Modeling freedom from progression for standard-risk medulloblastoma: A mathematical tumor control model with multiple modes of failure

N. Patrik Brodin, Ivan R. Vogelius, Thomas Björk-Eriksson, Per Munck Af Rosenschöld, Søren M. Bentzen

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Purpose As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available.

Original languageEnglish (US)
Pages (from-to)422-429
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume87
Issue number2
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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