Intermittent Hormone Therapy Models Analysis and Bayesian Model Comparison for Prostate Cancer
Bibliographic record
Abstract
The prostate is an exocrine gland of the male reproductive system dependent on androgens (testosterone and dihydrotestosterone) for development and maintenance. First-line therapy for prostate cancer includes androgen deprivation therapy (ADT), depriving both the normal and malignant prostate cells of androgens required for proliferation and survival. A significant problem with continuous ADT at the maximum tolerable dose is the insurgence of cancer cell resistance. In recent years, intermittent ADT has been proposed as an alternative to continuous ADT, limiting toxicities and delaying time-to-progression. Several mathematical models with different biological resistance mechanisms have been considered to simulate intermittent ADT response dynamics. We present a comparison between 13 of these intermittent dynamical models and assess their ability to describe prostate-specific antigen (PSA) dynamics. The models are calibrated to longitudinal PSA data from the Canadian Prospective Phase II Trial of intermittent ADT for locally advanced prostate cancer. We perform Bayesian inference and model analysis over the models' space of parameters on- and off-treatment to determine each model's strength and weakness in describing the patient-specific PSA dynamics. Additionally, we carry out a classical Bayesian model comparison on the models' evidence to determine the models with the highest likelihood to simulate the clinically observed dynamics. Our analysis identifies several models with critical abilities to disentangle between relapsing and not relapsing patients, together with parameter intervals where the critical points' basin of attraction might be exploited for clinical purposes. Finally, within the Bayesian model comparison framework, we identify the most compelling models in the description of the clinical data.
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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 | 0.010 | 0.034 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".