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Tumor multifocality or bilaterality is associated with increased risk of papillary thyroid carcinoma (PTC) recurrence. However, its prognostic value in clinical outcomes remains controversial. This study aimed to evaluate the association of multifocality or bilaterality with recurrence and survival after total thyroidectomy.This was a retrospective study of 2390 consecutive patients with pathologically confirmed PTC who underwent total thyroidectomy. Multifocality and bilaterality were decided based on the final pathology results, that is, if there were two or more tumor foci and bilateral location, respectively. Primary outcomes were recurrence-free survival (RFS). Cox proportional hazards regression analyses were used to assess the associations of multifocality, bilaterality, and other clinicopathological factors with RFS.Multifocal and bilateral PTC were found in 892 (37.3%) and 593 (24.8%) patients, respectively. Multivariate analyses showed that multifocality, lymphovascular invasion, N category, and number of positive lymph node (5) were significant independent variables predictive of RFS (all P 0.05). Multifocality was associated with adjusted hazard ratios for RFS of 1.93 (95% confidence interval = 1.33-2.80; P = 0.001). In a subset analysis, the prognostic value of multifocality was found to be significant in those patients with PTC 1 cm, but not in papillary thyroid microcarcinoma.Tumor multifocality is an independent risk factor of PTC recurrence after total thyroidectomy. This indicate a more progressive state of disease, being included in risk stratification.

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 Conclusions 18F-FDG PET/CT detected more distant metastases and synchronous cancer than CXR + hnCT and more synchronous cancer than chest CT + hnCT.

The recently published 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system was significantly updated following the thyroid cancer-related guidelines to provide better predictability of survival but not focus on recurrence. Therefore, we compared the predictive values of the 7th and 8th editions of the AJCC staging systems for recurrence-free survival (RFS) and overall survival (OS) after thyroidectomy for papillary thyroid carcinoma (PTC).This retrospective study included 2930 patients who underwent thyroidectomy and neck dissection for previously untreated PTC between 2006 and 2014. TNM stage was defined according to 7th and 8th editions. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between variables and RFS or OS. Multivariate models for the AJCC TNM stages were adjusted for clinical and pathological variables.A significant number of patients classified as T3 with overall TNM stages II-IV in the AJCC 7th edition were down-staged in the 8th edition. Unadjusted T classification and overall TNM staging in both the 7th and 8th editions were significantly associated with RFS and OS rates (P 0.001). After adjustment for clinicopathological factors, the overall TNM stage according to the AJCC 8th edition, but not the 7th edition, remained significantly associated with RFS and OS (P 0.05), with better predictability of recurrence and survival, in patients with PTC.The 8th edition AJCC staging system down-staged a large proportion of PTC patients, resulting in better predictability of recurrence and survival compared to the previous staging system.This study compared the abilities of the 7th and 8th edition AJCC staging systems to predict recurrence and overall survival in 2930 patients with papillary thyroid carcinoma. The updated guidelines down-staged a large proportion of patients, resulting in better prediction of recurrence and survival than the previous staging system.

Pre- and post-treatmentThis 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 hadPPV 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 positivePost-treatment

Objectives Adenoid cystic carcinoma (AdCC) in the salivary gland shows a high rate of distant metastasis, which is related to the resulting poor prognosis. We therefore examined the role of pretreatment 18F-FDG PET/CT for prediction of distant metastasis, recurrence/progression, and survival in AdCC. Methods This study included 52 patients who underwent pretreatment 18F-FDG PET/CT scanning and subsequent treatments for AdCC. Maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between the quantitative measurements of 18F-FDG PET, and progression-free survival (PFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS). Results Distant metastases were found in 20 (39%) patients: 6 (12%) at initial diagnosis and 14 (27%) during the median follow-up of 72 months after treatment. Univariate analyses showed that all the 18F-FDG PET parameters of SUVmax, SUVmean, SUVpeak, MTV, and TLG were significantly associated with overall PFS, DMFS, and OS (all P 14.8 mL showed a 5.9-fold higher risk of distant metastasis and a 4.2-fold higher risk of disease-specific death than those with a lower MTV. Conclusions Quantitative measurements using 18F-FDG PET/CT are useful for predicting tumor progression, distant metastasis, and survival in patients with AdCC.

Soft tissue sarcomas of the head and neck (HNSTS) show various histological types and clinical behaviour. Recently, the 8th edition of the American Joint Committee on Cancer (AJCC) proposed a staging system for HNSTS independent of other body soft tissue sarcomas, which requires validation. Therefore, we evaluated the prognostic factors for the survival of HNSTS patients through a comparison between previous and current AJCC staging systems.This study involved 135 consecutive HNSTS patients who underwent primary surgery, chemoradiotherapy or chemotherapy. Patients were grouped into staged (S) and not staged (NS) cancer according to the AJCC 8th edition staging. Cox proportional-hazard regression analyses were used to identify factors associated with overall survival (OS), and progression-free survival (PFS) in all, S or NS patients.Median follow-up period was 75 months and the 5-year OS and PFS rates of all patients were 67.8% and 53.4%, respectively, which was similar between S and NS groups. Age, tumour size and grade, overall stage (7th edition) and resection margin were the significant prognostic factors for OS and PFS in all patients and NS group (all P 0.05), whereas positive resection margin was the only significant factor for OS and PFS in the S group (P 0.001). While OS was poorly discriminated among different 8th edition T-categories, different 7th edition showed good discrimination among overall stages in all patients and the NS group.The revised staging system may not provide an improved risk stratification for survival of HNSTS patients.

Objectives Diminished skeletal muscle mass (SMM) is a reliable marker of poor survival outcomes in patients with cancer. SMM or body composition is generally assessed at the third lumbar vertebra (L3) by abdominal computed tomography (CT) scans, not routinely evaluated in patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the effectiveness of head and neck CT images to assess SMM in patients with HNSCC for predicting their overall survival. Materials and Methods SMM was assessed in 305 consecutive patients with stage III–IV HNSCC by measuring the cross-sectional area (CSA) at the third lumbar and cervical (C3) vertebrae levels. A formula for predicting the L3 SMM was established using linear regression analysis obtained from C3 CSA and other clinical factors. The actual SMM CSAs measured at L3 level and those obtained from the prediction model were compared using correlation analysis. The predictive power of our formula for estimating overall survival was compared using C-index. Results Median SMM CSAs at the L3 and C3 levels were 174.5 cm2 and 56.3 cm2, respectively, and were not strongly correlated (adjusted R2 = 0.421). Prediction model 2 included the strongest predictive factors including sex, age, weight, and C3 SMM CSA, and significantly increased the L3 SMM correlation power (adjusted R2 = 0.721). The C-index of the prediction model was 0.713 (95% confidence interval 0.692–0.747). Conclusions Head and neck CT imaging might be useful to estimate L3 SMM and predict overall survival in HNSCC patients.

Summary 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.

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 Conclusions Post-treatment 18F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC.

Objectives: PI3K/Akt/mTOR pathway is commonly activated in most cancers and is correlated with resistance to anticancer therapies such as radiotherapy. Therefore, PI3K is an attractive target for treating PI3K-associated cancers. Material and Methods: We investigated the basal expression and the expression after treatment of PI3K inhibitor or Src inhibitor of PI3K/Akt pathway-related proteins in AMC-HN3, AMC-HN3R, HN30 and HN31 cells by performing immunoblotting analysis. The sensitivity to PI3K inhibitors or Src inhibitor was analyzed by MTT assay and clonogenic assay. To determine the antitumoral activity of combination treatment with PI3K inhibitor and Src inhibitor, we used using xenograft mouse model. Results: We found that PI3K regulatory subunit p85 was predominantly phosphorylated in radioresistant head and neck cancer cell line (HN31), which showed resistance to PI3K inhibitors. Next, we investigated mechanism through which PI3K p85 phosphorylation modulated response to PI3K inhibitors. Of note, constitutive activation of Src was found in HN31 cells and upon PI3K inhibitor treatment, restoration of p-Src was occurred. Src inhibitor improved the efficacy of PI3K inhibitor treatment and suppressed the reactivation of both Src and PI3K p85 in HN31 cells. Furthermore, downregulation of PI3K p85 expression by using a specific siRNA suppressed Src phosphorylation. Conclusions: Together, our results imply the novel role of the PI3K regulatory subunit p85 in the development of resistance to PI3K inhibitors and suggest the presence of a regulatory loop between PI3K p85 and Src in radioresistant head and neck cancers with constitutively active PI3K/Akt pathway.

Adenoid cystic carcinoma (AdCC) in the salivary gland shows a high rate of distant metastasis, which is related to the resulting poor prognosis. We therefore examined the role of pretreatmentThis study included 52 patients who underwent pretreatmentDistant metastases were found in 20 (39%) patients: 6 (12%) at initial diagnosis and 14 (27%) during the median follow-up of 72 months after treatment. Univariate analyses showed that all theQuantitative measurements using

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.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.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 (P0.05). 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%, P0.001) and 3-year overall survival rate lower (54% vs. 87%, P0.001) in patients with than without SLE.Patients with T2-4 laryngohypopharyngeal cancers are at higher risk of SLE development and tumor recurrence after radiotherapy that can be properly detected by (18)F-FDG PET/CT.

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.

(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P

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.

Endovascular treatments for carotid blowout syndrome (CBS) have been advocated by interventional neuroradiologists. We therefore retrospectively evaluated the efficacy of endovascular treatments of CBS in 16 patients with head and neck cancers (HNC). The clinical, treatment and outcome data were evaluated in 16 HNC patients with CBS, all of whom underwent permanent embolization or covered stent graft of the affected carotid artery. All patients received multimodal treatments, including radiotherapy (mean total dose, 78.5 Gy). CBS was caused by tumor carotid invasion in 8 patients, pharyngocutaneous fistula in 7, and laryngeal chondroradionecrosis in 1, with the external and common carotid arteries being the most common rupture sites. CBS was occluded by embolization or revascularized by covered stent placement. Immediate hemostasis was achieved in all patients; however, 7 patients had recurrent CBS, all of whom were retreated effectively by endovascular management. Three patients had strokes and four had extrusion of intervention materials from the infected wounds. Most patients died of tumor progression, with a mean survival time of five months from initial CBS; only two patients survived. Endovascular therapy, by both permanent occlusion and stent grafts, is effective in hemostasis of CBS but its long-term efficacy may not be high in these HNC patients.

The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in identifying bone metastases in patients with head and neck cancer is not clear. We compared the ability of FDG-PET and bone scintigraphy (BS) to detect bone metastases in patients with upper aerodigestive tract (UADT) malignancies. Patients with histologically confirmed malignancies in the UADT underwent both FDG-PET and BS at initial staging or follow-up. The two methods were compared in patients and in seven skeletal regions. Maximum standard uptake value (SUVmax) on PET was calculated in each lesion and compared between true- and false-positive lesions. This study included 564 eligible patients, of whom 17 had bone metastases. The spine was the most frequently involved site, followed by the lungs and liver. Both FDG-PET and BS had high specificity, accuracy, and negative predictive values for detecting bone metastases (>95% each), and the two methods did not differ in sensitivity, specificity, and predictive values (P>0.05). Both FDG-PET (n=15) and BS (n=14) yielded a significant number of false-positive results, which could be corrected by further work-ups and follow-up imaging. Compared with true-positive lesions, the false-positive lesions on FDG-PET were usually single (86.7% vs. 12.5%, P

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

The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells. The purpose of this study was to investigate the relationship between the expression of Ku70/80 and sensitivity to radiation in cancer cell lines of the head and neck. The sensitivity to radiation in various head and neck cancer cell lines (AMC-HN-1 to -9) was analyzed by colony forming assay. Of the nine cell lines examined, the most radiosensitive cell line (AMC-HN-3) and the most radioresistant cell line (AMC-HN-9) were selected for this experiments. The expression of Ku70/80 was examined after irradiation using real time PCR, Western blotting and immunofluorescence in two different cell lines. Cell cycle distribution after irradiation were analysed. A differential radioresponse was demonstrated by expression of Ku70/80 in AMC-HN-3 and AMC-HN-9 cells. While the expression of Ku70 was slightly increased in the radioresistant AMC-HN-9 cell line, the expression of Ku80 was remarkably increased, suggesting a correlation between Ku80 expression and radiation resistance. Overexpression of Ku80 plays an important role in the repair of DNA damage induced by radiation. Ku80 expression may provide an effective predictive assay of radiosensitivity in head and neck cancers.

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 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. 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 1 month after completion of RT was not too rapid for evaluating the response to radiation.

We evaluated the clinical utility of combined [(18)F]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%, P0.01 and 93% vs. 89%, P0.01, respectively) and contralateral (52% vs. 36%, P0.01 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.

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-1alpha 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-1alpha 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-1alpha-expressing, hypoxic cancer cells.

Few studies have used positron emission tomography (PET) to identify metastases or simultaneous thoracic malignancies in patients with head and neck cancer (HNC). We retrospectively investigated the role of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting thoracic malignancies in patients with previously untreated HNC. Patients (n=86) with HNC and intrathoracic lesions on PET were divided into those who had abnormal FDG uptake in the mediastinum (n=29), lungs (n=34), or both (n=23). Whole body PET and chest computed tomography (CT) results were blindly reviewed and scored by two observers. The accuracy of FDG PET and CT were drawn from patients in whom diagnosis was confirmed, by histopathology or follow-up imaging, and risk factors for thoracic malignancy were analyzed. Malignancy was suspected in 23 of 86 patients (27%) with FDG uptake. Most of the lesions (83%) with abnormal FDG uptake were benign, with thoracic malignancy confirmed in 15 patients (17%). The overall sensitivity, specificity, and accuracy of FDG PET for intrathoracic malignancy in these patients were 80%, 85%, and 84%, respectively. The likelihood of thoracic malignancy in the HNC patients was associated with high FDG uptake of thoracic lesions. FDG PET may reveal lung and mediastinal malignancies with high accuracy in patients with HNC. The thoracic staging by FDG PET may be helpful in therapeutic planning for these patients.

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 (2–6 months, 6–12 months, 12–24 months, and >24 months) 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 14 months 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 6 months after completion of treatment and the proper timing of next routine PET scan for subclinical patient with initial negative PET result might be 1 year after initial PET scan.

Although the practice of neck dissection has greatly advanced from radical to function-preserving surgery, the impact of the sensory nerve-preserving neck surgery on the pain and quality of life (QOL) of patients has received little study. We evaluated neck morbidity and its impact on QOL associated with selective or modified radical neck dissection with or without preservation of cervical root branches. We conducted a retrospective cohort study comparing 24 patients who had their cervical root branches preserved to 29 patients whose root branches were removed during neck dissection. The spinal accessory nerve was preserved and sex, age, pathologic status, side and extent of neck dissection, and radiotherapy were comparable between groups. The groups were compared based on sensory and motor functions of the neck and shoulder and questionnaires on depression and QOL at follow-up of mean 18.7 (range 12-34) months after surgery. The nerve-preserved patients showed a low incidence and severity of neck and shoulder pain compared to the nerve-removed subjects (p.05). Loss of sensation was more frequently experienced in the nerve-removed group on the earlobe and the lateral neck of the operated side (p.05). Depression and QOL scores were higher in the nerve-removed group and significantly correlated with pain intensity. Preservation of the cervical root branches reduces postoperative pain as well as permanent anesthetic areas of the neck. This may also improve the mental state and QOL of patients undergoing neck dissection.

Purpose Tumors originating in the parapharyngeal space (PPS) are rare and comprise of 0.5% of all head and neck tumors. Malignant PPS tumor is associated with unfavorable clinical outcomes but is not reliably detected by preoperative imaging tools. Therefore, we investigate the malignancy rate and the diagnostic values of fine needle aspiration biopsy (FNAB) and imaging tools such as computed tomography (CT)/magnetic resonance imaging (MRI) for detecting malignant tumors in PPS tumors. Material and methods The 35 consecutive patients with surgically treated PPS tumors were retrospectively reviewed at our institution from 1996 to 2010. All study patients were assessed by CT/MRI before surgery. Of them, 24 patients were performed FNAB before surgery. Histopathologic diagnosis was used as the gold standard in assessing preoperative diagnostic modalities. The malignancy rate and their diagnostic value of CT/MRI and FNAB were assessed and compared with those with final diagnosis. Results The malignancy rate of the PPS tumors was 29%. With histologic correlation, both FNAB and CT/MRI for detection of malignant tumor showed low sensitivity (50% and 25%, respectively). The specificity of FNAB and CT/MRI for detection of malignant tumor was 94% and 94%, respectively. There were four false-negative cases that they diagnosed as benign tumors in preoperative fine needle aspiration biopsy. One of them was considered as malignant lesion in CT/MR imagings. There were six false-negative cases that they diagnosed as benign tumors in preoperative imaging. Three of them were considered as malignant lesion in FNAB. Conclusions Diagnostic value for CT/MRI and imaging were relatively low despite not uncommon incidence of malignant PPS tumors. Therefore, even though preoperative diagnosis was benign lesion, malignant possibility should be considered for proper preoperative treatment planning.