Prognostic value of clinical and molecular markers in advanced ovarian cancer (AOC): importance of residual (Rs) disease. Translational study using tumor specimens from EORTC 55931/NCIC OV10 Phase III Randomized Clinical Trial (RCT)
Bibliographic record
Abstract
5005 Background: Rational selection of therapy in AOC requires molecular and prognostic profiling. We analyzed clinical (clin) and molecular (mol) markers from patients (pts) who participated in a multi-centre phase III RCT that demonstrated superiority of cisplatin (c)/paclitaxel over c/cyclophosphamide, and put these results in context of progression free survival (PFS) and overall survival (OS). Methods: EORTC 55931/NCIC OV10 was a RCT that enrolled 680 pts between 1994 and 1995, with 391 from EORTC and NCIC CTG. Paraffin fixed tumor tissue was retrospectively retrieved and analyzed from 95 pts. Demographics of pts whose tissue was available were similar to the entire randomized population. 96% of pt had stage III/IV disease and 80% had Rs disease > 1cm when they commenced chemotherapy. Mol markers analyzed were P53, BCL2, P21, Mib-1, c-Erb B2, DNA ploidy, S-phase and mitotic index. Median follow-up time was 6.4 years. Mol and clin factors were analyzed as potential prognostic factors for PFS and OS, with stratification for treatment in univariate (UV) and multivariate (MV) analyses. P53 was measured independently in Amsterdam and Toronto for the entire group, with the results blinded to the testing laboratories. The concordance between the two data sets was a measure of quality control and reproducibility. Results: The correlation between the two laboratories for P53 status was high (Cohen’s Kappa coefficient 0.8; p<0.001). UV analysis: there was significant (S) correlation between size of Rs disease and PFS (p=0.002) as well as OS (p=0.02). Stage and mitotic index were S predictors of OS (p=0.05 and 0.02), but not PFS. MV analysis: only Rs tumor mass remained S for PFS (p=0.002) and OS (p=0.02). The Hazard Ratio for patients with Rs disease > 1cm compared with <1cm was 2.4 for OS and 2.8 for PFS. Other mol and clin factors provided no additional information and were not retained in the final model. Conclusion: Assessment of clin and mol markers in women with AOC demonstrates that Rs tumor volume is S for predicting PFS and OS. None of the mol factors measured were independent predictors of these outcomes. No significant financial relationships to disclose.
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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 | 0.007 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 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".