Prognostication using serum levels of components of the folate metabolic pathway in patients (PTS) treated with capecitabine for advanced colorectal cancer (ACRC)
Bibliographic record
Abstract
3764 Background: Capecitabine [Xeloda (XEL)] is an oral pro-drug of 5-fluorouracil, which in turn forms a terniary complex with thymidylate synthase and reduced folate. Folate metabolism could therefore have an impact on the clinical efficacy of XEL. Players include homocysteine, which is converted to methionine in a reaction forming tetrahydrofolate in the presence of vit B12. These and other factors may play a prognostic role in pts with ACRC. Methods: A multicentre phase I/II trial of XEL 2000mg/m2 d1–14 q21d was conducted in 139 pts in one or more of the following subsets: age > 65 years (99 pts), ECOG performance status (PS) >1 (85 pts), LDH (43 pts), prior pelvic radiation (36 pts), liver enzyme abnormalities (4 pts). A substudy is reported on the prognostic significance of serum and RBC folate, vit B12, homocysteine, LDH, LDH isoenzymes, and ECOG PS. Results: 86 pts were evaluable for homocysteine levels, 122 for LDH, and 137 for ECOG PS. High homocysteine (n=37) predicted for markedly shorter median overall survival (MS) vs normal levels (n=49). Serum folate, RBC folate, and vit B12 did not predict for survival, though high folate predicted for tumour response. High LDH (n=71) predicted for shorter MS vs normal LDH (n=51), and lower response rate. Pts with high LDH have a lower proportion of LDH isoenzyme 1 (15.1%) vs pts with normal LDH (21.5%), p<0.0001. Less LDH isoenzyme 1 depression predicted for better MS (p=0.08). ECOG PS 0 (n=52) had worse MS vs ECOG PS 1 to 2 (n=85). Pts with normal LDH and high homocysteine had a poor MS (9.4 mos), suggesting homocysteine is a more powerful prognostic factor. Conclusions: High serum homocysteine, high LDH and poor PS are poor prognostic factors in pts with ACRC treated with XEL. Accrual continues and updated results including multivariate analysis will be presented. Supported by Hoffman-La Roche Canada. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-LaRoche Canada
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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".