What is the future of treatment de-escalation for HPV-positive oropharyngeal cancer? A review of ongoing clinical trials
Bibliographic record
Abstract
Background: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased in incidence in recent decades. With higher cure rates in younger populations, long-term survivors may live with acute- and long-term toxicity, leading to increased interest in de-escalation treatment strategies for HPV-related OPSCC. Herein, we have examined the current landscape of clinical trials in this context. Methods: A review of active clinical trials related to de-escalation of HPV-associated OPSCC treatment was performed using the clinicaltrials.gov database from inception to January 2022. A search using the key words "oropharyngeal cancer" and "HPV" was completed. Three investigators independently reviewed each trial, with any discrepancies settled by a fourth. Data collected from each study included study phase, study design, primary, and secondary endpoints, and de-escalation treatment strategies. A final 24 articles were selected for full text review. Results: Many trials (n=19, 79%) were non-randomized, and most studies employed a phase II design (n=14, 58%). Only 13% (n=3) were randomized trials, and 8% (n=2) included a phase III component. The most frequent primary endpoint was progression-free survival (PFS) (n=9, 37.5%). With regards to the identified de-escalation strategies, all the studies (n=24) had at least one component assessing changes in RT dose/fractionation and/or a reduction in RT volumes. A smaller percentage of trials assessed surgical interventions (n=9, 37.5%) and/or changes in systemic therapy (n=8, 33.3%). Conclusion: A small number of randomized trials are underway, and a transition to more randomized phase III trials in the future will be important to change clinical practice.
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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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.008 | 0.001 |
| 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".