Background: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). Methods: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan–Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. Results: A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018–1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000–1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002–1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010–1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ² = 4.674, p = 0.031), DFS (χ² = 7.134, p = 0.008), LRFS (χ² = 5.937, p = 0.015), and DMFS (χ² = 4.832, p = 0.028)]. Conclusions: The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC.

Over the past century, the treatment of superficial malignant tumors has largely remained within systemic therapies. The major drawback of systemic administration lies in its limited killing effects specifically to superficial tumors while causing potentially severe damage to other organs. Currently, transdermal drug administration for superficial tumors is still minimal, primarily constrained by the poor permeability and specificity in tumorous/precancerous tissue. In this study, we develop an ADC-like nano-medicine utilizing cationization-induced endocytosis and transcytosis. A γ-glutamyl transpeptidase (GGT)-catalyzed polymer-drug conjugate with MMAE payload is synthesized to treat a variety of cancers with elevated GGT expression. For the first time, this research develops a conjugate treating superficial malignant tumors by transdermal administration and names it gaOCD (GGT enzyme-activated oral coating chemotherapeutic drug). Given the superficial nature and the high GGT expression level, oral squamous cell carcinoma (OSCC) is used as a representative to evaluate the efficacy of gaOCD. The electroneutral gaOCD could be cleaved by the highly expressed GGT on OSCC cell membranes. Furthermore, some cationized gaOCD is exocytosed and internalized by neighboring cancer cells to enable deep penetration. The conjugate demonstrates promising anti-tumor efficacy and biosafety when transdermally applied on 4NQO-induced OSCC and intravenously medicated in OSCC transplanted mouse models.

The management of locally advanced oral squamous cell carcinoma (LAOSCC) continues to pose significant challenges. Although surgery combined with adjuvant radiotherapy or chemoradiotherapy remains the standard treatment modality, the 5-year overall survival rate for LAOSCC patients is only approximately 50%. Neoadjuvant therapy aims to reduce tumor burden, improve surgical resectability, and decrease distant metastasis risk, yet its clinical value in LAOSCC has not been fully established. In recent years, the remarkable survival benefits demonstrated by immune checkpoint inhibitors in recurrent/metastatic head and neck squamous cell carcinoma have spurred exploration of neoadjuvant immunotherapy (NAIT). However, the efficacy and safety profile of NAIT in LAOSCC still require systematic evaluation. This review synthesizes current evidence and challenges regarding neoadjuvant therapeutic strategies for LAOSCC, encompassing chemotherapy, chemoradiotherapy, targeted therapy, and immunotherapy (as monotherapy or combination regimens), while examining their implications for clinical practice.

Background: To evaluate derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC), and the survival benefits from docetaxel, cisplatin, and 5-FU (TPF) induction chemotherapy (IC); Methods: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were built and area under the curve was computed to determine dNLR cutoff points. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis; (3) Results: 224 patients were identified (median age, 55.4 yr; range, 26 to 75 yr; median follow-up, 90 months; range, 3.2 to 93 months); Cutoff points for dNLR was 1.555. Multivariate analysis showed dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018-1.309, P = 0.025, disease-free survival (DFS): HR = 1.123, 95% CI: 0.260-1.000, P = 0.050, local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002-1.283, P = 0.047, distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010-1.300, P = 0.035). Low dNLR combining cTNM stage III disease predicts benefit from TPF IC for the patients [OS (χ² = 4.674, P = 0.031), DFS (χ² = 7.134, P = 0.008), LRFS (χ² = 5.937, P = 0.015) and DMFS (χ² = 4.832, P = 0.028)]; (4) Conclusions: dNLR is an independent negative predictive factor in LAOSCC patients. Patients of cTNM stage III and low dNLR can benefit from TPF IC.