184 | GENOMIC PROFILING OF EXTRANODAL DISEASE IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMA: A COMBINED ANALYSIS OF POLARIX AND GOYA
Bibliographic record
Abstract
Introduction: Next-generation sequencing (NGS) of cell-free DNA (cfDNA) is used for non-invasive molecular profiling of cancers.MSK-ACCESS Heme (Memorial Sloan Kettering-Analysis of Circulating cfDNA to Examine Somatic Status) is a cfDNA assay that employs unique molecular indexing and ultradeep sequencing to detect somatic alterations in 115 genes related to hematologic malignancies.We present the initial clinical experience with MSK-ACCESS HEME among patients (pts) with B-cell lymphoma.Methods: Patients diagnosed with B-cell lymphoma underwent prospective MSK-ACCESS Heme testing at initial diagnosis or progression of disease between January and July 2024.A subset of 40 pts had matched tissue-based NGS testing with the MSK-IMPACT 468 gene panel (Ptashkin RN, et al.Nat Commun. 2023).Results: A total of 60 pts were initially enrolled: 44 untreated at diagnosis and 16 at the time of disease progression.Samples were excluded if obtained after treatment initiation (n = 6) or if PET-CT showed no evidence of active disease (n = 5).Consequently, the mutational landscape was assessed in 49 pts: DLBCL (n = 11), FL (n = 13), HL (n = 10), MCL (n = 6), and other B-cell subtypes (n = 9).The mean coverage was 1100x (range: 320x-1911x).At least one mutation was detected in 47 of 49 cases (96%), with a median of 6 mutations per sample (range: 0-22).The most frequently mutated genes identified in plasma were KMT2D, TNFAIP3, CREBBP, TNFRSF14, SOCS1, STAT6, TP53, CARD11, and EP300.In the target regions with ACCESS and IMPACT overlapping, a total of 283 mutations were identified; 69% (n = 196) were detected by both assays, while 8% (n = 23) and 23% (n = 64) were uniquely identified by MSK-IMPACT tumor sequencing and MSK-ACCESS plasma sequencing, respectively.The MSK-ACCESS Heme assay demonstrated an 89.5% concordance rate in detecting mutations previously reported by MSK-IMPACT.Notably, HL and FL exhibited the highest proportion of mutations detected exclusively in plasma (50% and 23%, respectively).Interestingly, no mutations were detected in the five pts with localized disease whose primary tumor had been surgically removed.Conclusions: MSK-ACCESS Heme successfully identified somatic alterations with high concordance to tissue-based testing, demonstrating its potential as an alternative method for determining tumor mutational profile and genetic classification.This assay contributes to the development of personalized treatment strategies in the future, and its performance in monitoring pts during and after therapies will be assessed.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".