Oral Cancer Survival Research Articles

Sarcopenia and Systemic Inflammation Synergistically Impact Survival in Oral Cavity Cancer.

Sarcopenia and systemic inflammation can affect survival of advanced-stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated. Retrospective review at a tertiary cancer center. Patients with stage III-IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex-specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C-reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models. A total of 174 patients were included in the study. The cut-off values for sarcopenia were set at SMI <52.4 cm2 /m2 (men) and < 36.2 cm2 /m2 (women) corresponding to the lowest sex-specific tertile. An mGPS 1-2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06-3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1-2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17-3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7-16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1-2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01-46.99; P < .001). Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced-stage OSCC patients. 4 Laryngoscope, 131:E1530-E1538, 2021.

The Role of Hospital Safety-Net Burden in the Treatment of Oral Cavity Cancers: Evaluating its Impact on Survival Outcomes

To investigate the relationships between hospital safety-net burden, clinicopathologic characteristics, and overall survival in oral cavity cancer (OCC) patients From the National Cancer Database, we identified 48,176 OCC patients diagnosed with oral cavity cancer between the years 2004 to 2015. Facilities treating 0-30th, >30-75th, and >75-100th percentiles of uninsured/Medicaid patients were defined as no safety-net burden hospitals (NBH), low safety-net burden hospitals (LBH), and high safety-net burden hospitals (HBH), respectively. Social demographic and clinicopathologic variables assessed were age, distance to treatment facility, time to first treatment, gender, race, Hispanic origin, insurance status, median household income, year of diagnosis, Charlson-Deyo score, location of primary site, AJCC stage, facility type and volume, and treatment modality. Safety-net burden of treatment facilities was used as the primary independent predictor in this analysis, and the primary outcome of interest was overall survival. Crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed using Cox regression modelling, where clustering of patients within facilities was accounted for using robust sandwich covariance matrix estimates. There were 380 NBH (29.9%), 573 LBH (45.2%), and 316 HBH (24.9%) identified among the 1,269 treatment facilities evaluated for their respective safety-net burden and survival outcomes in oral cavity cancer patients. The median percentage of uninsured/Medicaid patients treated was 23.5% (range 18.6-100%) at HBH, 11.6% (range 1.2-18.5%) at LBH, and 0% (range 0-0%) at NBH. Median follow-up in all surviving patients was 49.0 months. A total of 22,466 deaths were reported, and the overall 5-year survival rate was 53.5% (median survival = 69.7 months). Median survival for NBH, LBH and HBH was 68.6, 74.8 and 55.0 months, respectively (p<0.0001). Compared to NBH and LBH, HBH facilities treated more patients of advanced cancers, lower socioeconomic status, and racial and ethnic minorities. After adjusting for the aforementioned social demographic and clinicopathologic variables, no significant survival difference was noted in LBH (aHR 0.97 95% CI 0.91-1.04, p = 0.405) or HBH (aHR 1.05 95% CI 0.98-1.13, p = 0.175) when compared to patients treated at NBH facilities. High safety-net burden hospitals treated disproportionately more patients of late-staged cancers, lower socioeconomic status, and racial and ethnic minorities. Thus, while lower actuarial survival rates were observed in HBH compared to LBH and NBH, these findings may be driven by socioeconomic and clinicopathologic characteristics, rather than hospital safety-net burden. Therefore, high burden safety-net hospitals may play a more critical role in caring for vulnerable populations with oral cavity cancer than it is attributed for at first glance.

Effect of Fluorescence Visualization–Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma

High local recurrence rates with aggressive disease remain the main concern in oral cancer survival. Use of a translational device using fluorescence visualization (FV) approved by the US Food and Drug Administration and Health Canada, has shown a marked reduction in the 3-year local recurrence rate of high-grade oral lesions in a single-center observational study. To determine whether FV- guided surgery can improve local control rates in the treatment of in situ or T1 to T2 category oral squamous cell carcinoma (OSCC). A multicenter randomized clinical trial was conducted in a surgical setting. A total of 457 patients were enrolled between January 18, 2010, and April 30, 2015. Data analysis of the intention-to-treat population was performed from April 3, 2019, to March 20, 2020. Patients with histologically confirmed high-grade dysplasia/carcinoma in situ or T1 to T2 category OSCC were randomized to receive traditional peroral surgery or FV-guided surgery. Fluorescence visualization during surgery. The primary outcome was local recurrence of OSCC. Secondary outcomes were failure of the first-pass margin, defined as a histologically confirmed positive margin for severe dysplasia or greater histologic change of the main specimen (ie, not the margins taken from the resection bed), regional or distant metastasis, and death due to disease. Of the 457 patients enrolled in the study, 443 patients (264 [59.6%] men; mean [SD] age, 61.5 [13.3] years) completed the randomized treatment: 227 FV-guided and 216 non-FV guided surgery. The median follow-up was 52 (range, 0.29-90.8) months. In total, 45 patients (10.2%) experienced local recurrence. The 3-year local recurrence rate was 9.4% in the FV-guided group and 7.2% in the non-FV group (difference, 2.2%; 95% CI, -3.2% to 7.4%). Other similarities between the FV vs non-FV groups included failure of first-pass margin (68/227 [30.0%]) vs 65/216 [30.1%]), regional failure (39/227 [17.2%] vs 37/216 [17.1%]), disease-specific survival (23/227 [10.1%] vs 19/26 [8.8%]), and overall survival (41/227 [18.1%] vs 38/216 [17.6%]) were also similar between groups. No adverse events were judged to be related to the intervention. In this randomized clinical trial, FV-guided surgery did not improve local control rates in the treatment of patients with in situ or T1 to T2 category oral cancer. Under a controlled environment, FV-guided surgery did not have an evident effect in reduction of local recurrence for localized OSCC. This result suggests that attention be directed to strategies other than improving definitions of nonapparent disease at clinical margins to identify the sources of local recurrence. ClinicalTrial.gov Identifier: NCT01039298.

The Impact of Hospital Safety-Net Burden on Survival Outcomes in Oral Cavity Cancer Patients

Safety-net hospitals, treating a large proportion of uninsured, Medicaid, or other vulnerable populations, have previously been regarded with achieving inferior patient outcomes. Recent studies, however, have shown non-significant survival differences for rectal, hepatocellular, pancreatic, and esophageal cancer patients being treated at high burden safety-net facilities. In this study, we seek to specifically evaluate patients with oral cavity cancers treated at higher safety-net burden hospitals, because survival outcomes for this particular cancer population have been shown to be stratified by various socioeconomic factors. To date, a robust analysis of survival outcomes and hospital safety-net burden for oral cavity cancer patients has not yet been done. To investigate the relationships between hospital safety-net burden, clinicopathologic characteristics, and overall survival in oral cavity cancer (OCC) patients. From the National Cancer Database, we identified 48,176 OCC patients diagnosed with oral cavity cancer between the years 2004 to 2015. Treatment facilities were defined as no safety-net burden hospitals (NBH), low safety-net burden hospitals (LBH), and high safety-net burden hospitals (HBH) based on percentiles of uninsured/Medicaid patients treated: 0-30%, >30-75%, and >75-100% defines treatment facilities as NBH, LBH, and HBH respectively. Social demographic and clinico-pathological variables assessed were age, distance to treatment facility, time to first treatment, gender, race, Hispanic origin, insurance status, median household income, year of diagnosis, Charlson-Deyo score, location of primary site, AJCC stage, facility type and volume, and treatment modality. Safety-net burden of treatment facilities was used as the primary independent predictor in this analysis and the primary outcome of interest was overall survival. Crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed using Cox regression modelling, where clustering of patients within facilities was accounted for using robust sandwich covariance matrix estimates. There were 380 NBH (29.9%), 573 LBH (45.2%), and 316 HBH (24.9%) identified among the 1,269 treatment facilities evaluated for their respective safety-net burden and survival outcomes in oral cavity cancer patients. The median percentage of uninsured/Medicaid patients treated was 23.5% (range 18.6-100%) at HBH, 11.6% (range 1.2-18.5%) at LBH, and 0% (range 0-0%) at NBH. Median follow-up in all surviving patients was 49.0 months. A total of 22,466 deaths were reported, and the overall 5-year survival rate was 53.5% (median survival=69.7 months). Median survival for NBH, LBH and HBH was 68.6, 74.8 and 55.0 months, respectively (p<0.0001). However, compared to NBH and LBH, HBH facilities treated more late-staged cancers, racial and ethnic minorities, and patients of a lower socioeconomic status (SES). Thus, after adjusting for the aforementioned social demographic and clinico-pathological variables, no significant survival difference was noted in LBH (aHR 0.97 95% CI 0.91-1.04, p=0.405) or HBH (aHR 1.05 95% CI 0.98-1.13, p=0.175) when compared to patients treated at NBH facilities. While lower actuarial survival rates are observed in HBH compared to LBH and NBH, these findings may be driven by socioeconomic, and clinicopathologic characteristics. Racial and ethnic minorities are more likely to receive care at HBH. These findings suggest that high burden safety-net hospitals provide vital care to vulnerable populations with oral cavity cancer.

Impact of 3mm margin on risk of recurrence and survival in oral cancer.

While positive surgical margins in oral squamous cell carcinoma (OSCC) is generally considered an adverse prognosticator, the significance of close (≤5 mm) margins is more debatable, and has not been widely adopted as an indicator for radiotherapy. Retrospective study of 244 patients undergoing primary surgical resection of OSCC. The impact on local control (LC), disease-specific survival (DSS) and overall survival (OS) of margins at 1mm intervals was studied. 65 patients had involved (<1 mm), 119 close (1-5mm), and 60 clear (>5 mm) main specimen margins. Involved margins was predictive of DSS (p=0.04), but not LC (p=0.20) or OS (p=0.09). Both the 2mm and 3mm margin cut-offs were significantly associated with LC (p=0.02, and p=0.01), DSS (p=0.02, and p=0.007), and OS (p=0.03. and p=0.005). In a 3-tier model, use of 3mm for demarcation between close and clear yielded good separation between survival curves of clear (≥3 mm), and close (1-<3 mm) or involved (<1 mm). Final margins, determined after incorporation of frozen sections and extra margins taken separately, was significant for LC (p=0.04), but not for DSS (p=0.05) or OS (p=0.17). On multivariate analysis, <3 mm margin, T-classification, nodal status, extranodal spread, and postoperative radiotherapy, were independent predictors of DSS and OS. For LC, only T-classification was significant. A 3mm main specimen margin is significantly associated with survival in OSCC and may be useful for demarcation between close and clear. Further study is required to determine any impact on survival of radiotherapy for patients with <3mm margins as sole indicator for radiotherapy.

Do betel quid and areca nut chewing deteriorate prognosis of oral cancer? A systematic review, meta-analysis, and research agenda.

To explore the correlations between the habit of betel quid and areca nut (BQ-AN) chewing and the prognosis of oral cancer (OC). We performed a systematic review and meta-analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ-AN chewers and non-chewers, measured in terms of 5-year overall survival (OS) and 5-year disease-specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5-year OS and 5-year DSS was calculated using a fixed-effects model. Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5-year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5-year DSS. Overall, the pooled HR evaluating BQ-AN chewers was 1.26 (95% CI: 1.09-1.46) for 5-year OS and 1.40 (95% CI: 1.15-1.70) for 5-year DSS, compared with non-chewers. There was a significant association between BQ-AN chewing and OC survival. Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC.

Abstract B40: Trends in lymph node yield for neck dissection and oral cavity carcinoma survival

Abstract Objectives: Lymph node yields (LNYs) following neck dissection have been associated with differences in oral cavity cancer survival. The objective of this study was to evaluate temporal trends in LNYs in neck dissections for oral cavity carcinoma. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER 18) database. Inclusion criteria included diagnosis of malignant oral cavity cancer (tongue and floor of mouth) squamous cell carcinomas diagnosed from January 1, 2006-December 31, 2016. Patients with AJCC 6th Edition Stages 1-4a who underwent surgery were included. All-cause age-adjusted mortality for tongue and floor of mouth cancers during this period was assessed using SEER*Stat. Results: The median LNY among 8,580 patients in the sample was 25 LNs (Interquartile range 14-39). LNY statistically increased over time from 22 LNs in 2004 to 27 in 2014 (p &amp;lt; 0.0001). In contrast, there was no change in the median number of positive LNs during the same period (median 2 positive LNs in 2004 and 2014). There was no significant difference in lymph node yield based on sex, region, insurance status, or relative location to a metropolitan center. After adjusting for patient age, sex, race, marital status, regional income, and percent current smokers in the county of residence, tumor subsite and TNM stage, LNY less than 18 was independently associated with a 44% greater risk of death from any cause, compared with greater LNYs (HR 1.44, 95% CI 1.29-1.60, p=.0001). During this period, all-cause age-adjusted mortality declined from 469.7 per 100,000 (468.2-471.2) to 429.0/100,000 (428.2-430.8). Conclusion: LNY following neck dissection for oral tongue and floor of mouth cancers increased significantly over a decade, during which survival also improved. The cause of improved LNY is not known but may nevertheless be contributing to declining mortality in patients with oral tongue and floor of mouth cancers. Citation Format: Punam Patel, Suraj Kedarisetty, Miriam Lango. Trends in lymph node yield for neck dissection and oral cavity carcinoma survival [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B40.

Bayesian disease mapping and the 'High-Risk' oral cancer population in Hong Kong.

Preventive and early diagnostic methods such as health promotion and disease screening are increasingly advocated to improve detection and survival rates for oral cancer. These strategies are most effective when targeted at "high-risk" individuals and populations. Bayesian disease-mapping modelling is a statistical method to quantify and explain spatial and temporal patterns for risk and covariate factor influence, thereby identifying "high-risk" sub-regions or "case clustering" for targeted intervention. Rarely applied to oral cancer epidemiology, this paper highlights the efficacy of disease mapping for the Hong Kong population. Following ethical approval, anonymized individual-level data for oral cancer diagnoses were obtained retrospectively from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (HA) database for a 7-year period (January 2013 to December 2019). Data facilitated disease mapping and estimation of relative risks of oral cancer incidence and mortality. A total of 3,341 new oral cancer cases and 1,506 oral cancer-related deaths were recorded during the 7-year study period. Five districts, located in Hong Kong Island and Kowloon, exhibited considerably higher relative incidence risks with 1 significant "case cluster" hotspot. Six districts displayed higher mortality risks than expected from territory-wide values, with highest risk identified for two districts of Hong Kong Island. Bayesian disease mapping is successful in identifying and characterizing "high-risk" areas for oral cancer incidence and mortality within a community. This should facilitate targeted preventive and interventional strategies. Further work is encouraged to enhance global-level data and comprehensive mapping of oral cancer incidence, mortality and survival.

The influence of cervical lymph node number of neck dissection on the prognosis of the early oral cancer patients

Background/purposeThe status of neck lymph nodes (LNs) plays an important role in survival of oral cavity cancer. Early stage oral cancer patients are still at a risk for locoregional metastasis. We aimed to determine the number of LNs that needs to be retrieved for adequate diagnosis and treatment of the neck tumor. Materials and methodsWe conducted a retrospective study of 126 oral cavity cancer patients who underwent wide excision and 3 types of neck dissection at MacKay Memorial Hospital, Taiwan. Data from the operative and pathology reports were collected and analyzed. The significant difference was defined as p < 0.05 by SPSS 21.0 and Prizm 5 software. ResultsThere was a significant difference between the total retrieved LNs and tumor differentiation and nerve invasion on multivariate analysis. Receiveroperating characteristic (ROC) curve showed significant difference in the total number of neck LNs between the survival and expired groups. The cut-off point was 36.5 nodes. However, there was no difference in survival between supraomohyoid and modified radical neck dissection. ConclusionRetrieval of adequate LNs can improve oral cancer survival rates. If total number of neck nodes examined is <37 with poor differentiation and/or nerve invasion, early oral cancer patients with neck dissection have a lower survival rate and are candidates for adjuvant therapy.

Prognostic and clinical implications of c-erbB-2 expression in patients with oral cancer: A meta-analysis.

Recently, many studies have suggested that the aberrant expression of c-erbB-2 existed in oral cancer (OC) patients and had a correlation with poor clinical features across OC patients. Considering the inconsistent results among published articles, we performed the meta-analysis to assess the prognostic and clinical effect of c-erbB-2 expression on oral tumors. Web of Science, Embase, and PubMed were retrieved to acquire relevant publications based on selection criteria, up to February 8, 2020. Pooled odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were applied to evaluate the associations between c-erbB-2 expression and overall survival (OS), disease specific survival, disease-free survival as well as clinicopathology of OC. A total of 30 literatures with 1499 patients for survival of OC were enrolled in this meta-analysis. The results indicated that c-erbB-2 overexpression was significantly associated with poor OS (HR = 2.40, 95% CI = 1.53-2.55, P < .05), disease specific survival (HR = 2.60, 95% CI = 1.11-4.10, P < .05) and disease-free survival (HR = 2.22, 95% CI = 1.46-2.99, P < .05). Subgroup analysis based on race showed that the significant prognostic value of c-erbB-2 in OC was found both in Caucasians and Asians (OS of Caucasians, HR = 2.90, 95% CI = 1.50-4.31, P < .05; OS of Asians, HR = 1.90, 95% CI = 1.27-2.53, P < .05). Moreover, OC patients with enhanced c-erbB-2 expression were prone to male (OR = 1.97, 95% CI = 1.22-3.19, P < .05), advanced TNM stage (OR = 1.84, 95% CI = 1.17-2.88, P < .05), lymph node metastasis (OR = 2.23, 95% CI = 1.47-3.36, P < .05) and advanced grade (OR = 1.98, 95% CI = 1.30-3.01, P < .05), but not associated with distant metastasis (OR = 1.65, 95% CI = 0.98-3.04, P > .05). c-erbB-2 may be a potential indicator in the prediction of prognosis and clinicopathological features in OC patients.

Outcome prediction of head and neck squamous cell carcinoma by MRI radiomic signatures

ObjectivesHead and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer.Materials and MethodsNative T1-weighted images of four independent, retrospective (2005–2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC).ResultsIn oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001).ConclusionsMRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters.Key Points• MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer.• MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models.• Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models.

Hypoxia regulates the differentiation and anti-tumor effector functions of γδT cells in oral cancer.

Hypoxia within the tumor microenvironment (TME) is a key factor contributing to immunosuppression in tumors, co-relating with poor treatment outcome and decreased overall survival in advanced oral cancer (OC) patients. Vδ2 is a dominant subset of gamma delta T cells (γδT cells) present in the peripheral blood which exhibits potent anti-tumor cytotoxicity and is evolving as a key player of anti-cancer cellular therapy. However, the fate of γδT cells in hypoxic oral tumors remains elusive. In the present study, we compared the effect of hypoxia (1% O2 ) and normoxia (21% O2 ) on the expansion, proliferation, activation status, cytokine secretion and cytotoxicity of γδT cells isolated from OC patients and healthy individuals. Hypoxia-exposed γδT cells exhibited reduced cytotoxicity against oral tumor cells. Our data demonstrated that hypoxia reduces the calcium efflux and the expression of degranulation marker CD107a in γδT cells, which explains the decreased anti-tumor cytotoxicity of γδT cells observed under hypoxia. Hypoxia-exposed γδT cells differentiated to γδT17 [γδ T cells that produce interleukin (IL)-17] cells, which corroborated our observations of increased γδT17 cells observed in the oral tumors. Co-culture of γδT cells with CD8 T cells in the presence of hypoxia showed that programmed cell death ligand 1 (PD-L1)high γδT cells brought about apoptosis of programmed cell death 1 (PD-1)high CD8 T cells which could be significantly reversed upon blocking PD-1. Thus, future immunotherapeutic treatment modality for oral cancer may use a combined approach of blocking the PD-1/PD-L1 signaling and targeting hypoxia-inducible factor 1α, which may help in reversing hypoxia-induced immunosuppression.

Prognostic value of quantitative FDG-PET in the prediction of survival and local recurrence for patients with advanced oral cancer treated with superselective intra-arterial chemoradiotherapy.

The current study aimed to evaluate the relationship between 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET-CT) standardized uptake value (SUV) [pre-treatment SUV (pre-SUV) and post-treatment SUV (post-SUV)] and treatment results in patients with advanced oral cancer treated with superselective intra-arterial chemoradiotherapy (SSIACRT). A total of 37 patients with advanced oral cancer were treated with SSIACRT. The treatment consisted of superselective intra-arterial chemotherapy (docetaxel (DOC) 40 mg/mm2 and nedaplatin (CDGP) 80 mg/mm2) and concurrent radiotherapy (60–70 Gy) for a period of seven weeks. Pre-SUV and post-SUV of the primary tumor were measured. Overall survival (OS) and local control (LC) rates were selected as endpoints to evaluate prognosis. The median follow-up was 40 months (range 6–112 months). The 5-year OS and LC rates were 64.5 and 85.5%, respectively, and SSIACRT achieved high LC rate even in advanced oral cancers. In the log-rank test, post-SUV was a significant prognostic factor for OS and LC rates. The results of the current study demonstrated that SSIACRT is a reliable treatment with respect to survival in advanced oral cancer and post-SUV was a significant prognostic factor for OS and LC rates.

Lymph node yield and survival in node-negative oral cavity cancer

Lymph node yield and survival in node-negative oral cavity cancer

Comorbidities: Are they an Independent Predictor for Overall Survival in Oral Cavity Cancer?

Comorbidities: Are they an Independent Predictor for Overall Survival in Oral Cavity Cancer?

α7-Nicotine acetylcholine receptor mediated nicotine induced cell survival and cisplatin resistance in oral cancer

ObjectiveTo investigate the effect of nicotine on cell survival and cisplatin resistance in oral cancer and the possible involvement of α7-nicotinic acetylcholine receptors (α7-nAChRs). DesignThe effects of nicotine on cell survival and cisplatin-induced apoptosis were assessed. Knockdown of α7-nAChRs by short hairpin RNA and the specific antagonist methyllycaconitine (MLA) was used to examine the involvement of α7-nAChRs in modulating the effects of nicotine. Apoptosis signal molecules were examined in nicotine- and cisplatin-treated cells. ResultsNicotine increased the survival of the oral cancer cells YD8 and OEC-M1 in a dose- and time-dependent manner. Nicotine treatment accelerated cell cycle progression in the oral cancer cells, and significantly reduced cisplatin-induced cell apoptosis. In the α7-nAChR-silenced cells, the prosurvival effect of nicotine in the cisplatin-treated cells was attenuated. Co-treatment of cisplatin and nicotine attenuated the effect of cisplatin on Bcl-2 expression. In addition, the effect of nicotine on cell survival under cisplatin treatment was attenuated with the addition of the Bcl-2 inhibitor ABT-737. ConclusionsTreating oral cancer cells with nicotine increased cell survival and cisplatin resistance, in which α7-nAChRs were involved.

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer.

Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment. Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil-to-lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI). All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8×109 /L as reference, patients with 4.8-9.1×109 /L neutrophils had 1.536 times higher risk of death (95% CI, 1.295-1.822), and patients with ≥9.1×109 /L had 3.076 times higher risk (95% CI: 2.170-4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort. Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC.

Interleukin 17F and vasculogenic mimicry: Potential therapeutic targets in oral tongue cancer?

Abstract Background We recently showed that IL-17F expression correlates with better overall survival in oral tongue cancer (OTSCC) patients. Moreover, IL-17F inhibited OTSCC cell proliferation and migration. However, anti-angiogenic drugs showed limited effects in cancer treatment, where cancer cells use “de novo” vessel-like channels called vasculogenic mimicry (VM) to enhance nutrient supplies. Therefore, we aimed to investigate the vasculogenic mimicry in OTSCC and the potential effect of IL-17F on such phenomenon. Methods we used qRT-PCR immunostaining, and Western blotting methods to investigate the expression of VM-related markers (such as CD31, CD34 and VEGFA) at both gene and protein level, respectively. The capacity to create tube-like (channel-like) structures in 3D matrices were assessed in two different OTSCC-derived cell lines (the highly-aggressive HSC-3; and the less-invasive SCC-25). Tube-formation assays were used to examine the effects of IL-17F on angiogenesis using cancer cell lines and human umbilical vein endothelial cells (HUVEC), with or without antiangiogenic agents. Results OTSCC cell lines showed differential expression of CD31, CD34 and VEGFA genes. The level of such markers was dependent on the 3D matrix (Matrigel). OTSCC cells expressed abundant CD31 and CD34 receptors. In addition, we confirmed the presence of VM in more advanced-stages of OTSCC patients. Importantly, both HSC-3 and SCC-25 created channel-like structures when cultured on Matrigel matrix. Interestingly, IL-17F inhibited the tube-formation in HUVEC cells, and showed promising anti-angiogenic effects in vitro. Conclusion Our findings confirm the role of VM in OTSCC carcinogenesis. Here, we suggest that IL-17F counteracts the tumorigenic activity in OTSCC, in part, through the antiangiogenic effect in the tumour microenvironment, and hence further studies are warranted. Harnessing IL-17F in the current management approaches in advanced OTSCC patients may lead to promising immunotherapeutic strategies against OTSCC. Legal entity responsible for the study University of Helsinki. Funding University of Helsinki, Doctoral program in clinical research (KLTO). Disclosure The author has declared no conflicts of interest.

Prognostic value of transforming growth factor beta receptor 1 polymorphisms in patients with oral cancer.

To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1). Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer. TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR=0.55, 95% CI=0.35-0.88) and dominant (GG+AG vs AA: HR=0.57, 95% CI=0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG+AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P=.001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed. This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings.

Social Determinants of Health and Oral Cavity Cancer Treatment and Survival: A Competing Risk Analysis.

Competing risk analysis is a powerful assessment for cancer risk factors and covariates. This method can better elucidate insurance status and other social determinants of health covariates in oral cavity cancer treatment, survival, and disparities. Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Data regarding patient characteristics, clinical stage at diagnosis, treatment, and survival data for 20,271 patients diagnosed with oral cavity cancer was extracted from the SEER 18 Regs Research Data including Hurricane Katrina Impacted Louisiana Cases from 1973 to 2014. All statistical analyses were performed using SAS 9.5 (SAS Institute Inc., Cary, NC). The Fine-Gray method for assessing impact, risk, and covariates was employed. Medicaid patients presented with later stage disease, larger tumor size, more distant metastases, and more lymph node involvement at diagnosis compared to insured patients. Medicaid patients were less likely to receive cancer-directed surgery. Medicaid status was also associated with worse cancer-specific survival (subhazard ratios 1.87, 95% confidence interval 1.72-2.04, P < .0001) after adjustment for all covariates. This is the first study examining specifically how Medicaid status and social determinants of health covariates impact oral cavity cancer treatment and outcomes and is the first using methods validated for complex covariates. Patients with Medicaid present with more extensive oral cavity disease burden are less likely to receive definitive therapy and have significantly worse overall survival than those with other forms of insurance. This better identifies disparities and the need for improving health literacy, specifically for the at-risk Medicaid population, and can guide clinicians. NA Laryngoscope, 130:2160-2165, 2020.