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F1000Research 2020Esophageal cancer (EC) is an aggressive malignancy with an increasing incidence and a poor prognosis. EC is histologically divided into two major categories:... (Review)
Review
Esophageal cancer (EC) is an aggressive malignancy with an increasing incidence and a poor prognosis. EC is histologically divided into two major categories: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). EAC and ESCC are molecularly different and therefore treatments should reflect the respective histological subtype. Combined modality therapy is needed for localized EC. When EC is advanced (stage 4), systemic therapy is the mainstay treatment for palliation. For localized EC, several strategies are considered standard, and more trials are necessary to determine a unified and more effective approach. The management for advanced EC is slowly evolving as immunotherapy is showing some promise for ESCC, but more data from ongoing studies are anticipated. Treatment advances will be based on high-definition genomic investigation of individual tumors. Herein, we review the contemporary trends in diagnosing and treating EAC and ESCC.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Combined Modality Therapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Immunotherapy
PubMed: 33042518
DOI: 10.12688/f1000research.22926.1 -
World Journal of Gastroenterology Jul 2015Esophageal cancer is one of the most unknown and deadliest cancers worldwide, mainly because of its extremely aggressive nature and poor survival rate. Esophageal cancer... (Review)
Review
Esophageal cancer is one of the most unknown and deadliest cancers worldwide, mainly because of its extremely aggressive nature and poor survival rate. Esophageal cancer is the 6(th) leading cause of death from cancer and the 8(th) most common cancer in the world. The 5-year survival is around 15%-25%. There are clear differences between the risk factors of both histological types that affect their incidence and distribution worldwide. There are areas of high incidence of squamous cell carcinoma (some areas in China) that meet the requirements for cost-effectiveness of endoscopy for early diagnosis in the general population of those areas. In Europe and United States the predominant histologic subtype is adenocarcinoma. The role of early diagnosis of adenocarcinoma in Barrett's esophagus remains controversial. The differences in the therapeutic management of early esophageal carcinoma (high-grade dysplasia, T1a, T1b, N0) between different parts of the world may be explained by the number of cancers diagnosed at an early stage. In areas where the incidence is high (China and Japan among others) early diagnoses is more frequent and has led to the development of endoscopic techniques for definitive treatment that achieve very effective results with a minimum number of complications and preserving the functionality of the esophagus.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Early Detection of Cancer; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Esophagoscopy; Humans; Incidence; Neoplasm Staging; Predictive Value of Tests; Racial Groups; Risk Factors; Treatment Outcome
PubMed: 26185366
DOI: 10.3748/wjg.v21.i26.7933 -
Nature Reviews. Disease Primers Jul 2017Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of... (Review)
Review
Oesophageal cancer is the sixth most common cause of cancer-related death worldwide and is therefore a major global health challenge. The two major subtypes of oesophageal cancer are oesophageal squamous cell carcinoma (OSCC) and oesophageal adenocarcinoma (OAC), which are epidemiologically and biologically distinct. OSCC accounts for 90% of all cases of oesophageal cancer globally and is highly prevalent in the East, East Africa and South America. OAC is more common in developed countries than in developing countries. Preneoplastic lesions are identifiable for both OSCC and OAC; these are frequently amenable to endoscopic ablative therapies. Most patients with oesophageal cancer require extensive treatment, including chemotherapy, chemoradiotherapy and/or surgical resection. Patients with advanced or metastatic oesophageal cancer are treated with palliative chemotherapy; those who are human epidermal growth factor receptor 2 (HER2)-positive may also benefit from trastuzumab treatment. Immuno-oncology therapies have also shown promising early results in OSCC and OAC. In this Primer, we review state-of-the-art knowledge on the biology and treatment of oesophageal cancer, including screening, endoscopic ablative therapies and emerging molecular targets, and we discuss best practices in chemotherapy, chemoradiotherapy, surgery and the maintenance of patient quality of life.
Topics: Adenocarcinoma; Africa, Eastern; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Carcinoma, Squamous Cell; Chemoradiotherapy; Endoscopy, Digestive System; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Middle Aged; Prognosis; Receptor, ErbB-2; South America; Survival Rate; Trastuzumab; Treatment Outcome
PubMed: 28748917
DOI: 10.1038/nrdp.2017.48 -
Lancet (London, England) Feb 2013Oesophageal carcinoma affects more than 450,000 people worldwide and the incidence is rapidly increasing. Squamous-cell carcinoma is the predominant form of oesophageal... (Review)
Review
Oesophageal carcinoma affects more than 450,000 people worldwide and the incidence is rapidly increasing. Squamous-cell carcinoma is the predominant form of oesophageal carcinoma worldwide, but a shift in epidemiology has been seen in Australia, the UK, the USA, and some western European countries (eg, Finland, France, and the Netherlands), where the incidence of adenocarcinoma now exceeds that of squamous-cell types. The overall 5-year survival of patients with oesophageal carcinoma ranges from 15% to 25%. Diagnoses made at earlier stages are associated with better outcomes than those made at later stages. In this Seminar we discuss the epidemiology, pathophysiology, diagnosis and staging, management, prevention, and advances in the treatment of oesophageal carcinoma.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Endosonography; Esophageal Neoplasms; Esophagectomy; Humans; Lymph Node Excision; Neoadjuvant Therapy; Neoplasm Staging; Positron-Emission Tomography; Risk Factors
PubMed: 23374478
DOI: 10.1016/S0140-6736(12)60643-6 -
Nature Jan 2017Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a...
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Genome, Human; Genomics; Humans; Molecular Targeted Therapy; Mutation; Stomach Neoplasms
PubMed: 28052061
DOI: 10.1038/nature20805 -
Frontiers in Cellular and Infection... 2023With the development of endoscopic technology, an increasing number of patients with esophageal disease are being diagnosed, although the underlying pathogenesis of many... (Review)
Review
With the development of endoscopic technology, an increasing number of patients with esophageal disease are being diagnosed, although the underlying pathogenesis of many esophageal diseases remains unclear. In recent years, a large number of studies have demonstrated that the occurrence and development of various intestinal diseases were related to intestinal flora. As a result, researchers have shifted their focus towards investigating esophageal flora to better understand the pathogenesis, early diagnosis, and treatment of esophageal diseases. This paper reviewed the normal esophageal flora and the changes of esophageal flora under different esophageal disease states. It was observed that there are distinct differences in the composition of esophageal microflora among Gastroesophageal Reflux, Barrett's esophagus, eosinophilic esophagitis and normal esophagus. The normal esophageal flora was dominated by gram-positive bacteria, particularly , while the esophageal flora under esophagitis was dominated by gram-negative bacteria. Furthermore, the diversity of esophageal flora is significantly decreased in patients with esophageal cancer. Several potential microbial biomarkers for esophageal cancer have been identified, among which showed a close association with esophageal squamous cell carcinoma's pathological stage and clinical stage.
Topics: Humans; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Barrett Esophagus; Esophageal Diseases
PubMed: 37274313
DOI: 10.3389/fcimb.2023.1145791 -
Nature Communications May 2017Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and...
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
Topics: Adult; Aged; Alcohol Drinking; Asian People; Carcinoma, Squamous Cell; Cell Cycle; China; DNA Copy Number Variations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagus; Ethanol; Female; Genome, Human; Humans; Male; Middle Aged; Mutation; Phosphatidylinositol 3-Kinases; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-akt; Receptors, LDL; Signal Transduction; Whole Genome Sequencing
PubMed: 28548104
DOI: 10.1038/ncomms15290 -
The Lancet. Oncology Aug 2017Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The... (Randomized Controlled Trial)
Randomized Controlled Trial
Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.
BACKGROUND
Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.
METHODS
The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up.
FINDINGS
Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group).
INTERPRETATION
Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting.
FUNDING
Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups).
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Dose Fractionation, Radiation; Esophagitis; Etoposide; Female; Follow-Up Studies; Humans; Intention to Treat Analysis; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Radiation Pneumonitis; Small Cell Lung Carcinoma; Survival Rate
PubMed: 28642008
DOI: 10.1016/S1470-2045(17)30318-2 -
Current Oncology (Toronto, Ont.) Jan 2022This review provides information regarding the preoperative examinations, indications for endoscopic resection (ER), and curability assessment in subjects with... (Review)
Review
This review provides information regarding the preoperative examinations, indications for endoscopic resection (ER), and curability assessment in subjects with superficial esophageal squamous cell carcinoma (SCC). Narrow-band imaging (NBI) is a more sensitive modality for detecting esophageal cancer than conventional observation, and esophageal observation using NBI is thus recommended for the detection of superficial esophageal cancer. It is also important to adjust the volume of air in the esophagus during observation. Workup by non-magnifying followed by magnifying endoscopy is a common process for diagnosing the invasion depth of superficial esophageal SCCs in Japan. Endoscopic ultrasonography carries a risk of overdiagnosis, and its routine use is therefore not recommended. The Japanese endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer considered the indications for ER based on the results of studies focusing on clinical MM/SM1 cancers, and concluded that clinical MM/SM1 carcinomas, except circumferential carcinoma, were an indication for ER. The curative effect of ER should be assessed based on histologic examination of the resected specimens. ER should be conducted based on a thorough understanding of the preoperative diagnosis, indication, curability, and additional treatment of esophageal SCC.
Topics: Carcinoma, Squamous Cell; Epithelial Cells; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Humans
PubMed: 35200548
DOI: 10.3390/curroncol29020048 -
Frontiers in Cellular and Infection... 2021Microbial imbalances have been well elucidated in esophageal adenocarcinoma. However, few studies address the microbiota in esophageal squamous cell carcinoma (ESCC) and...
Microbial imbalances have been well elucidated in esophageal adenocarcinoma. However, few studies address the microbiota in esophageal squamous cell carcinoma (ESCC) and esophagitis (ES). We aimed to explore the association of esophageal microbiota with these patients. Esophageal tissues were obtained from healthy controls and ES and ESCC patients undergoing upper endoscopy. 16S rRNA gene sequencing was applied to analyze the microbiome. The α and β diversity differences were tested by Tukey test and partial least squares-discriminant analysis (PLS-DA), respectively. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. A total of 68 individuals were enrolled (control = 21, ES = 15, ESCC = 32). Microbial diversity was significantly different between the ESCC patients and healthy controls by Chao1 index, Shannon index, and PLS-DA. , , , , and were the five dominant bacterial phyla among the three groups. , , , and showed a significantly continuous decreasing trend from the control group to the ESCC group at the genus level. When compared with the control group, decreased at phylum level and , , , and at genus level were detected. ESCC samples also displayed a striking reduction of , , , and in comparison with the ES patients. LEfSe analysis indicated a greater abundance of , , , , and in the ESCC group. Our study suggests a potential association between esophageal microbiome dysbiosis and ESCC and provides insights into potential screening markers for esophageal cancer.
Topics: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagitis; Humans; Microbiota; RNA, Ribosomal, 16S
PubMed: 34858881
DOI: 10.3389/fcimb.2021.774330