ArticleCancer chemotherapy and pharmacology2019
A novel method to address the association between received dose intensity and survival outcome: benefits of approaching treatment intensification at a more individualised level in a trial of the European Osteosarcoma Intergroup.
Article in Cancer chemotherapy and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- Trial
- A Multiple Imputation Approach to Distinguish Curative From Life-Prolonging Effects in the Presence of Missing Covariates.Biometrical journal. Biometrische Zeitschrift · 2026Article
- Exosomal Gene Biomarkers in Osteosarcoma: Mifepristone as a Targeted Therapeutic Revealed by Multi-Omics Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Osteosarcoma Cell-Derived Migrasomes Promote Macrophage M2 Polarization to Aggravate Osteosarcoma Proliferation and Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Causal effect of chemotherapy received dose intensity on survival outcome: a retrospective study in osteosarcoma.BMC medical research methodology · 2024Article
- A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma.Scientific reports · 2024Article
- Significance of exosomes in osteosarcoma research: a systematic review and meta-analysis of a singular clinical investigation.Frontiers in cell and developmental biology · 2024Article
- Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways.Cancers · 2023Article
- Studies related to osteosarcoma and metabolism from 1990 to 2022: A visual analysis and bibliometric study.Frontiers in endocrinology · 2023Article
- Employing machine learning using ferroptosis-related genes to construct a prognosis model for patients with osteosarcoma.Frontiers in genetics · 2023Article
- Research trends and hotspots in the immune microenvironment related to osteosarcoma and tumor cell aging: a bibliometric and visualization study.Frontiers in endocrinology · 2023Article
- No Effect on Tumorigenesis in MG63 Cells Induced by Co-Cultured Mesenchymal Stem Cells.Journal of oncology · 2022Article
- Identification of an Iron Metabolism-Related lncRNA Signature for Predicting Osteosarcoma Survival and Immune Landscape.Frontiers in genetics · 2022Article
- Recognize the role of CD146/MCAM in the osteosarcoma progression: an in vitro study.Cancer cell international · 2021Article
- Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma.Nature communications · 2020Article
- Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies.International journal of molecular sciences · 2020Review
- The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: a network meta-analysis.Journal of orthopaedic surgery and research · 2020Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
purposeThere is lack of consensus on the prognostic value of received high dose intensity in osteosarcoma survivorship. Many studies have not shown a clear survival benefit when dose intensity is increased. The aim of this study is to go beyond chemotherapy intensification by arm-wide escalation of intended dose and/or compression of treatment schedule, while conversely addressing the relationship between treatment intensity and survival at the patient level. The study focusses on the difference in outcome results, based on a novel, progressively more individualised approach to dose intensity.
methodsA retrospective analysis of data from MRC BO06/EORTC 80931 randomised controlled trial for treatment of osteosarcoma was conducted. Three types of post hoc patient groups are formed using the intended regimen: the individually achieved cumulative dose and time on treatment, and the increase of individual cumulative dose over time. Event-free survival is investigated and compared in these three stratifications.
resultsThe strata of intended regimen and achieved treatment yields equivalent results. Received cumulative dose over time produces groups with evident different survivorship characteristics. In particular, it highlights a group of patients with an estimated 3-year event-free survival much larger (more than 10%) than other patient groups. This group mostly contains patients randomised to an intensified regimen. In addition, adverse events reported by that group show the presence of increased preoperative myelotoxicity.
conclusionsThe manuscript shows the benefits of analyzing studies by using longitudinal data, e.g. recorded per cycle. This has impact on the drafting of future trials by showing why such a level of detail is needed for both treatment and adverse event data. The novel method proposed, based on cumulative dose received over time, shows that longitudinal treatment data might be used to link survival outcome with drug metabolism. This is particularly valuable when pharmacogenetics data for metabolism of cytotoxic agents are not collected.
trial registrationISRCTN86294690.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.