The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Acute radiation dermatitis among patients with nasopharyngeal carcinoma treated with proton beam therapy: Prognostic factors and treatment outcomes.

A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This observational study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Treatment of ARD included topical corticosteroid alone in 24 (42.1%) patients, topical corticosteroid plus silver sulfadiazine in 33 (57.9%) patients, and non-adhering silicone dressing to cover severe skin wound area in 25 (43.8%) patients. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking (odds ratio [OR]: 5.2, 95% confidence interval [CI]: 1.3-18.8, P = .012) and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6-15.4, P = .006) as independent predictors of grade 2 and 3 ARD. The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid, silver sulfadiazine, and non-adhering silicone dressing are effective for treating ARD induced by PBT.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Stigma, depression, and anxiety among patients with head and neck cancer.

PURPOSE: Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients' stigma, depression, and anxiety, and elucidate the underlying relationships among them. METHODS: This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. RESULTS: Those patients having stressors of worry about health (t = 5.21, p < 0.001), worry about job (t = 2.73, p = 0.007), worry about family (t = 2.25, p = 0.026), or worry about economic problems (t = 2.09, p = 0.038) showed significantly higher SSS score than those having no such stressor. The SSS total score was significantly correlated with HAM-A (r = 0.509, p < 0.001), HAM-D (r = 0.521, p < 0.001), and EMIC (r = 0.532, p < 0.001) scores. Structural equation modeling was used to propose the possible effect of stigma on anxiety (ß = 0.51, p < 0.001), and then the possible effect of anxiety on depression (ß = 0.90, p < 0.001). CONCLUSION: Stigma is significantly correlated with anxiety and depression and might in HNC patients. Proper identification of comorbidities and a reduction of stigma should be advised in mental health efforts among patients with HNC.

Angiotensin II receptor blockers valsartan and losartan improve survival rate clinically and suppress tumor growth via apoptosis related to PI3K/AKT signaling in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common type of head and neck cancer in Asia. Adverse effects occur in over 90% of NPC patients treated with radiotherapy or chemoradiation. Angiotensin II receptor blockers (ARBs) are commonly used to treat hypertension without serious adverse effects. However, the anticancer activity of ARBs in NPC remains unclear. METHODS: We investigated the survival impacts of ARBs among NPC patients in a retrospective study. The anticancer effects and related signaling pathways of the ARBs valsartan and losartan were also evaluated in vitro and in vivo. RESULT: A total of 927 patients with NPC who had hypertension were enrolled in the study, 272 (29.3%) of whom received ARBs. Kaplan-Meier analysis revealed that patients who used ARBs had higher rates of 5-year overall survival (OS; 87.8% vs 75.1%; P = .002) and disease-specific survival (DSS; 95.4% vs 77.7%; P < .001) than those who did not receive this treatment. Additionally, ARBs inhibited cell proliferation and induced apoptosis by increasing levels of cleaved caspase-3, cleaved caspase-9, and cytochrome C; the cell population in the sub-G1 phase; and caspase-3 activity in NPC-TW01 cells. ARBs inhibited tumor growth and angiogenesis via apoptosis in an NPC xenografts model. Interestingly, ARBs inhibited phosphorylation of PI3K/AKT signaling in vitro and in vivo, which is markedly attributed to their antitumor effects in NPC. CONCLUSION: These data indicate that ARBs not only improve 5-year OS and DSS among patients with NPC but also exert antiproliferative and antiangiogenesis effects by inducing apoptosis in NPC, supporting that ARBs may be promising agents for treatment of NPC.

Static Magnetic Fields Dampen Focused Ultrasound-mediated Blood-Brain Barrier Opening.

Background Focused ultrasound combined with microbubbles has been used in clinical studies for blood-brain barrier (BBB) opening in conjunction with MRI. However, the impact of the static magnetic field generated by an MRI scanner on the BBB opening outcome has not been evaluated. Purpose To determine the relationship of the static magnetic field of an MRI scanner on focused ultrasound combined with microbubble-induced BBB opening. Materials and Methods Thirty wild-type mice were divided into four groups. Mice from different groups were sonicated with focused ultrasound in different static magnetic fields (approximately 0, 1.5, 3.0, and 4.7 T), with all other experimental parameters kept the same. Focused ultrasound sonication was performed after intravenous injection of microbubbles. Microbubble cavitation activity, the fundamental -physical mechanism underlying focused ultrasound BBB opening, was monitored with passive cavitation detection. After sonication, contrast-enhanced T1-weighted MRI was performed to assess BBB opening outcome. Intravenously injected Evans blue was used as a model agent to evaluate trans-BBB delivery efficiency. Results The microbubble cavitation dose decreased by an average of 2.1 dB at 1.5 T (P = .05), 2.9 dB at 3.0 T (P = .01), and 3.0 dB at 4.7 T (P = .01) compared with that outside the magnetic field (approximately 0 T). The static magnetic field of an MRI scanner decreased BBB opening volume in mice by 3.2-fold at 1.5 T (P < .001), 4.5-fold at 3.0 T (P < .001), and 11.6-fold at 4.7 T (P <.001) compared with mice treated outside the magnetic field. It also decreased Evans blue trans-BBB delivery 1.4-fold at 1.5 T (P = .009), 1.6-fold at 3.0 T (P < .001), and 1.9-fold at 4.7 T (P < .001). Conclusion Static magnetic fields dampened microbubble cavitation activity and decreased trans-blood-brain barrier (BBB) delivery by focused ultrasound combined with microbubble-induced BBB opening. © RSNA, 2021 An earlier incorrect version of this article appeared online. This article was corrected on July 8, 2021.

Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study.

BACKGROUND: Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been identified as a histone 3 lysine 27 (H3K27) demethylase and acted as a tumor suppressor gene or oncogenic function. The current study was to explore the significance of UTX in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection. METHODS: A total of 148 OTSCC patients who underwent surgical resection were identified, including 64 patients (43%) with overexpression of UTX and 84 patients (57%) harboring low expression of UTX. We also used two OTSCC cell lines, SAS and Cal 27, to determine the modulation of cancer. Chi-square test was used to investigate the difference of categorical variables between the groups; survival outcome was analyzed using the Kaplan-Meier method in univariate analysis, and a Cox regression model was performed for multivariate analyses. RESULTS: Univariate and multivariate analyses showed overexpression of UTX were significantly related to worse disease-free survival (P = 0.028) and overall survival (P = 0.029). The two OTSCC cell lines were treated with GSK-J4, a potent inhibitor of UTX, and transwell migration and invasion assays showed an inhibitory effect with a dose-dependent manner. In addition, western blot analyses also revealed the inhibition of cell cycle and epithelial-mesenchymal transition. CONCLUSION: Our study suggests that UTX plays an important role in the process of OTSCC and overexpression of UTX may predict poor prognosis in OTSCC patients who received surgical resection.

Dynamic contrast-enhanced magnetic resonance imaging in correlation with tongue cancer stages.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a significant role in tumor stage as it can be used to measure tissue perfusion and permeability of tumors. PURPOSE: To investigate the relationships between both quantitative and semi-quantitative variables obtained from DCE-MRI and tongue cancer stages. MATERIAL AND METHODS: Mean values of Ktrans, enhancement ratio (ER), wash-in slope (slope), and the 95th percentile (95%) values of the distribution for Ktrans, ER, and slope values (Ktrans (95%), ER (95%), and slope (95%), respectively) were calculated for 53 patients with tongue cancers (American Joint Committee on Cancer 8th Edition stage group: 10 in stages I and II, 14 in stage III, 21 in stage IVa, and eight in stage IVb as determined by histopathologic assessment). The relationship between tumor staging and each of the six DCE-MRI parameters was assessed separately using ordinal logistic regression. RESULTS: The logistic regression analysis revealed that both mean and 95th percentile values of Ktrans were significantly and positively correlated with tongue cancer stage (P < 0.01). More aggressive tumor stages had larger kinetic parameter. Moreover, the semi-quantitative parameters, such as ER (95%) and slope (95%), may be more significant predictors for evaluating tongue cancer stages than the mean ER and mean slope. CONCLUSION: Both quantitative and semi-quantitative imaging biomarkers are useful for evaluating the stages of tongue cancer, and the indices obtained from DCE-MRI were positively correlated with the tumor stages. These parameters have the potential to non-invasively evaluate the stages of tongue cancer in the clinical setting.

Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

Treatment patterns and survival outcomes of advanced hypopharyngeal squamous cell carcinoma.

BACKGROUND: This study evaluated the treatment outcomes of the primary surgery (PS) or concurrent chemoradiotherapy (CCRT) as the initial treatment for hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: This retrospective cohort study included patients with stages III-IV HPSCC from four tertiary referral centers consecutively enrolled from 2003 to 2012; of them, 213 (32.6%) and 439 (67.4%) had received PS and CCRT as their primary treatments, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the Kaplan-Meier method and Cox regression models. RESULTS: In patients undergoing PS and CCRT, OS rates were 45.0% and 33.1% (p < 0.001), respectively, and DFS rates were 36.2% and 28.9% (p = 0.003), respectively. In subgroup analysis, in patients with stage IVA HPSCC, PS was associated with higher OS rate (p = 0.002), particularly in those with T4 or N2 classification (p = 0.021 and 0.002, respectively). Multivariate analysis indicated that stage IVA HPSCC, stage IVB HPSCC, and CCRT were independent adverse prognostic factors for OS rate (p = 0.004, < 0.001, and 0.014, respectively). Furthermore, in patients with stage IVA HPSCC aged ≥ 65 years and with N2 classification, CCRT was significantly associated with lower OS rates than was PS (p = 0.027 and 0.010, respectively). CONCLUSIONS: In patients with advanced HPSCC, PS was significantly associated with better prognosis than CCRT. PS could be a favorable primary treatment modality for the management of patients with stage IVA HPSCC, particularly those aged ≥ 65 years and with T4 and N2 classification.

Patients with oral cancer do not undergo surgery as primary treatment: A population-based study in Taiwan.

BACKGROUND: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. METHODS: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named "Reason for No Surgery of Primary Site" were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan-Meier method with log-rank test. RESULTS: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p < 0.001). The mean age of the patients with and without surgery were 54.8 and 59.3, respectively (p < 0.01). Female patients were commoner in group 3 (p < 0.01). The patients without surgery was commoner in the middle (15.7%) and southern (14.8%) than in Northern Taiwan (12.1%). All groups without surgery had more advanced stage and lower BMI (p < 0.01). CONCLUSION: One-sevenths of patients were not treated surgically because of refusal, poor condition, older age, low BMI, and advanced stage. It is necessary to encourage the patients to undergo surgery with shortening the diagnosis-to-treatment interval.

Development of a Multiplexed Assay for Oral Cancer Candidate Biomarkers Using Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry.

Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva. We successfully produced 363 clones of mouse anti-peptide monoclonal antibodies (mAbs) against 36 of 49 selected targets, and characterized useful mAbs against 24 targets in terms of their binding affinity for peptide antigens and immuno-capture ability. Comparative analyses revealed that an equilibrium dissociation constant (KD ) cut-off value < 2.82 × 10-9 m could identify most clones with an immuno-capture recovery rate >5%. Using these mAbs, we assembled a 24-plex SISCAPA-MRM assay and optimized assay conditions in a 25-µg saliva matrix background. This multiplexed assay showed reasonable precision (median coefficient of variation, 7.16 to 32.09%), with lower limits of quantitation (LLOQ) of <10, 10-50, and >50 ng/ml for 14, 7 and 3 targets, respectively. When applied to a model saliva sample pooled from oral cancer patients, this assay could detect 19 targets at higher salivary levels than their LLOQs. Finally, we demonstrated the utility of this assay for quantification of multiple targets in individual saliva samples (20 healthy donors and 21 oral cancer patients), showing that levels of six targets were significantly altered in cancer compared with the control group. We propose that this assay could be used in future studies to compare the clinical utility of multiple oral cancer biomarker candidates in a large cohort of saliva samples.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

The proposed physiology-based FDG PET/CT criteria in reducing false-positive results in advanced head and neck cancer after chemoradiotherapy.

BACKGROUND: Distinguishing benign complications after concurrent chemoradiotherapy (CCRT) from a local residual tumor in advanced head and neck squamous cell carcinoma (HNSCC) remains a clinical challenge. In this study, we propose criteria when considering physiological uptake patterns on F-18-fluorodeoxyglucose (FDG) PET/CT in patients with advanced HNSCC after CCRT. METHODS: We retrospectively reviewed FDG PET/CT images of 62 patients with advanced HNSCC, which were taken within 16 weeks following CCRT. Visual interpretation criteria were rated by three nuclear medicine physicians, independently, according to the uptake patterns of the primary site. The Cohen k coefficient was calculated to assess inter-reader agreement. The histology of the primary site within a 1 month of the PET/CT study was used as the gold standard for sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: PET/CT was arranged at a median interval of 10.5 weeks (range 4-16 weeks) after CCRT, and the pathologic residual rate was 55.7% at the primary site. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of identifying residual disease were 91.1%, 50.0%, 68.9%, 82.3%, and 72.6%, respectively, by the previously established criteria, and 88.2%, 92.9%, 93.8%, 86.7%, and 90.3%, respectively, by our physiology-based criteria. Our visual rating criteria corrected 12 of 14 (84.6%) false-positive results from the established criteria, while two more false-negative cases identified with our criteria were proven to be small residual tumors. CONCLUSIONS: By incorporating physiological changes following CCRT, our visual rating criteria improved the accuracy of the currently used FDG PET/CT visual rating system, especially the number of false-positive cases with advanced HNSCC after CCRT.

Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway.

Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells. Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to measure capsaicin-induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway. Capsaicin induced autophagy by increasing levels of the autophagy markers LC3-II and Atg5, enhancing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis, suggesting a correlation of blocking the PI3K/Akt/mTOR pathway with the above-mentioned anticancer activities. Taken together, these data confirm that capsaicin inhibited the growth of human NPC cells and induced autophagy, supporting its potential as a therapeutic agent for cancer.

The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell Carcinoma with Partial or Complete Response After Radical Chemo-Intensity-Modulated Radiotherapy (IMRT).

BACKGROUND: This study investigated the therapeutic benefit of radical resection (SRR) for clinical T4b oral cavity squamous cell carcinoma (OSCC) with partial or complete response after radical chemoradiotherapy (CRT). METHODS: At the authors' institution, 79 patients with newly diagnosed non-metastatic T4b OSCC were treated with CRT from January 2009 to December 2014. All of them were irradiated using intensity-modulated radiotherapy (IMRT), with a radical dose (median 70 Gy; range 66-76 Gy) in the gross tumor area. Of the 65 cases achieving partial or complete response after CRT, 33 were treated further with SRR and 32 with adjuvant chemotherapy or observation. The locoregional control (LRC), overall survival (OS), and cancer-free survival (CFS) rates were compared between the two groups. RESULTS: The 3-year LRC, OS, and CFS rates were respectively 72.3, 75.1, and 72.6 % in the SRR group compared with 32.8, 47.7, and 44.3 % in the non-SRR group (p < 0.05). Multivariate analysis showed that SRR was the only statistically significant prognostic factor related to LRC, OS, and CFS. For those with SRR, pathologic downstaging was observed in 27 cases (81.8 %). Perioperative flap failure was observed in three cases (9.2 %) and neck wound necrosis in four cases (12.1 %). CONCLUSIONS: For T4b OSCC, incorporating SRR in the therapy is technically safe and has survival benefit, with a significant response after CRT applied by IMRT, with a radical dose in the gross tumor area.