Efficacy of Tegafur-Uracil Maintenance Therapy in Non-Metastatic Head and Neck Squamous Cell Carcinoma: A Meta-Analysis With Trial Sequential Analysis
Bibliographic record
Abstract
Background: Patients with non-metastatic head and neck squamous cell carcinoma (HNSCC) face high risks of recurrence after curative-intent treatment. Maintenance therapy aims to prolong disease control during this vulnerable period. Tegafur-uracil (UFT), an oral fluoropyrimidine with a favorable toxicity profile, has demonstrated efficacy in other solid tumors. This study systematically evaluated the survival benefits of UFT as a maintenance therapy in HNSCC. Methods: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with the protocol registered on the Open Science Framework. PubMed, Embase, and CENTRAL were searched through May 2025. Eligible studies included adult patients with non-metastatic HNSCC who received UFT after curative treatment, with comparison to observation or standard care. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were pooled using random-effects models. Trial sequential analysis (TSA) was performed to assess the conclusiveness of the findings. Results: Six observational studies including 1,373 patients were analyzed. UFT maintenance therapy was associated with improved PFS (HR: 0.68; 95% confidence interval (CI): 0.56 - 0.81; P < 0.001) and OS (HR: 0.54; 95% CI: 0.42 - 0.71; P < 0.001) compared with observation. TSA suggested that the available evidence may be sufficient to support a potential benefit for PFS, while for OS, further studies are still needed to strengthen the conclusions. Sensitivity analyses showed broadly consistent results; however, most included studies carried a moderate to serious risk of bias due to their non-randomized designs, which warrants cautious interpretation. Conclusions: UFT maintenance therapy may be associated with improved survival outcomes in patients with non-metastatic HNSCC. Its oral formulation, relatively low toxicity, and potential cost-effectiveness suggest that it could represent a feasible treatment option. However, these observations currently indicate only a possible trend and should not be regarded as definitive conclusions. Further prospective randomized controlled trials are required to validate the efficacy of UFT maintenance therapy and to establish standardized protocols for patient selection and dosing.
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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 | 0.026 | 0.040 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.021 | 0.063 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".