Evaluating metrics of circulating tumor DNA response and progression using a high sensitivity tumor-agnostic assay in metastatic HR+/HER2- breast cancer receiving endocrine therapy and a CDK4/6-inhibitor.
Notice bibliographique
Résumé
1043 Background: CDK4/6-inhibitors (-i) and endocrine therapy (ET) are first-line treatment for HR+/HER2- metastatic breast cancer (mBC). Clinical evaluation and cross-sectional imaging are used for treatment response assessment. The relationship between clinical/radiographic response and ctDNA dynamics using a high sensitivity tumor-agnostic assay is unknown in HR+/HER2- mBC. ctDNA monitoring in mBC may support clinical decision-making, enable new strategies for response assessment in clinical trials, and facilitate enrolment of patients lacking measurable disease (bone-only). Methods: Patients (pts) with HR+/HER2- mBC receiving ET and CDK4/6i were enrolled in a prospective cohort study. Plasma samples were collected at baseline (BL) and regularly on-treatment. Samples were analyzed using Guardant Infinity, a tumor-agnostic genomic and epigenomic platform. ctDNA-response (-R) was defined as a ≥50% decrease (dec) in methylation tumor fraction (mTF) from BL. ctDNA-progression (-P) was defined as a <50% dec in mTF from BL or any subsequent increase in mTF above an absolute mTF of 0.001% (cohort specific definition). Imaging outcomes and dates of treatment discontinuation (TD) were collected. Results: 57 pts with 350 clinical timepoints were evaluated. Median follow up was 28.2m (range: 1.6-66.0m). 42/57 (74%) pts received palbociclib and 40/57 (70%) received an aromatase inhibitor. ctDNA-R/-P was evaluable in 49/57 patients. ctDNA-P identified within the first 90d on CDK4/6i was not prognostic of TD (p=0.7972); when assessed between 90-180d it was prognostic of early TD (med: 6.3m vs. not reached; HR: 5.17, 95%CI: 1.04-25.7; p=0.0003). 156 matched radiographic and ctDNA assessments (blood collected within 30d of CT) were evaluable for ctDNA-R/-P and imaging concordance. Excluding those with clinician-identified sclerotic bone changes suggestive of treatment effect (n=5 events), adjudicated radiographic progression did not occur in the setting of ctDNA-R (NPV: 100%, sensitivity: 100%); no pts had clinical progression in the presence of ctDNA-R. ctDNA rise in the absence of radiographic progression occurred in 13 pts; 7/13 had TD (med: 10.1m, range: 3.0-21.9m) in the follow up period reflecting a molecular lead time. Blood first monitoring, using these metrics, could have avoided 104/150 (69%) staging CT scans in this cohort. Conclusions: ctDNA dynamics are associated with clinical outcomes in HR+/HER2- mBC. The use of a high sensitivity assay permits assessment of response in nearly all patients and suggests the possibility that radiographic surveillance could be reduced in patients with ctDNA-R. Prospective validation of these findings are required. Additional ctDNA-R/-P definitions and relationship with RECIST 1.1 criteria will be presented at the meeting.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».