T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy.

BACKGROUND: Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20-30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. OBJECTIVES: To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. DESIGN AND METHODS: Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. RESULTS: Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. CONCLUSIONS: Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

Objectives: The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. Materials and methods: This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. Results: From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Conclusion: Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. Clinical trial registration: https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

The baseline oral microbiota predicts the response of locally advanced oral squamous cell carcinoma patients to induction chemotherapy: A prospective longitudinal study.

PURPOSE: Among oral squamous cell carcinoma (OSCC) patients who receive docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy, those with a favorable pathological response tend to obtain satisfactory clinical outcomes, while the total population exhibit no survival benefit. Thus, there is an urgent need to improve the therapeutic effect of TPF by applying personalized treatment according to distinct biomarkers. METHODS AND MATERIALS: In the present study, we collected oral rinse samples from 44 OSCC patients enrolled in our prospective multicenter random phase II trial before TPF induction chemotherapy to conduct 16S rRNA gene sequencing and metagenomic analysis. Patients were administrated with two cycles of TPF induction chemotherapy (75 mg/m2 cisplatin and 75 mg/m2 docetaxel on day 1 and 750 mg/m2 fluorouracil from the first to the fifth day), and then divided into responsive and nonresponsive groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RESULTS: In the 16S rRNA gene sequence analysis, Fusobacterium and Mycoplasma were more enriched in the nonresponsive group, while Slackia was more enriched in the responder group at the genus level. In the metagenomic shotgun sequencing analysis, Fusobacterium nucleatum was more enriched in the nonresponsive group. Functional analysis showed that the platinum drug resistance pathway and microRNAs in cancer and RNA degradation pathways were remarkably associated with patient sensitivity to induction chemotherapy. CONCLUSIONS: Our data suggest that the oral microbiome may play an important role in the OSCC patient sensitivity to TPF induction chemotherapy and offer novel potential biomarkers for predicting the response to TPF induction chemotherapy.

Influence of 4-week or 12-week glucocorticoid treatment on metabolic changes in patients with active moderate-to-severe thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a serious, progressive, vision-threatening and difficult-to-treat organ-specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High-dose intravenous glucocorticoid (IVGC) therapy is considered a first-line treatment for active moderate-to-severe TAO, but there is still insufficient evidence regarding the treatment duration. Long-term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty-eight patients with active moderate-to-severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12-week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p < 0.001), and low-density lipoprotein (p < 0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (p < 0.001). A significant decrease in thyroglobulin antibody levels was found in the 4-week group (p = 0.006). The change in the ADC was higher in the 4-week group than in the 12-week group (p = 0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4-week IVGC therapy was recommended for patients with TAO with glucose and lipid disorders.

The value of scintigraphy, computed tomography, magnetic resonance imaging, and single-photon emission computed tomography/computed tomography for the diagnosis of ectopic thyroid in the head and neck: A STROBE-compliant retrospective study.

Because of its rarity, the exact imaging features of ectopic thyroid are poorly known.To analyze the value of scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT)/CT in the diagnosis of ectopic thyroid in the head and neck.First, we retrospectively analyzed the scintigraphy, CT, MRI, and SPECT/CT images from 25 masses (22 patients) suspected of head and neck ectopic thyroid from 2006 to 2017 at the Shanghai Ninth People's Hospital. Each mass was imaged by nuclear imaging (scintigraphy with or without SPECT/CT) and radiological exam (CT and/or MRI). Pathological examination was considered as the gold standard. Secondly, thirteen malignant ectopic thyroids in the head and neck reported in the English literature from 2001 to 2017 were retrieved for comparison.The accuracy of scintigraphy was not significantly higher than that of CT (94.7%, vs 89.5%, P > .99) or MRI (92.3%, vs 84.6%, P > .99). Five masses which underwent scintigraphy with SPECT/CT were all true positive, while 1 was false negative on MRI, and 2 were false negative on CT. Compared to the benign ectopic thyroids in our study, the 13 malignant ectopic thyroids retrieved from the literature were grossly the same in shape, margins, and invasion on CT or MRI.The number of patients was limited, but scintigraphy combined with SPECT/CT could be a reliable method for the diagnosis of ectopic thyroid. Benign and malignant ectopic thyroids appear to be similar in shapes, margins, and invasion on CT or MRI.

[Effect of "Xinjingjie mouthrinse" on prevention and treatment of radiation-induced oral mucositis].

PURPOSE: To investigate the effect of "Xinjingjie compound lysostaphin antibacterial collutorium" on prevention and treatment of radiation-induced oral mucositis in a prospective, randomized and double-blind clinical trial. METHODS: Sixty patients with oral cancer to be treated with radiotherapy were randomized into the experimental and control group. The experimental group (30 patients) was treated with "Xinjingjie mouthrinse" during the full course of radiotherapy, 4 times daily with 5 mL and 5 min each time. The control group (30 patients) rinsed the mouth in the same way with normal saline. Oral mucositis was assessed according to the RTOG criteria. The severity of mucositis and the degree of pain were recorded and photographed. Patients shouldn't be treated with other drugs until the level of oral mucositis reached above grade III. The results were statistically analyzed using Stata 12.0 software packages. RESULTS: Age, gender, radiotherapy techniques and dose showed no significant difference between the 2 groups (P>0.05). The first onset of oral mucositis in the experimental group was later than that in the control group (11.0 times:9.1 times,P<0.05), and the incidence of pain at the early time of radiotherapy was lower (36.7%: 70.0%, P<0.05). Also, the onset time of grade III oral mucositis in the emperimental group was later than that in the control group (18.9 times:15.9 times,P<0.05), and the incidence of grade III oral mucositis in the experimental group was lower (63.3% vs. 90.0%, P<0.05). CONCLUSIONS: "Xinjingjie mouthrinse" is worthwhile to be used in clinic because it can delay the occurrence time of radiation-induced oral mucositis, alleviate pain and reduce the indication of grade III oral mucositis.

Exploring the dynamic core microbiome of plaque microbiota during head-and-neck radiotherapy using pyrosequencing.

Radiotherapy is the primary treatment modality used for patients with head-and-neck cancers, but inevitably causes microorganism-related oral complications. This study aims to explore the dynamic core microbiome of oral microbiota in supragingival plaque during the course of head-and-neck radiotherapy. Eight subjects aged 26 to 70 were recruited. Dental plaque samples were collected (over seven sampling time points for each patient) before and during radiotherapy. The V1-V3 hypervariable regions of bacterial 16S rRNA genes were amplified, and the high-throughput pyrosequencing was performed. A total of 140 genera belonging to 13 phyla were found. Four phyla (Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria) and 11 genera (Streptococcus, Actinomyces, Veillonella, Capnocytophaga, Derxia, Neisseria, Rothia, Prevotella, Granulicatella, Luteococcus, and Gemella) were found in all subjects, supporting the concept of a core microbiome. Temporal variation of these major cores in relative abundance were observed, as well as a negative correlation between the number of OTUs and radiation dose. Moreover, an optimized conceptual framework was proposed for defining a dynamic core microbiome in extreme conditions such as radiotherapy. This study presents a theoretical foundation for exploring a core microbiome of communities from time series data, and may help predict community responses to perturbation as caused by exposure to ionizing radiation.

Effects of intensity-modulated radiotherapy on human oral microflora.

This study aimed to evaluate changes in the biodiversity of the oral microflora of patients with head and neck cancer treated with postoperative intensity-modulated radiotherapy (IMRT) or conventional radiotherapy (CRT). Pooled dental plaque samples were collected during the radiation treatment from patients receiving IMRT (n = 13) and CRT (n = 12). Denaturing gradient gel electrophoresis (DGGE) was used to analyze the temporal variation of these plaque samples. The stimulated and unstimulated salivary flow rates were also compared between IMRT and CRT patients. Reductions in the severity of hyposalivation were observed in IMRT patients compared with CRT patients. We also observed that the temporal stability of the oral ecosystem was significantly higher in the IMRT group (69.96 ± 7.82%) than in the CRT group (51.98 ± 10.45%) (P < 0.05). The findings of the present study suggest that IMRT is more conducive to maintaining the relative stability of the oral ecosystem than CRT.

Fixation, registration, and image-guided navigation using a thermoplastic facial mask in electromagnetic navigation-guided radiofrequency thermocoagulation.

OBJECTIVE: For fixation, registration, and image-guided navigation, the aim of this study was to evaluate a thermoplastic facial mask with plastic markers in achieving frameless stereotactic radiofrequency thermocoagulation (RFT). STUDY DESIGN: A thermoplastic facial mask was remolded according to each subject's face. Six markers were placed on the surface and 6 inside. Series of 1.25-mm- and 2.5-mm-slice computerized tomography (CT) scans were made to provide radiologic data. During the phantom study, each plastic sphere inside was selected in turn as the target for frameless stereotaxy. The clinical Hartel puncture of the foramen ovale (FO) was imitated using an electromagnetic navigation system. Navigation-guided RFT was tried in 3 patients. RESULTS: The mean location error was 1.29 mm (SD ± 0.39 mm). No significant difference (P > .05) was proven between 1.25-mm and 2.5-mm CT slice acquisition for the image datasets used. The FO punctures in clinical trials were successful and confirmed by CT. CONCLUSIONS: Registration and fixation via a fiducial marker-based thermoplastic facial mask is accurate and feasible for use in navigation-guided RFT.

Computed tomography findings in radiation-induced osteosarcoma of the jaws.

OBJECTIVE: The objective of this study was to report the CT appearances of radiation-induced jaw osteosarcomas (RIJOS) following therapeutic irradiation. STUDY DESIGN: The CT studies of 7 subjects with RIJOS were reviewed retrospectively. RESULTS: RIJOS developed at 3 to 14 years following radiotherapy. Four patients had tumors in the maxilla and 3 in the mandible. Five tumors were osteoblastic, with 1 osteolytic and 1 mixed lesions. Osteoid tumor matrix mineralization was identified in 6 subjects. Periosteal reaction was demonstrated in 6 cases. All subjects showed a soft tissue extension component beyond the area of bone destruction. CONCLUSION: CT is a useful tool to identify RIJOS and plays an important role in preoperative assessment of the extent of the tumor.

FDG-PET/CT of head and neck squamous cell carcinoma in a rat model.

PURPOSE: The aim of this study was to demonstrate the ability to use human clinical positron emission tomography/computed tomography (PET/CT) to detect and investigate head and neck cancers chemically induced by 4-nitroquinoline-1-oxide (4-NQO) in a rat model. STUDY DESIGN: The study design was prospective animal research. PROCEDURES: A head and neck squamous cell carcinoma was established in 20 immunocompetent rats, who drank a 4-NQO solution during 16 weeks. 2-Deoxy-2-[F-18]fluoro-D: -glucose (FDG)-PET/CT was performed for five of them, 34 weeks after the start of the experiment to characterize the tumors. A day following the FDG-PET/CT, rats were euthanized and pathological features were evaluated by hematoxylin-eosin staining. RESULTS: All rats had head and neck tumor at various locations at 34 weeks. Among the five rats selected for having FDG-PET/CT, the clinical examination detected exophytic tumors grown in the oral cavity for three of them (one on the inferior lip, one on the hard palate, and one on the internal side of the cheek). FDG-PET/CT confirmed the presence of those tumors and detected ones located on the base of tongue for three of them. Tumor extensions were characterized and tumor metabolic volumes were measured. The smallest lesion detected measured 3 x 3 x 4 mm. Pathologic examination using hematoxylin-eosin staining confirmed squamous cell carcinoma. CONCLUSIONS: This study demonstrated that FDG-PET/CT is a feasible examination to detect occult primary tumors in rat models. It is useful to follow tumor progression and evaluate therapeutics efficacy.