Abstract B74: Heterogeneity analysis of hypoxia in surgical samples of pancreatic cancer.
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".