Risk of Clonal Hematopoiesis of Indeterminate Potential after Cancer Radiation Therapy
Bibliographic record
Abstract
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a condition associated with aging and increased risk of hematologic malignancies and chronic diseases. While radiation therapy (RT) has been implicated as a risk factor for CHIP, the specific radiation parameters influencing the development of CHIP remain unclear. This study aimed to investigate the association between RT and CHIP and identify relevant radiation parameters affecting CHIP risk. We conducted a retrospective cohort study of cancer patients with RT exposure from an institutional biobank. DNA sequencing was performed to detect mutations in 22 CHIP-associated genes. Multivariable logistic regression models were used to evaluate the association between clinical characteristics, RT parameters, and CHIP. We identified 736 cancer patients with RT exposure and compared their risk of CHIP to a control cohort of 13,605 individuals. RT was found to be an independent risk factor for developing CHIP (OR 1.39, 95% CI 1.08-1.77, p=0.009). The prevalence of CHIP in RT patients was 22.8%. Compared to controls, RT patients showed significantly increased mutations in DNMT3A , PPM1D , TP53, and BRCC3. A positive correlation was observed between CHIP risk and biological equivalent dose of radiation. Stereotactic radiation was also associated with increased CHIP prevalence (OR 2.24, 95% CI 1.14-4.33, p=0.02). This study demonstrates that RT is associated with an increased risk of CHIP development, particularly mutations in DNA damage response genes. These findings have important implications for cancer care and long-term patient monitoring, emphasizing the need for further research into the mechanisms and consequences of RT-related CHIP. Key Points Radiation therapy significantly increases the risk of developing clonal hematopoiesis of indeterminate potential (CHIP) in cancer patients CHIP risk is higher in those who receive higher total dose and stereotactic radiation, with increased mutations in DNA damage repair genes
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".