Complex biologic heterogeneity of <i>de novo</i> hormone naïve metastatic prostate cancer (HNPCa): Comparison of early progressors and prolonged responders to initial systemic treatment.
Bibliographic record
Abstract
5055 Background: Given the absence of biologically based biomarkers current therapy allocation strategies for men with mHNPCa are based on anatomic distribution and volume of metastases. We sought to determine the strength of the association between clinical predictors (including met volume) and outcomes in men with mHNPCa at extremes of response to initial systemic therapy (ST). Methods: Data from a population screened for a phase II trial of Best ST +/- local therapy in mHNPCa was analyzed (NCT01751438). Pts had to have sustained responses to ST (≥6 mos) in order to be randomized. Early Progressors (EP, castration resistant progression <6 mos from start of ST per PCWG2) were not randomized. Prolonged Responders (PR) were defined as those with progression free survivals (PFS) > median for the 109 randomized pts. Baseline demographics were compared between groups (Fisher’s exact test for categorical and Wilcoxon rank-sum test for continuous variables) and Kaplan Meier estimates of OS determined. Immunohistochemistry and genomic sequencing of untreated tumor biopsies are ongoing. Results: Of 208 screened pts, 27 (13%) were identified as EPs, with a median PFS of 5.9 mos (95%CI: 5.3-6.5). The median PFS for the randomized cohort was 16.8 mos (95%CI: 12.7-37.6). 55 (50%) pts were identified as PRs, with median PFS not reached (NR) at a median follow up of 31 mos (range: 7.5-75). Patients’ demographics are below (Table), grouped by EP and PR cohorts. Median OS was 24.8 mos vs NR in the Eps compared to PRs (p<0.001). Conclusions: The EP group was enriched for high risk features and had a worse outcome. However, 33% of men in the EP group had low volume disease and 22% in the PR group had high volume disease. This suggests that clinical volume is an inadequate predictor of biologic response and highlights the need for biologic sub-typing of de novo mHNPCa. [Table: see text]
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".