Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival

Author(s):  
Mizuki Tagami ◽  
Anna Kakehashi ◽  
Atsushi Sakai ◽  
Norihiko Misawa ◽  
Atsuko Katsuyama-Yoshikawa ◽  
...  
2000 ◽  
Vol 18 (7) ◽  
pp. 1458-1464 ◽  
Author(s):  
Branislav Jeremic ◽  
Yuta Shibamoto ◽  
Biljana Milicic ◽  
Nebojsa Nikolic ◽  
Aleksandar Dagovic ◽  
...  

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.


2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.


2019 ◽  
Vol 99 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Youfang Xun ◽  
Maohua Wang ◽  
Haiyong Sun ◽  
Shujun Shi ◽  
Bing Guan ◽  
...  

Objective: The purpose of this study was to demonstrate the prognostic role of inflammatory biomarkers in patients with laryngeal squamous cell carcinoma. Methods: For this study, we enrolled 151 patients who had undergone surgery for laryngeal squamous cell carcinoma. We assessed the preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume, red cell distribution width, and alkaline phosphatase. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were conducted on overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival of patients with laryngeal squamous cell carcinoma. Results: Both Kaplan-Meier analysis and univariate analysis showed significant prognostic differences with age, laryngectomy methods, Tumor Node Metastasis (TNM) staging, tumor location, NLR, PLR, MLR, and mean platelet volume. Multivariate analysis indicated that NLR (overall survival: hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 1.28-7.10, P = .011), PLR (overall survival: HR = 0.33, 95% CI: 0.14-0.78, P = .011; progression-free survival: HR = 0.016,95% CI: 0.10-0.79, P = .016), and MLR (overall survival: HR = 0.29, 95% CI: 0.11-0.76, P = .012) were independent prognostic factors for 5-year survival. However, red cell distribution width and alkaline phosphatase had no significant difference in overall survival and progression-free survival. Conclusions: Preoperative high NLR, PLR, and MLR were associated with poor prognosis. They were found to be effective and reliable inflammatory biomarkers for patients with laryngeal squamous cell carcinoma.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6053-6053
Author(s):  
A. Sukari ◽  
H. Mulrenan ◽  
K. Almhanna ◽  
Z. Kafri ◽  
H. Kim ◽  
...  

6053 Background: In advanced head and neck squamous cell carcinoma (HNSCC), the five-year survival rate is less than 40%. Although the efficacy and tolerability of continuous IV 5-Fluorouracil (5FU) therapy has been established in HNSCC, the feasibility and tolerability of long-term therapy of oral capecitabine has not been established in HNSCC. Our primary objective is to assess the feasibility of treating patients with squamous cell carcinoma of the head and neck (HNSCC) with adjuvant Capecitabine after undergone definitive treatment. The secondary objectives are to estimate time to recurrence, local-regional control and survival rates along with incidence of second primary tumors. Methods: Eligible patients with newly diagnosed locally advanced HNSCC received capecitabine 1,000 mg orally once daily for one year, after undergone definitive treatment. Patients’ compliance with oral capecitabine as will as the side effects profile was evaluated on monthly basis over the first 12 months. Feasibility, survival, progression and progression free survival were measured over 36 months. Results: Thirty five patients were enrolled in the study. 17 patients had stage IV b, 7 had stage III, and 5 had unknown primary HNSCC. All but one took at least 60% of dispensed tablets. Twenty six patients completed at least 7 months of capecitabine. Sixteen patients completed at least 10 month of capecitabine. Two years overall survival rate was 97%. Three years progression free survival was 86%. Conclusions: Adjuvant capecitabine in locally advanced HNSCC is a feasible approach with minimum side effects. A favorable 3-year progression-free survival was found as compare to historical results. We recommend a randomized phase III trail to examine the effect of one year of adjuvant capecitabine versus placebo in locally advanced HNSCC after definitive treatment. No significant financial relationships to disclose.


2021 ◽  
Author(s):  
Ting Yan ◽  
lili liu ◽  
Meilan Peng ◽  
Zhenpeng Yan ◽  
Qingyu Wang ◽  
...  

Abstract Objectives: To construct a prognostic model for preoperative prediction based on computed tomography (CT) images of esophageal squamous cell carcinoma (ESCC). Methods: Radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) with high throughput radiomics features that extracted from the CT images of 272 patients (204 in training and 68 in validation cohort), who were pathologically confirmed ESCC. Multivariable logistic regression was adopted to build the radiomics signature and another predictive nomogram model, which was composed with radiomics signature, traditional TNM stage and clinical features. Then its performance was assessed by the calibration and decision curve analysis (DCA). Results: 16 radiomics features were selected from 954 to build a radiomics signature,which were significantly associated with progression-free survival (PFS) (p<0.001). The area under the curve (AUC) of performance was 0.891 (95% CI: 0.845-0.936) for training cohort and 0.706 (95% CI: 0.583-0.829) for validation cohort. The radscore of signatures’ combination showed significant discrimination for survival status in both two cohort. Kaplan-Meier survival curve further confirmed the radscore has a better prognostic performance in training cohort. Radiomics nomogram combined radscore with TNM staging showed significant improvement over TNM staging alone in training cohort (C-index, 0.802 vs 0.628; p<0.05), and it is the same with clinical data (C-index, 0.798 vs 0.660; p<0.05). Findings were confirmed in the validation cohort. DCA showed CT-based radiomics model will receive benefit when the threshold probability was between 0 and 0.9. Heat maps revealed associations between radiomics features and tumor stages.Conclusions: Multiparametric CT-based radiomics nomograms provided improved prognostic ability in ESCC.


2020 ◽  
Author(s):  
HUAN WANG ◽  
Masayuki Kano ◽  
Yasunori Matsumoto ◽  
Takeshi Toyozumi ◽  
Satoshi Endo ◽  
...  

Abstract Background: Exosomes are nano-sized extracellular vesicles and are detectable in most body fluids. Circulating exosomal microRNAs are an easily obtained, and they could be minimally invasive biomarker for cancer treatment. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas. Radiotherapy is one of the most important treatment option for ESCC, and it would thus be extremely crucial to predict therapeutic sensitivity and the patient prognosis in advance. Methods: A search for miRNAs with a therapeutic biomarker in ESCC was performed using the miRNA expression signatures obtained from ESCC plasma before radiotherapy. miR-191-5p was selected because it was found to be associated with the prognosis in ESCC based on the findings of previous reports. As a result, we decided to perform more studies to elucidate the significance of miR-191-5p. Gain-of-function analyses were performed to evaluate the functional significance of miR-191-5p in ESCC progression. The effects of miR-191-5p on ESCC radiosensitivity were determined by cell proliferation, a clonogenic survival assay and an apoptosis assay. A gene set enrichment analysis was used to investigate the downstream signaling pathway related to the miR-191-5p functions. The 5-year progression-free survival (PFS) rate was used to directly compare the usefulness of these biomarkers for determining the patient prognosis between the miR-191-5p high expression patients and low expression patients. Results: A subset of seven microRNAs (miR-628, miR-363, miR-191-5p, miR-185, miR-148a, miR-320d, miR-30e) was identified to be candidates of therapeutic biomarker for ESCC patients underwent radiotherapy in a global microRNA expression analysis. A high miR-191-5p expression promoted ESCC cell proliferation, invasion and migration and induced G0/G1 to S/G2M transition. miRNA-191-5p overexpression promoted cell survival and reduced cell apoptosis after irradiation. Mechanistically, miR-191-5p may directly target death-associated protein kinase 1 (DAPK1) to induce radiation resistance via the MAPK-JNK pathway. The 5-year progression-free survival rate for ESCC patients who underwent radiotherapy with high circulating exosomal miR-191-5p expression was significantly lower than in those with a low expression. Conclusion: Tumor-derived exosomal miR-191-5p is a potential non-invasive biomarker for predicting the prognosis in esophageal cancer patients after radiotherapy.


Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 106-116
Author(s):  
He Huang ◽  
Juan Liu ◽  
Haiyan Wu ◽  
Fang Liu ◽  
Xiaoxi Zhou

Abstract Objective Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, which was involved in the progression of malignant tumors including non-small cell lung cancer (NSCLC). Material/methods Ferroptosis inhibiting gene solute carrier family 7 member 11 (SLC7A11) mRNA expression was investigated in the database of TCGA and Oncomine and compared between the cancer tissue and the normal corresponding tissue of NSCLC patients. SLC7A11 gene mutation of NSCLC was investigated in the TCGA database by the online data analysis tool of Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. The protein–protein interaction (PPI) network of SLC7A11 and associated genes were constructed with the STRING database. Gene ontology (GO) and the KEGG pathway of genes involved in the PPI network were explored and demonstrated by a bubble plot. Progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) between SLC7A11high and SLC7A11low expression groups were compared and demonstrated by the survival curve. Results SLC7A11 mRNA was upregulated in cancer tissues compared to paired normal tissues in colorectal adenocarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma rectum adenocarcinoma and uterine corpus endometrial carcinoma. Missense and synonymous substitutions were 66.67% and 16.67% for lung squamous cell carcinoma. For lung adenocarcinoma, the missense and synonymous substitutions were 66.67% and 33.33% respectively. In the case of single nucleotide mutation, A>T, C>G, G>A, G>T for lung squamous cell carcinoma and G>T, C>A, G>A, T> for lung adenocarcinoma were the most common mutations in the SLC7A11 coding strand. Fifty-one genes were included in the PPI network with an edge number of 287, average node degree of 11.3 and local clustering coefficient of 0.694, which demonstrated that the PPI network was enriched significantly (p = 1.0 × 10−16). In terms of the KEGG pathway, the SLC7A11 and PPI-involved genes were mainly enriched in ferroptosis, NSCLC, pathways in cancer, tp53 signaling pathway, etc. The overall survival (OS) in the SLC7A11high group was significantly lower than those of SLC7A11low groups in NSCLC (HR = 1.15, 95% CI: 1.02–1.31, p = 0.027). However, the progression-free survival (PFS) (HR = 1.17, 95% CI: 0.97–1.42, p = 0.098) and postprogression survival (PPS) (HR = 1.00, 95% CI: 0.78–1.29, p = 0.97) between SLC7A11high and SLC7A11low expression groups were not statistically different. Conclusion SLC7A11 was upregulated in NSCLC and correlated with the patient’s poor overall survival. SLC7A11 may be a potential target for NSCLC treatment through the ferroptosis pathway.


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