The valuable role of dynamic 18F FDG PET/CT-derived kinetic parameter Ki in patients with nasopharyngeal carcinoma prior to radiotherapy: A prospective study.

BACKGROUND AND PURPOSE: Dynamic positron emission tomography/computed tomography (PET/CT) served the potential role of characterizing malignant foci. The main objective of this prospective study was to explore the advantage of dynamic PET/CT imaging in characterizing nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Patients with probable head and neck disease underwent a local dynamic PET/CT scan followed by a whole-body static scan. Patlak analysis was used to generate parametric influx rate constant (Ki) images from 48 frames obtained from a dynamic PET/CT scan. By delineating the volumes-of-interest (VOIs) of: primary tumor (PT), lymph node (LN), and normal nasopharyngeal tissues (N), we acquired the corresponding Ki mean and SUVmean of each site respectively to perform the quantitative statistical analysis. RESULTS: Qualified images of 71 patients with newly diagnosed NPC and 8 without nasopharyngeal malignant lesions were finally included. We found the correlations between Ki mean-PT and critical clinical features, including clinical stage (r = 0.368), T category (r = 0.643) and EBV-DNA copy status (r = 0.351), and Ki mean-PT differed within the group. SUVmean-PT showed correlations with clinical stage (r = 0.280) and T category (r = 0.472), but could hardly differ systematically within group of clinical features except T category. Ki mean-LN offered the positive correlations with N category (r = 0.294), M category (r = 0.238) and EBV-DNA copy status (r = 0.446), and differed within the group. In addition, Ki mean represented a sensitivity of 94.4 % and a specificity of 100 %, in distinguishing NPC from the non-NPC, when the cut-off was defined as 0.0106. When the cut-off of SUV being defined as 2.03, the sensitivity and specificity were both 100 %. CONCLUSION: Our research confirmed Ki compared favorably to SUV in characterizing NPC and found that Ki can serve as an effective imaging marker of NPC.

Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial.

BACKGROUND: Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC. MATERIALS AND METHODS: A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate. RESULTS: The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR. CONCLUSION: Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570.

Insight of a Metabolic Prognostic Model to Identify Tumor Environment and Drug Vulnerability for Lung Adenocarcinoma.

Metabolic reprogramming is a novel method for the treatment of malignant tumors. The exploration of metabolism procedures between radiosensitive and radioresistant tumors may provide novel perspectives for lung adenocarcinoma (LUAD) patients after radiation therapy. In our study, metabolic reprogramming and immune response changes were found between radioresistant cell line (A549RR) and its parent cells (A549) using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Nucleotide/amino acid, lipid, and glucose metabolic process, including Alanine, aspartate and glutamate metabolism, Tryptophan/Tyrosine metabolism, Butanoate metabolism, Purine/Pyrimidine metabolism, were screened out. Then molecular signatures database and The Cancer Genome Atlas Program (TCGA) lung adenocarcinoma datasets were used to identify metabolism-related genes (MRGs) between radiosensitive and radioresistant lung adenocarcinoma (LUAD) cells. A metabolism-based prognostic model, receiver operating characteristic (ROC) curve and nomogram were constructed using Metabolism Score calculated by 14 metabolism-related genes (MRGs). Three independent public datasets, (GSE72094, GSE3141, GSE8894) and one immunotherapy cohort (IMvigor210) were used as external validation cohorts. Expression of 14 hub genes in cells, normal and LUAD specimens were explored by Human Protein Atlas, TIMER2.0 and RT-qPCR. Patients with low-Metabolism Scores were correlated with longer survival times, higher response rates to immune checkpoint inhibitors (ICIs), different immune cell infiltrations and drug vulnerability. Our study demonstrated a comprehensive landscape between radiosensitive and radioresistant LUAD, and provide novel targets for NSCLC, especially those patients received radiation therapy. Moreover, this metabolism-based prognostic model may help to investigate connections between radiosensitivity, immune response, metabolic reprogramming, and patients' prognosis.

Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis.

Introduction: Previous studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear. Methods: We collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC. Results: Patients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04-12.77, p = 0.004). Conclusions: The present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.

Clinical Characteristics and Prognosis of Small Cell Carcinoma in the Nasopharynx: A Population-Based Study.

BACKGROUND: Nasopharyngeal small cell carcinoma (SmCC) is a rare histological type of nasopharyngeal cancer, and its prognosis remains poor. This study aimed to determine the clinical characteristics and survival prognostic factors of nasopharyngeal SmCC. METHODS: Detailed clinicopathologic and therapeutic characteristics of a patient diagnosed with nasopharyngeal SmCC were determined. Nasopharyngeal SmCC cases reported previously were reviewed and summarized. Furthermore, a retrospective analysis was performed on data from the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier analysis was conducted to compare survival within groups. Univariate and multivariate analyses were performed to investigate prognostic factors. RESULTS: A nasopharyngeal SmCC patient treated with chemoradiotherapy who achieved 46 months long-term survival was reported. In reviewing 16 reported cases with epidemiologic and therapeutic details, we found most of nasopharyngeal SmCC patients were diagnosed with advanced grades and received chemoradiotherapy. In total, 13,993 cases of nasopharyngeal cancer were extracted from the SEER database, from which 57 nasopharyngeal SmCC cases were eventually screened out. The mean age of the patients was 55.70 years, and 64.9% of these cases were either grade III or IV; the median overall survival (OS) was 18 months. Statistically significant differences were observed in the OS values of groups categorized by age (P = .025) or radiotherapy (P = .037). Age (<70 years) and radiotherapy were identified as independent survival and prognostic factors. CONCLUSION: Patients with nasopharyngeal SmCC are usually diagnosed with advanced grades and have poor prognoses; nevertheless, they can benefit from radiotherapy with prolonged overall survival.

Pathological and genomic phenotype of second neuroendocrine carcinoma during long-term follow-up after radical radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Second head and neck neuroendocrine carcinoma (NEC) after radical radiotherapy for nasopharyngeal carcinoma (NPC) treatment is rarely reported. The prognosis of second cancer is poor, and our research focuses on finding a breakthrough in the treatment. In this study, we aimed to investigate clinicopathological characteristics and to identify the genomic landscape of second head and neck NECs. METHODS: We collected five second head and neck NEC cases in the recent three years from our patient database. Clinicopathological data and images were obtained. Genomic analysis was performed using high-throughput second generation sequencing. KEGG pathway enrichment analyses between high-frequency mutations were performed using the STRING database. RESULTS: All patients had been diagnosed with second NEC, according to the pathological observations. The interval between diagnosis of NPC and NEC ranged from 10 to 18 years. Two patients had brain or liver metastasis at three and nine months, respectively, after the diagnosis of NEC. Three patients died of the disease with the overall survival time ranging from three to nine months. Commonly altered genes (50%) in second head and neck NECs included TP53, RB1, NOTCH2, PTEN, POLG, KMT2C, U2AF1, EPPK1, ELAC2, DAXX, COL22A1, and ABL1. Those genetic lesions might affect p53 signaling, MAPK signaling, PI3K-Akt signaling, sphingolipid signaling, and neurotrophin signaling pathways. CONCLUSIONS: Second head and neck NECs had poor prognosis. We revealed, for the first time, the mutational landscape, high-frequency somatic mutations, and potential signaling pathways of second head and neck NECs. Its optimal treatment model needs to be further studied in future clinical trials.

Anlotinib as a promising inhibitor on tumor growth of oral squamous cell carcinoma through cell apoptosis and mitotic catastrophe.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism. METHODS: Data from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe. RESULTS: Higher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p < 0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe. CONCLUSIONS: Anlotinib could exert an antitumor effect on oral cancer cell lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.