Rapid, real-time central pathology review for E1412: A novel and successful paradigm for future National Clinical Trials Network diffuse large B cell lymphoma studies.
Bibliographic record
Abstract
7547 Background: E1412 statistical design is based on results of lenalidomide/RCHOP (R2CHOP) vs RCHOP in ABC-DLBCL as determined by NanoString gene expression profiling (GEP). Central pathology review (CPR) was conducted to confirm diagnosis and to ensure adequate tissue for GEP. Initially, CPR occurred after randomization and treatment initiation. Due to high ineligibility rate (IR), the protocol was amended to include real-time CPR to determine patient eligibility prior to study enrollment. We describe the revision and how it affected the IR. Methods: Pre-amendment, CPR was done retrospectively. Post-amendment, CPR was done prior to enrollment, in real time, on a submitted tissue block, H&E, and CD20 slides. Based on CPR, if a diagnosis of DLBCL was confirmed, and sufficient tissue remained for GEP, a patient was deemed eligible and the submitter was notified by fax. Protocol goal was notification within 2 working days (WD) of receipt of materials at the CPR site. Results: Pre-amendment, 219 patients were enrolled. Material was typically received at the CPR site 6-9 months after patient registration. The IR with CPR was 36% for all those enrolled, and 26% for patients with adequate tissue for GEP. Post-amendment, 218 patients were submitted for CPR: 145 (67%) were eligible; 73 (33%) were ineligible. Reasons for ineligibility included insufficient tissue (n=27) or a diagnosis other than de novo DLBCL (n=46). Notification of eligibility occurred in a median of 2 WD (Mean 2 WD; Range 1-5 WD). 90% were notified within the protocol goal of 2 WD. GEP for all enrolled was completed within 6 weeks of CPR. Conclusions: The success of this novel, real-time CPR serves as a model for the future of NCTN DLBCL trials. When CPR is performed rapidly prior to enrollment, study slots may more accurately reflect the target population and eliminate excess costs. In the precision medicine era, rapid collection of relevant pathology and biomarker data is essential to trial success. Study Coordinated by ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs), supported by NCI grant # CA180820, CA180794, CA180790, CA180799, CA180833.
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 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 | 0.163 | 0.076 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.012 | 0.003 |
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".