External validation of the diffuse intrinsic pontine glioma survival prediction model: a collaborative report from the International DIPG Registry and the SIOPE DIPG Registry

We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in t...

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Published in:	Journal of neuro-oncology Vol. 134; no. 1; pp. 231 - 240
Main Authors:	Veldhuijzen van Zanten, Sophie E. M., Lane, Adam, Heymans, Martijn W., Baugh, Joshua, Chaney, Brooklyn, Hoffman, Lindsey M., Doughman, Renee, Jansen, Marc H. A., Sanchez, Esther, Vandertop, William P., Kaspers, Gertjan J. L., van Vuurden, Dannis G., Fouladi, Maryam, Jones, Blaise V., Leach, James
Format:	Journal Article
Language:	English
Published:	New York Springer US 01.08.2017 Springer Nature B.V
Subjects:	Adolescent Brain cancer Brain Stem Neoplasms - diagnostic imaging Brain Stem Neoplasms - mortality Brain Stem Neoplasms - therapy Brain tumors Calibration Chemotherapy Child Child, Preschool Clinical Study Cohort Studies Female Glioma Glioma - diagnostic imaging Glioma - mortality Glioma - therapy Humans Image Processing, Computer-Assisted Infant Infant, Newborn Kaplan-Meier Estimate Magnetic Resonance Imaging Male Medicine Medicine & Public Health Neurology Oncology Prognosis Registries Regression Analysis Risk groups Survival Cox proportional hazards modeling Discrimination Calibration External validation Prognostic modeling
ISSN:	0167-594X, 1573-7373, 1573-7373
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Abstract	We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan–Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice.
AbstractList	We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan-Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice.We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan-Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice. We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan–Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice.
Author	Kaspers, Gertjan J. L. van Vuurden, Dannis G. Lane, Adam Jansen, Marc H. A. Leach, James Jones, Blaise V. Sanchez, Esther Chaney, Brooklyn Fouladi, Maryam Doughman, Renee Vandertop, William P. Heymans, Martijn W. Veldhuijzen van Zanten, Sophie E. M. Hoffman, Lindsey M. Baugh, Joshua
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Keywords	Cox proportional hazards modeling Discrimination Calibration External validation Prognostic modeling
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SubjectTerms	Adolescent Brain cancer Brain Stem Neoplasms - diagnostic imaging Brain Stem Neoplasms - mortality Brain Stem Neoplasms - therapy Brain tumors Calibration Chemotherapy Child Child, Preschool Clinical Study Cohort Studies Female Glioma Glioma - diagnostic imaging Glioma - mortality Glioma - therapy Humans Image Processing, Computer-Assisted Infant Infant, Newborn Kaplan-Meier Estimate Magnetic Resonance Imaging Male Medicine Medicine & Public Health Neurology Oncology Prognosis Registries Regression Analysis Risk groups Survival
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Title	External validation of the diffuse intrinsic pontine glioma survival prediction model: a collaborative report from the International DIPG Registry and the SIOPE DIPG Registry
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