Abstract 5575: A multiplexed RE-qPCR cell-free DNA assay to assess response and resistance to cancer therapy
Bibliographic record
Abstract
Abstract A qPCR multiplex that utilizes two types of multi-copy retrotransposable elements (RE) in the human genome, as target loci, has been developed and validated. The single-well, qPCR reaction amplifies 80bp, 265bp and an internal-positive-control simultaneously, within 2 hours and with high PCR efficiencies. The selected RE targets comprise over 1500 copies in the genome and allow robust detection of low level cell-free (cf) DNA pg/µL) from <0.5mL plasma. The 80bp target measures total cfDNA. The 265bp target is used to assess cfDNA fragmentation and is presented as the DNA Integrity Index (DII=265/80) which is a ratio of the 265bp quantity divided by 80bp quantity. cfDNA concentration and integrity assessment has shown great promise as a highly sensitive, minimally invasive blood biomarker for multiple cancer types. InnoGenomics has developed an accurate, extremely sensitive liquid biopsy blood test for improved management of cancer patient care. Utilizing standard qPCR platforms for rapid and cost-effective processing, this test can reliably obtain results from small blood volumes (<0.5 mL of plasma), and possesses exceptionally high analytical sensitivity with a detection capability of < 0.1 pg of DNA (LOD). The developed assay demonstrated high predictive capacity in discriminating a group of 39 CRC stage IV patients from 40 healthy controls using cfDNA concentration and DNA Integrity Index (DII-265/80) values. All markers displayed high Area Under the receiver operating characteristic Curve (AUC) values - 80bp target: 0.9891, 265bp target: 0.9859, and DII-265/80: 0.8603. The DNA integrity ratio (DII) showed great potential as a prognostic marker for progression free survival (P=0.019). A retrospective cohort study of 3 patients demonstrated the potential use of this RE-qPCR cfDNA assay for cancer treatment monitoring. NCI SBIR Phase I studies showed high predictive capacity in discriminating metastatic colorectal cancer (CRC) patients from non-cancer healthy controls, with a significant increase in sensitivity and specificity compared to the CEA test, a serum biomarker currently used for CRC patient monitoring. Retrospective patient case studies demonstrated the test's ability to detect resistance to therapy and disease progression more accurately than CEA results and earlier than CT imaging. These results suggest strong potential clinical utility in several applications: (1) treatment monitoring for CRC stage IV patients, (2) recurrence surveillance for CRC stage I-III patients, (3) assessment of residual disease and (4) as a prognostic tool to help predict CRC patient outcomes which can serve as a tool to guide personalized/effective treatment regimens. A detailed prospective study will be undertaken during Phase II research, in collaboration with MD Anderson Cancer Center, to clinically validate the test. ACKNOWLEDGEMENT: This project was funded by an SBIR Phase I contract from NCI. Citation Format: Sudhir K. Sinha, Hiromi Brown, Zhide Fang, Mathilde Couetoux, Karen Gambaro, Gerald Batist. A multiplexed RE-qPCR cell-free DNA assay to assess response and resistance to cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5575.
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 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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".