19P The prognostic value of soluble CD73 in advanced triple-negative breast cancer: An exploratory analysis of the SYNERGY trial
Bibliographic record
Abstract
Overexpression of CD73 in breast cancer is associated with immunosuppressive, pro-angiogenic tumor microenvironment and with poor patient clinical outcomes. Anti-CD73 antibodies are being investigated in combination with immune checkpoint inhibitors in clinical trials. Here, we investigated the prognostic value of the soluble form of CD73 (sCD73) in patients with advanced triple negative breast cancer (TNBC) treated with first-line durvalumab and chemotherapy, with or without anti-CD73 antibody oleclumab in the randomized, phase II SYNERGY trial (NCT03616886). sCD73 levels were measured by ELISA in baseline plasma of 124 patients included in SYNERGY and in 24 healthy donors (HD). We explored association between sCD73 levels and baseline clinical characteristics, treatment response, and survival. Tumor-infiltrating lymphocytes (TILs) were assessed on H&E staining; PD-L1 was analyzed using immunohistochemistry. TNBC patients had significantly higher baseline sCD73 levels than HD (Mann-Whitney, p<0.001). High baseline levels of sCD73 were associated with liver metastases, high neutrophil-to-lymphocyte ratio (>5), and elevated CA 15-3 at baseline. sCD73 levels showed no association with clinical benefit at 24 weeks or with progression-free survival (PFS). Median overall survival (OS) was significantly shorter in patients with high baseline sCD73 levels compared to those with low sCD73 (18.8 vs. 26.4 months; log-rank, p=0.03). Higher TILs levels correlated with better PFS (log-rank, p=0.04) and OS (log-rank, p=0.03). High PD-L1 expression correlated with better PFS (log-rank, p=0.004). No association was observed between sCD73 levels and TILs or PD-L1 expression. Multivariate analysis (including treatment arm, TILs, PD-L1, sCD73 and disease presentation) confirmed the independent prognostic value of sCD73 (OS; HR=0.5; p=0.02). In our analysis high baseline sCD73 levels were associated with negative prognostic clinical factors at baseline and with worse OS. The role of sCD73 as independent prognostic factor requires external validation.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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 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".