Tertiary lymphoid structures in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Smoking, drinking, and human papillomavirus (HPV) infection are the main risk factors. Early-stage patients can benefit from radical surgery, chemotherapy, and radiotherapy, but the prognosis of locally advanced, recurrent, or metastatic patients is poor. Programmed cell death receptor 1 (PD-1) inhibitor significantly prolongs the survival of these patients, but only about 20 % of the population can benefit significantly. Exploring effective predictive indicators of immunotherapy efficacy and new therapeutic targets is necessary. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ formed in non-lymphoid tissues, which usually occurs in chronic inflammation including autoimmune diseases, infectious diseases, and tumors. The structure and function of TLS are similar to those of secondary lymphoid organs. The existence of TLS is closely related to the favorable prognosis and immune response of patients. This article will review the formation, prognosis, and predictive value of TLS as well as inducing TLS neogenesis in HNSCC.

Impact of Nutrition Counseling in Head and Neck Cancer Sufferers Undergoing Antineoplastic Therapy: A Randomized Controlled Pilot Study.

Head and neck cancer (HNC) sufferers usually encounter arduous nutritional problems when they are receiving antineoplastic therapy. Consequently, the presence of anxiety and depression is commonly observed in this population. This study aimed to explore the physical and psychological influence of nutritional counseling in patients with HNC. Patients receiving concurrent chemo-radiotherapy were randomly assigned to the nutritional counseling group (n = 32, 52.45%) and the control group (n = 29, 47.54%) according to their treatment patterns. In the nutritional counseling group, registered dietitians provided face-to-face counseling during the antineoplastic treatment course at least every two weeks. Nutrient intake amount, relevant nutritional indexes, quality of life, and the degree of anxiety and depression were compared between the two groups. We observed a decrease in the calorie and protein intake amount in both groups, while the decrease in the control group is even worse. The weight loss is more obvious in the control group. The HADS scores in the intervention group were significantly lower than that in the control group (p < 0.05). The Karnofsky Performance Status (KPS) scores in the intervention group were significantly higher than that in the control group (p < 0.05). The level of serum total protein, serum albumin, transferrin, and the thickness of the triceps skin fold decreased less in the intervention group (p < 0.05). Our findings suggest that nutrition counseling is essential for the maintenance of calorie and protein intake in HNC suffers, which contributes to an improvement in the physical and psychological states. The impacts observed in this pilot study warrant further exploration in a larger prospective trial.

The prognostic value of before treatment neutrophil-to-lymphocyte ratio in nasopharyngeal carcinoma.

OBJECTIVE: The aim of this analysis was to evaluate the prognostic significance of inflammatory biomarkers (NLR, dNLR, PLR and LMR) in NPC patients. METHODS: This was a retrospective analysis of 111 NPC patients from January 2013 and December 2016. Receiver-operating characteristic (ROC) curve was plotted to determine the cut-off values of these inflammatory biomarkers. Univariate analysis and multivariate Cox regression model were used to evaluate the association between these parameters and progression-free survival (PFS) and overall survival (OS). RESULTS: The optimal critical value of NLR was 2.02, by which cases were divided into high NLR group (NLR ≥ 2.02) and low NLR group (NLR < 2.02). The elevated NLR was significantly associated with decreased OS (P = 0.009) and remained significant in multivariate analysis (HR 8.48, 95% CI 1.69-42.46, P = 0.009). CONCLUSIONS: The before treatment NLR may be an independent prognostic biomarker for OS in patients with NPC. NLR, dNLR and PLR might be a useful complement to TNM staging in the prognosis evaluation of NPC patients.

Mepitel Film is superior to Biafine cream in managing acute radiation-induced skin reactions in head and neck cancer patients: a randomised intra-patient controlled clinical trial.

INTRODUCTION: We previously showed that Mepitel Film decreased the severity of acute radiation-induced skin reactions in head and neck cancer patients. In the current study, we compared the effect of Mepitel Film and Biafine cream on skin reaction severity in a larger cohort of head and neck cancer patients. METHODS: A total of 44 head and neck cancer patients were recruited with 39 patients contributing full data sets for analysis. Patients received a dose of 50 Gy in 25 fractions to the bilateral lymph nodes in the neck. Left and right lymph node areas were randomised to either Mepitel Film or Biafine cream, applied prophylactically. Skin reaction severity was measured using Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and expanded Radiation Oncology group (RTOG) grades. Skin dose was measured using gafchromic Film. RESULTS: Skin reaction severity (combined RISRAS score) underneath Mepitel Film was decreased by 30% (P < 0.001) and moist desquamation rates by 41% (P < 0.001). Skin dose underneath Mepitel Film and Biafine cream was similar (P = 0.925) and unlikely to have affected skin reaction severity. The vast majority (80%) of patients preferred Mepitel Film over Biafine cream. Negative aspects of Mepitel Film included poor adherence (11/39) and discomfort (16/39) during hot weather and showering and itchy skin underneath Mepitel Film (12/39). CONCLUSIONS: Mepitel Film was superior to Biafine cream in reducing the severity of acute radiation-induced skin reactions and moist desquamation incidence in our head and neck patient cohort.

Use of Radiomics Combined With Machine Learning Method in the Recurrence Patterns After Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Preliminary Study.

Objective: To analyze the recurrence patterns and reasons in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to investigate the feasibility of radiomics for analysis of radioresistance. Methods: We analyzed 306 NPC patients treated with IMRT from Jul-2009 to Aug-2016, 20 of whom developed with recurrence. For the NPCs with recurrence, CT, MR, or PET/CT images of recurrent disease were registered with the primary planning CT for dosimetry analysis. The recurrences were defined as in-field, marginal or out-of-field, according to dose-volume histogram (DVH) of the recurrence volume. To explore the predictive power of radiomics for NPCs with in-field recurrences (NPC-IFR), 16 NPCs with non-progression disease (NPC-NPD) were used for comparison. For these NPC-IFRs and NPC-NPDs, 1117 radiomic features were quantified from the tumor region using pre-treatment spectral attenuated inversion-recovery T2-weighted (SPAIR T2W) magnetic resonance imaging (MRI). Intraclass correlation coefficients (ICC) and Pearson correlation coefficient (PCC) was calculated to identify influential feature subset. Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were employed to assess the capability of each feature on NPC-IFR prediction. Principal component analysis (PCA) was performed for feature reduction. Artificial neural network (ANN), k-nearest neighbor (KNN), and support vector machine (SVM) models were trained and validated by using stratified 10-fold cross validation. Results: The median follow up was 26.5 (range 8-65) months. 9/20 (45%) occurred in the primary tumor, 8/20 (40%) occurred in regional lymph nodes, and 3/20 (15%) patients developed a primary and regional failure. Dosimetric and target volume analysis of the recurrence indicated that there were 18 in-field, and 1 marginal as well as 1 out-of-field recurrence. With pre-therapeutic SPAIR T2W MRI images available, 11 NPC-IFRs (11 of 18 NPC-IFRs who had available pre-therapeutic MRI) and 16 NPC-NPDs were subsequently employed for radiomic analysis. Results showed that NPC-IFRs vs. NPC-NPDs could be differentiated by 8 features (AUCs: 0.727-0.835). The classification models showed potential in prediction of NPC-IFR with higher accuracies (ANN: 0.812, KNN: 0.775, SVM: 0.732). Conclusion: In-field and high-dose region relapse were the main recurrence patterns which may be due to the radioresistance. After integration in the clinical workflow, radiomic analysis can be served as imaging biomarkers to facilitate early salvage for NPC patients who are at risk of in-field recurrence.

Modulatory effects of the acid polysaccharide fraction from one of anamorph of Cordyceps sinensis on Ana-1 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis has been used as a precious herbal medicine for thousands of years in China. Its polysaccharide fraction has been confirmed possessing immunomodulatory function and we have reported the acid polysaccharide fraction (APSF), from an anamorph of C. sinensis, has stimulating activity on macrophages. The mechanism still needs to be further elucidated. MATERIALS AND METHODS: In order to investigate the effects of APSF on macrophage's phenotypes, Ana-1 mouse macrophages were polarized to M2 phenotype by culturing the cells with culture supernatant of H22 cells. M2 phenotype was determined by measuring the expression of TNF-α and checking cell surface markers mannose receptor (MR) and scavenger receptor (SR). After cultured with H22 supernatant for 72 h, the TNF-α level of Ana-1 cells was decreased while the SR and MR expressions were up-regulated, suggesting that Ana-1 cells were polarized towards M2 macrophages. Then the effects of APSF on M2 macrophages were investigated by measuring mRNA levels of TNF-α, inducible nitric oxide synthase (iNOS), IL-12 and IL-10. Nuclear NF-κB was detected by Western blotting. RESULTS: APSF treatment increased the expressions of TNF-α, IL-12 and iNOS, and reduced the expression of IL-10 of Ana-1 cells. Besides, the expressions of SR and MR were down-regulated by APSF. And the result of Western blotting showed NF-κB level was decreased in M2 macrophages and up-regulated after APSF treatment. CONCLUSIONS: APSF may convert M2 macrophages to M1 phenotype by activating NF-κB pathway.

Effects of the acid polysaccharide fraction isolated from a cultivated Cordyceps sinensis on macrophages in vitro.

The acid polysaccharide fraction (APSF) extracted from the mycelia of cultivated Cordyceps sinensis is water-soluble polysaccharide. In this study we evaluated the modulating effects of APSF on murine macrophage cell line RAW264.7. Phagocytotic assay by neutral red and FITC-dextran internalization showed that APSF stimulated the phagocytosis of macrophages. The nitrite levels in the culture supernatant determined using Griess reagent revealed the elevation of NO production after treatment with APSF. RT-PCR and immunocytochemistry assay indicated that APSF promoted both the mRNA and protein expressions of inducible nitric oxide synthase (iNOS). Furthermore, Western blotting demonstrated that NF-kappaB levels in nucleuses increased after APSF treatment, suggesting that APSF probably stimulated macrophage activities by activating the IkappaB-NF-kappaB pathway.