Identifying the optimal post-surgical timing of molecular residual disease (MRD) detection in colorectal cancer (CRC) using an ultra-sensitive assay: Interim results from the VICTORI study.
Bibliographic record
Abstract
275 Background: While detection of MRD using ctDNA is prognostic for recurrence in CRC, some patients still recur prior to MRD detection. VICTORI is prospectively investigating NeXT Personal, an ultra-sensitive NGS-based MRD assay, to profile patients with resected CRC. Methods: Patients with CRC treated with curative intent (all stages) are tested for MRD using NeXT Personal, a bespoke assay with up to ~1,800 tumor-informed single nucleotide variants (SNVs) identified from whole-genome sequencing. Plasma is collected prior to surgery, every 2 weeks post-surgery up to week 8 (MRD landmark window), and every 3 months for up to 3 years (surveillance). We present preliminary results on 397 samples from the first 62 patients. Results: A total of 62 patients (N=36 rectal [58%], N=26 colon [42%]; N=46 stage I-III [74%], N=16 stage IV [26%]) were included in our analysis. Baseline pre-surgical sensitivity (treatment naive) was 93.5% [N=29/31]. Pre-surgical positivity rate in patients who had received neoadjuvant therapy and had residual cancer at the time of surgery was 67% [N=16/24]. 60 patients were evaluable for clinical outcomes. At a median follow-up of 355 days, 15 patients (25%) had a recurrence. Of these, all patients were ctDNA-positive prior to recurrence (100%, 14/14; 1 pt excluded due to lack of samples prior to recurrence). ctDNA detection preceded clinical relapse by a median of 194 days [range: 5-397]); ctDNA for 78.6% (N=11/14) were first detected in the MRD landmark window. All landmark-positive recurrences occurred within one year of surgery. The 14 recurrent cancers with samples were first detected at a median ctDNA concentration of 28.7 parts per million (PPM) (range 2.4-111,120), with 64.3% (9/14) of those detections in the ultra-low range of <100 PPM. MRD detection at week 4 and week 8 had the greatest reduction in RFS (HR 12.86 [2.74-60.28], p=0.0012 week 4; HR 16.14 [3.52-74.09], p=0.0004 week 8), with weeks 4, 6 and 8 having similar higher prevalence of ctDNA detection (36.0% [18/50], 35.3% [18/51], 38.5% [20/52] respectively). Week 2 detection rate was 17.0% (8/46). cfDNA concentration was highest at week 2 (4.63ng/ml vs. 2.22 at baseline, p=0.00028) and 4 (3.68 vs. 2.22, p=0.0081), returning to baseline levels at week 6 (2.28 vs. 2.22, p=0.67) and 8 (2.48 vs. 2.22, p=0.64). Conclusions: In this interim report after a median ~1 year follow-up, NeXT Personal detected MRD for all patients prior to disease recurrence. Most initial MRD detection was in the ultra-sensitive range <100ppm and detection at 4-8 weeks after surgery was highly prognostic for recurrence.
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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 | 0.003 | 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".