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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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

Fingerprint

Medulloblastoma
progressions
tumors
Uncertainty
confidence
Confidence Intervals
intervals
dosage
Neoplasms
Rare Diseases
biomarkers
Disease-Free Survival
estimates
stratification
acceleration (physics)
Cohort Studies
Biomarkers
Pediatrics
Recurrence
sampling

ASJC Scopus subject areas

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

Cite this

Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure. / Brodin, Nils P.; Vogelius, Ivan R.; Björk-Eriksson, Thomas; Munck Af Rosenschöld, Per; Bentzen, Søren M.

In: International Journal of Radiation Oncology Biology Physics, Vol. 87, No. 2, 01.10.2013, p. 422-429.

Research output: Contribution to journalArticle

Brodin, Nils P. ; Vogelius, Ivan R. ; Björk-Eriksson, Thomas ; Munck Af Rosenschöld, Per ; Bentzen, Søren M. / Modeling freedom from progression for standard-risk medulloblastoma : A mathematical tumor control model with multiple modes of failure. In: International Journal of Radiation Oncology Biology Physics. 2013 ; Vol. 87, No. 2. pp. 422-429.
@article{c1b5c74651574b0d81c671ef9de2ac95,
title = "Modeling freedom from progression for standard-risk medulloblastoma: A mathematical tumor control model with multiple modes of failure",
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.",
author = "Brodin, {Nils P.} and Vogelius, {Ivan R.} and Thomas Bj{\"o}rk-Eriksson and {Munck Af Rosensch{\"o}ld}, Per and Bentzen, {S{\o}ren M.}",
year = "2013",
month = "10",
day = "1",
doi = "10.1016/j.ijrobp.2013.06.008",
language = "English (US)",
volume = "87",
pages = "422--429",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Modeling freedom from progression for standard-risk medulloblastoma

T2 - A mathematical tumor control model with multiple modes of failure

AU - Brodin, Nils P.

AU - Vogelius, Ivan R.

AU - Björk-Eriksson, Thomas

AU - Munck Af Rosenschöld, Per

AU - Bentzen, Søren M.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84882874068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882874068&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2013.06.008

DO - 10.1016/j.ijrobp.2013.06.008

M3 - Article

C2 - 23910711

AN - SCOPUS:84882874068

VL - 87

SP - 422

EP - 429

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 2

ER -