Adjuvant modified FOLFIRINOX for resected pancreatic adenocarcinoma: clinical insights and genomic features from a large contemporary cohort
Bibliographic record
Abstract
BACKGROUND: Adjuvant modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). Data are limited on adjuvant modified FOLFIRINOX outcomes outside clinical trials. METHODS: We queried institutional databases to identify patients with resected PDAC who received 1 or more doses of adjuvant modified FOLFIRINOX. Primary endpoints were recurrence-free survival (RFS) and overall survival. Secondary endpoints were clinical factors and genomic features associated with outcomes. We estimated RFS and overall survival by using the Kaplan-Meier method. A Cox proportional hazards regression model was used to associate clinicogenomic features with survival outcomes. RESULTS: A search revealed 147 individuals with PDAC between January 2015 and January 2023. Median patient age was 67 years, with 57 (39%) patients older than 70 years. Unfavorable prognostic features included 52 (36%) patients with N2 nodal status, 115 (78%) patients with lymphovascular invasion, and 133 (90%) patients with perineural invasion. Median time from surgery to initiation of modified FOLFIRINOX was 1.78 months (IQR = 1.45-2.12). In total, 124 (84%) patients completed 12 doses; 98 (67%) patients stopped oxaliplatin early because of neuropathy (median = 10 doses, range = 4-12 doses). Further dosing characteristics are summarized in Table S3, with a median follow-up of 35.1 months, a median RFS of 26 months (95% confidence interval [CI] = 19 to 39), and a median overall survival not reached. For the cohort older than 70 years of age, the median RFS was 23 months (95% CI = 14 to not reached) and the median overall survival was 51 months (95% CI = 37 to not reached). Modified FOLFIRINOX started sooner than 8 weeks from resection was associated with improved RFS (hazard ratio = 0.62, 95% CI = 0.41 to 0.96; P = .033) and overall survival (hazard ratio = 0.53, 95% CI = 0.3 to 0.94; P = .030). KRAS variation and whole-genome doubling trended to shorter RFS and overall survival. Homologous recombination deficiency status did not confer improved survival outcomes. CONCLUSIONS: Adjuvant modified FOLFIRINOX was effective and tolerated in patients with resected PDAC in a nontrial setting, including for patients older than 70 years of age.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| 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".