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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]

Objective: To evaluate the prognostic values of tumor‐related leukocytosis (TRL) as a reliable biomarker predictive of recurrence and survival after definitive surgery for oral cavity squamous cell carcinoma (OSCC). Materials and methods: This retrospective study involved 322 patients who underwent tumor extirpation combined with neck dissection for treatment‐naïve OSCC between 2006 and 2014. Multivariate binary logistic regression analyses were used to analyze the relationship between TRL and pathological variables. Cox proportional hazard regression analyses were used to find associations between factors and disease‐free survival (DFS) or overall survival (OS). Results: TRL was significantly related to advanced disease status, tumor size, invasion depth, poor differentiation, and T and N classifications, resulting in increased post‐treatment recurrence rate, particularly in the distant site. Multivariate logistic regression analyses showed that only the T classification was significantly associated with baseline TRL (p = 0.018). Multivariate analyses also showed that the tumor depth of invasion, pathological N classification, extranodal extension, and TRL remained the independent variables predictive of DFS and OS (all p < 0.05). TRL was related to a more than twofold increased risk of post‐treatment recurrence and mortality. Conclusions: TRL is associated with advanced tumor disease and increased recurrence and mortality in OSCC patients. [ABSTRACT FROM AUTHOR]

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Background: This study evaluated the prognostic role of Fluorine 18‐fluorodeoxyglucose positron emission tomography/CT (18F‐FDG PET/CT) parameters quantitatively measured in patients with recurrent oral cavity cancer. Methods: Cox proportional hazards regression analyses were used to assess the associations between quantitative 18F‐FDG PET/CT parameters and other clinicopathological factors and progression‐free survival (PFS) and overall survival (OS). Results: All of the 18F‐FDG PET parameters (SUVmax, SUVmean, SUVpeak, metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were significantly associated with poor PFS and OS outcomes after salvage treatment (P < .01). In multivariate analyses, Karnofsky performance score, recurrence site, MTV, and TLG were independent variables predictive of both PFS and OS (P < .05). High MTV (>8.8 mL) or TLG (>29.4 g) values at recurrent lesions were associated with >5‐fold increased risk for tumor progression and mortality after salvage surgery. Conclusions: The PET parameters of MTV and TLG measured at recurrent lesions may predict tumor progression and survival after salvage treatment. This study examined the role of 18F‐FDG PET/CT at recurrent staging for predicting tumor progression and survival in 71 consecutive patients with recurrent oral cavity squamous cell carcinomas. Of 18F‐FDG parameters, metabolic tumor volume and total lesion glycolysis were independent factors predictive of tumor progression and survival after salvage treatment. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the expression of CD44 and cystine‐glutamate transporter SLC7A11 (xCT) in primary oral cavity squamous cell carcinoma (SCC) and the relationships of expression to tumor recurrence and patient survival. Methods: Associations between CD44 and xCT expression and clinicopathologic results were analyzed in 231 patients with oral cavity SCC. Cox proportional hazard analyses were used to identify factors associated with recurrence‐free survival (RFS), disease‐specific survival (DSS), and overall survival (OS). Results: Overexpression of CD44 and/or xCT was associated with advanced T classification, perineural invasion, and lymphovascular invasion (P <.05 each). High expression of xCT was also associated with nodal metastasis and depth of invasion (P <.01 each). Multivariate analysis indicated that high expression of xCT and both xCT and CD44 were independent predictors of poor RFS, DSS, and OS (P <.05 each). Conclusion: Overexpression of xCT or xCT plus CD44 may predict posttreatment recurrence and survival in patients with oral cavity SCC. [ABSTRACT FROM AUTHOR]

Amplification of fibroblast growth factor receptor 1 (FGFR1) has been reported in many squamous cell carcinomas, and human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma has been characterized as a distinct subset with favorable prognosis. Here, we investigated the FGFR1 amplification and HPV status in tonsillar squamous cell carcinoma (TSCC) and analyzed the clinical characteristics. HPV in situ hybridization (HPV ISH) and FGFR1 fluorescence in situ hybridization (FISH) were performed using tissue microarray from 89 cases of TSCC. Fourteen of 89 (15.7%) TSCC cases had FGFR1 amplification, and HPV was detected in 59 of 89 (66.3%) cases. FGFR1 amplification status was not associated with HPV positivity (p =0.765). Outcomes were not significantly different between FGFR1 amplified and non-amplified patients. Although FGFR1 amplified patients (n =4) in the HPV ISH–negative group (n =30) had a tendency for poorer overall survival, no statistical significance was identified (p =0.150, log-rank). FGFR1 protein overexpression showed better disease-free survival (p =0.031, log-rank) in HPV-negative TSCC. This study suggests FGFR1 amplification may be important in the pathogenesis of TSCC regardless of HPV status. [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]

Background The purpose of this study was to identify the prevalence of cancer cachexia and its prognostic impact in patients with advanced head and neck squamous cell carcinoma (HNSCC). Methods The prevalence of cancer cachexia was analyzed according to the follow-up periods during the first year after curative initial treatment. Recurrences, noncancer health events (NCHEs), and cause-specific survival outcomes were also analyzed according to the incidence of cancer cachexia during follow-up. Results Cancer cachexia was identified in 22 (6.1%), 148 (41%), 66 (18.4%), and 65 (18.7%) of 361 enrolled patients at pretreatment, immediately after treatment, 6-months after treatment, and 12-months after treatment, respectively. Sustained or newly developed cachexia at 6 and 12 months showed a significant association with recurrence and NCHE occurrence ( p < .05). In cause-specific survival analysis, patients with cachexia had a higher probability of cancer-specific death, noncancerous death, and overall death ( p < .05). Conclusion Cachexia prevalence at 6 and 12 months after treatment for HNSCC indicates a higher chance of recurrence, NCHE, and death. © 2016 Wiley Periodicals, Inc. Head Neck 39: 716-723, 2017 [ABSTRACT FROM AUTHOR]

ConclusionThe application of adjuvant RT to reduce recurrence should be tailored in cases of pathologically negative node metastasis.ObjectivesThe treatment modality following surgical resection of advanced laryngeal cancer is determined by adverse factors. Aside from lymph node metastasis (LNM) or positive margins, definite risk factors supporting adjuvant radiation therapy (RT) have not been clearly suggested. The aim of this study was to analyze the risk factors for advanced laryngeal cancer without LNM and the role of RT.Materials and methodsPathologically T3 and T4-staged laryngeal squamous cell carcinoma without LNM were reviewed. The patients were classified into RT (+) (n = 22) and RT (−) (n= 38) groups.ResultsFive-year overall survival (OS) of the RT (+) and RT (−) groups was 84.4% and 83.8%, respectively. Five-year disease-specific survival of the RT (+) and RT (−) groups was 88.4% and 93.9%. Five-year local control rate of the RT (+) and RT (−) groups was 94.7% and 91.3%. The factors affecting OS were smoking history and recurrence history (p = 0.02). By multivariate analysis, smoking history and recurrence history were determining factors for 5-year OS (p = 0.024 andp = 0.047, respectively). [ABSTRACT FROM PUBLISHER]

Purpose: Cancer incidence in the elderly population has been continuously rising, and their treatment is an increasing concern among oncologists. This study aimed to evaluate the incidence and risk factors for morbidity and mortality after major oncological surgery in elderly patients with head and neck squamous cell carcinoma (HNSCC). Methods: The 196 HNSCC patients aged 55 and older who underwent major curative surgery. Patients were categorized into three groups: far-old (≥75 years; n = 41); old (65-74 years; n = 72); or middle-aged (55-64 years; n = 83). The rates of early and late postoperative complications, hospital stays, and mortality were compared among groups. Univariate and multivariate analyses were performed to identify the factors associated with early postoperative complications. Results: No study patients had mortality during surgery or within 3-month postoperation. Karnofsky performance status, frail functional status, comorbidity, and index cancer and noncancer mortality were the poorest in the far-old group. The far-old group demonstrated significantly higher rates of early overall complications, readmission within 1 month, and recurrence rates ( P < 0.05 each). Multivariate analysis showed that age, postoperative hemoglobin, and C-reactive protein are independent predictors of early postoperative complications ( P < 0.05 each). Conclusions: In elderly patients, chronological age affects the increased risk of early postoperative morbidity and later mortality following major HNSCC surgery. In combination with these risk factors, older patients who are diagnosed with HNSCC should be carefully monitored in order to determine the potential occurrence of postsurgical complications. [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]

Background: The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC).Methods: For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and <14, respectively. Univariate and multivariate analyses were performed to assess whether the presence of depression was associated with overall survival, disease-free survival (DFS), or posttreatment changes in nutritional status and laboratory data.Results: Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P < .05). Depressive patients had lower pretreatment serum albumin levels than nondepressive patients (P < .05).Conclusions: There was a significant correlation between pretreatment depression and pretreatment QOL, nutritional status, and survival outcomes in patients with HNSCC. [ABSTRACT FROM AUTHOR]

Background We examined the prognostic value of lymph node density in predicting cancer-specific mortality (CSM) for patients with lymph nodes positive (pN+) laryngeal squamous cell carcinoma (SCC) after laryngectomy. Methods The records of 156 patients with laryngeal SCC who initially underwent curative resection of the primary tumor combined with neck dissection were reviewed. Results The 5-year cumulative incidence of CSM was 20.4%. N classification and extralaryngeal spread (ELS) were independent variables for CSM in all patients. Univariate analyses in 71 pN+ patients showed that ELS, number of positive lymph nodes >4, and lymph node density >0.044 were significantly associated with increased CSM, whereas pN classification was not ( p = .218). On multivariate analysis, lymph node density ≥0.044 remained an independent predictor of CSM ( p = .001). Conclusion Among the pN+ patients with laryngeal SCC, no pN classification but lymph node density was noted to have an independent impact on CSM. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1319-1325, 2015 [ABSTRACT FROM AUTHOR]

Purpose: Standardized uptake value (SUV) and metabolic tumour volume (MTV) measured by F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers. However, their prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) has been investigated in only a few studies and with small cohorts. In the present study we evaluated the ability of SUV, MTV, and total lesion glycolysis (TLG) measured on pretreatment F-FDG PET/CT to predict recurrence and survival outcomes in OPSCC. Methods: The study included 221 patients with OPSCC who underwent pretreatment F-FDG PET/CT imaging and received definitive treatment at our tertiary referral centre. The PET imaging parameters SUV, SUV, MTV and TLG were measured in primary tumours with focal F-FDG uptake. Clinical and imaging variables significantly associated with overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate analyses using the Cox proportional hazards model. Results: Overall 5-year OS and DFS rates were 72.0 % and 79.5 %, respectively, during a median follow-up of 61 months (range 18 - 122 months). The cut-off values of tumour SUV, SUV, MTV and TLG for prediction of DFS were 7.55, 6.80, 11.06 mL and 78.56 g, respectively. Univariate analyses showed that age >60 years, advanced tumour stage, and high tumour SUV, SUV, MTV and TLG were significantly associated with decreased OS and DFS ( P < 0.05 each). Age, tumour SUV and MTV remained independent variables for OS and DFS ( P < 0.05 each) in the multivariate analyses. Conclusion: SUV and MTV measured on pretreatment F-FDG PET/CT may be useful in predicting the clinical outcomes in OPSCC patients. Condensed abstract: This study investigated the clinical prognostic value of imaging parameters from pretreatment F-FDG PET/CT in 221 patients who underwent definitive treatment for oropharyngeal squamous cell carcinoma. High maximum standardized uptake value and metabolic tumour volume were independently associated with decreased disease-free and overall survival outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND The prognostic role of swallowing-related, pretreatment subjective and objective findings has not been investigated in detail. The authors evaluated the association between pretreatment MD Anderson Dysphagia Inventory (MDADI) or videofluorographic swallowing study (VFSS) results and standard outcomes, including early recurrence and survival, in patients with treatment-naïve head and neck squamous cell carcinoma (HNSCC). METHODS Patients with HNSCC (n = 191) who received treatment at the authors' institution and were examined by self-administered MDADI questionnaires and VFSS were prospectively enrolled. MDADI and VFSS findings were analyzed in correlation with clinicopathologic variables, and factors that predicted 2-year disease-free survival (DFS) and overall survival (OS) were identified using a Cox proportional-hazards regression model. RESULTS The 2-year OS and DFS rates were 80.1% and 77.5%, respectively. Clinical tumor (T) and lymph node (N) classifications, overall TNM stage, sex, tumor site, and educational level were significantly associated with specific MDADI subdomains, whereas Karnofsky performance score was significantly associated with all MDADI subdomains. After controlling for clinical factors, total scores, global assessment scores, and emotional and physical MDADI subscores were significantly predictive of 2-year OS and DFS ( P < .05 for each). VFSS findings were not significantly associated with survival ( P > .05). CONCLUSIONS The current results provide evidence of the prognostic role of the MDADI in predicting early survival outcomes in patients with HNSCC. The MDADI may be a practical and noninvasive method for the identification of patients at risk who would benefit from close follow-up. Cancer 2015;121:1588-1598. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND This study was aimed at investigating the change in the prevalence of human papillomavirus (HPV) genotypes in tonsillar squamous cell carcinoma (TSCC) and the association of the HPV genotype with the prognosis. METHODS This multicenter study included 175 patients with TSCC from 3 general hospitals between 1991 and 2009. HPV DNA was detected in paraffin-embedded tissues with genotyping chips. A survival analysis that considered clinicopathological factors, the HPV genotype, and the expression of p53, retinoblastoma protein, p16, and epidermal growth factor receptor (assessed with immunohistochemistry) was performed with Cox regression analysis. RESULTS High-risk HPV types were found in 23.4% of the cases. The prevalence of HPV-18 (10.3%) was as high as that of HPV-16 (10.3%). The proportion of high-risk HPV-positive tumors increased from 5.9% in 1991 to 31.6% in 2009. HPV-16 positivity was associated with an advanced stage and lymph node metastasis, whereas HPV-18 positivity was associated with old age and an advanced T stage. The survival analysis showed that old age and T classification were poor prognostic factors, whereas the expressions of various biomarkers were not associated with prognosis. HPV-18-positive cases had a poorer prognosis than HPV-16-positive cases and non-HPV-related TSCC cases. A multivariate analysis revealed that HPV-18 positivity, old age, and an advanced T stage were independent prognostic factors for predicting poor outcomes for patients with TSCC. CONCLUSIONS The proportion of HPV-positive tonsillar cancer cases has increased during the last 20 years in the Republic of Korea. The presence of HPV-18 may serve as a biomarker for a poor prognosis. Cancer 2015;121:535-544. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives. Patients with head and neck squamous cell carcinoma (HNSCC) often develop second primary tumors in the upper aerodigestive tract. Early detection of synchronous esophageal squamous cell neoplasm (ESCN) is important because the prognosis of HNSCC can be affected by the statuses of second primary tumors. Methods. In a prospective study, 308 patients with HNSCC were screened for synchronous ESCN between May 2010 and April 2012. All patients underwent conventional white-light endoscopic examination with Lugol chromoendoscopy and narrow band image. Results. The median age was 61 years (range, 26-87 years), and the male-to-female ratio was 4.2:1. Two hundred and thirty-four patients (76.0%) were current or ex-smokers, 207 patients (67.2%) had a history of alcohol consumption and 56 patients (18.2%) had previous history of cancer. Synchronous ESCN was detected in 22 patients (7.1%), and most patients were at an early stage. The locations of index HNSCC in these patients were as follows: hypopharynx ( n = 12), larynx ( n = 6), oropharynx ( n = 2) and oral cavity ( n = 2). Synchronous ESCN was detected in 25.5% (12/47) of hypopharyngeal cancer and in 27.8% (15/54) of HNSCC involving the pyriform sinus. Multivariate analysis showed that smoking (current smoker vs. never smoker, Odds Ratio [OR] 8.3, p = 0.028), a history of cancer (OR 5.0, p = 0.002) and pyriform sinus involvement (OR 9.2, p < 0.0001) increased the risk of developing synchronous ESCN. Conclusions. Patients with HNSCC, especially those who are current smokers, have a history of cancer and have pyriform sinus involvement, should undergo intensive endoscopic screening to detect synchronous ESCN. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Methods: Of 162 patients with OSCC evaluated preoperatively by F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUV), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). Results: The median (range) SUV, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV ( P = 0.018) and TLG ( P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV ( P = 0.001) and TLG ( P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV ( P = 0.001), TLG ( P = 0.002) and the involved resection margin ( P = 0.007) were independent predictive factors for OS. Conclusion: Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC. [ABSTRACT FROM AUTHOR]

Significant loss of body weight (SLW) by patients treated for squamous cell carcinomas of the oral cavity and oropharynx (OSCC) may affect treatment completion and results. We assessed factors predicting SLW and its correlation with disease-free survival (DFS) in these patients. We evaluated 226 consecutive patients with previously untreated, operable OSCC whose body weight was recorded before, during, and for up to 1 year after treatment. SLW was defined as ≥10% reduction in pretreatment body weight. Clinicopathologic parameters were compared in patients with and without SLW. Of the 226 patients, 94 (41.6%) experienced SLW and 132 (58.4%) did not. Univariate analyses showed that factors significantly associated with SLW included T3–4, N+, stage III–IV, and oropharyngeal tumors, nonsurgical (radiotherapy or chemotherapy) vs. surgical treatment, posttreatment recurrence, histologic differentiation, involved resection margin, and number of metastatic lymph nodes (pLNs) ≥ 3 (P< 0.05). Multivariate analyses showed that radiotherapy, recurrence, and number of pLNs were significant independent predictors of SLW (P< 0.005). DFS rate was significantly higher in patients without than with SLW (P< 0.01). OSCC patients with multiple pLNs, those undergoing radiotherapy, and those with posttreatment recurrences may require close nutritional monitoring and support. [ABSTRACT FROM PUBLISHER]

Conclusions: p16 immunohistochemistry (IHC) status correlated with less exposure to smoking and/or alcohol in Korean patients with locally advanced tonsillar squamous cell carcinoma (TSCC), and was an independent prognostic factor for survival. Objective: TSCC is more likely to be human papillomavirus (HPV)-positive than other head and neck squamous cell carcinoma (HNSCC) subtypes. The objective of this study was to ascertain the HPV status of TSCC in Korean patients and to determine its relationship with clinical parameters and prognosis. Methods: The locally advanced TSCCs of 79 patients who were treated between 2000 and 2008 were tested by p16 IHC and HPV in situ hybridization (ISH) with a tissue microarray. Results: Sixty-three patients (80%) were positive for p16 IHC, while 54 (68%) were positive by HPV ISH. p16 IHC status correlated significantly with lower exposure to smoking and alcohol ( p < 0.05) but did not correlate with T and N stage classification, histological differentiation, age, or gender. The p16-positive group had a significantly higher 5-year overall survival rate in comparison with the p16-negative group (78% vs 63%, hazard ratio (HR) = 0.347, 95% CI = 0.14, 95% C p = 0.025). p16 IHC was a favorable independent prognostic factor for overall survival, even after adjustment for age and T stage (HR = 0.283, 95% CI = 0.103, 95% p = 0.015). [ABSTRACT FROM AUTHOR]

Background We investigated whether the addition of narrow band imaging (NBI) to standard diagnostic workups could enhance the detection of primary lesions in patients with carcinoma of unknown primary (CUP). Methods Thirty patients with CUP underwent NBI endoscopy and fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) after thorough conventional diagnostic workups between 2009 and 2011. Sites suspected of harboring primary tumors, as determined by NBI and/or FDG-PET/CT, were biopsied for histologic confirmation. Results Occult primary tumors were identified in 33.3% (10/30), including 13.3% (4/30) by NBI and 20.0% (6/30) by FDG-PET/CT. All of diagnosed lesions by NBI were confirmed histologically as squamous cell carcinomas with T1 classification and identified at 2 supraglottis, 1 hypopharynx, and 1 esophagus, respectively. Conclusions NBI endoscopy may be a useful method for detecting primary tumors, especially for small and superficial squamous cell carcinomas of the upper aerodigestive tract, after conventional workup in patients with CUP. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

The article presents a study on identification of risk factors related to distant metastases (DM) and survival of patients with head and neck squamous cell carcinoma (HNSCC) which is presented through a database analysis and chart review. The study used univariate and multivariate analyses for the risk factors of DM. The study concluded that patients with advanced tumors, nodal involvement, or locoregional recurrences may require more frequent surveillance for the development of DMs.

Conclusion. Surgical treatment of carotid invasion may give an improved 2-year survival in selected patients without significant morbidity. Objective. To evaluate survival outcomes in patients with head and neck squamous cell carcinomas invading the carotid artery. Patients and methods. At the time of carotid invasion, 23 patients underwent surgery (n=11), chemoradiotherapy (n=6), or palliation (n=6). Surgical methods included carotid resection and ligation (n=5), carotid resection and reconstruction with saphenous vein (n=4), and peeling (n=2). Survival outcomes among different treatments were compared. Results. None of the 11 surgical patients experienced perioperative mortality or major neurologic complications. Three of these patients survived, but two had recurrent disease at last follow-up; their 2-year overall survival and disease-free survival rates were 24.5% and 18.2%, respectively. In contrast, all patients treated with chemoradiation or palliation died within 15 months. Median survival time was 16.5 months in the surgery group, 11.5 months in the chemoradiation group, and 3 months in the palliation group (p=0.025). [ABSTRACT FROM AUTHOR]

Objective: De novo cancers of head and neck area in solid organ transplantation recipients show standardized incidence ratio (SIR) of 3.8. Immunosuppression following transplantation is suggested to play as a crucial factor in pathogenesis of secondary malignancy. Prognosis of head and neck cancer arising in solid organ transplantation recipients is proven to have poor prognosis. The incidence, risk, prognosis, and survival of de novo malignancy of head and neck area in solid organ transplantation recipients in single-tertiary medical center followed up for 20 years.Methods: A retrospective medical record review of the patients who received solid organ transplantation in Asan Medical Center from 1997 to 2016 was conducted. Patients confirmed as de novo malignancy in the head and neck area after organ transplantation were included, and presented as in the case-series format. Patients with previous history of head and neck malignancy, irradiation history of head and neck area, cutaneous malignant lesion, hematopoietic malignant lesion, malignancy of thyroid and parathyroid gland and metastatic lesions newly developed in head and neck area were excluded. The incidence of head and neck malignancy in South Korea were reviewed from the National Cancer Information Center of South Korea. For the statistical analysis, standardized incidence ratio (SIR) was obtained with 95% confidence interval.Results: Solid organ transplantation recipients show 20 times higher incidence of de novo cancer of head and neck area compared to general population. Of 13 de novo head and neck malignancy arising after solid organ transplantation, 2 (15.4%) patients were unable to withstand definitive management due to poor general condition. 2 (15.4%) patients had loco-regional recurrence, 1 (7.7%) patient with distant metastasis, and 3 (23.1%) patients died of cancer progression.Conclusion: Immunosuppression following solid organ transplantation gives a twenty-fold increased risk for the development of de novo head and neck cancer. A more precise and frequent checkup on head and area should be planned, suggesting a multi-disciplinary approach in combination with organ transplantation team. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is commonly associated with a high risk of malnutrition and sarcopenia, related to adverse clinical outcomes. This study evaluated the prognostic values of body composition on recurrence and survival in patients with advanced-stage HNSCC. This study prospectively enrolled 258 consecutive patients with definitive treatments for advanced-stage HNSCC. For the determination of sarcopenia, the cross-sectional area of the skeletal muscles (SMs) was measured at the level of the third lumbar vertebra on the computed tomography images of whole-body 18F-fluorodeoxyglucose positron-emission tomography/computed tomography before and after treatments. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the prognostic factors of disease-free survival (DFS) and overall survival (OS). Pretreatment and post-treatment diminished SM masses (sarcopenia) were found in 17 (6.6%) and 32 (12.4%) of 258 included patients, respectively. All values of body composition, SM index, visceral fat area, lean body mass, fat mass and body mass index significantly decreased after treatment (all P < 0.05). Multivariable analyses showed that age, Charlson comorbidity index, pretreatment and post-treatment sarcopenia, pretreatment hypoalbuminaemia, p16 status and tumour site remained the independent variables predictive of DFS and OS outcomes (all P < 0.05). Patients with sarcopenia before or after treatment had about threefold increased risk of overall recurrence or death. Diminished SM mass may predict recurrence and survival after definitive treatments in patients with advanced-stage HNSCC. • Skeletal muscle mass was measured from computed tomography images at L3 before and after treatment. • Pretreatment and post-treatment sarcopenia were found in 6.6% and 12.4%, respectively. • Most body composition parameters significantly decreased after treatment. • Sarcopenia is the independent risk factor for disease-free and overall survival after treatment. • Sarcopenia was associated with about threefold increased risk of overall recurrence or death. Condensed Abstract : This study evaluated the prognostic values of body composition on recurrence and survival in 258 patients with advanced-stage head and neck squamous cell carcinoma. Sarcopenia was the independent risk factor for poorer disease-free and overall survival outcomes after definitive treatments, showing about threefold increased risk of overall recurrence or death. [ABSTRACT FROM AUTHOR]

Objectives: Current guidelines recommend chest computed tomography (CT) with locoregional CT/magnetic resonance imaging for patients with head and neck squamous cell carcinoma (HNSCC), and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT is suggested for stage III-IV patients. However, whole body screening with 18F-FDG PET/CT may provide better detection of distant metastases and synchronous cancer than conventional imaging. We evaluated the utility of 18F-FDG PET/CT in detecting distant metastasis and synchronous cancer.Methods: This prospective study enrolled 740 consecutive patients with previously untreated HNSCC diagnosed between September 2010 and December 2015. Synchronous cancer was histologically confirmed and distant metastases were confirmed by biopsy or serial imaging follow-ups. McNemar test was used to compare the true-positive detection rates of chest radiography (CXR) + head and neck CT (hnCT) (A) versus 18F-FDG PET/CT (C) and chest CT + hnCT (B) versus 18F-FDG PET/CT.Results: Distant metastases and synchronous cancer were found in 23 (3.1%) and 55 (7.4%) patients, respectively. A, B, and C detected distant metastases in 10 (1.3%), 19 (2.6%), and 21 (2.8%) patients, respectively. The absolute differences were 1.5% (A versus C, P = 0.003) and 0.3% (B versus C, P = 0.687). A, B, and C detected synchronous cancer in 15 (2.0%), 22 (2.9%), and 36 (4.9%) patients, respectively. The absolute differences were 2.8% (A versus C, P < 0.001) and 1.4% (B versus C, P = 0.013).Conclusions: 18F-FDG PET/CT detected more distant metastases and synchronous cancer than CXR + hnCT and more synchronous cancer than chest CT + hnCT. [ABSTRACT FROM AUTHOR]

Background Circulating biomarker (CB) is a convenient, emerging predictive tool for treatment response and outcomes in human cancers. Therefore, we examined the prognostic value of pre-treatment and early post-treatment CBs and their summated scores in patients with head and neck squamous cell carcinoma (HNSCC). Methods This study prospectively included 310 consecutive patients who underwent definitive treatment for previously untreated advanced-stage HNSCC between 2010 and 2015. The CB score was determined by complete blood counts (CBCs) and blood chemistry before and 2 months after the treatment, and the number of abnormal CB was counted from 0 to 10. Univariate and multivariate analyses with Cox proportional hazards models were used to find factors associated with disease-free survival (DFS) and overall survival (OS). Results Most CBC profiles were significantly changed at 2-months post-treatment compared with those at pre-treatment. Univariate analyses showed that hypoalbuminemia, leucocytosis, C-reactive protein, high CB scores (≥6), age, performance status and comorbidity and tumour site were significantly associated with DFS and OS (all P < 0.05). Both pre- and post-treatment CB scores were independent factors predictive of DFS and OS outcomes in the multivariate analyses ( P < 0.05). High CB scores at pre-treatment were associated with 7–10-fold increased risk of unfavourable DFS and OS outcomes, and those at 2-months post-treatment were associated with 2 to 4-fold increased risk of poor survival outcomes (all P < 0.05). Conclusions CB scores at pre-treatment and early post-treatment are useful for predicting survival outcomes in patients with advanced-stage HNSCC. [ABSTRACT FROM AUTHOR]

Background Posttreatment detection of recurrence may lead to salvage treatment and prognostic prediction in patients with head and neck squamous cell carcinoma (HNSCC). We evaluated the diagnostic and prognostic values of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) after definitive treatment of HNSCC. Methods This prospective study included 278 consecutive patients who underwent curative surgery ( n = 143, 51.4%) or definitive radiotherapy/chemoradiotherapy ( n = 135, 48.6%) for previously untreated HNSCC. The patients were regularly followed up and evaluated by 18 F-FDG PET/CT, head and neck CT/magnetic resonance imaging (MRI), and chest CT at regular intervals after treatment. The imaging interpretations were compared with the histological results for recurrence. Receiver operating characteristics curves analysis, McNemar's test and logistic regression using generalised estimating equations were used to compare the diagnostic accuracy of 18 F-FDG PET/CT and standard imaging of CT/MRI or chest CT, and a Cox proportional hazards model was used to assess the prognostic value of PET/CT. Results During a median follow-up of 44 months (range, 24–62 months), 73 patients (26.3%) had recurrence or persistent diseases. The area under curves for 18 F-FDG PET/CT and CT/MRI were 0.975 (0.964–0.992) and 0.789 (0.713–0.874), respectively ( P < 0.001). 18 F-FDG PET/CT detected 65 of 66 recurrences (98.5%) not suggested by physical examination and endoscopy. Positive findings on 18 F-FDG PET/CT scans were independent predictors of poorer cancer-specific and overall survival outcomes ( P < 0.01). Conclusions Posttreatment 18 F-FDG PET/CT surveillance helps to properly detect recurrence and to predict the survival following treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Purpose Malnutrition and systemic lymphopenia are common in many cancers and are associated with tumor progression. The purpose of this study was to investigate the prognostic values of nutritional and hematologic markers in patients with head and neck squamous cell carcinoma (HNSCC). Methods This prospective study included 153 patients with treatment-naïve HNSCC who underwent definitive chemoradiotherapy. Body weight, serologic and hematologic parameters were measured at baseline and after 2 months of treatment. Univariate and multivariate analyses using Cox proportional hazards model were used to identify predictors of progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results Body weight, body mass index (BMI), serum albumin, total serum proteins, hemoglobin, and circulating neutrophil, lymphocyte, monocyte, and platelet counts significantly decreased, but neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) significantly increased after 2 months of treatment ( P < 0.05 each). Multivariate analyses showed that pretreatment hypoalbuminemia and high NLR were independent predictors of PFS ( P < 0.01 each). ECOG performance status, BMI < 18.5 kg/m 2 and NLR were independent predictors of CSS and OS ( P < 0.01 each). Conclusions Our data support the evidence that several nutritional and hematologic markers are associated with the prognosis of HNSCC. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) (+) tonsil squamous cell carcinoma (TSCC) responds well to concurrent chemoradiation therapy (CCRT) and demonstrates a favorable prognosis. However, cases of HPV (+) TSCC-related death remain unresolved. We evaluated the distribution and prognostic value of inflammatory cells in HPV (+) TSCC.Methods: We reviewed the medical records of 53 patients who were diagnosed with TSCC. HPV (+) TSCC was confirmed using HPV DNA PCR and immunohistochemical p16 overexpression. The numbers of CD4 (+), CD8 (+), and CD68 (+) stained cells were used to evaluate peritumoral lymphocyte infiltration. Patients were divided into two groups according to the mean numbers of stained cells and the mean ratios of each cell type.Results: HPV (+) was noted in 39 patients. During the follow-up period, 27 patients had no evidence of disease, 2 patients showed disease, and 10 patients died of disease. In this group, advanced T and N stages were not related to overall or disease-specific survival outcomes. The overall survival rate was affected by a high CD68 (+) (HR=19.8; P=0.040) and low CD8/CD4 ratio (HR=7.7, P=0.025). The disease-specific survival rate was affected by a high number of CD68 (+) cells (HR=15.2; P=0.03) and low CD8 (+)/CD4 (+) ratio (HR=3.3; P=0.04).Conclusions: The number of CD68 (+) cells and the distribution of cytotoxic or immunosuppressive T lymphocytes could be determining factors for CCRT outcomes in HPV (+) TSCC patients. [ABSTRACT FROM AUTHOR]

Background Interleukin-4 (IL-4) and interleukin-13 (IL-13) are anti-inflammatory and immunomodulatory cytokines that play crucial roles in cancer progression. However, the clinical significance of the expression of these cytokines and their receptors (IL-4R) in oral cavity squamous cell carcinoma (OSCC) is unknown. Therefore, we evaluated the expression of IL-4R in OSCC specimens by immunohistochemistry (IHC) and analysed its relationship to recurrence and survival. Methods A total of 186 patients with OSCC were enrolled, and the expression of IL-4Rα and IL-13Rα1 on their primary tumour specimens was evaluated by IHC and correlated to clinicopathologic parameters, recurrence and survival. Findings High expression of IL-4Rα and IL-13Rα1 was observed in 60 (32.3%) and 165 (88.7%) patients, respectively. IL-4Rα expression was inversely correlated with parameters reflecting primary tumour burden, including tumour size, tumour stage and depth of invasion at the initial diagnosis ( P < 0.05). High expression of IL-4Rα also correlated with a greater risk of recurrence ( P = 0.002), but was unrelated to cancer-specific survival (CSS, P = 0.118). Conversely, high IL-13Rα1 expression correlated with reduced recurrence ( P < 0.001) and increased CSS ( P < 0.001) in OSCC patients. Interpretations High expression of IL-4Rα correlated with increased recurrence, while high IL-13Rα1 expression had an inverse relationship to recurrence and CSS in OSCC patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] Abnormal 18F-FDG uptakes in the head and neck (HN) region can be carefully interpreted as being index primary, second primary cancer (SP) or benign. [•] 18F-FDG PET/CT identified 91.9% primary HN squamous cell carcinomas (HNSCC). [•] The specificity and negative predictive value of 18F-FDG PET/CT for identification of SP were as high as 98.7% and 99.3%, respectively. [•] Proper detection of primary tumors and SP in the HN region may promote appropriate therapeutic planning of HNSCC patients. [ABSTRACT FROM AUTHOR]

Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry were used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Central compartment lymph node metastasis (CLNM) in patients with laryngeal, hypopharyngeal, or cervical esophageal squamous cell carcinoma is associated with unfavorable clinical outcomes, but cannot be reliably detected using computed tomography (CT)/magnetic resonance imaging (MRI). Therefore, we assessed the clinical utility of using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to identify CLNM in these patients. Patients and methods: A total of 62 patients were preoperatively evaluated using 18F-FDG PET/CT and CT/MRI. Histopathologic analysis of the dissected neck tissues was used as the gold standard for assessing these imaging techniques. The diagnostic value of 18F-FDG PET/CT for detecting CLNM was calculated and compared with CT/MRI. Univariate and multivariate analyses were utilized to determine the factors predictive of CLNM. Results: Of the 62 patients in the study cohort, 12 (19%) had CLNM. Compared with histology, both 18F-FDG PET/CT and CT/MRI demonstrated low sensitivity for detecting CLNM (58% vs 42%, respectively, P =0.625). The specificities of 18F-FDG PET/CT and CT/MRI for the detection of CLNM were 88% and 90%, respectively (P =1.000). Univariate and multivariate analyses showed that clinical metastasis to any cervical lymph node was significantly associated with CLNM (P =0.018). Conclusions: Neither 18F-FDG PET/CT nor CT/MRI is a sensitive diagnostic imaging modality for detecting CLNM. Routine elective central compartment dissection or radiotherapy should be advocated for the treatment of these patients. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Human papillomavirus (HPV), a causative agent of oropharyngeal squamous cell carcinoma (SCC), may be detected in metastatic cervical lymph nodes (MCNs). We investigated whether HPV and p16 expression in MCNs can help identify oropharyngeal primaries in patients with cervical lymph node metastases from an unknown primary tumor (CUP) and predict their survival outcomes. Materials and methods: SCC MCNs of 58 patients with CUP were assayed for HPV by in situ hybridization and for p16 and p53 expression by immunohistochemistry. The presence of HPV and p16 in MCN was correlated with oropharyngeal tumor location and prognosis. Results: Oropharyngeal primaries were found in 20 patients. The sensitivity and negative predictive value (NPV) of HPV for oropharyngeal localization were 90.0% and 92.6%, respectively, and the sensitivity and NPV of p16 were 80.0% and 86.2%, respectively. Multivariate analyses showed that the location of the largest MCN (P =0.035) and HPV (P =0.004) were independent predictors of oropharyngeal tumors. Multivariate analyses showed that p16 expression was an independent predictor of disease-free survival (P =0.030; hazard ratio (HR)=0.286; 95% CI, 0.092–0.887) and that p53 expression (P =0.017; HR=3.154, 95% CI=1.288–8.103) and extracapsular extension of MCN (P =0.010; HR=3.924, 95% CI=1.387–11.097) were independent predictors of overall survival. Conclusion: Detection of HPV and p16 may help identify hidden oropharyngeal primaries in CUP patients and predict their survival outcomes. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Significant laryngeal edema (SLE) after radiotherapy for squamous cell carcinoma of the larynx and hypopharynx may be associated with upper airway obstruction or tumor recurrence. We assessed the risk factors predictive of SLE and those differentiating tumor recurrence from SLE. Patients and methods: We evaluated 127 patients with laryngohypopharyngeal squamous cell carcinomas who were primarily treated with radiotherapy with/without chemotherapy, had no previous major head and neck surgery, and underwent laryngoscopic examinations after radiotherapy. SLE was defined as RTOG grades ⩾2 and patient characteristics and imaging, treatment and survival results were compared in patients with and without SLE. Results: Of the 127 patients, 56 (44%) had SLE. Univariate analyses showed that tumor location, T and N classifications, overall stage, pathologic differentiation, and chemotherapy were significantly predictive of SLE (P <0.05). Multivariate analysis revealed that T classification remained an independent predictor of SLE (T1 vs. T2–4; odds ratio=5.070, 95% confidence interval=1.999–12.857; P =0.001). Twenty-seven (21%) patients had tumor recurrences, diagnosed by PET/CT (sensitivity 88%; specificity 92%) and CT (sensitivity 68%; specificity 88%). Twenty-seven patients with severe SLE were treated but only 9 (33%) had improvement. Tumor recurrence rate was higher (39% vs. 7%, P <0.001) and 3-year overall survival rate lower (54% vs. 87%, P <0.001) in patients with than without SLE. Conclusion: Patients with T2–4 laryngohypopharyngeal cancers are at higher risk of SLE development and tumor recurrence after radiotherapy that can be properly detected by 18F-FDG PET/CT. [ABSTRACT FROM AUTHOR]

Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2–4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT. [Copyright &y& Elsevier]

Summary: We evaluated the clinical utility of combined [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT), as well as CT and magnetic resonance imaging (MRI) in identifying nodal metastases in the contralateral neck in patients with head and neck squamous cell carcinoma (HNSCC). A total of 114 patients were preoperatively evaluated with PET/CT and CT/MRI. Histopathologic analysis from bilateral neck dissection tissues was used as the gold standard in assessing these imaging techniques. Of the 114 patients, 63 (55%) had neck metastases and 26 (23%) had contralateral neck metastases. On a per-level basis, FDG PET/CT was significantly more sensitive and accurate than CT/MRI in the ipsilateral (88% vs. 70%, P <0.01 and 93% vs. 89%, P <0.01, respectively) and contralateral (52% vs. 36%, P <0.01 and 91% vs. 90%, P =0.039, respectively) neck. PET/CT and CT/MRI were less sensitive in detecting contralateral than ipsilateral neck metastases due to the lower incidence of metastases and smaller nodes on the contralateral side. Combined PET/CT is superior to CT/MRI in detecting metastatic neck nodes in HNSCC patients. However, PET/CT may not abrogate the need for contralateral neck surgery or radiotherapy in these patients. [ABSTRACT FROM AUTHOR]

Summary: Targeting hypoxia-inducible factor-1 (HIF-1) active cells in tumors may be an excellent strategy to improve the outcome of radiation therapy. On the basis of the reported role of YC-1 as a HIF-1 inhibitor with anti-cancer activity, we tested the therapeutic efficacy of YC-1 against radioresistance in vitro. The AMC-HN3 cancer cell line, developed from squamous cell carcinoma of the larynx, was cultured under hypoxic conditions or in the presence of cobalt chloride. Both treatments induced nuclear accumulation of HIF-1α protein. Cells cultured under normoxic or hypoxic conditions with and without YC-1 treatment were irradiated and analyzed using flow cytometry and clonogenic assays. In the absence of YC-1 treatment, irradiation induced a greater cytotoxic effect in normoxic cells than in cobalt-treated cells. Treatment of cobalt-treated cells with YC-1 effectively inhibited HIF-1α expression, and enhanced the sensitivity of cells to radiation, decreasing the surviving fraction to that of normoxic cells. Flow cytometry confirmed these results, showing that the sub-G1 fraction was increased in YC-1-treated hypoxic cells after irradiation. Our results suggest that YC-1 treatment may be an effective therapeutic strategy for overcoming the radioresistance of HIF-1α-expressing, hypoxic cancer cells. [Copyright &y& Elsevier]

Summary: The purpose of this study was to evaluate the effect of neuromuscular electrical stimulation (NMES) in patients suffering from dysphagia following treatment for head and neck cancer. In a prospective, double blinded, randomized case control study between January 2006 and December 2007, 14 patients were randomized to 30min of NMES and 30min of traditional swallowing training for 5 days per week for 2 weeks (experimental group), and 12 patients were randomized to sham stimulation plus traditional swallowing training (control group). Effects were assessed using the clinical dysphagia scale (CDS), the functional dysphagia scale (FDS), the American speech-language-hearing association national outcome measurement system (ASHA NOMS) and the M.D. Anderson dysphagia inventory (MADI). Pretreatment evaluation showed no significant differences between the two groups for all parameters. Average changes of FDS score were 11.4±8.1 for the experimental group and 3.3±14.0 for the control group (P =0.039). CDS, ASHA NOMS and MADI showed some difference with treatment, but the changes were not significant (P >0.05). NMES combined with traditional swallowing training is superior to traditional swallowing training alone in patients suffering from dysphagia following treatment for head and neck cancer. [Copyright &y& Elsevier]

Purpose: Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and –II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). Methods and Materials: To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. Results: Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. Conclusion: The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma. [Copyright &y& Elsevier]

Summary: Tumor hypoxia is associated with poorer outcome in patients with head and neck carcinomas, but little is known about hypoxia biomarkers in oral tongue cancer. We evaluated whether hypoxia biomarkers and clinicopathologic variables were prognostic predictors in patients with T2-staged squamous cell carcinoma (SCC) of the oral tongue. Tissue microarrays were constructed from formalin-fixed tumor blocks of 43 patients with T2-staged tongue SCCs treated by surgical resection and neck dissection. Tissue samples were stained with monoclonal antibodies to hypoxia-inducible factor (HIF)-1α, HIF-2α, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR). Locoregional control and survival rates were calculated by the Kaplan-Meier method, and prognostic factors were calculated from uni- and multivariate analyses. Tumor thickness was correlated with expression of CA-9 and GLUT-1 and nodal classification was correlated with GLUT-1 expression. The nodal metastasis rate was 51%, and the 5-year locoregional control and disease-specific survival (DSS) rates were 59% and 69%, respectively. Univariate analysis showed that HIF-1α and EPOR expression were significantly related to DSS. Multivariate analysis showed that EPOR expression was an independent predictor of DSS (P =0.030). EPOR expression may be an independent predictor for DSS in patients with T2-staged SCC of the oral tongue. [Copyright &y& Elsevier]

Summary: The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%–97% vs. 86–88% for primary; 92%–93% vs. 85%–86% for neck on a level-by-level basis; P <.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection. [Copyright &y& Elsevier]

Summary: In order to determine the efficacy and proper timing of routine PET scans for surveillance of recurrent head and neck squamous cell carcinoma (HNSCC), we evaluated the diagnostic performance of routine PET scans in relation to time interval from completion of treatment. Amongst 206 retrospectively evaluated post-treatment PET scans of 159 patients with HNSCC, 156 were performed for routine surveillance in subclinical cases. Diagnostic performance of PET scan and follow-up outcome were evaluated in relation to the time interval (2–6months, 6–12months, 12–24months, and >24months) of PET scan from the completion of treatment. Overall sensitivity and NPV of these PET scans for recurrence were 92.5% and 94.8%, compared with 55.0% and 76.9% for conventional evaluation methods. In the 156 routine scans, the diagnostic sensitivity, specificity, and NPV for locoregional recurrence were 90%, 91% and 97%, respectively, and the values for distant metastases and second primary cancers were 100%, 97% and 100%, respectively. The diagnostic accuracy of routine PET scans was not significantly altered by the time interval. Most (97%) of true negative cases on routine PET scans had no recurrence during a median 14months follow-up. PET scan may be a useful tool in routine surveillance for detection of recurrence in subclinical patients. For routine surveillance, the initial PET scan should be performed within 6months after completion of treatment and the proper timing of next routine PET scan for subclinical patient with initial negative PET result might be 1year after initial PET scan. [Copyright &y& Elsevier]

Summary: The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1month before RT, and follow-up FDG-PET scans were performed 1month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1month after completion of RT was not too rapid for evaluating the response to radiation. [Copyright &y& Elsevier]

Objectives: Pre- and post-treatment 18F-FDG PET/CT may have a prognostic role in human cancers. 18F-FDG PET/CT after primary surgery for head and neck cancer might also predict survival. Therefore, we evaluated the prognostic value of post-treatment 18F-FDG PET/CT in primary surgical patients with advanced-stage head and neck squamous cell carcinoma (HNSCC).Materials and Methods: This prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also had 18F-FDG PET/CT scanning at a median 6 months after surgery. Post-treatment 18F-FDG PET/CT was considered positive, based on interpretation by experienced nuclear medicine physicians with integrating clinical information. Positive and negative predictive values (PPV and NPV) for positive 18F-FDG PET/CT in association with recurrence were calculated. Predictors for positive post-treatment 18F-FDG PET/CT were evaluated using binary logistic regression. Survival analysis was performed using Cox proportional hazard regression analysis.Results: PPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P < 0.001). Five-year overall survival rates for patients with positive and negative PET/CT were 48.1% and 92.3%, respectively. Corresponding 5-year disease-free survival rates were 22.5% and 82.4%, respectively. Perineural invasion, positive resection margin, positive pathological node, and extranodal extension were the independent predictors of positive 18F-FDG PET/CT (all P < 0.05).Conclusions: Post-treatment 18F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC. [ABSTRACT FROM AUTHOR]