scholarly journals Prediction of Locoregional Recurrence-Free Survival of Oesophageal Squamous Cell Carcinoma After Chemoradiotherapy Based on an Enhanced CT-Based Radiomics Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Kong ◽  
Shuchai Zhu ◽  
Gaofeng Shi ◽  
Zhikun Liu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Training Group ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Lasso Regression ◽  
Validation Group ◽  
Clinical Value ◽  
Free Survival ◽  
Enhanced Computed Tomography

Background and PurposeChemoradiotherapy is the standard treatment for moderate and advanced oesophageal cancer. The aim of this study was to establish a predictive model based on enhanced computed tomography examination, and to evaluate its clinical value for detecting locoregional recurrence-free survival (LRFS) in cases of oesophageal squamous cell carcinoma after radiotherapy.Materials and MethodsIn total, 218 patients with pathologically diagnosed oesophageal squamous cell carcinoma who received radical chemoradiotherapy from July 2016 to December 2017 were collected in this study. Patients were randomly divided into either a training group (n=153) or a validation group (n=65) in a 7:3 ratio. Clinical patient information was then recorded. The enhanced computed tomography scan images of the patients were imported into 3D-slicer software (version 4.8.1), and the radiomic features were extracted by the Python programme package. In the training group, the dimensionality reduction of the radiomic features was implemented by Lasso regression, and then a radiological label, the model of predicting LRFS, was established and evaluated. To achieve a better prediction performance, the radiological label was combined with clinical risk factor information to construct a radiomics nomogram. A receiver operating characteristic curve was used to evaluate the efficacy of different models. Calibration curves were used to assess the consistency between the predicted and observed recurrence risk, and the Hosmer-Lemeshow method was used to test model fitness. The C-index evaluated the discriminating ability of the prediction model. Decision curve analysis was used to determine the clinical value of the constructed prediction model.ResultsOf the 218 patients followed up in this study, 44 patients (28.8%) in the training group and 21 patients (32.3%) in the validation group experienced recurrence. There was no difference in LRFS between the two groups (χ2 =0.525, P=0.405). Lasso regression was used in the training group to select six significant radiomic features. The radiological label established using these six features had a satisfactory prediction performance. The C-index was 0.716 (95% CI: 0.645–0.787) in the training group and 0.718 (95% CI: 0.612–0.825) in the validation group. The radiomics nomogram, which included the radiological label and clinical risk factors, achieved a better prediction than the radiological label alone. The C-index was 0.742 (95% CI: 0.674–0.810) in the training group and 0.715 (95% CI: 0.609–0.820) in the validation group. The results of the calibration curve and decision curve analyses indicated that the radiomics nomogram was superior in predicting LRFS of oesophageal carcinoma after radiotherapy.ConclusionsA radiological label was successfully established to predict the LRFS of oesophageal squamous cell carcinoma after radiotherapy. The radiomics nomogram was complementary to the clinical prognostic features and could improve the prediction of the LRFS after radiotherapy for oesophageal cancer.

scholarly journals Comparison of short- and long-term outcomes between 3-field and modern 2-field lymph node dissections for thoracic oesophageal squamous cell carcinoma: a propensity score matching analysis

2019 ◽  
Vol 29 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Ningbo Fan ◽  
Han Yang ◽  
Jiabo Zheng ◽  
Dongni Chen ◽  
Weidong Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Short And Long Term ◽  
Disease Free

Abstract OBJECTIVES Our goal was to compare short- and long-term outcomes between 3-field lymphadenectomy (3-FL) and modern 2-field lymphadenectomy (2-FL) in patients with thoracic oesophageal squamous cell carcinoma. METHODS We reviewed clinical outcomes for 298 patients with thoracic oesophageal squamous cell carcinoma who underwent 3-FL or modern 2-FL from March 2008 to December 2013 at a major cancer hospital in Guangzhou, southern China. Propensity score matching was used to balance baseline differences, and 83 pairs of cases were selected. Postoperative complications, recurrence patterns and survival outcomes were compared between the 2 groups. RESULTS Compared with modern 2-FL, 3-FL led to higher overall operative morbidity rates [78.3% vs 61.4%, odds ratio (OR) 2.266, 95% confidence interval (CI) 1.143–4.490; P = 0.019], with higher recurrent nerve palsy rates (47.0% vs 19.3%, OR 3.712, 95% CI 1.852–7.438; P < 0.0001), more respiratory failures (18.1% vs 6.0%, OR 3.441, 95% CI 1.189–9.963; P = 0.023) and longer postoperative hospital stays (23 vs 17 days, P = 0.002). The 5-year overall survival rate (58.5% vs 59.4%; P = 0.960) and the 5-year disease-free survival rate 50.1% vs 54.5%; P = 0.482) were comparable between the 2 groups. Multivariable analysis showed that additional cervical lymph node dissection was not associated with overall survival [hazard ratio (HR) 1.039, 95% CI 0.637–1.696; P = 0.878] and disease-free survival (HR 0.868, 95% CI 0.548–1.376; P = 0.547). The overall recurrence rate and cervical nodal recurrence rate were not significantly different between the 2 groups. CONCLUSIONS Additional cervical lymphadenectomy did not lead to added survival benefit when compared with modern 2-FL in patients with thoracic oesophageal squamous cell carcinoma. Recurrence was similar in patients undergoing 3-FL and modern 2-FL. 3-FL resulted in more postoperative complications.

The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma

2011 ◽  
Vol 121 (10) ◽  
pp. 437-447 ◽  
Author(s):  
Tengfei Zhang ◽  
Qiming Wang ◽  
Dan Zhao ◽  
Yaling Cui ◽  
Bangrong Cao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Reporter ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Validation Group ◽  
Serum Samples ◽  
Total N ◽  
Normal Controls

miR-31 (microRNA-31) is frequently altered in numerous cancers. The aim of the present study was to investigate the role of miR-31 in ESCC (oesophageal squamous cell carcinoma). We measured miR-31 in 45 paired ESCC tissues and 523 serum samples using real-time RT (reverse transcription)–PCR. The serum samples were divided into a discovery group (120 ESCCs and 121 normal controls), a validation group (81 ESCCs and 81 controls), and a final group comprising six other common tumours (colorectal, liver, cervical, breast, gastric and lung cancers; total n=120). A Mann–Whitney U test and Wilcoxon matched-pairs test were used for the statistics. miR-31 was up-regulated in 77.8% of the ESCC tissues. Serum miR-31 levels in ESCC patients were significantly higher than in normal controls (P<0.001). It yielded an ROC (receiver operating characteristic) AUC (area under the curve) of 0.902 [95% CI (confidence interval), 0.857–0.936] in the discovery group and a similar result in the validation group [ROC AUC, 0.888 (95% CI, 0.819–0.939)]. Patients with high-levels of serum miR-31 also had a poorer prognosis in relapse-free survival (P=0.001) and tumour-specific survival (P=0.005). In vitro studies showed that miR-31 promoted ESCC colony formation, migration and invasion. Luciferase reporter and Western blot assays confirmed that three tumour suppressor genes, namely EMP1 (epithelial membrane protein 1), KSR2 (kinase suppressor of ras 2) and RGS4 (regulator of G-protein signalling 4), were targeted by miR-31. We conclude that miR-31 plays oncogenetic functions and can serve as a potential diagnostic and prognostic biomarker for ESCC.

scholarly journals Expression Levels and Clinical Significance of miR-21-5p, miR-let-7a, and miR-34c-5p in Laryngeal Squamous Cell Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Massimo Re ◽  
Giuseppe Magliulo ◽  
Federico M. Gioacchini ◽  
Arisa Bajraktari ◽  
Andrea Bertini ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Disease Free Survival ◽  
Clinical Value ◽  
Free Survival ◽  
Normal Tissues ◽  
Disease Free

Objective. Altered microRNAs (miRNAs) expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). The aim of this study was to determine the role and clinical value of three LSCC-related miRs, such as miR-21-5p, miR-let-7a, and miR-34c-5p in a homogeneous cohort of patients with primary LSCC treated by primary surgery. Methods. Expression levels of miR-21-5p, miR-let-7a, and miR-34c-5p were detected in 43 pairs of LSCC and adjacent normal tissues by reverse-transcription quantitative PCR. Overall survival and disease-free survival were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results. miR-21-5p is significantly upregulated, while miR-let-7a is significantly downregulated in LSCC tumor tissues compared with the corresponding adjacent normal tissues. The downregulation of miR-34c-5p expression significantly correlated with a shorter disease-free survival and, in the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. Conclusions. miR-21-5p, miR-let-7a, and miR-34c-5p seem to play a critical role in LSCC carcinogenesis and might have a diagnostic and prognostic clinical value. The miR-let-7a levels could have a predictive role for lymph node metastases and miR-34c-5p might be a promising biomarker of patient outcome.

scholarly journals Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells

2021 ◽  
Author(s):  
Zhigeng Zou ◽  
Wei Zheng ◽  
Hongjun Fan ◽  
Guodong Deng ◽  
Shih-Hsin Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
High Throughput Sequencing ◽  
Combined Treatment ◽  
Oesophageal Squamous Cell Carcinoma

Abstract Background Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. Methods We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. Results ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. Conclusions ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.

scholarly journals Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1735
Author(s):  
Patricia García-Cabo ◽  
Fernando López ◽  
Mario Sánchez-Canteli ◽  
Laura Fernández-Vañes ◽  
César Álvarez-Marcos ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Organ Preservation ◽  
Matched Pair ◽  
Primary Tumors ◽  
Free Survival ◽  
Tumor Node Metastasis Stage ◽  
Significant Difference

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1,18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.

scholarly journals Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323276
Author(s):  
Jin Zhou ◽  
Zhong Wu ◽  
Zhouwei Zhang ◽  
Louisa Goss ◽  
James McFarland ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Scale ◽  
Cell Cancer ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Squamous Cancer ◽  
Striking Success

ObjectiveOesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition.DesignWe combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer.ResultsWe identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC.ConclusionThese results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.

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