Outcome prediction based on single nucleotide polymorphisms (SNPs) in DNA repair paths in patients (pts) with esophageal adenocarcinoma (EAC) treated with preoperative (preop) cisplatin (C)-based chemoradiation (CRT): Results from the Eastern Cooperative Oncology Group (ECOG)
Bibliographic record
Abstract
4530 Background: EAC has eluded cure even with platin-based CRT. Stratifying pts by likelihood of success is one approach to improving outcomes. We assessed whether SNPs in DNA repair paths are associated with complete pathologic response (pCR) in EAC pts who received C-based CRT followed by surgery. Methods: Patients and specimens: Pretreatment biopsy or post-CRT resection samples were obtained from pts (EAC, stage II-IVa) treated on a randomized phase II trial, E1201 (n=86), of preop CRT (RT to 45 Gy). Arm A: Preop C 30 mg/m2 + irinotecan (I) 50 mg/m2 days (d) 1, 8, 22, 29 with RT. Post-op C 30 mg/m2 + I 65 mg/m2 d 1, 8 q21 days x 3. Arm B: Preop C 30 mg/m2 + paclitaxel (P) 50 mg/m2 d 1, 8, 15, 22, 29 with RT. Post-op C 75 mg/m2 + P 175 mg/m2 d 1 q21 days x 3. Clinical outcome - pCR: (A) 14% [95% CI 5.5%, 28.5%]; (B) 16% [95% CI 6.7%, 30.1%]. Median overall survival (OS): (A) 34.9 m (months) [90% CI 23.5, not reached]; (B) 20.9 m [90% CI 17.4, 46.7]. Experimental procedure: Normal tissue was microdissected from unstained sections of paraffin-embedded tissue. DNA was extracted (Qiagen). Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight (Sequenom) for all SNPs. Each SNP was dichotomized a priori into: (1) major homozygote vs (2) minor (heterozygote plus minor homozygote) allele groups. Data analysis was performed centrally, with lab investigators blinded to clinical data. Exact logistic regression was used to derive ORs for non-pCR, using the major homozygote as the reference (2-sided p values). Results: Germline DNA was available in 68 pts; 60 were eligible and began therapy ( Table ). Conclusions: In this homogenous, well-defined cohort, the XRCC1 Arg399Gln minor allele group was associated with lower pCR (p=0.06). Lab data on a panel of additional SNPs have been collected and are under analysis for presentation at the meeting. [Table: see text] [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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 |
| 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".