Abstract PO-045: Utility of circulating tumor tissue modified viral (TTMV)-HPV DNA to resolve clinically indeterminate findings in patients following definitive treatment for HPV-driven oropharyngeal cancer
Bibliographic record
Abstract
Abstract Introduction: Indeterminate results of clinical or imaging examinations are common across the care continuum, and decisions made can lead to overtreatment and psychological and financial harms for the patient. Additionally, due to the emergence of highly sensitive circulating tumor DNA assays, an indeterminate clinical status can also arise when molecular detection precedes clinical or radiological evidence of recurrence for a period of time. We recently reported >99% negative and >95% positive predictive value of circulating tumor tissue modified viral (TTMV)-HPV DNA for recurrence detection in a large, real-world cohort of patients with HPV-driven oropharyngeal cancer. Here we quantified the frequency of clinically indeterminate findings (CIF) in this patient cohort and assessed the prognostic value of TTMV-HPV DNA to resolve these CIF. Methods: This IRB-approved, retrospective observational cohort study included 543 patients across eight U.S. centers who were ≥3 months post-treatment for HPV-driven OPSCC. Patients had one or more TTMV-HPV DNA results (NavDx®, Naveris Laboratories) obtained during surveillance between February 2020 and January 2022 (n=1372 total tests), with mean follow-up time of 24 months (range: 4.9-185). Test results were correlated with physician-reported exam and imaging findings to assess disease status in follow-up. Results: Of the 543 patients, 245 patients (45.1%) had 797 CIF by imaging and/or clinical examination during their surveillance period. Of these 245 patients, 71 patients had 93 CIF that had a coincident TTMV-HPV DNA result (either negative or positive) available within 3 months of the CIF. The TTMV-HPV DNA result was able to correctly predict the presence or absence of recurrence across 91 of the 93 (97.8%) individual CIF. Both incorrectly predicted CIF were in the setting of an undetectable TTMV-HPV DNA result. One patient had their recurrence detected by chest CT 63 days later and had a positive TTMV-HPV DNA test the same day. The second patient had a positive TTMV-HPV DNA test during their subsequent immunotherapy. In contrast to the 45% of patients with CIF as a result of imaging and/or clinical examination, only 18 patients (3.3%) had CIF due to a positive TTMV-HPV DNA result that was not accompanied by clinical evidence of recurrence within 3 months. Importantly, of these 18 patients, 15 patients had confirmed recurrence at a subsequent time point (median time to recurrence: 232 days), leaving only 3 of 543 (0.6%) patients with an ongoing indeterminate recurrence status. Conclusion: Clinical indeterminate findings as a result of imaging and/or clinical examination are common, whereas clinically indeterminate status due to circulating TTMV-HPV DNA testing is rare. Our findings strongly support the clinical utility and value of monitoring circulating TTMV-HPV DNA during post-treatment surveillance to inform interpretation of indeterminate clinical findings. Citation Format: Scott Roof, Glenn Hanna, James Jabalee, Eleni Rettig, Rocco Ferrandino, Sida Chen, Marshall R. Posner, Krzysztof J. Misiukiewicz, Eric M. Genden, Raymond L. Chai, John Sims, Elaine Thrash, Scott Stern, Noah S. Kalman, Sreenija Yarlagadda, Adam Raben, Lydia Clements, Abie Mendelsohn, John M. Kaczmar, Yadav Pandey, Mihir Bhayani, Piyush Gupta, Charlotte Kuperwasser, Catherine Del Vecchio Fitz, Barry M. Berger. Utility of circulating tumor tissue modified viral (TTMV)-HPV DNA to resolve clinically indeterminate findings in patients following definitive treatment for HPV-driven oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-045.
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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 | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".