Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis
Bibliographic record
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88–0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78–0.83; P < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 (P < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels (P < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis. Significance: In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.020 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.012 | 0.003 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 teacher head, 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".