Abstract 3774: Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study
Notice bibliographique
Résumé
Abstract Background: Circulating tumor (ctDNA) for detection of minimal residual disease (MRD) in colorectal cancers is prognostic, however, many cancers are not detected prior to clinical recurrence. Chemotherapy and surgery may limit detection of ctDNA due to increased shedding of DNA. We are exploring the use of an ultra-sensitive MRD assay (NeXT Personal®) in a prospective study of colorectal cancers (VICTORI) undergoing resection, with the aim to determine the optimal timepoint post-surgery to detect MRD. Methods: Patients enrolled undergo whole genome sequencing on tissue samples to generate a personalized panel of up to ∼1800 somatic variants for MRD detection, enabling detection of ctDNA down to ∼1 part per million (PPM). Blood draws are taken prior to surgery, within the MRD landmark window (weeks 2, 4, 6 and 8), and on follow-up thereafter every 3 months for 3 years. Results: We present preliminary results on 474 samples from the first 68 patients (N=40 rectal [59%], N=28 colon [41%]; N= 51 stage I-III [75%], N=17 stage IV [25%]) with a median follow up of 387 days. Pre-surgery positivity in treatment-naïve patients was 93.8% (n=30/32; negative are both stage I), and 72.4% in patients that received neoadjuvant therapy (n=21/29). Sixty-seven patients were evaluable for clinical outcomes, of which 23 had a recurrence. Of these, all evaluable patients were ctDNA-positive prior to recurrence (100%, 21/21; 2 patients were excluded due to lack of plasma samples prior to recurrence). ctDNA detection preceded clinical relapse determined by standard of care imaging by a median of 194 days (range 1-416 days). Most recurrences had ctDNA detected in the MRD landmark window (86%, 18/21). Of the three detected after the landmark window, one (stage IV) had neoadjuvant therapy prior to surgery, and was detected at the first follow-up timepoint (month 3). Another (stage III) was detected at month 6, and the third (stage II) at month 9. The median level of detection for the first post-surgical MRD positive sample was 54.9 PPM (range 2.45-111,120 PPM), and the ctDNA level at the first detection was correlated with disease-free survival (r=-0.47, p=0.05, Spearman). Detection of MRD at each individual timepoint in the MRD landmark window was associated with reduced disease-free survival (week 2 HR 4.75 [95% CI:1.63-13.84], p=0.0043; week 4 HR 11.72 [3.87-35.47], p=1.33x10-5; week 6 HR 7.73 [2.79-21.41], p=8.4x10-5; week 8 HR 16.70 [4.85-57.49], p=8.08x10-6). Conclusions: The VICTORI study is an ongoing study to understand the prognostic value of ultra-sensitive ctDNA detection and determine the optimal timepoint for detecting MRD post-surgery. Preliminary results indicate NeXT Personal detects MRD at ultra-low levels and is prognostic as early as two weeks post-surgery for recurrences. Citation Format: Emma Titmuss, Joao Paulo Solar Vasconcelos, Fabio C. Navarro, Neeraja Ravi, Charles Abbott, Brendan Chia, James T. Topham, Gale Ladua, Daniela Hegebarth, Sophie C. Chuang, Howard J. Lim, Karamjit Gill, Sharlene Gill, Carl J. Brown, Amandeep Ghuman, Adam Meneghetti, David F. Schaeffer, Richard O. Chen, Sean M. Boyle, Jonathan M. Loree. Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3774.
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 | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».