Pen-Yuan Chu

Head and neck squamous cell carcinoma (HNSCC) remains associated with high rates of locoregional recurrence and distant metastasis despite definitive treatment. Metronomic tegafur‐uracil (UFUR), an oral fluoropyrimidine comprising tegafur and uracil, has emerged as a potential maintenance strategy because of its cytotoxic, immunomodulatory, and anti‐angiogenic mechanisms mediated by 5‐fluorouracil (5‐FU) and gamma‐hydroxybutyric acid (GHB). This narrative review summarizes current evidence on UFUR maintenance in both resectable and unresectable HNSCC. Most available evidence is derived from retrospective and observational studies using maintenance durations ranging from approximately 6 months to 2 years. A recent meta‐analysis of six observational studies ( n = 1373) reported pooled hazard ratios of 0.68 for progression‐free survival and 0.54 for overall survival; however, trial sequential analysis supported sufficient evidence only for progression‐free survival, whereas the overall‐survival evidence remained inconclusive. Published cohorts suggest potential benefits in selected high‐risk patients and a generally manageable toxicity profile, but their findings remain susceptible to selection bias, residual confounding, and immortal‐time bias. Prospective randomized trials are needed to confirm clinical benefit and define optimal treatment duration, patient selection, and potential integration with contemporary immunotherapy.

Background: Modified type III cordectomy provides satisfactory oncological and voice outcomes in selected patients with early glottic cancer. However, the factors associated with local recurrence following this procedure remain unclear. This study investigated the predictors of local recurrence following modified type III cordectomy and evaluated subsequent salvage management. Methods: Patients who underwent modified type III cordectomy for glottic cancer at a tertiary referral center between 2006 and 2022 were retrospectively reviewed. Clinicopathological factors, including tumor stage, pathology, morphology, involved subsites, surgical margin status, and history of biopsy or surgery, were analyzed for their association with local recurrence. Salvage treatment outcomes were evaluated. Results: A total of 58 patients were included in this study. The cohort was predominantly male (95%) with a median age of 61 years. The mean follow-up period was 78 months. Local recurrence occurred in 13 patients (22%) at a mean interval of 22 months after surgery. Tumor pathology and morphology were significantly associated with recurrence. Spindle cell carcinoma and endophytic tumors were associated with a substantially higher risk of recurrence than conventional squamous cell carcinoma and exophytic lesions. All recurrent tumors were treated with salvage transoral laser microsurgery (TLM), and six patients received postoperative radiotherapy. Successful salvage with laryngeal preservation was achieved in 11 (85%) patients. Conclusion: Endophytic morphology and spindle cell carcinoma pathology are significant predictors of local recurrence after modified type III cordectomy. Careful postoperative surveillance is particularly important in these patients. Primary treatment with TLM preserves multiple salvage treatment options and enables high rates of laryngeal preservation in patients with recurrent disease.

Multispectral immunofluorescent staining for analyzing the infiltrated immune cells in HNSCC samples.

Characteristics of the HNSCC patients for in situ hybridization and immunohistochemistry analysis (n = 29).

HIF1A-AS2 does not influence the characteristics of HNSCC cells.

Primers for cloning constructs and plasmid information.

Representative images of HIF-1α, HLA-ABC, and HIF1A-AS2 in the stroma, epithelium, and tumor part of a HNSCC sample.

Primary antibodies used in this study.

Characteristics of the HNSCC patients for immunohistochemistry analysis (n = 57).

The impact of ectopic HIF1A-AS2 on the expression of HLA-ABC in different human cancer cell lines.