Clinical utility of tumor next-generational sequencing (NGS) panel testing to inform treatment decisions for patients with advanced solid tumors.
Notice bibliographique
Résumé
3119 Background: There is limited information about the clinical utility of targeted NGS panel testing to inform decision-making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is an ongoing prospective study that enrolled over 4,500 solid tumor patients for NGS panel testing. We performed a retrospective survey of 21 medical oncologists enrolling OCTANE patients at a single academic institution to evaluate the impact of NGS testing on treatment decisions. Methods: Patients and treating oncologists were identified at the Princess Margaret Cancer Centre between 2016-2021. Tumor-only sequencing was performed using a custom hybridization capture panel of 555 cancer genes (Hi5) or a commercial 161-gene amplicon DNA/RNA panel (Oncomine Comprehensive v3). Oncologists were asked to review testing results for individual patients and complete a survey indicating whether NGS testing impacted treatment decisions. Mutations were defined as actionable based on clinical judgment and compared to classifications provided by OncoKB, an FDA-recognized precision medicine knowledgebase. The primary outcome of this study was rate of treatment change based on mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed effects model. Results: Two cohorts were surveyed, the first between 2017-2019 and the second in 2021. Of the 582 surveys sent, 394 (67.7%) were completed. Each physician completed a median of 19 surveys (range, 9-48). We found that 188 (47.7%) patients had a mutation classified as actionable by the oncologist, of whom 134 (71.3%) had ≥1 OncoKB-defined actionable mutation(s). 62/394 (15.7%) patients were matched to a treatment, of whom 37 were enrolled in a clinical trial, 13 received an approved drug, 4 were prescribed off-label therapy and 8 avoided ineffective treatment. 127/188 (67.5%) patients with actionable mutations did not receive treatment due to lack of available therapy, stability on current regimen, clinical deterioration or patient decision. Rate of treatment change was highest for bowel (15/37, 40.5%), breast (14/52, 27.5%), biliary tract (6/22, 27.3%) and lung (4/17, 23.5%) cancers. Treatment decisions were not associated with patient age, gender, physician clinical experience, physician gender, testing experience, OncoKB mutation level or time from biopsy to sequencing. There was no difference in overall survival between patients with matched vs. no matched treatment ( p = 0.55, median survival not reached). Conclusions: OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors. Patient, test, and physician characteristics were not significantly associated with treatment change.
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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 | 0,004 | 0,013 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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 ».