Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant therapy is currently established in the treatment of osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma. Of the 12 reported randomized studies of adjuvant chemotherapy for soft tissue sarcoma, only 2 show a significant overall survival advantage for chemotherapy (the most important endpoint). In three randomized trials, the survival of the observation arm exceeds that of the chemotherapy arm. In two additional studies, subset analyses currently indicate a significant DFS advantage for adjuvant chemotherapy in extremity lesions, but no significant improvement in survival. Although initial NCI reports showed significantly prolonged survival for the subset of chemotherapy-treated extremity primaries, survival on longer follow-up is no longer significantly different. In the subset analysis of retroperitoneal sarcomas in the same NCI study, the survival of the control group is superior to the treatment group. Doxorubicin associated cardiotoxicity has occurred in about 10% of treated patients, occasionally contributing to treatment-related deaths. Based on these data, adjuvant chemotherapy should be considered investigational for adult soft-tissue sarcomas of any primary site. Future randomized trials should include patients at high risk for metastases (large, high-grade lesions) with a reasonable likelihood of local control by radical resection, or resection with uninvolved margins and subsequent radiotherapy. Low-grade sarcomas are currently cured by surgical resection in 80% of cases, and thus should not be included in adjuvant trials.
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PMID:Adjuvant therapy for sarcomas. 177 77

The authors review the mean steps for the treatment of osteogenic osteosarcoma from the 1970's: 1), demonstration of the effectiveness of HDMTX and possibility of weekly administration, dose-response effect, interest of other drugs (BCD, ADR, CDDP, IFX); 2), use of the primary as chemosensibility witness; 3), extent of conservative surgery. In order to optimize the good results obtained by Rosen (more than 80% DFS at 5y) the authors studied the HDMTX pharmacokinetics, the value of the seric peak at the end of infusion as an effective test and individualized the HDMTX treatment in each patient following his own pharmacokinetics. This individual approach allows us to obtain more than 90% actuarial event-free survival at 4 years in patients treated by conservative surgery.
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PMID:Osteogenic osteosarcoma: a model of curable disease by multidisciplinary approach of treatment. 209 6

This report updates experience with the CONPADRI-I, COMPADRI-II, and COMPADRI-III adjuvant chemotherapy programs for the treatment of nonmetastatic osteosarcoma. A total of 200 patients received one of the three regimens. The analysis of response to treatment is based on disease-free survival time (DFS time). The effect of treatment, age, sex, site of disease involvement, and race on DFS time were investigated. Cox's life-table regression analysis found only sex to have a significant effect on DFS time with males having 1.8 times the risk of recurrence or death per unit time as female patients (P = 0.004). An analysis of the 81 patients still alive and disease-free 18 months after the start of treatment shows significantly longer DFS time for CONPADRI-I than COMPADRI-II patients (P = 0.01). This trend is true for both male (P = 0.12) and female (P = 0.08) patients.
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PMID:Adjuvant chemotherapy in nonmetastatic osteosarcoma: a Southwest Oncology Group Study. 700 43

The authors analysed the patterns of recurrence of osteosarcoma of the extremities treated between 1959 and 1989 either with surgery alone (1959-71) or with combined surgery and adjuvant (1972-82) or neoadjuvant chemotherapy (1983-89). In a total of 452 patients with recurrent osteosarcoma, the initial site of metastasis was the lung in 88% of cases independently of the type of treatment received. The mean period of onset of pulmonary metastasis differed according to the type of treatment performed: 8 months for patients treated with surgery alone; 15.9 months for those treated with adjuvant chemotherapy and 20.3 months for patients treated with neoadjuvant chemotherapy. The incidence of metastases appearing within 12 months of FU was 87%, 56% and 21% respectively. In a most recent and effective neoadjuvant protocol (66% DFS), the incidence of recurrence owing to pulmonary metastasis during the first year of FU was 2% and as much as 75% of all recurrences were concentrated in the following 18 months. Surgery for pulmonary metastasis in patients undergoing chemotherapy was performed in 54 cases with secondary healing in 14 (26%). On the basis of these results the authors suggest a scheme of radiological follow-up for patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy with intensified controls (every 2 months) during the period with the highest risk of recurrence (13-20 months) and four-monthly controls during the first year and after 31 months of FU. In order to increase the efficacy of FU controls during the high-risk period, the a. propose using CT controls instead of chest X-rays at months 14, 20 and 26.
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PMID:[Non-metastatic osteosarcoma of the extremities: the pattern of relapse as a function of the type of treatment and of the modulation of the radiological follow-up of the thorax]. 861 28

A neoadjuvant chemotherapy protocol (1/93-1/95) for extremity osteosarcoma preoperatively using high-dose methotrexate (HDMTX) as single agent per cycle and three different combinations of other drugs (CDP/IFO,CDP/ADM,IFO/ADM) is reported. The four drugs were used postoperatively as single agents. Treatment was uniform, but suspended earlier if total necrosis was attained. An improvement was found in the results of the previous study using only IFO postoperatively, with 16/119 patients (97%) avoiding amputation, and 38 (32%) attaining complete necrosis. At a 3-year (2-4 years) mean follow-up, 92 patients (76%) remained continuously disease-free, 2 died of chemotherapy-related toxicity and 25 suffered relapse. Projected 3-year DFS also improved (75% vs. 60%; p = 0.04). Despite limb salvage, local recurrences (6.3%) and infections were few, although postoperative chemotherapy was restarted within a week. Therefore, until new effective drugs are found, expertise in using the four known drugs may improve cure rate and help to avoid amputation in almost all patients.
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PMID:Neoadjuvant chemotherapy for extremity osteosarcoma--preliminary results of the Rizzoli's 4th study. 957 53

We report on the clinical course and outcome of 28 patients, treated at The Istituti Ortopedici Rizzoli between 1995 and 1997 for osteosarcoma of the extremities metastatic to the lung at presentation. The treatment for these patients was the following: primary chemotherapy with cisplatin, adriamycin and high dose of methotrexate and ifosfamide followed by simultaneous resection of primary and metastatic lesions (when feasible), and further chemotherapy. After primary chemotherapy, lung metastases disappeared in 6 patients, whereas metastases in 3 remained surgically unresectable. These 9 patients received surgical treatment of the primary tumor only. In the remaining 19 patients, after chemotherapy, a simultaneous resection of the primary and metastatic tumor was performed. The resection of metastatic lesions was complete in 18 cases and incomplete in one. Three of the 4 patients who did not achieve a tumor-free status died in a few months and one is still alive with uncontrolled disease. With a median follow-up of 32 months (19-43) of the 24 patients who achieved remission, 12 (55%) remained continuously free of disease, 11 relapsed with new metastases and 1 died of chemotherapy-related toxicity. The 2-year DFS and OS were 36% and 53% respectively. These results are much worse than those achieved in 114 contemporary patients with localised disease (2-year DFS: 81%) treated in the same period and they are superimposible to the results achieved in 23 patients previously treated with the same protocol, but with standard dose of ifosfamide (2-year DFS: 32%). However, it must be underlined that, as regards prognosis, patients with metastatic disease at presentation are a hetero-geneous group. The DFS was significantly higher for patients with only one or two metastatic lesions than for patients with 3 or more lesions (2 year DFS: 78% vs. 28%). In 12 of the 19 patients who had a complete simultaneous resection of the primary and metastatic tumor, a strong correlation between the degree of necrosis of the primary and metastatic lesions was found. We conclude that in patients with osteosarcoma of the extremity with lung metastases at presentation: a) the combination of aggressive chemotherapy with simultaneous resection of primary and metastatic tumors works very well only for those patients who present with one or two metastatic nodules whereas for patients with 3 or more pulmonary metastases the prognosis is very poor; b) within the 4-drug regimen used in this study, the increment of ifosfamide dose from 10 g/m2 to 15 g/m2 for cycle does not improve prognosis; c) the strong correlation found between the histologic response of the primary tumor and metastases supports the strategy, largely used nowadays in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemo-therapy on the basis of the primary tumor histologic response to preoperative chemotherapy.
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PMID:Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide. 1067 83

Primary sarcomas of the breast are extremely rare, with less than 0.1% of all malignant tumours of the breast. Mayo Clinic Surgical Pathology database was searched for all breast sarcoma from 1910 to 2000. Pathology reports and slides were reviewed and tumour types were determined. Metaplastic carcinomas and phyllodes tumours were excluded. There were 25 women ranging in age 24-81 years (mean 45 years). All but one patient presented with a palpable lump. Mastectomy was performed in 19 patients and lumpectomy in five patients. Histopathological diagnoses were fibrosarcoma (six), angiosarcoma (six), pleomorphic sarcoma (six), leiomyosarcoma (two), myxofibrosarcoma (three), hemangiopericytoma (one) and osteosarcoma (one). Tumour size ranged from 0.3 to 12 cm (mean 5.7). Low-grade lesions were observed in 10 cases and high-grade in 15. Overall, mean follow-up was 10.5 years. Local recurrence was observed in 11 patients and ranged from 2 to 36 months (mean 15 m), while distant metastasis was observed in 10 patients (40%) affecting lungs, bones, liver, spleen, and skin. Of the 25 patients, 12 have died of disease and six of other causes. Five-year overall (OS) and cause-specific survival (CSS) were 66 and 70%, respectively. OS and DFS at 5 years were 91% for tumours < or =5 cm and 50% for tumours >5 cm. Tumour size was significantly associated with OS (risk ratio=1.3 per 1 cm increase; 95% CI, 1.02-1.7; P=0.036). There was no significant difference in OS or CSS between low- and high-grade lesions. In this series, tumour size was a more valuable prognostic factor than tumour grade.
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PMID:Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature. 1518 96

Twist, a basic helix-loop-helix transcription factor, and E-cadherin are both correlated with the metastatic progression of several types of cancer. However, it is currently unknown whether their activations have relevance to the progression of osteosarcoma. The purpose of the present study was to investigate the clinicopathological and prognostic value of Twist and E-cadherin in osteosarcoma. Twist and E-cadherin expressions were determined by immunohistochemistry. Patient survival rates were determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. The positive rates of Twist and E-cadherin in 107 osteosarcoma specimens were 31.8 % (34/107) and 20.6 % (22/107), respectively. Twist expression was significantly correlated with that of E-cadherin (r = -0.209, P = 0.031). The positive expression of Twist and E-cadherin was significantly associated with metastasis in 107 osteosarcoma specimens (both P < 0.05). Patients with positive Twist expression had significantly poorer overall survival (OS; P < 0.05) and disease-free survival (DFS, P < 0.05) when compared with patients with the negative expression of Twist. Patients with positive expression of E-cadherin had significantly poorer OS (P < 0.05) when compared with patients with negative E-cadherin expression, but not a significantly poorer DFS (P = 0.081). On multivariate analysis, Twist expression and age were found to be independent prognostic factors for OS (both P < 0.05) and DFS (both P < 0.05). Our results suggest that Twist was expressed significantly more and E-cadherin significantly less in osteosarcoma with metastasis, and expression of both might be related to the prediction of metastasis potency and poor prognosis for patients with osteosarcoma.
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PMID:Prognostic value of Twist and E-cadherin in patients with osteosarcoma. 2284 1

Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.
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PMID:EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma. 2448 62

The aim of this study was to facilitate and deepen the understanding of the associations of the microRNA-29 (miR-29) family with tumor progression and patients' prognosis of primary osteosarcoma. We examined expression levels of miR-29a, miR-29b, and miR-29c in tumor tissues and patients' sera of 80 cases of primary osteosarcomas by quantitative real-time reverse transcriptase-polymerase chain reaction. The correlations of their serum levels with clinicopathological characteristics and patient prognosis were also analyzed. The expression levels of miR-29a, miR-29b, and miR-29c in osteosarcoma tissues and patients' sera were all significantly higher than those in normal controls (all P < 0.05). The serum levels of miR-29a and miR-29b in the patients with higher tumor grade (both P = 0.01), positive metastasis (both P = 0.006), and positive recurrence (both P = 0.006) were both markedly higher than those with lower tumor grade, negative metastasis, and negative recurrence. According to the survival analysis of 80 osteosarcoma patients, cases in the miR-29a-high and miR-29b-high-expression groups both showed shorter overall survival (OS, both P < 0.001) and disease-free survival (DFS, both P < 0.001). Furthermore, the serum levels of miR-29a and miR-29b were both independent prognostic factors for OS and DFS of osteosarcoma patients. However, high miR-29c level was not related to any clinicopathological characteristics and patient prognosis of osteosarcomas (P > 0.05). The findings from the present study reveal that the miR-29 family may play crucial roles in the development and progression of human osteosarcoma. In particular, the serum levels of miR-29a and miR-29b may well estimate the prognosis of patients with this malignancy.
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PMID:Prognostic value of the microRNA-29 family in patients with primary osteosarcomas. 2501 94


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