Association of plasma tumor tissue modified viral HPV DNA (TTMV) with tumor burden, treatment type, and outcome: A translational analysis from NRG-HN002.
Bibliographic record
Abstract
6006 Background: NRG-HN002 was a phase II trial that randomized patients with p16-positive oropharynx cancer to 60 Gy IMRT with concurrent cisplatin (IMRT-C) or 60 Gy accelerated IMRT. The protocol specified plasma collection at pretreatment (t0), intratreatment (20-28 Gy, t1), and 2 weeks to 1 month posttreatment (t2); at these timepoints, TTMV was assayed. A prespecified analysis evaluated: association of t0 TTMV to gross tumor volume (GTV) of primary and lymph nodes; t0-t1 decrease in TTMV; and association of t2 TTMV to treatment and outcome. Methods: TTMV was quantified as fragments/mL of plasma. If TTMV-HPV16 was not detected (<5 fragments/mL) or was a low value, the specimen was tested for TTMV-HPV18, -HPV31, -HPV33, and -HPV35. The distribution of t0 TTMV fragments was highly skewed, so these data were log-transformed; their correlation to GTV was measured by Pearson coefficient. Paired and two-sample t-tests were used to compare t0 and t1 log-transformed fragments within and between arms. Proportions of TTMV detection at t2 between arms were compared using Fisher’s exact test. Rates of undetectability and fragment clearance (≥94% reduction from t0) at t2 were estimated. The negative predictive value (NPV) was estimated for 2-year locoregional failure (LRF) and progression-free survival (PFS). Results: Of 306 eligible patients, 164 (53.6%) donated at least one specimen. The median collection time/RT dose was -2.6 days before RT (Q1-Q3, -4.0-0.0), at 24 Gy (22-28), and 25.5 days after RT end (18-31). The t0, t1, and t2 patient participation rates were 53.6%, 45.4%, and 42.5%. Zero TTMV fragments were detected in 10.4% at t0, 19.4% at t1, and 93.1% at t2. At t0, t1, and t2, 83.5%, 79.1%, and 6.2% had detectable TTMV; 78.0%, 73.4%, and 5.4% had TTMV-HPV16. In correlating GTV to t0 TTMV fragments, the Pearson coefficient was 0.30 (95% CI 0.15-0.44). In a linear model, T stage (p=0.01) and N stage (p=0.004) were positively associated with t0 TTMV fragments. On the IMRT-C arm, the t0-to-t1 mean change was -1.06 (p=0.0009), and for IMRT, it was -0.22 (p=0.35) (p=0.03 between arms). The t2 TTMV detectability rate was 3.3% for IMRT-C vs 8.7% for IMRT (p=0.28). The t2 TTMV undetectability rate was 93.8% and the fragment clearance rate was 95.4%. Two-year LRF and PFS were 6.2% and 91.4%. The NPV of t2 undetectability was 95.0% (95% CI 89.4-98.1) for 2-year LRF and 93.3% (95% CI 87.3-97.1) for 2-year PFS, and for fragment clearance was 94.3% and 92.7%. Conclusions: Feasibility of the TTMV-HPV assay in clinical trial specimens was established. About 10% of p16-positive patients had zero TTMV fragments at baseline. Among those with TTMV detectability, 6.6% had types other than TTMV-HPV16. T and N stage were positively associated with TTMV fragments. The IMRT-C arm achieved rapid TTMV undetectability unlike IMRT. The NPV of posttreatment undetectability was 93-95% for 2-year LRF and PFS.
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 | 0.007 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".