GATA6 Expression as a predictor of response to perioperative chemotherapy in resectable pancreatic adenocarcinoma: A multicenter Canadian phase II study (NeoPancONE).
Bibliographic record
Abstract
TPS638 Background: Prospective studies of the benefit of neoadjuvant chemotherapy in resectable pancreatic adenocarcinoma (PDAC) have been reported. The ideal peri-operative regimen is yet to be determined. Adjuvant FOLFIRINOX (mFFX) in resected PDAC has been proven to improve overall survival (OS) relative to adjuvant gemcitabine. An accepted perioperative approach involves delivering the majority of chemotherapy (6-8 cycles) in the pre-operative setting, while the remainder (of 12 cycles) is administered post-operatively. This pre-operative treatment period may allow for chemosensitivity assessment, and better patient selection for surgery, thereby improving R0 resection rates and reducing the frequency of early post-operative recurrence. Data from the COMPASS trial (NCT02750657) has shown that shown that low levels of the transcription factor GATA6 expression is a putative surrogate for the RNA Moffit signature and predictive of a chemoresistant phenotype in advanced PDAC. NeoPancONE will evaluate clinical outcomes and molecular biomarkers including GATA6 and radiomic biomarkers in pts with resectable PDAC treated with perioperative mFFX. Methods: NeoPancONE is a Phase 2, open-label, single arm study in pts with resectable PDAC. Tissue and serum are collected for biomarker testing, including GATA6 by FISH and IHC (1) with expression levels measured by RNAseq, and longitudinal ctDNA analysis. Pts with histologically confirmed, resectable PDAC and ECOG PS 0-1 will be recruited over 2.5 years. Resectability will be determined by central review as per NCCN guidelines. The primary objective is to evaluate disease-free survival in resectable PDAC treated with peri-operative mFFX according to baseline tumor GATA6 expression level. The ratio of GATA6-high to low is expected to be approximately 4:1[1]. Assuming 1-year disease-free survival of 65% in the GATA6-high, compared to 34% in the GATA6-low cohort, this corresponds to a hazard ratio of 2.5. With 80% power and a 5% 2-sided significance level, a total of 84 patients will be enrolled with 67 events expected in the GATA6 high cohort and 17 in GATA6 low. Participants will receive up to 6 cycles of neoadjuvant mFFX. After neoadjuvant chemotherapy, definitive surgical resection will proceed as deemed appropriate by a hepatobiliary surgeon. Post-operatively, pts will receive up to 6 cycles of adjuvant chemotherapy. Secondary objectives include determination of overall response rate, incidence of R0 resection, OS, Moffit gene expression profiling (RNAseq), ctDNA, and radiomic signatures to predict outcomes. Enrolment for NeoPancONE began in October 2020 and is being conducted at 8 sites across Canada. To date, 23 pts have been recruited. The study duration will be five years. Reference: O’Kane G M et al. Clin Can Res Sep 2020. Clinical trial information: NCT04472910.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".