A prospective study to compare qPCR to IHC and FISH for the detection of anaplastic lymphoma kinase (ALK) fusions in FFPE specimens from NSCLC patients (<i>PCRTALK</i>).
Bibliographic record
Abstract
TPS11136 Background: Lung cancer is the most common cause of cancer-related deaths in North America. A number of pharmaceutical firms currently have therapies that target ALK-driven lung cancers in development, with the first-in-class FDA-approved ALK inhibitor Xalkori (crizotinib, Pfizer) demonstrating excellent anti-tumor responses without significant toxicities. There is now substantial interest in ensuring the accurate identification of those NSCLC patients who harbor ALK fusions. The ALK qPCR assay is a quantitative real-time PCR assay that offers high throughput, 24-48 hour TAT, and easily interpretable results. We are performing a clinical diagnostic trial, PCRTALK (PCR tumor ALK), with the primary objective of this trial being to unequivocally demonstrate the performance of the ALK qPCR assayagainst current ALK testing modalities in screening FFPE lung cancer biopsy specimens. The study is recruiting multiple clinical centers throughout Canada for patient enrollment. Once PCRTALK has been completed, our goal is to accomplish the following: (1) the trial will provide clinically relevant data on which types of lung cancer biopsies (bronchoscopy, FNA, CNB, pleural fluid thoracentesis) provide sufficient tissue for the different modalities of ALK testing and report on the number of cases rejected for ALK testing by IHC and FISH due to insufficient tissue; and (2) provide therapeutic outcome data for cases with discordant ALK diagnostic results. A second arm of the study is to conduct a correlative study analyzing both matched FFPE and blood collected from NSCLC patients using various non-invasive methodologies. Methods: The study will proceed according to the following work flow: (1) ALK IHC (ALK IHC-5A4, Leica Biosystems) conducted by BCCA laboratories; (2) 72 individual ALK IHC 5A4-positives and 72 ALK IHC 5A4-negatives selected according to their respective IHC scores and reflexed to 3 - 5; (3) ALK FISH (Abbott Diagnostics) performed on all 144 specimens; (4) The ALK qPCR assay performed on all 144 specimens; and (5) Sanger and/or NGS to determine true status. Initial PCRTALK clinical trial data will be presented together with conclusions based on the results. Clinical trial information: NCT02010047.
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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 | 0.005 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".