Predicted Breast Cancer Risk after Mediastinal Radiotherapy for Pediatric Hodgkin Lymphoma: Analysis of a Multi-Institutional Children’s Oncology Group Trial
Bibliographic record
Abstract
Introduction There are limited data regarding the risk of breast cancer (BrCa) following contemporary involved site radiation therapy (ISRT) for pediatric Hodgkin Lymphoma (HL). We sought to quantify this risk and identify factors associated with breast dose and subsequent BrCa risk. Methods On the multi-institutional Children’s Oncology Group study AHOD1331 (2015-2019), patients 2-21 years of age with high-risk cHL received 5 cycles of systemic therapy, followed by 21 Gy ISRT to sites of large mediastinal adenopathy (LMA) and slowly responding lesions+/- 9 Gy to sites of partial metabolic response. In females who received mediastinal RT on AHOD1331, we collected detailed breast dosimetry and applied radiobiologic models to estimate the lifetime attributable risk (LAR) at 70 years of age (LAR 70 ) of BrCa, (i.e. the absolute increased risk of BrCa above baseline risk at 70 years of age due to RT; mean baseline rate at 70 years of age in the US is 8.9% https://seer.cancer.gov/data/). Results Among 587 patients treated on AHOD1331, 296 (50%) received protocol-directed mediastinal RT and had complete dosimetric data available. Their median age was 15 years, and 98% had LMA. 163 (55.1%) were female, so were eligible for this analysis. The RT technique was proton therapy in 25%, photon intensity modulated RT (IMRT) in 45%, and photon 3-dimensional conformal RT (3D-CRT) in 28%. The RT prescription dose was 21 Gy in 84% and 30 Gy in 16%. The mean dose to the breasts was 4.2 Gy with substantial variation among individuals (range 0.2-14.5 Gy). The mean LAR 70 of breast carcinoma was 2.92% (range: 0.17-8.43%). The mean LAR 70 was 1.45% (range 0.17-7.23%) after proton therapy; 4.36% (range 0.66-8.43%) after IMRT; and 1.82% (range 0.67-5.98%) after 3D-CRT (P<0.0001). Patients in the lowest quartile of risk were significantly more likely to have been treated with proton therapy than those in the highest quartile of risk (58% vs 10%, P<0.001). Conclusion Breast doses associated with contemporary mediastinal ISRT are predicted to result in lower BrCa risks than observed in historic cHL cohorts, with proton therapy being associated with lower doses and risks than IMRT. There is significant variation in breast dose and predicted risk among individuals nominally receiving the same treatment, indicating the need for subsequent screening recommendations to be based on breast dose, not prescribed nodal dose. Publication History Article published online: 02 December 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".