Quantification of tumor stroma as a biomarker in pancreatic adenocarcinoma.
Bibliographic record
Abstract
4021 Background: Desmoplastic tumor stroma (TS) characterizes the primary tumor in pancreatic ductal adenocarcinoma, but its role in tumor progression and metastasis is less clear. The objective of this study was to evaluate the presence and prognostic significance of TS at primary and metastatic sites. Methods: Tissue sections of primary tumors from 57 patients who underwent curative resections and 46 primary and metastatic tumors from 15 patients with metastatic pancreatic cancer were digitally annotated for tumor epithelium and TS, reviewed by a pathologist, and quantified using Spectrum WebScope. Tumor stroma density (TSD) was quantified as TS per total tumor area. Resected patients received no adjuvant chemotherapy. Association of TSD with overall survival (OS) and recurrence-free survival (RFS) was performed using the multivariate Cox proportional hazards model from the “survival” R statistical package (3.1.1); where significance was determined with log-rank test p-value less than 0.05. Results: Median TSD in primary tumors was 0.57. TSD was no different in the primary tumors of patients who had localized compared to metastatic disease. TSD was decreased in solid organ (0.12) and lymph node metastases (0.22) (ANOVA, p = 0.0001). Furthermore in patients who underwent curative resections, high TSD was associated with longer OS (HR = 0.237; p = 0.009), with a median OS of 11 months in the low TSD ( < 0.57) group and 21.5 months in the high TSD ( ≥ 0.57) group. TSD was also associated with RFS (HR = 0.286, p = 0.022), with a median RFS of 9 months in the low TSD group and 19 months in the high TSD group. The association of TSD with OS and RFS was adjusted for tumor grade, T, N and overall stage, ASA score, and smoking status. Conclusions: We demonstrate that stromal content is a measurable biomarker in this disease with meaningful clinical associations.Our results nominate that TSD should be used as an objective, quantitative assessment of TS in correlative and therapeutic trials of pancreatic cancer. TS appears to be associated with restraining tumor growth with decreasing TSD in patients with more aggressive disease. Also, the low TSD at metastatic sites should be considered in the context of stroma modulating therapies.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| 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".