosarcoma and other non-bone-derived tumors, but also classify osteosarcoma according to the content and distribution of BMP and the patient's clinical situation, thus providing a scientific basis for clinical treatment.

Adolescent↗
PubMedDate not supplied

Accuracy of magnetic resonance imaging for estimating intramedullary osteosarcoma extent in pre-operative planning of canine limb-salvage procedures.

The objective of this work was to compare the accuracy of radiographs and magnetic resonance imaging (MRI) for estimating appendicular osteosarcoma margins. The accuracy of computed tomography (CT) and bone scintigraphy was also assessed when these studies were available. Eight dogs with appendicular osteosarcoma underwent radiographic and MRI of affected limbs. In addition, bone scintigraphy was performed in six dogs and CT examination was performed in five dogs. Two observers jointly measured tumor length on all imaging studies. Correlative gross and histologic evaluation of all affected limbs was performed to determine tumor extent as measured from the nearest articular surface. Results from imaging studies were compared to gross and microscopic morphometry findings to determine the accuracy of each modality for determining tumor boundaries. MRI images were accurate with a mean overestimation of actual tumor length of 3 +/- 13%. T1-weighted non-contrast images were superior in identifying intramedullary tumor margins in most instances whereas contrast-enhanced images provided supplemental information in two dogs. Lateromedial and craniocaudal radiographs overestimated tumor length by 17 +/- 28% and 4 +/- 26%, respectively. Scintigraphy and CT overestimated tumor margins by 14 +/- 28% and 27 +/- 36%, respectively. MRI appears to be an accurate diagnostic imaging modality in determining intramedullary osteosarcoma boundaries. MRI should be considered as part of a pre-operative assessment of appendicular osteosarcoma, particularly when a limb-sparing procedure is contemplated.

Animals↗
PubMed1978

FBJ osteosarcoma virus in tissue culture. III. Isolation and characterization of non-virus-producing FBJ-transformed cells.

Hamster and rat cell lines have been established that have been transformed by FBJ murine sarcoma virus (FBJ-MuSV) but that do not produce virus. The hamster cell line originated from an osteosarcoma that appeared in a hamster inoculated at birth with an extract of a CFNo1 mouse FBJ-osteosarcoma. The rat cell line was obtained by transferring the FBJ-MuSV genome to normal rat kidney cells in the absence of the FBJ type C virus (FBJ-MuLV), which, usually in high concentration, accompanies the FBJ-MuSV. Both transformed hamster and rat cell lines contain the FBJ-MuSV genome, which can be rescued by ecotropic and xenotropic murine type C viruses. This rescued genome produces characteristic FBJ-MuSV foci in tissue culture and, in appropriate animal hosts, induces osteosarcomas typical of those induced by FBJ-MuSV. FBJ-MuSV was isolated originally from a parosteal osteosarcoma that occurred naturally in a mouse. Since there was no previous history of passage of the agent through any other animal species, these non-virus-producing hamster and rat cells transformed by FBJ-MuSV should be very helpful in molecular studies examining the origin of spontaneous sarcoma genomes in mice.

Animals↗
PubMed2002

The expression of bone morphogenetic proteins in osteosarcoma and its relevance as a prognostic parameter.

AIMS: The expression of bone morphogenetic proteins (BMPs) was analysed in 47 osteosarcomas to determine differences in the expression of BMP subtypes and to correlate expression with response to chemotherapy, in addition to the disease free and overall survival of patients. METHODS: The expression of BMPs was examined immunohistochemically in 47 biopsy specimens of osteosarcoma using commercially available antibodies against different subtypes (BMP-2/4 (A-20), BMP-3 (N-19), BMP-4 (N-19), BMP-5 (N-19), BMP-6 (N-19), BMP-7 (N-19), BMP-8 (N-19)). The avidin-biotin-immunoperoxidase method was used for all antibodies. RESULTS: The expression of BMP subtypes varied considerably: 28 of the 47 tumours expressed BMP-2/4, 24 expressed BMP-3, 41 expressed BMP-5, 31 expressed BMP-6, 43 expressed BMP-7, and 42 expressed BMP-8. High expression of BMP-6 was found in those parts of the osteosarcoma with a chondroid differentiation (p = 0.016, Mann-Whitney test). No correlation was observed between the response to chemotherapy and the expression of BMPs (p > 0.05, Mann-Whitney test). Univariate analysis showed no correlation between overall survival or progression free survival and the expression of BMPs (p > 0.05, log rank test). CONCLUSIONS: BMP-7 and BMP-8 are highly expressed in osteosarcoma. Moreover, high expression of BMP-6 correlates with a chondroid differentiation. In contrast to conclusions derived from previous studies in which small numbers of tumours were investigated, these results indicate that the expression of BMPs does not help to predict the outcome of patients.

Adolescent↗
PubMed1987

Identification of a human osteosarcoma-associated glycoprotein with monoclonal antibodies: relationship with alkaline phosphatase.

The molecular nature of an osteosarcoma-associated antigen was investigated with the three monoclonal antibodies Ost6 (immunoglobulin (IgG1), Ost7 (IgG1), and Ost15 (IgG2a), which selectively react with frozen sections of osteosarcoma and chondrosarcoma tissues. When tested with a panel of 41 human cell lines in the mixed hemadsorption assay, the antibodies reacted similarly with three of six osteosarcomas, one choriocarcinoma, one teratoma, and one osteoblast-like culture, but failed to react with 32 lines of normal and other tumor cell types. Immunoprecipitation plus sodium dodecyl sulfate (SDS)--polyacrylamide gel electrophoresis and sequential immunoprecipitation studies revealed that in [35S]methionine- or [14C]glucosamine-labelled osteosarcoma cells the three antibodies detected a single glycoprotein, with an apparent molecular mass of 86 kilodaltons (kDa), which was not affected by reducing conditions. Tunicamycin treatment and pulse-chase experiments showed glycosylation of this molecule to be N-linked; it arose from a 54-kDa polypeptide precursor. Alkaline phosphatase activity was detected in the material rich in 86-kDa molecules that was immunoprecipitated from serologically reactive cell lines with each antibody. These antibodies also cross-reacted with two isoenzymes of alkaline phosphatase (strongly with the liver and bone, and moderately with the placental isoenzyme), but not with the intestinal form.

Alkaline Phosphatase↗