Harnessing patient-specific response dynamics to optimize evolutionary therapies for metastatic clear cell renal cell carcinoma – Learning to adapt
Bibliographic record
Abstract
Abstract Renal cell carcinoma (RCC) is one of the ten most common and lethal cancers in the United States. Tumor heterogeneity and development of resistance to treatment suggest that patient-specific evolutionary therapies may hold the key to better patients prognosis. Mathematical models are a powerful tool to help develop such strategies; however, they depend on reliable biomarker information. In this paper, we present a dynamic model of tumor-immune interactions, as well as the treatment effect on tumor cells and the tumor-immune environment. We hypothesize that the neutrophil-to-lymphocyte ratio (NLR) is a powerful biomarker that can be used to predict an individual patient’s response to treatment. Using randomly sampled virtual patients, we show that the model recapitulates patient outcomes from clinical trials in RCC. Finally, we use in silico patient data to recreate realistic tumor behaviors and simulate various treatment strategies to find optimal treatments for each virtual patient.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".