Chemopredictive diagnostic project in patients (pts) receiving capecitabine (X) or 5-FU/leucovorin (LV) as first-line chemotherapy for metastatic colorectal cancer (MCRC)
Bibliographic record
Abstract
9652 Background X (Xeloda®) is a tumor-activated oral fluoropyrimidine, with superior response rate and improved safety compared to bolus 5-FU/LV in 1st-line MCRC. Variation in tumor expression levels of thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) may impact efficacy or toxicity of X-containing regimen. We are retrospectively evaluating the relationship of the expression of these enzymes to outcomes in a 1st-line MCRC phase III trial of X vs 5-FU/LV (Hoff, JCO 2001). 9 Canadian sites participated in the trial (N=164). Methods Pts were eligible if they received at least one dose of chemotherapy. We obtained informed consent through next-of-kin or Ethics Committee waiver. We obtained formalin-fixed, paraffin-embedded tissue from primary tumors +/- synchronous metastases. We analyzed TP, DPD and TS expression levels using immunohistochemistry (IHC) and quantitative reverse transcriptase - polymerase chain reaction (RT-PCR) kits, both from Roche Diagnostics. Overall IHC score was calculated using tumor and stromal staining intensity and pattern. IHC intensity and percentage of staining were scored blinded to pt treatment and clinical outcome.Results Tumor blocks from 37/164 pts have been analyzed to date, 34 primaries (see table), 4 metastases (not shown). Data on correlation of IHC and RT-PCR results to clinical outcomes will be presented at the meeting. Conclusions Retrospective sample collection was feasible in a large multicenter trial. Sophisticated molecular analysis of archival samples was performed with a success rate of 97%. Results of this biomarker analysis could generate a hypothesis to be tested in further prospective research with X, eventually allowing tailored therapy for the individual patient. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Hoffmann-La Roche Hoffmann-La Roche
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".