ctDNA-guided adjuvant chemotherapy escalation in stage III colon cancer: Primary analysis of the ctDNA-positive cohort from the randomized AGITG dynamic-III trial (intergroup study of AGITG and CCTG).
Notice bibliographique
Résumé
3503 Background: Despite adjuvant chemotherapy (ACT) a proportion of patients (pts) with stage III colon cancer (CC) will recur. Most at risk are those with detectable ctDNA, whereas those with undetectable ctDNA have a reduced recurrence risk. The DYNAMIC-III study explored the impact of ACT de-escalation or escalation as informed by post-surgery ctDNA results. Here, we report the primary analysis on the impact of treatment escalation in ctDNA-positive pts. Outcome data for treatment de-escalation in ctDNA-negative pts is immature. Methods: DYNAMIC-III is a multi-center, randomized, phase II/III trial. Eligible pts had resected stage III CC and were fit for ACT. Pts were randomly assigned 1:1 to ctDNA-informed or standard of care (SOC) management. Clinicians nominated the selected SOC ACT regimen prior to randomization. For ctDNA-informed management, a ctDNA-positive result at 5-6 weeks after surgery with a tumor-informed assay prompted an escalation ACT strategy (from single agent fluoropyrimidine [FP] to oxaliplatin-based doublet, from 3 months doublet to 6 months doublet or FOLFOXIRI [clinician choice], or from 6 months doublet to FOLFOXIRI). The primary efficacy endpoint for the ctDNA-positive cohort was 2-year RFS. The target sample size of 250 provided 80% power with 90% confidence to confirm superiority of ctDNA-informed treatment escalation compared to SOC with a HR of 0.746. Results: Of 961 eligible pts randomized between Oct 2017 and Apr 2023, 259 (27%) were ctDNA-positive. Of these, 113 (44%) had clinical low risk disease (non-N2 + non-T4). Median follow-up was 42.2 months (range 0.78 – 63.0). 115 (89%) of 129 ctDNA-informed pts received ACT escalation, with 65 (56%) receiving FOLFOXIRI. Of 130 SOC pts, 14 (11%) and 112 (86%) received single agent FP and oxaliplatin doublet, respectively. 2-year RFS for ctDNA-informed treatment escalation was 52% (90% CI: 44 - 59%) vs 61% (90% CI: 54 - 68%) for SOC (HR 1.11, 90% CI: 0.83 - 1.48; P = 0.6). The 3-year RFS for ctDNA-positive pts receiving FOLFOXIRI and FOLFOX/CAPOX was similar (47% vs 51%, HR 1.09, 90% CI 0.78 to 1.53; P = 0.7). In a pre-specified correlative analysis of all ctDNA positive pts, recurrence risk increased with ctDNA burden, with 3-year RFS of 78%, 63%, 36% and 22% for tumor-derived mutant molecules/mL quartiles < 0.06, 0.06 – 0.17, 0.18 – 1.31, and > 1.31, respectively (P < 0.01). Treatment-related hospitalisation was similar for escalated and SOC pts (OR 1.21, P = 0.58). Analysis of post-ACT ctDNA is underway. Conclusions: In this first randomised study of ctDNA-informed management in stage III CC, we confirm the prognostic significance of detectable ctDNA, with the novel finding of recurrence risk increasing markedly with ctDNA burden. Treatment escalation, including to FOLFOXIRI, did not improve RFS. Future studies in ctDNA positive pts should explore other escalation strategies. Clinical trial information: ACTRN12617001566325 .
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| 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 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».