Abstract B74: Heterogeneity analysis of hypoxia in surgical samples of pancreatic cancer.
Notice bibliographique
Résumé
Background: Tumoral hypoxia (defined as pO2 < 10mmHg) has demonstrated relevance in promoting aggressive tumor biology and treatment resistance. We initiated the PIMO-PANC trial ([NCT01248637][1]) to characterize hypoxia in the tumors of patients (pts) presenting with resectable pancreatic cancer (PaCa) using the exogenous hypoxia marker pimonidazole. This 2-nitroimidazole is reduced at pO2 < 10mmHg, forming adducts detectable by immunostaining. The objective of this analysis was to characterize the intra- and interpatient heterogeneity of tumoral hypoxia. Methods: Eligible pts were those scheduled for surgical resection of PaCa. Enrolled pts received one dose of pimondazole (0.5 gm/m2) intravenously, the day before surgery. Pathology samples of 16 patients accrued were analyzed. Histology was reviewed and > 5 blocks (where available) representing different tumor areas were selected. Serial sections from each tumor block were immunostained for pimonidazole and hematoxylin and eosin (H&E) for histology. Regions for analysis were selected based on H&E-stained sections. Automated image analysis (on Aperio's histology pattern recognition program Genie) was conducted to delineate epithelial and stromal compartments and to quantify hypoxia defined as pimonidazole-positive tumor regions. A qualitative analysis was performed independently. Variance component analysis (VCA) was used to estimate intra/inter-pt heterogeneity. Results: From Nov 2010 to Sept 2011 n=16 patients received pimonidazole. Five did not complete resection due to having advanced/metastatic disease intraoperatively and one common bile duct cancer was excluded; analysis was therefore conducted on ten primary tumors and included 3 to 7 sections per patient tumor. Eight tumors demonstrated a range of hypoxia between 1% and 26% and minimal positive staining was noted (< 5%) in two pts. Hypoxia was detected in both epithelial (range of 1-39%) and stromal (range of 1-13%) compartments. The proportion of the stromal component ranged 38-78%. No correlation between extent of stromal reaction and hypoxia was found. VCA demonstrated the greatest stability in hypoxia in the epithelial tumor compartment (vs. whole tumor or stroma) with a ratio of intratumoral to total variance of 0.21. There was good correlation between qualitative scoring and automated analysis (r = 0.91; p = 0.0003). Conclusions: Pancreatic carcinomas demonstrate a range of hypoxia with greater inter- than intra-pt variability. Our analysis of 10 pts suggests that selecting 2-3 representative sections per pt is adequate to provide a reliable estimate of hypoxia in the epithelial tumor compartment. Our preliminary data suggest that there may be a subset of patient cancers with minimal hypoxia. Citation Format: Neesha C. Dhani, Stefano Serra, Joerg Schwock, Jing Xu, Melania Pintilie, Steven Gallinger, Richard Hill, David W. Hedley. Heterogeneity analysis of hypoxia in surgical samples of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B74. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01248637&atom=%2Fcanres%2F72%2F14_Supplement%2FB74.atom
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 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) | 0,001 | 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 | 0,000 |
| 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 ».