Advanced Oral Squamous Cell Carcinoma Research Articles

The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma.

In advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC. In this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT. Overall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 - 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 - 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 - 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 - 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 - 4.27, p = 0.03) were significant risk predictors. Delays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.

The impact of tumor budding and single-cell invasion on survival in patients with stage III/IV locally advanced oral squamous cell carcinoma- results from a prospective cohort study.

Tumor budding (TB) refers to the presence of small clusters of tumor cells at the invasive front of a malignant tumor. Single tumor cell invasion (SCI) is an extreme variant of TB, in which individual loose tumor cells are present at the invasive front. Both TB and SCI are important histomorphologic risk factors postulated to indicate loss of cellular cohesion. In this study, we investigated the influence of TB and SCI on different survival outcomes in patients with locally advanced oral squamous cell carcinoma (OSCC). We included 129 patients with locally advanced OSCC (pT3-4) from a single-center, prospectively maintained cohort. We examined the association of TB and SCI with the presence of occult lymph node metastasis using a logistic regression model. Survival probabilities were estimated using the Kaplan-Meier method and cumulative incidence functions. The association of TB and SCI on overall survival (OS), oral cancer-specific survival (OCSS), and local recurrence-free survival (LRFS) was investigated using Cox's proportional hazards regression models. TB was detected in 98 (76%) of the tumors, while SCI was observed in 66 (51%) patients. There was a significant association between TB and the occurrence of occult lymph node metastasis (OR=3.33, CI: 1.21-10.0). On multivariate analysis, TB had no detectable impact on survival outcomes. However, SCI showed a higher risk for local recurrence (Hazards ratio (HR): 3.33, CI: 1.19 - 9.27). This study demonstrates that TB and SCI in locally advanced OSCC function as an independent risk factor for occult lymph node metastases, as well as local recurrences. Both histomorphologic risk factors could serve as an additional parameter for stratifying therapy and escalating multimodal treatment approaches.

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Antiapoptotic PON2 expression and its clinical implications in locally advanced oral squamous cell carcinoma.

Locally advanced oral squamous cell carcinoma poses a significant challenge in oncology due to its rising incidence and mortality rates. Despite therapeutic progress, understanding molecular intricacies is essential. This study explored the role of PON2, a multifunctional enzyme implicated in antiapoptotic mechanisms. Aberrant PON2 expression in oral cancers raises questions regarding its involvement in evading programmed cell death and treatment resistance. Patients with locally advanced disease were enrolled, and molecular analyses were undertaken on the collected tumor and normal tissues. Utilizing computational datasets, this study used in silico gene expression analysis, differential gene expression analysis in our patient cohort, survival analysis, and gene set enrichment analysis to unravel role of PON2 in disease prognosis. The results showed elevated PON2 levels in advanced tumor stages, correlating with factors such as tobacco exposure, higher tumor grade, and nodal metastasis. Survival analysis revealed prognostic relevance of PON2, with lower expression linked to extended survival rates. Gene set enrichment analysis identified pathways aiding in cancer metastasis influenced by PON2. This study underscores the significance of PON2 expression as a prognostic marker for oral malignancies, with increased expression associated with advanced disease stages. Understanding the molecular profile of the PON2 gene suggests its potential as a valuable biomarker for the management of cancer.

Phase Ⅱ clinical trial of PD-1 inhibitor combined with chemotherapy for locally advanced resectable oral squamous cell carcinoma

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

Abstract 5091: Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study

Abstract Background: This study aims to investigate the effectiveness of neoadjuvant chemoimmunotherapy (NACI) regimens in treating advanced oral squamous cell carcinoma (OSCC). Methods: We analyzed clinicopathologic features of advanced OSCC patients who received PD-1 inhibitors in combination with carboplatin and paclitaxel before surgical tumor resection between 2020 and 2022. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and pathologic response were used to evaluate the efficacy of the NACI treatment. Adverse events apparently related to NACI treatment were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier survival curves and compared using the log rank test. Additionally, we calculated the area under curve (AUC) to compare the predictive value of PD-L1 expression with baseline serum lipid biomarkers for patient response. Results: Our analysis involved 104 advanced OSCC patients who received NACI. Notably, the top three grade 1-2 treatment-related adverse events (TRAEs) were Alopecia (104; 100%), Anemia (81; 77.9%) and Pruritus (62; 59.6%). Only one patient developed grade 3-4 TRAEs due to increased aminotransferases. The pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. Importantly, patients achieving MPR exhibited higher CPS. The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol (TC) level. Our findings from DFS and OS suggested that patients who underwent NACI before surgery experienced improved survival compared to those who accepted the surgery alone. Conclusions: The data from this study proved evidence that NACI treatment is safe and encouragingly efficacious in treating advanced OSCC patients. Citation Format: Jinsong Li, Bowen Li, Shule Xie, Haotian Cao, Zhaoyu Lin, Qunxing Li, Song Fan. Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5091.

Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma

Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo. This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.

Involvement of ferroptosis‐defensive xCT/GPX4 axis in radioresistance and its impacts on prognosis in oral squamous cell carcinoma

AbstractAimRadiotherapy, the mainstay treatment for patients with advanced oral squamous cell carcinoma (OSCC), has low clinical efficacy, resulting in poor prognosis. Radiation induces ferroptosis, a form of cell death driven by iron‐dependent lipid peroxidation. Since the xCT/glutathione peroxidase 4 (GPX4) axis is predominantly involved in the ferroptosis defense system, targeting this axis may potentiate cancer cell vulnerability to ferroptosis.MethodsWe examined the expression of xCT and GPX4 in the tumor cells of biopsy specimens using immunohistochemistry and evaluated the radiation‐mediated antitumor effects of the ferroptosis inducers, erastin and RSL3, that act by inhibiting xCT and GPX4, respectively.ResultsUnivariate analysis revealed that high immunohistochemical expression of xCT was correlated with shorter survival, and high GPX4 expression was an independent poor prognostic factor, indicating that the xCT/GPX4 axis influences the clinical outcome of OSCC. Analyses using two types of OSCC cell lines revealed that the clonogenic survival of irradiated cells was increased by the ferroptosis inhibitor ferrostatin‐1 and decreased by erastin and RSL3. The enhanced antitumor effects of erastin and RSL3 were accompanied by increased lipid peroxidation, which was suppressed by the iron chelator deferoxamine. Erastin and RSL3 enhance the effects of radiation on OSCC cells in a mouse xenograft model; these effects were associated with increased expression of the lipid peroxidation marker 4‐hydroxynonenal in tumor cells.ConclusionsxCT/GPX4 axis is involved in the tumor resistance against radiation through the inhibition of ferroptosis in OSCC. Furthermore, radiotherapy combined with ferroptosis induction by targeting the xCT/GPX4 axis may improve patient prognosis in advanced OSCC.

Expression of PTGS2 along with genes regulating VEGF signalling pathway and association with high-risk factors in locally advanced oral squamous cell carcinoma.

PTGS2 encodes cyclooxygenase-2 (COX-2), which catalyses the committed step in prostaglandin synthesis. Various invivo and invitro data suggest that COX-2 mediates the VEGF signalling pathway. In silico analysis performed in TCGA, PanCancer Atlas for head and neck cancers, demonstrated significant expression and co-expression of PTGS2 and genes that regulate VEGF signalling. This study was designed to elucidate the expression pattern of PTGS2 and genes regulating VEGF signalling in patients with locally advanced oral squamous cell carcinoma (OSCC). Tumour and normal tissue samples were collected from patients with locally advanced OSCC. RNA was isolated from tissue samples, followed by cDNA synthesis. The cDNA was used for gene expression analysis (RT-PCR) using target-specific primers. The results obtained were compared with the in silico gene expression of the target genes in the TCGA datasets. Co-expression analysis was performed to establish an association between PTGS2 and VEGF signalling genes. Tumour and normal tissue samples were collected from 24 OSCC patients. Significant upregulation of PTGS2 expression was observed. Furthermore, VEGFA, KDR, CXCR1 and CXCR2 were significantly upregulated in tumour samples compared with paired normal samples, except for VEGFB, whose expression was not statistically significant. A similar expression pattern was observed in silico, except for CXCR2 which was highly expressed in the normal samples. Co-expression analysis showed a significant positive correlation between PTGS2 and VEGF signalling genes, except for VEGFB which showed a negative correlation. PTGS2 and VEGF signalling genes are upregulated in OSCC, which has a profound impact on clinical outcomes.

Prospective observational study of surgery alone for locally advanced oral squamous cell carcinoma: a real-world study

IntroductionA prospective observational study was modified to assess the efficacy of surgery alone for the treatment of locally advanced oral squamous cell carcinoma. (LA-OSCC)Materials and methodsThis prospective, single-institution, single-arm study involved 174 patients who underwent major surgery for LA-OSCC. Participating patients did not receive postoperative radiation. After initial curative treatment, patients were routinely monitored via clinical examination and imaging. The follow-up period was 3–70 months. Tumour recurrence and death were considered as the Clinical End Point in Research.ResultsThe 5-year overall survival (OS), disease-free survival (DFS), and locoregional control rates for 174 patients were 66.7% (95% confidence interval [CI], 59.8 to 73.6), 66.1% (95% CI, 59.2 to 73.0), and 82.4% (95% CI, 76.5 to 88.3), respectively.ConclusionA study of patients with LA-OSCC treated with surgery alone may have the optimal therapeutic impact for LA-OSCC, as evidenced by solid data for our next RCT trial. This conclusion still needs to be validated in higher-level RCTs.

Comparison between upfront surgery vs salvage surgery following definitive chemoradiation in the treatment of potentially curable locally advanced oral cavity cancer: a retrospective study

Background: We conducted a study to compare the outcomes of upfront surgery and salvage surgery following definitive chemoradiation in locally advanced oral cavity squamous cell carcinoma. This study aims to compare the short-term outcomes (postoperative morbidity, recurrence) &amp; long-term outcomes (overall survival, disease-free survival) between upfront surgery and salvage surgery following definitive chemoradiation in locally advanced oral cavity squamous cell carcinoma. Methods: A total of sixty patients with locally advanced oral cavity squamous cell carcinoma (T4a, N1-N2b) were retrospectively analyzed between January 2021 and August 2023. Thirty patients underwent upfront surgery followed by adjuvant radiation (group 1) while another thirty patients underwent salvage surgery following definitive chemoradiation (group 2) (radiation dose- 66-70 Gy) Results: Morbidity was found to be significantly higher in the salvage surgery group (group 2) when compared to the upfront surgery group (group 1) with a p value of 0.003. There was no statistical significance between the two groups in terms of disease-free survival and overall survival. Conclusions: This retrospective study shows that there are no significant differences in overall survival and disease-free survival amongst patients of locally advanced oral cavity squamous cell carcinoma treated with upfront surgery and salvage surgery following definitive chemoradiation. Morbidity is significantly higher in the salvage surgery group.

In-house virtual surgical planning and guided mandibular reconstruction is less precise, but more economical and time-efficient than commercial procedures.

To compare an in-house and a commercially available surgical planning solution for mandibular reconstruction in terms of postoperative reconstruction accuracy and economic benefit. Twenty-nine consecutive patients with advanced oral squamous cell carcinoma (OSCC) requiring segmental mandibular reconstruction were enrolled. Fifteen patients underwent in-house surgical planning and 14 patients underwent a commercially available planning solution. A morphometric comparison of preoperative and postoperative computed tomography (CT) data sets and a cost-benefit comparison were performed. Volumes of planned and reconstructed bone segments differed significantly for both in-house planning (p = 0.0431) and commercial planning (p < 0.0001). Significant differences in osteotomy angles were demonstrated for in-house planning (p = 0.0391). Commercial planning was superior to in-house planning for total mandibular deviation (p = 0.0217), intersegmental space volumes (p = 0.0035), and lengths (p = 0.0007). No significant difference was found between the two planning solutions in terms of intersegmental ossification and the incidence of wound healing disorders. In-house planning took less time than commercial planning (p < 0.0001). Component manufacturing costs (p < 0.0001) and total cumulative costs (p < 0.0001) were significantly lower for in-house planning. In-house surgical planning is less accurate but has a cost advantage and could be performed in less time.

The impact of comorbidity on the diagnosis delay, treatment options and prognosis for advanced oral cancer: A retrospective result of the POROMS database

This study aimed to reveal the underlying mechanisms linking advanced oral squamous cell carcinoma (OSCC) with its comorbidities. Data extracted from the POROMS database included 448 advanced OSCC patients in stage III or IV (AJCC 8th) with primary tumors between August 2015 and August 2021. Time to diagnosis delay increased from 4.5, 5.3–6.5 months when the Adult Comorbidity Evaluation-27 (ACE-27) worsened from none, mild (RR: 1.155, 1.043–1.279; P = 0.006) to moderate-severe (RR: 1.431, 1.251–1.636; P < 0.001). With the number of comorbidities increased from 0, 1–2 (RR: 1.188, 1.078–1.310; P = 0.001) to 3 (RR: 1.563, 1.296–1.885; P < 0.001), the time to diagnosis delay increased from 4.5, 5.4–7.1 months. As the level and number of comorbidities increased, the likelihood of treatment completion gradually declined, especially in those older than 65 years (P = 0.003). The presence of comorbidity was an independent prognostic factor for disease-free survival (HR: 1.431, 1.022–2.005; P = 0.037). Comorbidities may lead to poorer prognosis by directly causing delays in diagnosis, limiting treatment options, and increasing the risk of death in advanced OSCC patients.

Up-regulation of TNF-alpha/NFkB/SIRT1 axis drives aggressiveness and cancer stem cells accumulation in chemoresistant oral squamous cell carcinoma.

Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.

OVEREXPRESSION OF CYCLIN D1 IN ORAL CANCER INCREASES TPF CHEMOTHERAPEUTIC DRUGS VIA ACTIVATING THE CASPASE-3 PATHWAY

Previous studies have indicated that induction chemotherapy can limit the possibility of early lesion eradication and lessen the severity of globally advanced tumors. This study aimed to ascertain if cyclin D1 expression in OSCC patients who were qualified for TPF induction chemotherapy might be regarded as a valid prognostic indicator for long-term outcomes. This study aimed to determine whether or not there was a connection between OSCC cell intervention and the production of cyclin D1 and chemosensitivity to TPF medicines through the apoptotic mechanism. The current work used immunohistochemistry to determine the expression of cyclin D1 in various tissues. To ascertain the survival rate of 232 people diagnosed with locally advanced oral squamous cell carcinoma (OSCC), the study utilized the log-rank test and Kaplan-Meier analysis. The participants in this historical clinical trial were observed for a mean duration of five years. Cytotoxicity assays were employed to assess the therapeutic effectiveness of TPF chemotherapy drugs. The activity of caspase-3 and PARP was evaluated in the HB96, CAL27, and HN30 cell lines following cyclin D1 inhibition, respectively. Long-term clinical outcomes were significantly better for patients with OSCC whose cancer cells expressed low amounts of cyclin D1 than those whose cells expressed high protein levels. Time to initial illness occurrence, time to initial local recurrence, time to mortality, and overall survival were among the metrics evaluated. The groups with low and high expression levels of cyclin D1 showed significantly different survival rates for disease-free survival, overall survival (OS), DMFS, local recurrence-free survival, and local recurrence-free survival (p0.001, 0.003, 0.004, and 0.001, respectively). Patients with cN2 oral squamous cell carcinoma (OSCC) with higher cyclin D1 expression had better distant metastasis-free survival (OS, P=0.024; DMFS, P=0.024) and overall survival (OS, P=0.024; DMFS, P=0.024) with TPF induction chemotherapy. However, patients with cN2 OSCC and low cyclin D1 expression did not show this survival advantage (P=0.024). Research has shown that oral squamous cell carcinoma (OSCC) is more sensitive to TPF-based chemotherapeutic drugs using caspase-3-mediated apoptosis that occurs when cyclin D1 expression rises. Based on these results, TPF induction chemotherapy may provide longer-term benefits than traditional treatment approaches for patients with cN2 OSCC and high cyclin D1 expression. Through a caspase-3-dependent mechanism, oral squamous cell carcinoma (OSCC) cell lines become more susceptible to TPF chemotherapeutic drugs when cyclin D1 is overexpressed.

CD103+CD8+T cells combined with neutrophil-to-lymphocyte ratio predict response to neoadjuvant chemoimmunotherapy in advanced oral squamous cell carcinoma

Objective: To investigate the relationship between the expression of CD103+CD8+T cells in locally advanced oral squamous cell carcinoma (LA-OSCC), and the response to neoadjuvant chemoimmunotherapy (NACI). Methods: Thirty LA-OSCC patients from the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who underwent NACI from June 2020 to December 2022 were analyzed, including 16 responders and 14 non-responders. Using multiple immunofluorescence technique to stain sections of patients to verify the correlation between the expression of CD103+CD8+T cells and the efficacy of NACI. CD103+CD8+T cell density was counted using Inform and HALO software. The Spearman correlation coefficient in rank correlation is used to describe the correlation between CD103+CD8+T cell and neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII) It's effectiveness as a predictive marker to NACI was analyzed by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Two-tailed t-test or Mann-Whitney U-test was used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. SPSS 22.0 and GraphPad prism 9.0 software were used for statistical analysis and plotting of relevant statistical graphs such as histograms. P<0.05 was considered a statistically significant difference. Results: The density of CD103+CD8+T cells has expanded in advanced OSCC patients who are responsive to NACI. The CD103+CD8+T cell densities in the responsive and nonresponsive groups were 118.30(41.92, 197.80) pcs/mm2 and 21.63(4.91, 71.92) pcs/mm2 respectively, with statistically significant differences(U=52.00, P=0.012). CD103+CD8+T cell abundance was negatively correlated with NLR, dNLR, PLR, and SII (P<0.05). ROC curve analysis showed that the AUC for predicting efficacy of NLR, dNLR, PLR, and SII were 0.781 (P=0.009, 95%CI: 0.5715-0.9910), 0.671 (P=0.105, 95%CI: 0.467-0.881), 0.679 (P=0.020 95%CI: 0.549-0.951), 0.750 (P=0.096, 95%CI: 0.461-0.896), respectively. The AUC for CD103+CD8+T cells alone was 0.861 (P=0.013, 95%CI: 0.585-0.950), and the AUC of combining CD103+CD8+T cells with NLR was 0.896 (P=0.025, 95%CI: 0.454-0.938). Conclusions: The density of CD103+CD8+T cells is expanded in advanced OSCC patients who are responsive to NACI. CD103+CD8+T cells positively predict favorable responses as a strong indicator to NACI in advanced OSCC patients. Co-interpretation of CD103+CD8+T cells and NLR value enhances the predictive accuracy of NACI in advanced OSCC patients.

Efficacy of docetaxel, cisplatin, and 5-fluorouracil as an induction chemotherapy in oral squamous cell carcinoma in a tertiary hospital in Saudi Arabia

ObjectiveTo assess the efficacy and safety of the induction chemotherapy's combination of docetaxel, cisplatin, and 5-fluorouracil (TPF) in Oral Squamous Cell Carcinoma (OSCC) patients and its positive outcomes on tumor size and surgical resection. MethodA retrospective chart review of patient's medical records was conducted from 2018 to 2023. All patients diagnosed with OSCC and who received induction chemotherapy combination of TPF were included in the study. Patients with other conditions that affect chemotherapy tolerability, other primary malignancy, or incomplete medical records were excluded. Descriptive analysis was undertaken to summarize the data pertaining to tumors before and after administration of the TPF chemotherapy. ResultFive patients met the inclusion criteria. All five patients experienced a reduction in tumor size after receiving the TPF induction chemotherapy. Three patients showed a downstaging to [stage 0] after surgical resection. Specifically, one patient demonstrated a reduction in overall stage from [IVb] to [IVa] after receiving TPF induction chemotherapy, and two patients demonstrated a noteworthy improvement in N staging, reducing from [N2c] to [N2b]. In contrast, the fourth patient slightly improved after the induction chemotherapy and surgical resection procedures. However, the stage of the fifth patient remained unchanged before and after the treatment approach. ConclusionThe study shows that implementing TPF induction chemotherapy to surgical resection improves clinical outcomes in a subset of patients with advanced OSCC without any harmful consequences.

Cold Atmospheric Plasma Jet Irradiation Decreases the Survival and the Expression of Oncogenic miRNAs of Oral Carcinoma Cells

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice

BackgroundNeo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. MethodsThis was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. ResultsA total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). ConclusionNACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: a real-world retrospective study.

The treatment of locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC) is surgery and radiotherapy or chemoradiotherapy but with unsatisfactory survival rate. Neoadjuvant programmed death-1 (PD-1) therapy are being used in several clinical trials. Therefore, in this retrospective study we aimed to determine the feasibility of neoadjuvant tislelizumab plus chemotherapy followed by surgery for LAOOPSCC. The clinical data of 33 patients with LAOOPSCC who received neoadjuvant PD-1 inhibitors and chemotherapy between April 2021 and October 2022 were retrospectively analyzed. Patients with stage III-IV LAOOPSCC received tislelizumab, albumin-bound paclitaxel, and cisplatin every 3 weeks (Q3W) for two cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. A median follow-up period was 20 months. The objective response rate (ORR) was 66.7%, with the major pathological response (MPR) rate at 54.5%, and the pathological complete response (pCR) rate was 33.3%. Sixteen patients underwent limited surgeries, and 15 patients were remitted from undergoing mandibulectomy and 9 patients were remitted from undergoing near total glossectomy or total glossectomy. A significant difference in the overall survival (OS) and disease-free survival (DFS) was observed in patients who achieved major pathological response (MPR) than who did not. The most common adverse events in neoadjuvant therapy were alopecia, decreased appetite or anorexia, leukopenia, and fatigue. Neoadjuvant PD-1 inhibitors combined with chemotherapy are feasible and safe, with a high pathological response and possible organ preservation in oral or oropharyngeal squamous cell carcinoma. However, further studies with a larger cohort of patients and longer follow-up period is required to strengthen our findings and evaluate the survival benefits of the treatment.