Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

Bielack, Stefan; Kempf-Bielack, Beate; Delling, G.; Exner, G. U.; Flege, Silke; Helmke, K.; Kotz, R.; Salzer-Kuntschik, M.; Werner, Matthias; Winkelmann, Winfried; Zoubek, A.; Jürgens, Heribert; Winkler, Kurt

doi:10.1200/jco.2002.20.3.776

Cited by 1,371 publications

(439 citation statements)

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“…The long‐term survival of osteosarcoma patients has improved dramatically because of the introduction of effective systemic chemotherapy 1, 2, 3, 4. Recent studies have demonstrated a more favorable outcome, especially for patients with nonmetastatic osteosarcoma 5, 6. Five‐year survival rates of 60% to 80% have been reported for patients receiving intensive multidrug chemotherapy and surgery for aggressive local control 5, 6, 7, 8, 9, 10, 11.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have demonstrated a more favorable outcome, especially for patients with nonmetastatic osteosarcoma 5, 6. Five‐year survival rates of 60% to 80% have been reported for patients receiving intensive multidrug chemotherapy and surgery for aggressive local control 5, 6, 7, 8, 9, 10, 11. However, despite the recent improvement in survival, a substantial number of patients still develop metastases or suffer tumor‐related death, so more accurate identification of patient subgroups with different levels of risk is substantially important.…”

Section: Introductionmentioning

confidence: 99%

“…However, in osteosarcoma, other prognostic factors, including patient age,14, 15, 16 tumor location,5, 16 pathologic fracture,17 and responses to preoperative chemotherapy, have been reported to correlate strongly with survival 5, 16, 18. Therefore, for the prediction of survival after treatment, it would be desirable to consider these factors, and a comprehensive and easy‐to‐use tool that incorporated all of them and could be used to assess individualized survival would be valuable for decision making.…”

Section: Introductionmentioning

confidence: 99%

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Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Ogura

Fujiwara

Yasunaga

et al. 2015

Cancer

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BACKGROUNDIn this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi‐institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis‐free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma.METHODSThis study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513).RESULTSA patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS.CONCLUSIONSThe nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery. Cancer 2015;121:3844–3852. © 2015 American Cancer Society.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Ogura

Fujiwara

Yasunaga

et al. 2015

Cancer

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“…This high-grade tumor is the most common primary bony malignancy and most often originates in the metaphysis of long bones of children and adolescents [1,2]. The incidence rate of osteosarcoma is about 1.7~4.4/1000,000 per year, and the average male-to-female ratio is 1.22:1 [3].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of abnormally expressed long non-coding RNAs in patients with osteosarcoma: a meta-analysis

Wu¹,

Shi²,

Mu³

et al. 2018

Oncotarget

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“…Osteosarcoma (OS), which affects rapidly growing bones, is the most common human primary malignant bone tumor among children and adolescents [1]. Despite significant advances in the treatment of OS, including surgery, multi-agent chemotherapy, and radiotherapy, the rate of relapse or distant metastasis remains high, with approximately 80% of patients developing metastatic disease after surgery [2].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-661 Enhances TRAIL or STS Induced Osteosarcoma Cell Apoptosis by Modulating the Expression of Cytochrome c1

Fan

Zhu

Qiu

et al. 2017

Cell Physiol Biochem

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Aim: Osteosarcoma (OS) is an aggressive bone malignancy that affects rapidly growing bones and is associated with a poor prognosis. Our previous study showed that cytochrome c1 (CYC1), a subunit of the cytochrome bc1 complex (complex III) of the mitochondrial electron chain, is overexpressed in human OS tissues and cell lines and its silencing induces apoptosis in vitro and inhibits tumor growth in vivo. Here, we investigated the mechanism underlying the modulation of CYC1 expression in OS and its role in the resistance of OS to apoptosis. Methods: qRT-PCR, luciferase reporter assay, western blotting, fow cytometry, and animal experiments were performed in this study. Results: MicroRNA (miR)-661 was identified as a downregulated miRNA in OS tissues and cells and shown to directly target CYC1. Ectopically expressed miR-661 inhibited OS cell growth, promoted apoptosis, and reduced the activity of mitochondrial complex III. miR-661 overexpression enhanced TRAIL or STS induced apoptosis and promoted the release of cytochrome c into the cytosol, which induced caspase-9 activation, and these effects were abolished by a caspase-3 inhibitor. Overexpression of CYC1 rescued the effects of miR-661 on sensitizing OS cells to TRAIL or STS induced apoptosis, indicating that the antitumor effect of miR-661 is mediated by the downregulation of CYC1. In vivo, miR-661 overexpression sensitized tumors to TRAIL or STS induced apoptosis in a xenograft mouse model, and these effects were attenuated by co-expression of CYC1. Conclusion: Taken together, our results indicate that miR-661 plays a tumor suppressor role in OS mediated by the downregulation of CYC1, suggesting a potential mechanism underlying cell death resistance in OS.

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Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

Abstract: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.

Cited by 1,371 publications

References 53 publications

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Prognostic value of abnormally expressed long non-coding RNAs in patients with osteosarcoma: a meta-analysis

MicroRNA-661 Enhances TRAIL or STS Induced Osteosarcoma Cell Apoptosis by Modulating the Expression of Cytochrome c1

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