Predictive model for survival and toxicity in early-phase trials in hematology.
Bibliographic record
Abstract
2547 Background: Strict criteria are used to limit toxicity for patients (pts) enrolled in phase I/II clinical trials, but the ability to survive beyond 12 weeks, a common inclusion criterion, is subjective and error-prone. A prognostic score with 3 variables was designed and validated as an independent predictor of OS in pts with solid tumors included in phase I trials (Arkenau, JCO 2009). We examined the ability of objective measures to predict OS and risk of grade ≥3 toxicity in pts with hematologic malignancies enrolled in early-phase trials. Methods: A retrospective analysis was conducted on 290 pts in Phase I (79 pts) and II (211 pts) trials from the NCIC - Clinical Trials Group and our institution from 1995 to 2009. Only pts with survival data up to 90 days were included. Univariate model (UVA) was used to identify factors significantly associated with OS. A Cox proportional hazards model (MVA) included all factors identified from the UVA. Six prognostic factors were identified in the MVA, and each assigned a score of 0 or 1. Pts were categorized as high or low risk based on the total scores that they received, ≥3 were assigned to the high risk group, and a ≤2 to the low risk group. Kaplan-Meier method was used to generate the survival distribution for the high and low risk groups. Multivariate logistic regression was used to identify the risk factors for grade ≥3 toxicity. Results: The overall median survival was 238 days (95% CI 237 to 331), and 27% of pts had grade ≥ 3 toxicity. In the MVA, albumin (alb), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lymphocytes, platelets (plts) and diagnosis were significantly associated with OS. Pts in the low risk group had a median survival of 10.6 months, relative to 2.4 months among pts in the high risk group. Survival at 90 days was 80% in lower risk vs. 36% in the high risk group. In addition, the MVA for toxicity showed that alb, ALP, LDH, plts and performance status were significantly associated with grade ≥3 toxicity. Conclusions: Our model predicts OS, 90 day survival and risk of grade ≥ 3 toxicity among pts with hematologic malignancies entered in Phase I/II trials. Future work will include a linear predictor score based on MVA to refine the prediction model. The model will also be validated using another dataset.
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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 | 0.012 | 0.033 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".