Development and validation of an AI-derived digital pathology-based biomarker to predict benefit of long-term androgen deprivation therapy with radiotherapy in men with localized high-risk prostate cancer across multiple phase III NRG/RTOG trials.
Notice bibliographique
Résumé
5001 Background: Androgen deprivation therapy (ADT) improves survival and reduces risk of metastasis in men with high-risk localized prostate cancer (PC) receiving radiotherapy (RT). Predictive biomarkers are needed to guide ADT duration to maximize benefits and minimize risks. We sought to train and validate the first predictive biomarker for long-term (LT) vs short-term (ST) ADT using multiple phase III NRG Oncology randomized trials. Methods: Pre-treatment prostate biopsy slides were digitized from six phase III NRG/RTOG randomized trials of men receiving RT +/- ADT. The artificial intelligence (AI)-derived clinical and histopathological predictive biomarker was trained on RTOG 9408, 9413, 9902, 9910, and 0521 to predict differential benefit of LTADT on distant metastasis (DM). After the AI biomarker was locked, it was validated on RTOG 9202, which randomized men to RT + STADT (4 mo) vs LTADT (28 mo). The predictive utility of the AI biomarker was evaluated for the primary and secondary endpoints of DM and PC-specific mortality (PCSM), respectively, for ADT duration with Fine-Gray interaction models. Event rates were estimated by the cumulative incidence method. Deaths from other causes were treated as competing risks. Results: The AI-derived biomarker was trained on 2,641 men (median follow-up of 9.8 years, IQR [8.2, 11.5]) and validated on 1,192 men from RTOG 9202 (median follow-up of 17.2 years, IQR [9.1, 19.6]), where 80% had at least one high/very high (H/VH) risk feature (cT3-4, Gleason 8-10, PSA > 20, or primary Gleason pattern 5). Consistent with published results, LTADT significantly improved DM (subdistribution HR [sHR] 0.64, 95% CI 0.50-0.82, p < 0.001) in the validation cohort. The AI biomarker was prognostic for DM (sHR 2.35, 95% CI 1.72-3.19, p < 0.001). A significant biomarker-treatment interaction was observed (p = 0.04), in which AI-biomarker (+) men (n = 785, 66%) had reduced DM with LTADT (sHR 0.55, 95% CI 0.41-0.73, p < 0.001), but no benefit was observed (sHR 1.06, 95% CI 0.61-1.84, p = 0.84) for AI-biomarker (-) men (n = 407, 34%). The 10-year DM rate difference between RT + LTADT vs RT + STADT was 13% in AI-biomarker (+) men vs 2% in AI-biomarker (-) men. Similar trends were observed for PCSM outcomes. Risk classification (NCCN intermediate [n = 221, 43% (+)] vs other H/VH risk [n = 954, 71% (+)]) was prognostic but not predictive of LTADT benefit. Conclusions: We have successfully validated the first predictive biomarker of LTADT benefit with RT in localized high-risk PC using an AI-derived digital pathology-based platform in the phase III NRG/RTOG 9202 trial. The predictive AI biomarker identified 34% of men that could derive similar benefit with STADT, avoiding the side effects of prolonged ADT, and 43% of intermediate risk men who would benefit from LTADT.
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 | 0,006 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,000 |
| 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 ».