Beta-Testing of Next-Generation DNA Sequencing for Patients With Advanced Cancers Treated at Community Hospitals
Notice bibliographique
Résumé
Multiple nonrandomized studies have demonstrated that cancer drug treatments selected on the basis of tumor genomic alterations are superior to nontargeted therapies. A pooled analysis of phase II single-agent studies reported that biomarkermatched therapy was an independent predictor of improved outcome. However, the prospective SHIVA randomized trial failed to show an improvement in progressionfree survival with the use of molecularly targeted agents matched to genomic alterations outside of their indications when compared with physician’s choice of nonmatched standard therapy. Many large academic institutions and cooperative research groups have launched nextgeneration sequencing (NGS) testing initiatives to facilitate enrollment in precision medicine clinical trials. There are also ongoing umbrella (histology-specific) and basket (histology-agnostic, aberrationspecific) clinical trials that incorporate the results of NGS testing for treatment assignment to genotype-matched therapies (Lung Master Protocol [Lung-MAP], NCT02154490; A Biomarker-Integrated Targeted Therapy Study-2 [BATTLE-2], NCT01248247; National Cancer Institute [NCI]-Molecular Analysis for Therapy Choice [MATCH], NCT02465060; My Pathway, NCT02091141). NGS profiling is also commercially available, and despite limited evidence of clinical usefulness, it is used increasingly to guide use of off-label therapy for patients with advanced refractory cancers. There are limited data about the clinical impact of targeted NGS profiling for patients treated at community hospitals. Although the majority of patients with cancer in the United States are treated in community settings, most clinical trial participants receive their primary cancer treatment at academic centers. It is estimated that only 3% of adult patients with cancer participate in clinical trials in the United States, and patients in rural areas have lower rates of participation compared with those in metropolitan regions. Even among patients who travel to an academic center for a clinical trial assessment, many ultimately do not participate because of the logistical challenges of receiving treatment far away from their home. For example, Meric-Bernstam et al recently reported their experience with 2,000 consecutive patients with advanced solid tumors who underwent genomic profiling at MD Anderson Cancer Center. They found that 17% of patients did not return to MD Anderson after testing, and 13% chose to be treated closer to home, underscoring the importance of integrating genomic profiling within the context of community-based cancer care. Mantripragada et al describe the results of a genomic profiling program that enrolled 200 patients with advanced solid tumors and hematologic malignancies
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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 | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,001 |
| 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 ».