title: Chemotherapy effectiveness and mortality prediction in surgically treated osteosarcoma dogs: A validation study.
abstract: Canine osteosarcoma is the most common bone cancer, and an important cause of mortality and morbidity, in large purebred dogs. Previously we constructed two multivariable models to predict a dog's 5-month or 1-year mortality risk after surgical treatment for osteosarcoma. According to the 5-month model, dogs with a relatively low risk of 5-month mortality benefited most from additional chemotherapy treatment. In the present study, we externally validated these results using an independent cohort study of 794 dogs. External performance of our prediction models showed some disagreement between observed and predicted risk, mean difference: -0.11 (95% confidence interval [95% CI]-0.29; 0.08) for 5-month risk and 0.25 (95%CI 0.10; 0.40) for 1-year mortality risk. After updating the intercept, agreement improved: -0.0004 (95%CI-0.16; 0.16) and -0.002 (95%CI-0.15; 0.15). The chemotherapy by predicted mortality risk interaction (P-value=0.01) showed that the chemotherapy compared to no chemotherapy effectiveness was modified by 5-month mortality risk: dogs with a relatively lower risk of mortality benefited most from additional chemotherapy. Chemotherapy effectiveness on 1-year mortality was not significantly modified by predicted risk (P-value=0.28). In conclusion, this external validation study confirmed that our multivariable risk prediction models can predict a patient's mortality risk and that dogs with a relatively lower risk of 5-month mortality seem to benefit most from chemotherapy.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Division of Pharmacoepidemiology and Clinicl Pharmacology, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands; Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, 3584 CL Utrecht, The Netherlands; Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, UK. Electronic address: amand.schmidt@ucl.ac.uk.
authors.forename: A F
authors.initials: AF
authors.lastname: Schmidt
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, 3584 CL Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Nielen
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Withrow
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Selmic
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA; University of California, Davis, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Davis, CA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Burton
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Division of Pharmacoepidemiology and Clinicl Pharmacology, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: O H
authors.initials: OH
authors.lastname: Klungel
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Division of Pharmacoepidemiology and Clinicl Pharmacology, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: R H H
authors.initials: RH
authors.lastname: Groenwold
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 8, Utrecht 3584 CM, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kirpensteijn
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D024221:Antineoplastic Protocols; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000662:veterinary*; D015331:Cohort Studies; D004283:Dog Diseases / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D004285:Dogs; D012516:Osteosarcoma / Q000188:drug therapy / Q000401:mortality / Q000601:surgery / Q000662:veterinary*
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents
keywords: Adjuvant; Bone tumor; Canine; Chemotherapy; Clinical prediction rule; Oncology; Personalized medicine