Abstract 2594: Reovirus replication in ovarian and peritoneal tumors after intravenous administration
Bibliographic record
Abstract
Abstract Background: Reovirus Serotype 3 - Dearing Strain is an oncolytic virus under clinical evaluation for treatment of solid tumor malignancies. We initiated a phase 1/2 study with reovirus in patients with ovarian, primary peritoneal and fallopian tube carcinoma. The objectives of the correlative studies in this trial include the verification of reovirus penetration and replication in ovarian and peritoneal tumors after IV and IP reovirus administration and to evaluate tumor RAS pathway activation status as a marker for reovirus activity in this patient population. Methods: Percutaneous tumor biopsies and ascites fluid were collected at various times during therapy from patients receiving reovirus via both IV and IP routes. Biopsied tissue and cell preparations from ascites were evaluated for reovirus capsid particles via electron microscopy (EM) and viral protein via immunohistochemistry (IHC). The presence of viral RNA and transcribed DNA are evaluated via reverse-transcriptase in situ PCR (RTISPCR). IHC for phosphorylated ERK (pERK) is applied to determine RAS pathway activation status. Results: To date, 5 patients have been accrued and treated on trial. Preliminary evaluation with IHC indicates the presence of viral protein in the biopsied ovarian and peritoneal tissue samples from a subset of these patients after IV administration of reovirus. Completion of EM, RTISPCR, and pERK IHC on biopsied tissues and ascites samples is in progress. Conclusions: Results to date display evidence of viral replication in peritoneal and ovarian cancer cells after IV administration of reovirus. This data represents the first observation of reovirus penetration into the peritoneal space after systemic drug administration. Completion of correlative analyses will further characterize the ability of reovirus to penetrate and replicate within the IP space and ascites after IV and IP administration. Furthermore, the selective viral infection and replication within RAS-pathway-activated tumor cells will be assessed. Results of all correlatives will be presented at the meeting. This work is supported by the NCI, grant U01CA076576 and contract NO1CM62207. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2594.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".