Princess Margaret Cancer Centre (PMCC) Integrated Molecular Profiling in Advanced Cancers Trial (IMPACT) using genotyping and targeted next-generation sequencing (NGS).
Bibliographic record
Abstract
11002 Background: IMPACT is an institution-wide screening program to identify patients (pts) treated at PMCC with somatic alterations that can be matched to targeted therapies. Methods: Pts with advanced breast, colorectal (CRC), non-small cell lung (NSCLC), ovarian cancers and selected other solid tumors treated at PMCC were eligible. Tumor DNA was isolated from a FFPE archived sample and genotyped using a customized Sequenom panel (23 genes, 280 mutations) in a CLIA-certified laboratory. Verified mutations were reported in pts electronic health records. Selected FFPE samples were further characterized by NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons, ≥500x coverage) for platform validation. Results: From Mar 1/12-Jan 10/13, 485 pts were enrolled with median 1 prior treatment for advanced disease (range 0-6). Of 33 (7%) screen failures, 5% were for insufficient tissue and 2% for clinical deterioration. Median DNA quantity from FFPE = 4250ng (range 15-32550ng). The median time from tissue receipt to reporting was 5 weeks (range 1-23). Mutations were identified by Sequenom in 137/349 (39%) pts, including 24/79 (30%) breast, 40/80 (50%) CRC, 54/88 (61%) NSCLC, 17/78 (22%) ovarian, and 2/24 (8%) other cancers. Mutations detected were: 76 KRAS, 35 PIK3CA, 22 EGFR, 5 NRAS, 5 ERBB2, 5 CTNNB1, 4 BRAF, and 1 AKT1. MiSeq was concordant with Sequenom in 112/113 (99%) pts, with mutations identified in 94/114 (82%). The average number of mutations detected by MiSeq was 1.72/pt (range 0-7) compared with 0.49/pt by Sequenom (range 0-2). After a median follow up of 5.0 months, 31/137 (23%) pts with mutations have been matched to targeted therapies, including 14 pts enrolled in clinical trials (15 trials) matched to their genotype. Of the 10 trial pts with at least one response assessment, 3 PR (1 confirmed) and 2 SD ≥ 24 weeks have been observed. Conclusions: Molecular profiling can be integrated into the routine care of advanced cancer pts. Genotyping and targeted NGS are feasible in a clinical laboratory using stored archival FFPE tumor samples. NGS identifies additional actionable mutations to inform clinical-decision making. Clinical trial information: NCT01505400.
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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 | 0.001 | 0.002 |
| 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".