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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
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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“These strata were based on studies showing that a shorter relapse-free interval and older age are prognostic for shorter OS in patients with osteosarcoma.”
From Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma (2024) · cites this paper as [33]
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“In addition, patients with unresectable primary or metastatic disease at diagnosis and those with disease relapse have extremely poor outcomes 2,126 .”
From Osteosarcoma (2022) · cites this paper as [2]
In the citing paper
“Otherwise, intralesional or marginal resections increase local recurrence rate, which is associated with reduced overall survival 2,134 .”
From Osteosarcoma (2022) · cites this paper as [2]
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“OS cells perform a high propensity to spread and metastasize, which seems to be the most important internal factor for poor prognosis in OS patients (2).”
BackgroundRPN2 Gene Confers Osteosarcoma Cell Malignant Phenotypes and Determines Clinical Prognosis
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“combined use of limb saving surgery and multidrug chemotherapy results in 5-year event-free survival rates (EFS) of approximately 50–70% in patients with localized OS in extremities (4,5).”
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Lahr, C. A., Landgraf, M., Sánchez‐Herrero, A., Dang, H. P., Wagner, F., Bas, O., Bray, L. J., Tran, P. A., Holzapfel, B. M., Shafiee, A., et al. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.10.006 · Cited by 25
Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective
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Direct conversion of osteosarcoma to adipocytes by targeting TNIK
Hirozane, T., Masuda, M., Sugano, T., Sekita, T., Goto, N., Aoyama, T., Sakagami, T., Uno, Y., Moriyama, H., Sawa, M., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.137245 · Cited by 24
“TNIK was expressed in all specimens before chemotherapy but was barely detectable in samples after chemotherapy, which were carefully collected from the viable portions of tumors that had shown a good response (37) (Figure 6E).”
BackgroundIwata, S., Tatsumi, Y., Yonemoto, T., Araki, A., Itami, M., Kamoda, H., Tsukanishi, T., Hagiwara, Y., Kinoshita, H., Ishii, T., et al. (2021) · Oncology Reports · doi:10.3892/or.2021.8086 · Cited by 25
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“Surgical resection, adjuvant chemotherapy, and small molecule targeted therapy have been used for OS treatment (4,5); however, because of the high propensity of metastasis and relapse the prognosis remains poor (6).”
González‐Billalabeitia, E., Hitt, R., Fernández, J., Conde, E., Martínez-Tello, F. J., de Salamanca, R. E., Cortés-Funes, H., & González‐Billalabeitia, E. (2009) · Clinical & Translational Oncology · doi:10.1007/s12094-009-0388-9 · Cited by 25
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“E It has been reported that the five‑year survival rate of patients who suffer from this disease remains at only 20% due to a high rate of systemic spread at the early phase and the strong chemotherapy resistance of osteosarcoma (1).”
RetractedSolitary skeletal osteosarcoma recurrence. Findings from the Cooperative Osteosarcoma Study Group
Franke, M., Hardes, J., Helmke, K., Jundt, G., Jürgens, H., Kempf‐Bielack, B., Kevric, M., Tunn, P., Werner, M., & Bielack, S. (2010) · Pediatric Blood & Cancer · doi:10.1002/pbc.22864 · Cited by 25
Self-citationFujiwara, T., & Ozaki, T. (2016) · Stem Cells International · doi:10.1155/2016/2603092 · Cited by 25
“With combined treatment (neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy), the 5-year survival rate for patients with no metastatic disease at diagnosis is 60%–80% [3–5].”
Rastogi, S., Aggarwal, A., Tiwari, A., & Sharma, V. (2017) · Journal of Global Oncology · doi:10.1200/jgo.2016.007336 · Cited by 25
“Percentagenecrosis assessment after neoadjuvant chemotherapy is one of themost robust prognostic markers for survival outcome in nonmetastatic OS.15,16 Those patients who have.”
BackgroundInfluentialLi, Z., Wang, L., Luo, N., Zhao, Y., Li, J., Chen, Q., & Tian, Y. (2018) · Oncology Letters · doi:10.3892/ol.2018.8297 · Cited by 25
Ali, B. A., Salman, M., Ghanem, K. M., Boulos, F. I., Haidar, R., Saghieh, S., Akel, S. R., Muwakkit, S. A., El‐Solh, H., Saab, R. H., et al. (2019) · Journal of Global Oncology · doi:10.1200/jgo.17.00241 · Cited by 26
“Multiple prognostic factors have been shown across several studies to influence outcome in pediatric osteosarcoma, including site and size of the primary tumor, presence of clinically detectable metastatic disease, surgical resectability and remission state, and response to chemotherapy as assessed by degree of tumor…”
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Molecular Characterisation of Canine Osteosarcoma in High Risk Breeds
Simpson, S., Dunning, M., de Brot, S., Alibhai, A. A., Bailey, C., Woodcock, C. L., Mestas, M., Akhtar, S., Jeyapalan, J. N., Lothion‐Roy, J. H., et al. (2020) · Cancers · doi:10.3390/cancers12092405 · Cited by 26
“Formation of metastases in OSA is a critical stage in disease progression associated with poor prognosis [79,80].”
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“The girl was treated with neoadjuvant chemotherapy according to protocol COSS-96 of the Cooperative Osteosarcoma Study Group (Bielack et al. 2002).”
InfluentialSelf-citationOutcome of Postradiation Osteosarcoma Does Not Correlate with Chemotherapy Response
Lewis, V. O., Raymond, K. A., Mirza, A. N., Lin, P. P., & Yasko, A. W. (2006) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000229306.05513.51 · Cited by 25
“Local control of osteosarcoma primarily is a surgical problem, but histologic response to neoadjuvant therapy is the single most important prognostic factor for long-term survival.(5,12,28) Several studies have shown the degree of necrosis induced by chemotherapy correlates with diseasefree survival.”
BackgroundChen, X., Jiang, M., Zhao, R., & Gu, G.-H. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.11.4659 · Cited by 24
“…estimated overall survival rate has Asian Pacific Journal of Cancer Prevention, Vol 16, 2015 4663 DOI:http://dx.doi.org/10.7314/APJCP.2015.16.11.4659 Quantitative Assessment of the Association between ABC Polymorphisms and Osteosarcoma Response: a Meta-analysis been reached (Bielack et al., 2002).”
BackgroundInfluentialModeling Continuous Prognostic Factors in Survival Analysis
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Survival after pulmonary metastasectomy for relapsed osteosarcoma
Liu, Z., Yin, J., Zhou, Q., Yang, J., Zeng, B., Yeung, S. J., Shen, J., & Cheng, C. (2020) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2020.10.137 · Cited by 24
Wang, Z., Fan, G., Zhu, H., Yu, L., She, D., Wei, Y., Huang, J., Li, T., Zhan, S., Zhou, S., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.980390 · Cited by 25
The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells
Tian, B., Du, X., Zheng, S., & Zhang, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416155 · Cited by 23
“The majority of OS cases arises in the metaphyseal regions adjacent to the physis, including the distal femur, proximal tibia and the proximal humerus, with a strong capacity for proliferation [5].”
BackgroundPulmonary metastasetomy for osteosarcoma: is it justified?
Diemel, K., Klippe, H. J., & Branseheid, D. (2009) · PubMed · Cited by 24
Xu, J., Wu, S., & Shi, X. (2010) · Journal of Orthopaedic Research® · doi:10.1002/jor.21178 · Cited by 24
“MATERIALS AND METHODS Patients and Tumor Samples We retrospectively identified 49 patients with primary osteosarcoma occurring between 2001 and 2004 who met the following criteria: (1) no metastasis at presentation; (2) no history of previous treatment; (3) adequate preoperative and postoperative chemotherapy; (4) tum…”
Method
Metadata
- 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
- Published
- 2002-02-01
- Volume
- 20
- Issue
- 3
- Pages
- 776-790
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- 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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