Search

For unresectable recurrent/metastatic head and neck cancer, pembrolizumab alone or pembrolizumab combined with cisplatin and 5-fluorouracil is the first-line therapy, depending on the PD-L1 combined positive score (CPS). However, this is based on clinical studies of head and neck cancer, and few similar studies have been conducted on oral cancer alone. This study aimed to investigate the current status of pharmacotherapy for unresectable, recurrent, or metastatic oral cancer. Patients with unresectable or recurrent/metastatic oral cancer who received cetuximab, nivolumab, or pembrolizumab as first-line treatment were reviewed. Overall survival (OS), progression-free survival (PFS), PFS 2 (PFS2), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events were obtained from medical records. A total of 155 patients were enrolled from six hospitals. The ORR in the nivolumab, pembrolizumab, and cetuximab groups was 17.2 %, 4.2 %, and 21.6 %, respectively, and the DCR was 37.9 %, 41.7 %, and 58.8 %, respectively. Median OS in nivolumab, pembrolizumab, and cetuximab groups was 10.3, 9.5, and 11.1 months, respectively. No significant differences were observed in survival among the three groups. The small number of cases and the retrospective nature of the study precluded the determination of the more effective first-line treatment among the three drugs. The current statuses of nivolumab, pembrolizumab, and cetuximab in unresectable recurrent metastatic oral cancer was reported. [ABSTRACT FROM AUTHOR]

Osteoradionecrosis of the jaw (ORN) often occurs in patients with head and neck cancer undergoing radiotherapy (RT). It has been recommended to extract the tooth before RT that may become source of infection, but in recent years, some investigators have reported that tooth extraction before RT increase the risk of developing ORN and therefore should be avoided. The purpose of the study is to evaluate the risk factors for ORN including tooth extraction before RT. This was a retrospective study of 366 patients with oral or oropharyngeal cancer who underwent RT of 50 Gy or more at six university hospitals, with follow-up of at least six months post-RT. The relationship between each factor and ORN incidence was analyzed using the Cox proportional hazard model. Periapical lesions, more than 50% loss of alveolar bone, and tooth extraction after RT significantly correlated with ORN. Intensity-modulated RT showed a lower incidence than three-dimensional conformal RT, although not statistically different. Tooth extraction before RT significantly reduced ORN incidence, after adjusting the background factors using propensity score matching. In patients with oral or oropharyngeal cancer who underwent RT, periapical lesions, more than 50% loss of alveolar bone, and tooth extraction after RT significantly increased the risk for ORN. Infected tooth extraction before RT significantly reduced the risk. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective study was to analyze the factors that had a significant effect on securing a successful surgical resection (surgical margin) in oral cancer surgery. One hundred forty-eight consecutive patients who underwent planned radical resection of oral squamous cell carcinoma (SCC) were analyzed. Successful resection was judged if pathological examination of the surgical specimen revealed a clear surgical margin (no SCC within 5 mm, n = 116), while an unsuccessful resection was judged if there was a close and involved surgical margin (SCC within 5 mm, n = 21; and SCC at margin, n = 11). Univariate analyses showed that gender, age, and T-classification had significant influence on successful surgical resection. The results of multivariate logistic regression analysis showed that age (odds ratio [OR] = 1.042, 95% CI = 1.001-1.084), T-classification (OR = 1.656, 95% CI = 1.060-2.587), and the presence of preoperative treatment (OR = 2.868, 95% CI = 1.047-7.85) had significant effects on successful surgical resection. The results of this study suggested that successful resection of oral SCC was difficult in patients with either older age or advanced (T4) tumor. It is also suggested that preoperative therapy had a positive effect on securing a pathologically clear surgical margin. [ABSTRACT FROM AUTHOR]

Objectives: Healthy life expectancy, an extension of the concept of life expectancy, is a summary measure of population health that takes into account the mortality and morbidity of a population. The aim of the present study was to retrospectively analyze the self-reliance survival times of oral squamous cell carcinoma (OSCC) patients.Materials and Methods: One hundred and twelve patients aged 75years or older with primary OSCC were included and examined at Shinshu University Hospital. To investigate healthy life expectancy, OSCC patients older than 75years were divided into 3 groups: 75-79, 80-84, and older than 85years. The Kaplan-Meier method was used to estimate the median times of healthy life expectancy. The Log-rank test was used to test significant differences between actual curves.Results: The median self-reliance survival times of patients aged 75-79, 80-84, and older than 85years were 5.7, 1.6, and 1.4years, respectively. Most patients with early stage cancers underwent curative treatments and showed a health expectancy of more than 5years. In patients with advanced cancers, health expectancy was poor (less than one year), except among patients aged 75-79years who underwent standard treatments.Conclusions: It seems that in patients with advanced cancers, health expectancy was poor (less than 1year), except among patients aged 75-79years who underwent standard treatments. In elderly patients, healthy life expectancy (self-reliance survival time) may be one of the measures of patient prognosis as well as overall survival times. [ABSTRACT FROM AUTHOR]

Objective The criteria for T4 staging of carcinoma of the mandibular gingiva are controversial. Oral cancer staged as T4 implies “invasion to an adjacent organ” such as the skin, extrinsic muscles of the tongue, masticator space, or mandibular bone. In this study, we compared different T classifications and retrospectively investigated the correlation between each classification and the prognosis of patients with carcinoma of the mandibular gingiva. Methods We investigated 81 patients with squamous cell carcinoma of the mandibular gingiva treated at two institutions. Results There was a significant correlation between soft tissue classification and local recurrence ( P < 0.05) and that the correlation with prognosis is borderline significant ( P = 0.05). Conclusions Soft tissue classification, which does not consider bone invasion, was the most useful for diagnosis, selecting the appropriate surgical procedure, and assessing the correlation to prognosis. We recommended using this classification to define T4. Because this classification is not new but is based on International Union Against Cancer classification, it could be easily adopted. However, the current study is a retrospective analysis of a small number of patients. A multi-institutional, prospective study is necessary to determine the appropriate criteria for the TNM staging of carcinoma of the mandibular gingiva. [ABSTRACT FROM AUTHOR]

Abstract: CT10 regulator of kinase (CRK) was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of CRKII as an appropriate molecular target for cancer gene therapy. The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated. Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of CRKII expression also reduced the expression of Dock180, p130Cas, and Rac1, and the actin-associated scaffolding protein cortactin. These results indicate that the overexpression of CRKII is tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. [Copyright &y& Elsevier]

Summary: Recent studies suggest that cancer stem cells may be responsible for tumorigenesis and contribute to some individuals’ resistance to cancer therapy. Some studies demonstrate that side population (SP) cells isolated from diverse cancer cell lines harbor stem cell-like properties; however, there are few reports examining the role of SP cells in human oral cancer. To determine whether human oral cancer cell lines contain a SP cell fraction, we first isolated SP cells by fluorescence activated cell sorting, followed by culturing in serum-free medium (SFM) using the SCC25 tongue cancer cell line, so that SP cells were able to be propagated to maintain the CSC property. Differential expression profile of stem cell markers (ABCG2, Oct-4 and EpCAM) was examined by RT-PCR in either SP cells or non-SP cells. Growth inhibition by 5-FU was determined by the MTT assay. Clonogenic ability was evaluated by colony formation assay. SCC25 cells contained 0.23% SP cells. The fraction of SP cells was available to grow in SFM cultures. SP cells showed higher mRNA expression of stem cell markers (ABCG2, Oct-4 and EpCAM) as compared with non-SP cells. Moreover, SP cells demonstrated more drug resistance to 5-FU, as compared with non-SP cells. The clone formation efficiency of SP cells was significantly higher than non-SP cells at an equal cell number (P <0.01). We isolated cancer stem-like SP cells from an oral cancer cell line. SP cells possessed the characteristics of cancer stem cells, chemoresistance, and high proliferation ability. Further characterization of cancer stem-like SP cells may provide new insights for novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Summary: The p53-inducible p53R2 gene has been isolated and shown to play a crucial role in DNA repair and synthesis after DNA damage. Moreover, the expression and activity of p53R2 has been reported to be associated with the anticancer agent resistance of human cancer cells. Previously, we reported that the presence of p53R2 expression was a predictive factor for regional lymph node metastasis in oral squamous cell carcinoma; however, the mechanism of cancer metastasis by p53R2 expression is still unclear. In the present study, we analyzed the correlation of p53R2 expression with cancer invasion in vitro. Three human oral cancer cell lines (SAS, HSC-3 and Ca9-22) were cultured, and the invasive potential of these cancer cells was evaluated using Matrigel invasion assay. To investigate the effect of p53R2 on cancer invasion, the down-regulation of p53R2 was examined by small interfering RNA (siRNA). Moreover, we examined the intracellular localization of cell adhesion molecules (E-cadherin and β-catenin) in subcellular extractions of cancer cells by immunoblotting. The proteolytic activity of matrix metalloproteinases (MMPs) was assessed by gelatin zymography. Down-regulation of p53R2 significantly enhanced the invasion potential (p <0.01), and enhanced nuclear translocation of β-catenin with loss of total cellular E-cadherin expression in p53 mutant cancer cells, but not in p53 wild-type cancer cells. These changes in the invasion index by p53R2 siRNA transfection were not accompanied by alterations in MMP activity and expression. These results suggested that the expression of p53R2 could be associated with the invasion of cancer cells, and indicated that p53R2 might promote cancer invasion via the E-cadherin/β-catenin pathway without the alteration of MMP activity. [Copyright &y& Elsevier]

• Eighth edition TNM staging improves oral cancer discrimination and prognostication. • Introduction of cDOI in the T category improved discrimination between T categories. • Incorporating cENE into the N category improved separation of N2 and N3 categories. • Important to restage oral SCC with 8th edition of TNM staging using cDOI and cENE. The 8th edition of the International Union Against Cancer Control/American Joint Committee on Cancer Staging System introduced depth of invasion (DOI) and extranodal extension (ENE) into the staging of oral cavity cancer. We evaluated the prognostic ability of this new staging system compared with the 7th edition using clinical DOI (cDOI) and clinical ENE (cENE). We retrospectively reviewed and restaged 2,118 patients with oral squamous cell carcinoma treated between 2001 and 2018 using cDOI and cENE. Overall and disease-specific survival were used as endpoints to compare the prognostic outcomes of the 7th and 8th editions using Harrell's concordance index (C-index). In total, 305 (14.4 %) cases were upstaged in the T category, 85 (4.0 %) cases were upstaged in the N category, and 280 (13.2 %) cases were upstaged in the overall TNM stage. The introduction of the cDOI increased the C-index and hazard ratio (HR) for each T category. The introduction of cENE increased the N3b category of 85 cases, bringing the total to 94 cases, thereby widening the differences between each N category. In the 8th edition, the C-index and HR for overall TNM stage increased, and the discrimination between stage groups improved. The 8th edition of the TNM clinical staging system using cDOI and cENE predominantly identified patients with a high mortality rate, thus improving the ability to discriminate and prognosticate oral cancer. [ABSTRACT FROM AUTHOR]