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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".