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Purpose: Oral cavity squamous cell carcinoma (OCC) can spread to the neck without apparent lymphadenopathy. Pretreatment detection or prediction of occult metastasis might contribute to proper management of clinically node-negative (cN0) OCC. We examined the role of tumour quantitative 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) measurements for predicting OCC occult metastasis and survival. Methods: This study included 130 cN0 OCC patients who underwent 18F-FDG PET/CT scanning and subsequent curative surgery and neck dissection. Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured on pretreatment 18F-FDG PET/CT. Binary logistic regression was used to identify factors predicting occult cervical metastasis. Univariate and multivariate Cox proportional hazard regression were used to find factors associated with overall survival (OS). Results: Pathological cervical metastasis (pN +) was found in 29 (22.3%) patients. Age, tumour differentiation, lymphovascular invasion, and T classification were significantly associated with pN + (all P < 0.05). After adjustment for these factors, MTV and TLG independently predicted pN + (P < 0.05). Invasion depth, lymphovascular invasion, T and N classifications, and overall TNM stage were significantly associated with OS. After adjustment for these factors, SUVmax and TLG independently predicted OS (all P < 0.05). Patients with TLG > 9.3 g had a 5.7-fold increased risk of overall mortality. Conclusions: Tumour 18F-FDG PET/CT parameters might predict occult metastasis and survival in cN0 OCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Adenoid cystic carcinoma (AdCC) is generally slow growing but has highly metastatic potential to distant organs. Several factors and biomarkers are associated with metastasis and treatment outcomes, although further definition is needed. Therefore, this study aimed to evaluate the risk factors for survival and distant metastasis in patients with head and neck AdCC. Methods: This study included 125 patients with previously untreated AdCC who underwent primary surgery with or without radiotherapy in our tertiary referral centre. Univariate and multivariate Cox proportional hazard regression analyses were used to identify risk factors associated with overall survival (OS), cause-specific survival (CSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS). Factors associated with OS in patients with distant metastasis were separately analysed. Results: During a median follow-up of 9.8 years (range 3.0–22.6 years), 58 patients (46.4%) had distant metastasis and 29 (23.2%) died of disease. Multivariate analyses showed that lymphovascular invasion, lymph node metastasis, and distant metastasis were independent factors of OS and CSS outcomes (all P < 0.05). The T classification and extranodal extension were independent factors of DFS and DMFS outcomes (P < 0.05). After patients presented with distant metastasis, the median survival was 5.8 years. Multivariate analyses showed that extranodal extension and regional recurrence were independent factors of survival after occurrence of distant metastasis (P < 0.05). Conclusion: Several clinicopathological factors can predict distant metastasis and survival of patients with AdCC treated with primary surgery. This may promote post-treatment surveillance in patients with AdCC. [ABSTRACT FROM AUTHOR]

Purpose: Cervical metastasis from unknown primary (CUP) is commonly classified as an advanced overall stage. P16 or human papillomavirus (HPV) positivity in metastatic lymph nodes (LN) might be associated with a favorable survival outcome of CUP. Therefore, we evaluated the prognostic values of p16 immuno-positivity in LN and other clinicopathological factors in patients with squamous cell carcinoma CUP (SCCUP). Methods: This study involved 83 patients who underwent therapeutic neck dissection and panendoscopic examination and biopsy for suspected CUP. P16 immunostaining and HPV typing in LN were performed in 56 patients. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS). Results: Postoperatively, primary tumors (PT) were found in 32 (38.6%) patients, mainly (90.6%) in the oropharynx, and not found in 51 (61.4%) patients. The clinicopathological data (except for histological grade) and 5-year OS and DFS rates did not significantly differ between patients with and without PT identification (all P > 0.05). P16 positivity was associated with favorable OS and DFS outcomes in the patients with PT (P < 0.05) but not in those without PT (P > 0.1). Multivariate analyses showed that age (> 60 years) and LN ratio (≥ 0.1) were the independent predictors of OS and DFS outcomes (all P < 0.05). P16 positivity or other factors were not independent factors. Conclusion: Age and LN ratio are significant risk factors of survival and recurrence after primary surgery for SCCUP. Prognostic significance of LN p16 positivity should be further studied. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic lymph node (LN) burden is one of the most important prognosticators in human solid cancers, but has rarely been examined in laryngeal and hypopharyngeal cancers (LHC). We evaluated the nodal factors predictive of recurrence and survival in patients with LHC. Methods: This study included 141 consecutive patients who underwent primary surgery and neck dissection for previously untreated LHC at our tertiary referral centre. Nodal factors included the presence of pathological LN metastasis, number of positive LNs, LN ratio, and extra-nodal extension (ENE). Our proposed N classification was analysed by recursive partitioning analysis and compared with the AJCC and other N classifications using the c-index. Univariate and multivariate Cox proportional hazard regression analyses were used to define significant predictors of post-treatment disease-free survival (DFS) and overall survival (OS). Results: Of the 141 patients, 66 (46.8%) had positive LNs, and 27 (19.1%) had ENE. In multivariate analyses, the number of positive LNs was strongly associated with DFS and OS outcomes (P < 0.01). Our new N classification was proposed with four categories, such as N0 (0 LN +), N1 (1 LN +), N2 (2–4 LN + or ENE) and N3 (≥ 5 LN +). The C-index of our new N classification improved the OS prediction (0.718) compared with the AJCC and the other N classifications (0.704–0.713). Conclusion: Metastatic LN burden is an important predictor of survival in patients with LHC. A proposed N classification using the number of positive LNs and ENE might improve the LHC survival prediction. [ABSTRACT FROM AUTHOR]

Purpose: Submandibular gland (SMG) carcinoma has an unfavorable clinical course and a low survival rate. Specific tumor and nodal findings might help predict posttreatment recurrence and survival in SMG carcinoma patients. This study evaluated factors predictive of posttreatment recurrence and survival in SMG carcinoma patients. Methods: This study enrolled 99 consecutive patients with previously untreated SMG carcinoma. All patients underwent tumor and metastatic lymph node resection along with or without radiation/chemo-radiation. The predictive clinical and pathological factors for disease-free survival (DFS), distant metastasis–free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were determined using univariate and multivariate Cox proportional hazards regression analyses. Results: The median tumor size was 2.7 cm and 53 patients (53.5%) had high-grade tumors. The rates of initial nodal and distant metastasis at initial presentation or follow-up were 45.5% and 42.4%, respectively. The actuarial 5-year DFS, DMFS, DSS, and OS rates were 46.4%, 55.9%, 61.5%, and 59.7%, respectively. The independent factors associated with poor DFS, DMFS, DSS, and OS outcomes (all p < 0.05) were T3–T4 classification and lymph node ratio. A histological high-grade tumor was an independent prognostic factor predictive of poor DMFS, DSS, and OS outcomes (all p < 0.05). Conclusions: A high rate of distant site failure is associated with SMG carcinoma, resulting in a poor survival rate. Lymph node ratio might help predict recurrence, distant metastasis, and death due to SMG carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Intracellular antioxidant enzymes are commonly upregulated in various cancer types and are associated with treatment outcomes. Because the relationship has rarely been examined in oral squamous cell carcinoma (OSCC), we aimed to evaluate the association between the levels of glutathione peroxidase (GPX)1, GPX4, and thioredoxin reductase (TrxR)1 expression and prognosis in patients with OSCC who underwent curative surgical resection. Methods: This study included 233 patients who underwent curative surgery for previously untreated OSCC between 2000 and 2012. Tumour GPX1, GPX4, and TrxR1 expression was evaluated by immunohistochemistry and was dichotomised to low and high values according to defined expression levels. The association between GPX1, GPX4, and TrxR1 expression and clinicopathological results was analysed. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables. Results: High GPX1, GPX4, and TrxR1 expression was observed in 99 (42.5%), 133 (57.1%), and 46 (19.7%) patients, respectively. GPX1 overexpression was significantly correlated with nodal metastasis, advanced overall stage, depth of invasion of >10 mm, high grade and perineural invasion ( P < 0.05). High GPX4 expression was also related to nodal metastasis, overall advanced stage and high grade ( P < 0.05). Univariate and multivariate analyses showed that increased GPX1 expression was significantly associated with poor disease-free, cancer-specific and overall survival (all P < 0.05), while increased GPX4 or TrxR1 expression was not (all P > 0.1). Conclusions: Tumour GPX1 expression is a useful biomarker predictive of recurrence and survival in OSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: To identify the clinical significance of primary tumour thickness (TT) and its direction in patients with oral tongue squamous cell carcinoma (OTSCC), we measured TT in all axial/coronal/sagittal views on magnetic resonance imaging (MRI) and evaluated their meaning.Methods: A total of 53 OTSCC patients were analysed who had undergone preoperative three-dimensional MRI and had been surgically treated. TT measured on axial (mediolateral direction), coronal (superoinferior direction), and sagittal (anteroposterior direction) views was compared to that in pathologic specimens. The association between TT on MRI and other pathologic parameters was also evaluated.Results: TT on MRI in each plane showed relatively high concordance rates with the histological measurements. TT in all three planes was significantly correlated with lymph node (LN) metastasis. Occult LN metastasis was found in 15 of 39 (38.5%) patients, and the cutoff value of TT in axial/coronal/sagittal MRI predicting occult LN metastasis was 6.7 mm, 7.2 mm, and 12.3 mm, respectively. TT on MRI did not show any significant association with recurrence and survival.Conclusions: TT on MRI in all three planes showed relatively high coincidence with TT on histopathology and presented a potential cut-off value as a predictive indicator for occult LN metastasis.Key Points: Three-dimensional measurement of tumour thickness (TT) is important for oral cancer treatment. Magnetic resonance imaging (MRI) is a useful diagnostic tool for oral cancer. TT on MRI has a high coincidence with TT on histopathology. TT on MRI is a predictive marker for occult lymph node metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Quality of life (QOL) scores in cancer patients are associated with disease course and treatment outcomes. The aim of this study was to prospectively evaluate the associations between pretreatment QOL scores and survival or functional outcomes in patients with head and neck squamous cell carcinoma (HNSCC).Methods: This prospective study enrolled a total of 141 patients with previously untreated HNSCC who underwent curative treatments from October 2010 to March 2012. Patients completed questionnaires on QOL including the European Organization of Research and Treatment of Cancer 30-item Core QOL questionnaire (EORTC QLQ-C30) and EORTC QOL questionnaire Head and Neck Cancer module (QLQ-H&N35). Univariate and multivariate analyses were used to identify QOL scores significantly associated with overall survival (OS), disease-free survival (DFS), and functional outcomes of gastrostomy or tracheostomy dependence.Results: The 2-year OS and DFS rates were 82.3 and 78.0%, respectively. The rates of gastrostomy and tracheostomy dependence were 9.2 and 14.9%, respectively. After controlling for clinical factors, specific QOL indices of 'dyspnea' (hazard ratio 1.023 [95% confidence interval 1.006-1.039]) and 'appetite loss' (1.020 [1.005-1.034]) were significantly associated with OS, while 'insomnia' (1.013 [1.002-1.025]) and 'appetite loss' (1.014 [1.001-1.026]) scores were significantly predictive of DFS (P < 0.05). Global health status score (0.967 [0.935-1.000]) and fatigue (1.048 [1.010-1.086]) were significantly associated with the dependence of tracheostomy (P < 0.05). There was no relationship between gastrostomy dependence and QOL indices.Conclusion: This study provides evidence of significant relationships between certain pretreatment QOL measures and survival or functional outcomes in HNSCC patients. [ABSTRACT FROM AUTHOR]