Molecular profiling of PDAC and response to chemotherapy: An update from the COMPASS trial
Notice bibliographique
Résumé
Background: Predictive mutational and transcriptional features in advanced PDAC are urgently needed for improved patient stratification and treatment selection. Methods: As part of the COMPASS trial patients (pts) with advanced PDAC are prospectively recruited prior to first-line combination chemotherapy for whole genome sequencing (WGS) and RNA sequencing (RNASeq). Fresh tumor tissue is acquired by percutaneous core needle biopsy. Laser capture microdissection ensures high-resolution genomic analyses with results available within 8 wks. Tumor responses and clinical outcomes in this update were correlated with molecular characteristics. Results: 121 pts underwent a biopsy between December 2015 and April 2018; WGS and RNASeq were successful in 120 (99%) and 119 (98%) respectively, meeting all QC endpoints. 113 genomes have been reported in pts planned to receive chemotherapy; the median time from biopsy to report was 35.5 days. The median age was 63 years (29-81), 53% were male, and 17 (15%) had locally advanced disease. 20 pts (18%) were non evaluable for response. 64 (57%) received modified FFX as first line treatment. 24 (21%) tumors displayed the Moffitt basal-like RNA expression signature which associated with chemotherapy resistance, with tumor shrinkage mainly observed in the classical RNA subtype (p = 0.002). GATA6 expression (log10 scale) clearly separated Moffitt subgroups with classical tumors exhibiting high expression (p < 0.0001). EGFR overexpression was associated with the basal subtype (p = 0.002). The tumor of 1 pt at progression, switched from a basal to a classical phenotype. Of 89 pts with ≥ 6 months follow-up, median overall survival in the classical group was 10 mths vs. 5.1 months in the basal group (HR 0.32 95% CI 0.16–0.68, p = 0.0025). Signatures of homologous recombination deficiency were found in 4 pts (4%) including 2 with germline BRCA2 mutations, 1 of which was newly detected. 2 of 3 pts with a novel duplicator phenotype responded to folfirinox. 30% of pts had potentially actionable genetic alterations. Conclusions: Prospective comprehensive profiling of advanced PDAC indicates that chemotherapy response differs according to genomic/transcriptomic subtypes, providing strong rationale for improved first line trial design. Clinical trial identification: NCT02750657. Legal entity responsible for the study: University Health Network. Funding: Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario. Wallace McCain Centre for Pancreatic Cancer Pancreatic Cancer Canada Foundation Princess Margaret Cancer Foundation Wallace McCain Centre for Pancreatic Cancer Pancreatic Cancer Canada Foundation Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario Princess Margaret Cancer Foundation. Disclosure: All authors have declared no conflicts of interest.
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 | 0,004 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».