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 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 | 0,001 | 0,001 |
| 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 | 0,000 | 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) | 0,001 | 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 ».