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Record W4402944297 · doi:10.1101/2024.09.27.24314321

Risk of Clonal Hematopoiesis of Indeterminate Potential after Cancer Radiation Therapy

2024· preprint· en· W4402944297 on OpenAlexaff
Shelby Crants, Sydney S Olson, Yajing Li, Caitlyn Vlasschaert, T. Mack, Yash Pershad, Ashwin Kishtagari, Sarah C. Reed, Sarah Croessmann, Dan M Roden, Travis Osterman, Eric T. Shinohara, Alexander G. Bick, Ben Ho Park, Leo Y. Luo

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldMedicine
TopicEffects of Radiation Exposure
Canadian institutionsQueen's University
FundersVanderbilt Institute for Clinical and Translational ResearchNational Institutes of HealthVanderbilt UniversityAlexander and Margaret Stewart Trust
KeywordsIndeterminateRadiation therapyHaematopoiesisCancerMedicineOncologyCancer researchInternal medicineBiologyGeneticsStem cell

Abstract

fetched live from OpenAlex

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

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.063
Threshold uncertainty score0.875

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.008
GPT teacher head0.284
Teacher spread0.276 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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