NRG/RTOG 1112: Randomized phase III study of sorafenib vs. stereotactic body radiation therapy (SBRT) followed by sorafenib in hepatocellular carcinoma (HCC).
Notice bibliographique
Résumé
489 Background: To determine if SBRT followed by sorafenib (SBRT/S) improves overall survival (OS), progression free survival (PFS) and quality of life (QOL) vs. sorafenib alone (S), in patients (pts) with HCC. Methods: Eligible pts had new or recurrent HCC, unsuitable for surgery, ablation or TACE, with Zubrod performance status (PS) 0-2, Child-Pugh (CP) A, BCLC stage B or C, ≤ 5 HCCs, sum of hepatic HCCs ≤ 20 cm, and distant metastases ≤ 3 cm. Pts were randomized 1:1 to S 400 mg BID vs. SBRT (27.5-50 Gy in 5 fractions) followed by S 200 mg BID, increased to 400 mg BID after 28 days. Primary endpoint was OS; reported secondary endpoints - PFS, adverse events (AEs - CTCAEv4), and QOL (improvement in FACT-Hep score by ≥ 5 points from baseline to 6 months). Planned sample size was 292 pts (238 OS events, HR=0.72, 80% power, 1-sided α=0.05). Accrual closed early, due to a change in HCC standard of care. Statistics were amended to report as of 7/1/2022, projecting 155 OS events, with 65% power and the same α. OS and PFS were estimated by Kaplan-Meier and arms compared using log-rank test. Cox proportional hazards models were used to analyze treatment effect. Secondary endpoints were tested with 2-sided α=0.05. Results: Of 193 pts accrued from April 2013 to March 2021 from 23 sites, 177 eligible pts were randomized to S (n=92) vs. SBRT/S (n=85). Median age was 66 yrs (27-84); 41% had Hep. C; 19% had Hep. B or B/C. 82% were BCLC stage C. 74% had macrovascular invasion (MVI), 63% with VP3 or VP4 MVI. 4% had metastases. Median sum of max diameter of HCCs was 8.2 cm for S and 6.7 cm for SBRT/S; 40% had a single HCC. Median follow-up for all and alive pts was 13.2 and 33.7 mo. 22% of S pts received SBRT after discontinuing S. With 153 OS events, median OS was improved from 12.3 mo. (90% CI 10.6, 14.3) with S to 15.8 mo. (90% CI 11.4-19.2) with SBRT/S (HR=0.77, 1-sided p=0.0554). After adjusting for PS, M stage, CP A5 vs. 6, and degree of MVI, OS was statistically significantly improved for SBRT/S (HR=0.72, 95% CI 0.52-0.99, 2-sided Cox p=0.042). Median PFS was improved from 5.5 mo. (95% CI 3.4-6.3) with S to 9.2 months (95% CI 7.5-11.9) with SBRT/S (HR=0.55, 95% CI 0.40-0.75, 2-sided p=0.0001). 8 grade (G) 3+ bleeds were seen: 5 in S arm (1 G3 variceal, 2 G3 upper GI, 1 G3 hepatic, and 1 G4 abdominal) and 3 post SBRT/S (2 G3 upper GI, 1 G3 lower GI). Treatment-related G3+ AEs were not significantly different (S - 42%; SBRT/S - 47%; p=0.52), with 3 G5 AEs (S - 1 hepatic failure, 1 death NOS; SBRT/S - 1 lung infection). 83 (47%) pts consented to QoL. Of 20 S and 17 SBRT/S pts with QoL assessments at baseline and 6 months, 10% on S improved in FACT-Hep score vs 35% on SBRT/S. Conclusions: Compared to S alone, SBRT improved OS & PFS in patients with HCC, with no observed increase in AEs, and a strong suggestion for QOL benefit at 6 months. Supported by U10CA180868 (NRG Onc. Op., U10CA180822 (NRG Onc. SDMC), UG1CA189867 (NCORP), and U24CA180803 (IROC) from the NCI. Clinical trial information: NCT01730937 .
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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,009 | 0,002 |
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 ».