Which dogs with appendicular osteosarcoma benefit most from chemotherapy after surgery? Results from an individual patient data meta-analysis

A. F. Schmidt, R. H.H. Groenwold, P. Amsellem, N. Bacon, O. H. Klungel, A. W. Hoes, A. de Boer, K. Kow, K. Maritato, J. Kirpensteijn, M. Nielen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Osteosarcoma (OS) is a malignant tumor of mesenchymal origin that produces osteoid. Given that the prognosis can vary considerably between dogs, we aimed to explore whether treatment could be tailored towards patient subgroups, characterized by their predicted risk of mortality. For the current study, a subset of five nonrandomized studies (400 subjects of whom 88 were dead at 5 months follow-up) was used from a previously published 20 study individual patient data meta-analysis. Missing data was dependent on observed variables and was imputed to correct for this dependency. Based on a previously published multivariable prognostic model, the 5-month mortality risk was predicted. Subsequently, in surgically treated dogs, using a logistic regression model with a random intercept for a study indicator, we explored whether chemotherapy effectiveness depended on predicted 5-month mortality risk. After adjustment for potential confounders the main effect of any chemotherapy was 0.48 (odds ratio) (95%CI 0.30; 0.78). Testing for chemotherapy by predicted 5-month mortality risk interaction revealed that the effects of any chemotherapy decreased with increasing predicted risk; interaction OR 3.41 (1.07; 10.84). Results from individually comparing carboplatin, cisplatin, doxorubicin and doxorubicin combination therapy to no chemotherapy, were similar in magnitude and direction. These results indicate that the main treatment effects of chemotherapy do not necessarily apply to all patients.

Original languageEnglish (US)
Pages (from-to)116-125
Number of pages10
JournalPreventive Veterinary Medicine
StatePublished - Mar 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by Research Focus Areas funding of the Utrecht University, which is a collaboration between the faculties of medicine, science, and veterinary medicine. The study sponsor was not involved in the design, collection, analysis or writing of this manuscript. This article is funded by VSNU .

Publisher Copyright:
© 2015 Elsevier B.V.


  • Bone tumor
  • Canine
  • Oncology
  • Personalized medicine


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