Association of excision repair cross-complementation group 1 (ERCC1) gene expression (GE) with outcome in stage II-III esophageal adenocarcinoma (EA) patients treated with preoperative platinum-based chemoradiation (CRT) in a phase II cooperative study (SWOG 0356).
Bibliographic record
Abstract
2 Background: Preoperative platinum-based CRT for operable esophageal cancer has improved overall survival (OS) compared to surgery alone. The phase II SWOG 0356 trial designed to test oxaliplatin (OXP) plus infusion 5-fluorouracil (5-FU) and external beam radiation prior to surgery for potentially curable EA has produced promising centrally confirmed complete pathologic response (pCR) rate (28.3%). After surgery patients were given a second cycle of OXP and 5FU. 2-year OS was 54.2%. However, treatment efficacy may be significantly compromised as a result of interindividual variations. We tested whether intratumoral GE levels in drug metabolism (DPD, GSTPi, TS and TP) and DNA repair (ERCC1 and XPD) predicted clinical outcome (CO). We also tested whether specific pattern of 12 polymorphisms in 8 genes (drug metabolism (GSTP, MTHFR and TS) and DNA repair (ERCC1, RAD51, XPD, XRCC1 and XRCC3)) predicted CO. Methods: A total of 90 patients from the SWOG 0356 study were eligible for the molecular correlative study. mRNA was extracted from laser-capture-microdissected tumor tissue. After cDNA was prepared by reverse transcription, quantitation of the candidate genes and an internal reference gene (ß-actin) was performed using a fluorescence-based real-time detection method (TaqMan). Established GE cutoffs were tested (ERCC1 <1.7 x 10-3; TS <4.0 x 10-3). DNA was extracted from blood and genotyped using PCR-RFLP techniques. Results: In univariate analysis, we found ERCC1 GE levels to be significantly associated with progression-free survival (PFS) and OS. Patients with high ERCC1 GE levels had worse 2-year PFS (17 vs 67%, p=0.004) and 2-year OS (37 vs 72%, p=0.04) compared to low GE levels. ERCC1 GE levels were not associated with pCR. All the other GE levels tested did not show significant association with CO. None of the tested polymorphisms showed any association with CO. Conclusions: Our data suggest that GE levels of ERCC1 may help to identify patients with stage II-III EA likely to experience longer survival when treated with preoperative OXP-based CRT. No significant financial relationships to disclose.
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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".