Cohort studyindependent cross-checkabstract checked I-CHM-122 standard review
Heart dose and heart attacks after breast radiotherapy: a check of Darby
Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures.
Overview
van den Bogaard VA et al.. J Clin Oncol 2017 · PMID 28095159 · DOI 10.1200/JCO.2016.69.8480
Risk of acute heart events rose by about 16.5% per Gy of heart dose; the typical heart dose was low (2.4 Gy).
Does the study support the specific claim? Yes · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Check the Darby dose-response
- How was the study done?
Cohort with 3D dose data
- How many people, animals or samples were studied?
910 Dutch women
- What was actually found?
Dose-response confirmed
- How large was the observed effect?
16.5%/Gy (0.6-35.0)
- What do the results mean in everyday life?
Lower heart dose means lower risk; modern doses are low
- What are the study's limitations?
Few events
- What does it say about Elawady's specific claim?
Supports the 7.4%/Gy claim as relative risk
- Do the results apply to Germany and Europe?
High
- What can explicitly not be concluded from this study?
Does not give absolute lifetime risk
Scientific in-depth review
1. Full reference
- Authors
- van den Bogaard VA et al.
- Journal
- J Clin Oncol
- Year
- 2017
- Identifier
- PMID 28095159 DOI 10.1200/JCO.2016.69.8480
- Verification
- verified – PubMed efetch 2026-10-26 (PublicationType and CommentsCorrections checked); Crossref 2026-10-26
- Retracted
- no
- Corrections
ErratumIn J Clin Oncol 2017;35(32):3736 (PubMed; Crossref 10.1200/jco.2017.76.2732); no retraction
- Extent checked
- abstract only
- Conflicts of interest and funding
Not stated in abstract.
2. Research question
Is the Darby relationship between mean heart dose and acute coronary events reproducible, and are other dose parameters better predictors?
3. Study design and population
- Study design
- Cohort study – Cohort study (validation of Darby model) with 3D CT-based dosimetry
- Population
910 consecutive women irradiated after breast-conserving surgery
- Country
Netherlands
- Period
Follow-up median 7.6 years (to 10.1)
- Sample size
910
- Inclusion and exclusion criteria
Consecutive patients with 3D planning data
4. Methods and endpoints
- Exposure / intervention
Mean heart dose and substructure doses
- Comparator
Lower doses
- Endpoints
Cumulative incidence of acute coronary events within 9 years
- Statistical methods
Cox/NTCP modelling
5. Actual results
- Results
Median mean heart dose 2.37 Gy (0.51-15.25); 30 acute coronary events; cumulative incidence increased by 16.5% per Gy (95% CI 0.6-35.0; P=.042); LV-V5 best predictor; model c-statistic 0.83.
- Absolute risks
30 events in 910 patients over a median 7.6 years (about 3.3% crude)
- Authors' conclusion
A significant dose-effect relationship for acute coronary events within 9 years was found; the relative increase per Gy was similar to the previous study.
6. Strengths
- Individual 3D dosimetry
- Modern techniques (low doses)
7. Weaknesses
- Few events; wide CI
- Single region
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Observational; few events.
9. Assessment of the statistical interpretation
Slope imprecise (0.6-35%/Gy). At the cohort's median mean heart dose (2.37 Gy) the implied relative increase is about 17% (Darby slope) to 39% (this slope) (stats/C-CHM-02.py).
10. Relevance to the specific claim
Replicates the Darby dose-response with modern CT-based dosimetry, supporting the 7.4%/Gy figure as a reasonable estimate (point estimate even higher, but imprecise).
11. Independent contrary findings
Taylor 2017 (I-CHM-06): absolute risk small with modern doses.
12. Transferability to Germany and Europe
Directly applicable (European cohort).
13. Overall methodological judgement
Independent replication of the dose-response.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Precise slope at very low doses.