Cited by 2,393Sarcoma Diagnosis and TreatmentBone Tumor Diagnosis and TreatmentsOvarian cancer diagnosis and treatment

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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

Bielack, Stefan S., Kempf-Bielack, Beate, Delling, Günter, Exner, G. Ulrich, Flege, Silke, Helmke, Knut, Kotz, Rainer, Salzer-Kuntschik, Mechthild, Werner, Matthias, Winkelmann, Winfried, Zoubek, Andreas, Jürgens, Heribert, Winkler, Kurt·2002·Journal of Clinical Oncology

DOI 10.1200/jco.2002.20.3.776

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Abstract

PURPOSE: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease. PATIENTS AND METHODS: A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions. RESULTS: Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-year survival ≥ 40, 41.6%; < 40, 60.2%; P = .012), tumor site (axial, 29.2%; limb, 61.7%; P < .0001), and primary metastases (yes, 26.7%; no, 64.4%; P < .0001), and for extremity osteosarcomas, also size (≥ one third, 52.5%; < one third, 66.7%; P < .0001) and location within the limb (proximal, 49.3%; other, 63.9%; P < .0001), had significant influence on outcome. Two additional important prognostic factors were treatment related: response to chemotherapy (poor, 47.2%; good, 73.4%; P < .0001) and the extent of surgery (incomplete, 14.6%; macroscopically complete, 64.8%; P < .0001). All factors except age maintained their significance in multivariate testing, with surgical remission and histologic response emerging as the key prognostic factors. CONCLUSION: Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.

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Background
Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence
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Reduced Argininosuccinate Synthetase Is a Predictive Biomarker for the Development of Pulmonary Metastasis in Patients with Osteosarcoma
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“The prognosis of osteosarcoma patients older than 40 years is generally poor, probably because of their lower tolerance to high-dose chemotherapy and higher rate of axial tumor origin (1, 4).”
BackgroundInfluential
Prediction of tumour necrosis fractions using metabolic and volumetric 18F-FDG PET/CT indices, after one course and at the completion of neoadjuvant chemotherapy, in children and young adults with osteosarcoma
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Characterization of the metastatic phenotype of a panel of established osteosarcoma cells
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“Limited improvement in outcomes and survival of OS patients has been seen since the introduction of chemotherapy in the 1970’s [8-10].”
Background
[F‐18]‐fluorodeoxy‐D‐glucose–positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults
Hawkins, D. S., Conrad, E. U., Butrynski, J. E., Schuetze, S. M., & Eary, J. F. (2009) · Cancer · doi:10.1002/cncr.24421 · Cited by 118
“If a favorable response to therapy is anticipated, then limb-sparing surgical resection may be more feasible.(5,11) However, osteosarcoma usually does not change significantly in size in response to chemotherapy, making computed tomography (CT) scanning or magnetic resonance imaging (MRI) insensitive methods with whic…”
Sarcomas of the head and neck
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Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression
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“However, osteosarcoma patients with metastasis have a 5-year survival rate of only 20%, and current therapies have a limited effect in the treatment of recurrent and metastatic osteosarcoma [3].”
Background
Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma
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Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma
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Background
WEE1 inhibition sensitizes osteosarcoma to radiotherapy
PosthumaDeBoer, J., Würdinger, T., Graat, H. C. A., van Beusechem, V. W., Helder, M. N., van Royen, B. J., & Kaspers, G. J. L. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-156 · Cited by 120
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Background
Current Status and Perspectives Regarding the Treatment of Osteosarcoma: Chemotherapy
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Background
Genomic Alterations and Allelic Imbalances Are Strong Prognostic Predictors in Osteosarcoma
Smida, J., Baumhoer, D., Rosemann, M., Walch, A. K., Bielack, S., Poremba, C., REMBERGER, K., Korsching, E., Scheurlen, W. G., Dierkes, C., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0284 · Cited by 115
“Nevertheless, 30-40% of the patients die because of tumor progression or relapse (1).”
BackgroundSelf-citation
Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison
Marko, T. A., Diessner, B. J., & Spector, L. G. (2016) · Pediatric Blood & Cancer · doi:10.1002/pbc.25963 · Cited by 115
“The German–Austrian–Swiss Osteosarcoma Study Group [8] observed an association of axial primary tumors (P 0.001, X2), metastases at diagnosis (P 0.007, X2), and increasing age (P 0.001, t-test) with prolonged history of symptoms before diagnosis.”
BackgroundInfluential
Potential therapeutic effects of curcumin mediated by JAK/STAT signaling pathway: A review
Ashrafizadeh, M., Rafiei, H., Mohammadinejad, R., Afshar, E. G., Farkhondeh, T., & Samarghandian, S. (2020) · Phytotherapy Research · doi:10.1002/ptr.6642 · Cited by 121
A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma
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“The 5-year survival rate of the patients with osteosarcoma has significantly improved over the past decades to approximately 60–70 % since the introduction of combinational chemotherapy [2].”
Background
Dynamic contrast‐enhanced magnetic resonance imaging as a prognostic factor in predicting event‐free and overall survival in pediatric patients with osteosarcoma
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Frequent Attenuation of the WWOX Tumor Suppressor in Osteosarcoma Is Associated with Increased Tumorigenicity and Aberrant RUNX2 Expression
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“Metastasis, a hallmark of malignancy (36), is found in up to 20% of patients with OS at initial diagnosis and is associated with a poor prognosis (33, 35).”
Background
Metastatic osteosarcoma
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Background
Platelet‐derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma
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Background
Curcumin inhibits proliferation and invasion of osteosarcoma cells through inactivation of Notch‐1 signaling
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Prognostic factors and survival rate of osteosarcoma: A single‐institution study
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Self-citation
Upregulation of miR-328 and inhibition of CREB-DNA-binding activity are critical for resveratrol-mediated suppression of matrix metalloproteinase-2 and subsequent metastatic ability in human osteosarcomas
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“The 5-year survival rate for OS patients with metastases is 20%, compared to 65% for patients with localized disease, and most deaths associated with OS are the result of metastatic disease (Bielack et al., 2002; Eccles and Welch, 2007; Rodriguez et al., 2008; Pradelli et al., 2009).”
Background
Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma
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Self-citation
Pathology of primary malignant bone and cartilage tumours
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Background
Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters
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BackgroundMethod
Overexpression of lncRNA UCA1 promotes osteosarcoma progression and correlates with poor prognosis
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BackgroundInfluential
Cytochrome P450 CYP3A4/5 Expression as a Biomarker of Outcome in Osteosarcoma
Dhaini, H. R., Thomas, D. G., Giordano, T. J., Johnson, T. D., Biermann, J. S., Leu, K. M., Hollenberg, P. F., & Baker, L. H. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.06.015 · Cited by 104
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Background
Twenty years of follow‐up of survivors of childhood osteosarcoma
Nagarajan, R., Kamruzzaman, A., Ness, K. K., Marchese, V. G., Sklar, C. A., Mertens, A. C., Yasui, Y., Robison, L. L., & Marina, N. M. (2010) · Cancer · doi:10.1002/cncr.25446 · Cited by 105
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BackgroundResult
Management of osteosarcoma pulmonary metastases
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International Collaboration is Feasible in Trials for Rare Conditions: The EURAMOS Experience
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Self-citation
Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors
Freeman, S. S., Allen, S. W., Ganti, R., Wu, J., Ma, J., Su, X., Neale, G. A. M., Dome, J. S., Daw, N. C., & Khoury, J. D. (2008) · Cancer · doi:10.1002/cncr.23782 · Cited by 105
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“Poor prognosis has been associated with axial locations (Bielack et al. 2002).”
BackgroundResultInfluential
A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma
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Genome‐wide analysis of somatic copy number alterations and chromosomal breakages in osteosarcoma
Smida, J., Xu, H., Zhang, Y., Baumhoer, D., Ribi, S., Kovac, M. B., von Luettichau, I., Bielack, S., O’Leary, V. B., Leib‐Mösch, C., et al. (2017) · International Journal of Cancer · doi:10.1002/ijc.30778 · Cited by 98
Self-citation
Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers
Odri, G. A., Tchicaya-Bouanga, J., Yoon, D. J. Y., & Modrowski, D. (2022) · Cancers · doi:10.3390/cancers14020360 · Cited by 108
Primary malignant bone tumors—recent developments
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Frontline treatment of localized osteosarcoma without methotrexate
Daw, N. C., Neel, M. D., Rao, B. N., Billups, C. A., Wu, J., Jenkins, J. J., Quintana, J. A., Luchtman‐Jones, L., Milena Villarroel, C., & Santana, V. M. (2011) · Cancer · doi:10.1002/cncr.25715 · Cited by 99
“Our rate of local recurrence (3%) was similar to the 2% to 10% rates cited by others.(2,29,33-35) A smaller bone resection margin improves the likelihood of preserving the growth plate in growing children and provides a greater area for fixation of the endoprosthesis.”
Result

Authors: Bielack, S. S., Kempf-Bielack, B., Delling, G., Exner, G. U., Flege, S., Helmke, K., Kotz, R., Salzer-Kuntschik, M., Werner, M., Winkelmann, W., Zoubek, A., Jürgens, H., & Winkler, K.
Affiliations: University of Münster (DE)
Corresponding author: Bielack, Stefan S.
ORCID: Bielack, Stefan S.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2002-02-01
Volume: 20
Issue: 3
Pages: 776-790
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2002.20.3.776
OpenAlex: W2148077417
Cited by: 2,393
References: 61
Citations by year: 2026: 85 · 2025: 95 · 2024: 112 · 2023: 162 · 2022: 159 · 2021: 167 · 2020: 166 · 2019: 121 · 2018: 114 · 2017: 106 · 2016: 122 · 2015: 139 · 2014: 124 · 2013: 106 · 2012: 75
FWCI: 34.99
Type: journal article
Language: en
Update notices: new_edition (2023-09-15)
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone Tumor Diagnosis and Treatments
Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
Keywords: high-grade osteosarcoma, prognostic factors, neoadjuvant chemotherapy, limb-sparing surgery, tumor location, tumor size, chemotherapy response, surgical remission, event-free survival, overall survival, histological response, patient age, sex differences
MeSH terms: Adolescent, Adult, Aged, Bone Neoplasms, Child, Child, Preschool, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Prognosis, Osteosarcoma, Survival Rate, Multivariate Analysis, Chemotherapy, Adjuvant

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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

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