Analysis of dose response for circulatory disease after radiotherapy for benign disease

Mark P. Little, Ruth A. Kleinerman, Marilyn Stovall, Susan A. Smith, Kiyohiko Mabuchi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy-1 of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy-1 of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

Original languageEnglish (US)
Pages (from-to)1101-1109
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume84
Issue number5
DOIs
StatePublished - Dec 1 2012

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radiation therapy
Radiotherapy
dosage
fission weapons
Nuclear Weapons
strokes
Myocardial Ischemia
Survivors
indication
Stroke
ulcers
Dose Fractionation
slopes
heart diseases
Peptic Ulcer
fractionation
curvature
Radiation
radiation

Keywords

  • Benign disease
  • Circulatory disease
  • Ischemic heart disease
  • Peptic ulcer
  • Stroke

ASJC Scopus subject areas

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

Cite this

Analysis of dose response for circulatory disease after radiotherapy for benign disease. / Little, Mark P.; Kleinerman, Ruth A.; Stovall, Marilyn; Smith, Susan A.; Mabuchi, Kiyohiko.

In: International Journal of Radiation Oncology Biology Physics, Vol. 84, No. 5, 01.12.2012, p. 1101-1109.

Research output: Contribution to journalArticle

Little, Mark P. ; Kleinerman, Ruth A. ; Stovall, Marilyn ; Smith, Susan A. ; Mabuchi, Kiyohiko. / Analysis of dose response for circulatory disease after radiotherapy for benign disease. In: International Journal of Radiation Oncology Biology Physics. 2012 ; Vol. 84, No. 5. pp. 1101-1109.
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AB - Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy-1 of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy-1 of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

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