Abstract B48: Feasibility study of molecular profiling (MP) in patients (Pts) with advanced solid cancers using targeted mutation analysis and targeted exome sequencing.
Notice bibliographique
Résumé
Abstract Background: As the development of molecularly targeted agents is increasingly linked to predictive biomarkers, there is a need for novel strategies of cancer genome characterization at the point of care. This study assesses the feasibility of biopsying pts with advanced solid cancers for MP using both targeted exome sequencing and targeted mutation analysis. Metrics of feasibility include delivering results within 21 days and identifying “actionable” mutations in at least 30% of pts. Method: Total accrual of 50–100 pts from 5 centers is planned. Enrolled pts undergo a tumor biopsy, blood sample and retrieval of archived tumor specimens. Each biopsy sample is divided for fixation by snap freezing and formalin. Following DNA extraction, germline and somatic mutations are evaluated using two platforms: 1) Targeted mutation analysis by Sequenom™ MassARRAY using Oncocarta 1.0 (238 mutations from 19 genes) in a CLIA certified laboratory and 2) Targeted exome sequencing by Pacific Biosciences™ PacBio RS initially sequencing exomes from the Oncocarta genes with planned expansion to over 1,000 genes. Identified mutations are confirmed by Sanger sequencing in a CLIA certified laboratory. An expert panel reviews MP results prior to generating reports. Customized MP reports detail mutations identified, platforms used, genes examined, failed mutation analyses and clinical significance of mutations detected according to literature review. Impact of MP on treatment decisions is recorded at regular intervals for up to 2 years. Results: We report results from the first 15 pts enrolled. Median age was 52 years (range 44–71). Most common primary tumor types were breast (5) and colorectal (3). Fourteen pts underwent successful tumor biopsies: 8 required radiological guidance, 4 were performed by clinicians at bedside and 2 had samples obtained during palliative surgery. One pt had tumor deemed inaccessible at time of biopsy. One adverse event of a minor skin infection at biopsy site was observed. Median number of cores per radiological biopsy was 4 (range 3–5). Median tumor cellularity in biopsy samples was 60% (range 0–90). MP was possible in 12 (86%) of the 14 biopsied pts: 2 pts had insufficient DNA from biopsy. In pts completing MP, median time for MP analysis was 14 days (range 8–28) and median time from consent to result was 22 days (range 15–35). Actionable mutations were identified in biopsy samples of 7 (57%) pts; mutated genes include PIK3CA (3), KRAS (3) and EGFR (1). An additional novel non Oncocarta somatic mutation was identified by PacBio RS and validated by Sanger: a PDGFRA mutation of unknown significance in a KRAS mutant colon cancer pt. Agreement between platforms was 100% for Oncocarta mutations. Snap freezing was abandoned in favor of formalin fixation alone as their comparisons revealed concordant results and greater DNA quantity was recovered from the latter. At the first follow up time-point, 3 (20%) pts had treatment decisions impacted by M P. Conclusion: Early results from this study demonstrate that biopsying pts with advanced tumors for MP using targeted exome sequencing and targeted mutation analysis is feasible. MP reports can be generated in a timely manner and “actionable” mutations are identified in 57% of pts. These early results demonstrate that identifying mutations by MP may impact treatment recommendations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B48.
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 ».