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Purpose: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC).Methods: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS).Results: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175).Conclusion: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates. [ABSTRACT FROM AUTHOR]

Abstract: We aimed to investigate the prognostic significance of combined pretreatment lymphocyte counts (LCs) and body mass index (BMI) in patients with head and neck cancer (HNC) treated with radiation therapy (RT). Nine hundred and twelve patients with HNC who were treated with RT were retrospectively reviewed. Survival was analyzed by stratifying the patients according to pretreatment LCs and BMI. Patients with low pretreatment LCs and BMI were characterized by a more advanced T stage, fewer nasopharyngeal subsites, less smoking and drinking, and fewer comorbidities. Patients with low pretreatment LCs and BMI had a significantly poorer overall and distant metastasis‐free survival than those with high pretreatment LCs and BMI. No significant differences were observed in terms of local or regional recurrence‐free survival. Combined pretreatment LCs and BMI may be more effective at predicting overall and distant metastasis‐free survival in patients with HNC treated with RT. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18 F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC.Study Design: Retrospective cohort study.Methods: We examined 101 patients with primary NPC who underwent pretreatment 18 F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features.Results: The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001).Conclusions: Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity.Level Of Evidence: 4 Laryngoscope, 127:E22-E28, 2017. [ABSTRACT FROM AUTHOR]

Objectives: Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme. Methods: A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures. Results: Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001). Conclusion: OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Reliable prognostic factors that serve as a guide to follow-up of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) have not yet been identified. We sought to investigate the prognostic implications of post-therapy PET in patients with NPC treated with chemoradiotherapy. Methods: Patients with locoregionally advanced NPC (stages III and IVa-b) who had completed primary curative treatment for 3 months were eligible. All of the patients underwent F-FDG PET and conventional work-up (CWU) for the assessment of treatment response. Results: A total of 165 patients were enrolled. Over a median follow-up of 58 months, 30 patients died and 41 had disease recurrence. The results of the 3-month post-therapy PET and total lesion glycolysis (TLG) of the primary tumor were independent predictors of overall survival. TNM tumor stage, TLG, and post-therapy PET findings were independently associated with disease-free survival (DFS). The results of post-therapy PET were more predictive of DFS than TNM tumor stage ( P < 0.001 vs. P = 0.005). Among patients with stage IVa-b disease, there was a trend toward better 5-DFS rates in patients with a complete metabolic response (CMR) on PET than in those who showed a complete response in the CWU (5-year DFS = 70.7 vs. 63.1 %). Notably, the 1- and 2-year DFS rates were significantly better in the former group compared with the latter. In contrast, the results of post-therapy CWU were not a reliable predictor for DFS. Conclusion: The results of post-therapy PET are an important independent prognostic factor in locoregionally advanced NPC. CMR on PET is associated with better DFS rates and could serve as a guidance to individualize the surveillance protocols for patients with stage IVa-b disease. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To investigate the role of PET-derived imaging markers in predicting metastatic nasopharyngeal carcinoma (NPC) outcomes. Materials and methods: A total of 56 patients with metastatic NPC were enrolled. Before treatment, all of the participants underwent 18F-FDG PET/CT. The following 18F-FDG PET parameters were assessed: standardised uptake value, metabolic tumour volume (MTV), and total lesion glycolysis. Multivariate Cox proportional hazards models were used to identify the independent predictors of survival. Results: The multivariate analysis showed that performance status>1 (P =0.007), Epstein–Barr virus (EBV) DNA titre>5000copies/mL (P =0.001), and MTV>110mL (P =0.013) were independent risk factors for progression-free survival (PFS). Male sex (P =0.004), performance status>1 (P <0.0001), EBV DNA level>5000copies/mL (P <0.0001), and MTV>110mL (P =0.003) independently predicted overall survival (OS). The 2-year PFS and OS rates of the patients with MTV⩽110mL were 23.2% and 43%, respectively, compared with 0% and 9.1%, respectively, for those with MTV>110mL. Combining the MTV with the EBV DNA titre allowed further survival stratification by dividing the patients into three groups with distinct PFS (2-year rates=30.8%, 7.1%, and 0%, P <0.0001) and OS (2-year rates=68.4%, 40%, and 0%, P <0.0001) rates. Conclusion: The MTV appears to be an independent risk factor in metastatic NPC patients. This factor is complementary to the EBV DNA titre for predicting survival in metastatic NPC. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus type 16 (HPV-16) positivity is associated with favourable survival in oropharyngeal squamous cell carcinoma (OPSCC). We report here a study of the prognostic significance of F-FDG PET/CT functional parameters and HPV-16 infection in OPSCC patients. Methods: We retrospectively analysed 60 patients with stage III or IV OPSCC who had had a pretherapy F-FDG PET/CT scan and had completed concurrent chemoradiotherapy ( n = 58) or curative radiotherapy ( n = 2). All patients were followed up for ≥24 months or until death. We determined total lesion glycolysis (TLG) and the maximal standardized uptake values (SUV) of the primary tumour and neck lymph nodes from the pretherapy F-FDG PET/CT scan. Optimal cut-offs of the F-FDG PET/CT parameters were obtained by receiver operating characteristic (ROC) curve analyses. Pretherapy tumour biopsies were studied by polymerase chain reaction to determine HPV infection status. Results: The pretherapy tumour biopsies were positive for HPV-16 in 12 patients (20.0 %). Cox regression analyses revealed HPV-16 positivity and tumour TLG >135.3 g to be independently associated with overall survival ( p = 0.027 and 0.011, respectively). However, only tumour TLG >135.3 g was independently associated with progression-free survival, disease-free survival and locoregional control ( p = 0.011, 0.001 and 0.034, respectively). A scoring system was formulated to define distinct overall survival groups using tumour TLG and HPV-16 status. Patients positive for HPV-16 and with tumour TLG ≤135.3 g experienced better survival than those with tumour TLG >135.3 g and no HPV infection ( p = 0.001). Conclusion: Tumour TLG was an independent predictor of survival in patients with locally advanced OPSCC. A scoring system was developed and may serve as a risk stratification strategy for guiding therapy. [ABSTRACT FROM AUTHOR]

Background To investigate the pretreatment copy number and the clearance rate of plasma Epstein-Barr virus (EBV) DNA as novel prognostic outcome markers for metastatic nasopharyngeal carcinoma (NPC). Methods Seventy-three patients with metastatic NPC were treated at outpatient department. Plasma EBV DNA concentrations and half-life values of plasma viral clearance rates, were determined by real-time quantitative polymerase chain reaction. Results Treatment response evaluated after 3 to 6 months of treatment showed that the overall response rate was 53.5%. The pretreatment plasma EBV DNA concentrations and the half-life of plasma EBV DNA clearance rates had significant effects on treatment response and overall survival prediction. In the chemotherapy regimen, gemcitabine plus cisplatin had a better treatment outcome than the cisplatin plus oral UFT and calcium folinate-based regimens. Conclusions The pretreatment plasma EBV DNA copy number and their clearance rates are significant predictors for NPC treatment outcome. © 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (>0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies. [ABSTRACT FROM AUTHOR]

Background: Sinonasal adenoid cystic carcinoma is a rare malignancy of the head and neck. Cavernous sinus invasion from sinonasal adenoid cystic carcinoma and its related management have rarely been investigated. This study evaluated the relationship between treatment outcome and cavernous sinus involvement in addition to other parameters. Methods: A retrospective case series study was conducted at a tertiary referral center. The medical records of 47 patients diagnosed with primary sinonasal adenoid cystic carcinoma between 1984 and 2015 were retrospectively reviewed. The survival impact of the primary treatment modalities and the anatomic sites of tumor involvement were analyzed. Results: Cavernous sinus invasion was observed in 8 patients (17%), of whom 7 had ACC tumors originating from the maxillary sinus. The results of univariate analysis revealed that tumor stage, primary surgery, and the absence of skull-base and infratemporal fossa invasion were associated with better overall survival (P = 0.033, P = 0.012, P = 0.011, and P = 0.040, respectively) and better disease-free survival (P = 0.019, P = 0.001, P = 0.017, and P = 0.029, respectively). Multivariate analysis identified primary surgery as the only independent prognostic factor for disease-free survival (P = 0.026). Cavernous sinus invasion by sinonasal adenoid cystic carcinoma was not associated with worse overall survival or disease-free survival (P = 0.200 and P = 0.198, respectively). Conclusions: Because maxillary adenoid cystic carcinoma is associated with a higher rate of cavernous sinus invasion, such cases warrant caution during preoperative planning. Primary surgery as the initial therapy provides better locoregional control and survival for patients with sinonasal adenoid cystic carcinoma. Cavernous sinus invasion did not significantly impact survival; thus, it should not be regarded as a contraindication for curative treatment. [ABSTRACT FROM AUTHOR]

• CT-simulation based radiomic models during radiotherapy carry significant prognostic value for both progression-free survival and overall survival in patients with laryngeal and hypopharyngeal cancer. • Mid-radiotherapy peritumoral and intratumoral radiomic models were superior to AJCC staging and tumor volume. • Mid-radiotherapy peritumoral and intratumoral radiomic models were superior to pre-radiotherapy intratumoral radiomic models. We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO–Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to evaluate whether texture features extracted from 18F-FDG PET/CT images may provide additional prognostic information in patients with metastatic nasopharyngeal carcinoma (NPC).Materials and Method: We retrospectively examined 52 patients with metastatic NPC who underwent assessment of EBV DNA titers and pretreatment 18F-FDG PET/CT imaging. All participants were followed up for at least two years. The following 18F-FDG PET parameters were analyzed: standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and texture parameters. Independent predictors of outcomes were identified using receiver operating characteristic curve analysis and multivariate Cox proportional hazards models.Results: On multivariate analysis, EBV DNA titers > 3500 copies/mL and TLG of metastatic lesions > 138 mL were identified as independent predictors of overall survival (OS) (P = 0.036 and P = 0.047, respectively). Patients were divided into two subgroups based on their EBV DNA titers (high versus low). In the high EBV DNA titer group, a lower homogeneity of distant metastatic lesions and higher TLG values of distant metastatic lesions were independent risk factors for OS (P = 0.033 and P < 0.001, respectively). In the low EBV DNA titer group, a reduced uniformity of distant metastatic lesions and a higher SUVmax of distant metastatic lesions were unfavorable risk factors for OS (P = 0.004 and P = 0.005, respectively). Based on these results, we devised two prognostic scoring systems for the prediction of 2-year OS in each EBV DNA titer group.Conclusion: Some of the PET-derived texture parameters are independent predictors of outcomes in patients with metastatic NPC and provide complementary information to EBV DNA titers. [ABSTRACT FROM AUTHOR]