PORTOS gene signature as a predictor of risk of adverse events after dose-escalated vs. lower-dose prostate radiation therapy in NRG/RTOG 0126.
Notice bibliographique
Résumé
375 Background: Dose-escalated radiation therapy is standard treatment for patients with prostate cancer. Dose-escalation improves cancer control but also increases the risk of treatment adverse effects. We hypothesized RNA-based tumor gene expression recapitulates normal tissue gene expression and therefore could identify patients at increased risk of adverse events after dose-escalated radiation. We specifically evaluated the 24-gene PORTOS score which characterizes response to DNA damage and radiation. Methods: PORTOS scores were calculated from biopsy samples obtained from 215 patients treated on the NRG/RTOG 0126 clinical trial that randomized patients with intermediate-risk prostate cancer between 70.2 Gy and 79.2 Gy delivered in 1.8 Gy fractions. In this trial, adverse events were categorized using RTOG criteria. Fine-Gray multivariable analysis of continuous and categorical PORTOS (tertiles) were used to calculate subdistribution hazard ratios (sHR), treating death without events as a competing risk, adjusting for age. Results: Median age was 70 years [IQR 65-74]. Fifty percent received 70.2 Gy (n=107), 50% received 79.2 Gy (n=108) and median follow up was 12.8 years. Patient and treatment characteristics were well balanced across treatment arms (all p>0.05) and across PORTOS groups (all p>0.05). Forty-five percent (n=97) of patients experienced grade 2 or higher adverse events after treatment. In patients receiving standard dose 70.2 Gy radiation, PORTOS was not associated with grade 2 or higher adverse events. However, in patients receiving dose-escalated 79.2 Gy radiation, higher PORTOS score was associated with a higher rate of grade 2 or higher adverse events (sHR = 1.12 [95% CI 1.03-1.22], p=0.01). There was a statistically significant interaction between continuous PORTOS scores and treatment arm for grade 2 or higher adverse events (p=0.01). Regarding treatment arm effects by PORTOS tertile, we observed that for patients with higher tertile PORTOS scores, dose-escalated radiation is more likely to cause grade 2 or higher adverse events compared to lower-dose radiation (sHR = 2.15 [1.04 - 4.44], p = 0.04; five-year cumulative incidence adverse events of 61% after 79.2 Gy vs. 36% after 70.2 Gy). In contrast, risk of grade 2 or higher adverse events was similar after treatment with dose-escalated vs. lower-dose radiation for patients with lower (p=0.41) or mid-tertile (p=0.78) PORTOS scores. Conclusions: HigherPORTOS scores were associated with an increased risk of adverse events after administration of dose-escalated radiation compared to standard-dose radiation. PORTOS is the first radiation sensitivity biomarker to be validated for toxicity with data from a phase III randomized trial and could be used to help personalize radiation therapy dose for patients to limit risk of treatment toxicity.
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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 | 0,001 |
| 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 | 0,000 |
| 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 ».