• cervical esophageal cancer
• definitive radiotherapy
• radiation target volume
• surgery
• technique and dose

• Humans
• Adenocarcinoma
• Carcinoma, Squamous Cell
• Esophagus

• Barrett's esophagus
• endoscopic resection
• esophageal carcinoma
• immune therapy
• multimodal therapy
• neoadjuvant radiochemotherapy
• perioperative chemotherapy

• Humans
• Adenocarcinoma/diagnosis
• Adenocarcinoma/therapy
• Adenocarcinoma/pathology
• Carcinoma, Squamous Cell/diagnosis
• Carcinoma, Squamous Cell/therapy
• Carcinoma, Squamous Cell/pathology
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/therapy
• Esophageal Neoplasms/pathology
• Combined Modality Therapy

• 70112585 Deutsche Krebshilfe
• Deutsche Krebshilfe

• Cervical esophageal cancer
• Free jejunal graft
• Gastric pull-up

• Humans
• Esophageal Squamous Cell Carcinoma/therapy
• Carcinoma, Squamous Cell
• Radiotherapy, Intensity-Modulated/adverse effects
• Radiotherapy, Intensity-Modulated/methods
• Esophageal Neoplasms/radiotherapy
• Retrospective Studies
• Propensity Score
• Chemoradiotherapy/adverse effects
• Chemoradiotherapy/methods
• Radiation Dosage
• Epithelial Cells/pathology

• Humans
• Quality of Life
• Prospective Studies
• Retrospective Studies
• Esophageal Neoplasms/therapy
• Chemoradiotherapy/adverse effects
• Dyspnea/etiology

• Chemoradiotherapy
• Esophageal cancer
• Local control
• Radiotherapy
• Survival
• Toxicity

• Humans
• Female
• Adult
• Middle Aged
• Aged
• Aged, 80 and over
• Retrospective Studies
• Esophageal Neoplasms/therapy
• Uterine Cervical Neoplasms
• Chemoradiotherapy
• Carcinoma

• Cervical esophageal cancer
• Chemoradiotherapy
• Esophagectomy
• Prognosis
• SEER database

• Chemoradiotherapy
• Progression-free survival
• Proximal esophagus
• Survival
• Upper esophagus

• anastomosis
• manual
• mechanical
• postoperative complications
• total pharyngolaryngoesophagectomy

• Cervical esophageal cancer
• Functional laryngeal preservation
• Laryngeal preservation
• Multicenter study

To evaluate the safety and effectiveness of nimotuzumab in combination with chemoradiotherapy for locally advanced cervical esophageal squamous cell carcinoma.

Retrospective analysis was conducted from September 2012 to February 2017 among 50 locoregional-advanced cervical esophageal carcinoma (CEC) patients who received concurrent chemoradiotherapy (CRT) combined with or without nimotuzumab at Ningbo Medical Center Lihuili Hospital. Intensity-modulated radiotherapy (IMRT) was administrated on all patients. All patients were divided into two groups, of which 26 (Group A) received 200 mg (22 of 50) or 400 mg (4 of 50) of nimotuzumab per week with CRT and 24 (Group B) received definitive CRT.

The median follow-up time was 23 months. The median overall survival (OS) and progression-free survival (PFS) were 40.6 and 21.1 months for all, respectively. The 1-, 2-, and 3-year OS rates on the whole were 79.6%, 62.1%, and 47.8%. There was no statistical difference in overall response rate and disease control rate between the two groups. Patients treated with nimotuzumab (group A) had better PFS than the definitive CRT group (group B) (P < 0.05). However, the median OS was 41.4 months in group A and 32.4 months in group B, respectively (P = 0.517). Multivariate analysis showed that PFS among those with lower Eastern Cooperative Oncology Group (ECOG) score (HR = 5.11; P < 0.01), stage II (HR = 9.52; P < 0.01) and the application of nimotuzumab combined with CRT (HR = 0.16; P < 0.01) was much longer. Furthermore, ECOG, stage, C-reactive protein (CRP) baseline, and histological grade can also be used as independent predictors of OS. Grade >3 adverse reactions were not observed. The most common adverse event related to nimotuzumab was mild fever and the occurrence rate was 19% (5 of 26). The incidence of anemia was 65.4% in group A and 87.5% in group B (P < 0.05).

For locoregional-advanced CEC, nimotuzumab combined with IMRT and concomitant chemotherapy was tolerated and effective. In addition, patients with a normal pretherapeutic serum CRP level (CRP < 10 mg/L) can achieve better OS.

• C-reactive protein
• cervical esophageal carcinoma
• chemoradiotherapy
• intensity-modulated radiotherapy
• nimotuzumab

• cervical esophageal cancer
• free jejunal graft
• morbidity
• oncological results
• pharyngolaryngectomy

• Chemoradiotherapy/methods
• Cohort Studies
• Denmark/epidemiology
• Esophageal Neoplasms/drug therapy
• Esophageal Neoplasms/surgery
• Humans
• Morbidity
• Retrospective Studies

Platinum derivatives are important treatment options for patients with esophageal carcinoma (EC), and a predictive marker for platinum-based therapy is needed for precision medicine.

This study contained two cohorts consisting of EC patients treated using platinum-based chemoradiation therapy (CRT) as the first-line and another external cohort of nationwide clinicogenomic data from the BioBank Japan (BBJ).

Genome-wide association study (GWAS) of therapeutic outcomes, refractory disease or not, following platinum-based CRT as first-line in 94 patients in the first cohort suggested the association of 89 SNPs using p < 0.0001. The top 10 SNPs selected from each chromosomal region by odds ratio were evaluated for progression-free survival (PFS) and overall survival (OS) hazard ratios in the first cohort, resulting in four candidates (p < 0.0025). The four selected candidates were re-evaluated in another cohort of 24 EC patients, which included patients prospectively enrolled in this study to fulfill the sample size statistically suggested by the results of the first cohort, and of the four, only rs3815544 was replicated (p < 0.0125). Furthermore, this candidate genotype of rs3815544 proceeded to the re-evaluation study in an external cohort consisting of EC patients treated with platinum derivatives and/or by radiation therapy as the first-line treatment in BBJ, which confirmed that the alternative allele (G) of rs3815544 was statistically associated with non-response (SD or PD) to platinum-based therapy in EC patients (odds ratio = 1.801, p = 0.048). The methylation QTL database as well as online clinicogenomic databases suggested that the region including rs3815544 may regulate MSX1 expression through CpG methylation, and this down-regulation was statistically associated with poor prognosis after platinum-based therapies for EC.

rs3815544 is a novel candidate predictive marker for platinum-based EC therapy.

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.

Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.

Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P < 0.001, hazard ratio (HR) = 1.832], sex [P < 0.001, HR= 1.867], histology [P = 0.001, HR = 0.366], surgery at the primary site [P = 0.021, HR = 0.553], radiotherapy (RT, P = 0.017, HR = 0.637) and chemotherapy (CT, P < 0.001, HR = 0.444). Comparison among the three treatment modalities demonstrated that a triple therapy regimen consisting of surgery, RT and CT was associated with a longer survival time than the other two treatment modalities before and after propensity score matching (PSM). However, triple therapy showed no significant survival benefit over double therapy (P = 0.496 before PSM and P = 0.184 after PSM).

Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.

• SEER
• cervical esophageal carcinoma
• surgery
• survival
• treatment modality

• Cervical esophageal cancer
• Multimodal therapy
• Prognostic factors
• Survival
• Treatment

• Chemoradiation
• Esophageal cancer
• Neoadjuvant
• Trimodality therapy

• Adenocarcinoma/therapy
• Carcinoma, Squamous Cell/therapy
• Chemoradiotherapy, Adjuvant
• Esophageal Neoplasms/therapy
• Esophagectomy
• Humans
• Neoadjuvant Therapy
• Treatment Outcome

• Cervical
• Chemoradiotherapy
• Esophagus
• Relapse
• Squamous cell cancer
• Upper thoracic

• PET-CT
• cervical esophageal cancer
• distance from the cricoid cartilage
• laryngeal preservation

This study aimed to retrospectively analyze the failure patterns and clinical outcomes in patients with locally advanced cervical esophageal carcinoma (CEC) after definitive radiotherapy (RT), and illustrate the mapping of regional failures.

We reviewed 82 patients with CEC confirmed as squamous cell carcinoma who had completed definitive RT from August 2008 to December 2017. Data on clinical characteristics were collected from the medical records system. Patterns of treatment failures and the survival follow-up were analyzed.

The median age was 58 (38–78) years. In 37 patients, the lesions were limited to the cervical esophagus, while in the remaining 45 patients, the disease got beyond the cervical esophagus (pharynx or thoracic esophagus involved). While 10 patients had stage Ⅱ disease, 72 had stage III disease. The completed median dose for 95% PGTV and 95% PTV was 66 Gy and 58 Gy. While the median follow-up was 27.6 months, the median progression-free survival (PFS) and overall survival (OS) was 16.1 and 28.3 months, respectively. The 3-year PFS and OS was 30.3% and 45.3%, respectively. Treatment failures were reported in 55 patients, of which 22, 8, 7, 9, 2, 3, and 4 patients had developed local, regional, distant, local-regional, regional-distant, local-distant and local-regional-distant failure, respectively. Of the 41 relapsed nodal sites, 28 were located “in-field” whereas 1 was “marginal” and 12 were “out-field”. The most frequent regional relapses were at level VIb, IV and the upper-middle mediastinum.

Regional recurrences focused on lower neck and upper-middle mediastinum, and mainly “in-field”, after definitive RT in patients with CEC.

• esophageal neoplasms
• prognosis
• radiotherapy
• recurrence
• squamous cell carcinoma

• esophageal squamous cell carcinoma (SCC)
• larynx-sparing surgery
• neoadjuvant concurrent chemoradiotherapy (CCRT)

• cervical esophageal squamous cell carcinoma
• chemoradiotherapy
• intensity-modulated
• planning study
• radiotherapy

• Aged
• Disease Progression
• Disease-Free Survival
• Dose-Response Relationship, Radiation
• Esophageal Neoplasms/radiotherapy
• Esophageal Squamous Cell Carcinoma/radiotherapy
• Female
• Humans
• Imaging, Three-Dimensional
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local/pathology
• Pharynx/radiation effects
• Radiometry
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted
• Radiotherapy, Intensity-Modulated
• Retrospective Studies
• Treatment Outcome

• Cervical esophageal squamous cell carcinoma
• Conformal radiotherapy
• Intensity-modulated radiotherapy
• Survival
• Tracheostomy dependence

• 5-Fluorouracil
• Chemoradiotherapy
• Cisplatin
• Docetaxel
• Esophageal squamous cell carcinoma

• Aged
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemoradiotherapy
• Cisplatin/administration & dosage
• Cisplatin/adverse effects
• Docetaxel/administration & dosage
• Docetaxel/adverse effects
• Esophageal Neoplasms/drug therapy
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/radiotherapy
• Esophageal Squamous Cell Carcinoma/drug therapy
• Esophageal Squamous Cell Carcinoma/pathology
• Esophageal Squamous Cell Carcinoma/radiotherapy
• Female
• Fluorouracil/administration & dosage
• Fluorouracil/adverse effects
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Neutropenia/chemically induced
• Retrospective Studies
• Survival Rate

• Cervical esophageal cancer
• Chemoradiotherapy
• High-dose radiotherapy
• Post-radiotherapy stenosis

• Adult
• Aged
• Aged, 80 and over
• Dilatation
• Disease-Free Survival
• Dose-Response Relationship, Radiation
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/radiotherapy
• Esophageal Stenosis/diagnostic imaging
• Esophageal Stenosis/epidemiology
• Esophageal Stenosis/etiology
• Esophageal Stenosis/mortality
• Esophagoscopy
• Esophagus/diagnostic imaging
• Esophagus/pathology
• Esophagus/radiation effects
• Esophagus/surgery
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Neck
• Radiation Injuries/diagnostic imaging
• Radiation Injuries/epidemiology
• Radiation Injuries/etiology
• Radiation Injuries/mortality
• Radiotherapy/adverse effects
• Radiotherapy/methods
• Radiotherapy Dosage
• Retrospective Studies
• Tracheoesophageal Fistula/diagnostic imaging
• Tracheoesophageal Fistula/epidemiology
• Tracheoesophageal Fistula/etiology
• Tracheoesophageal Fistula/mortality
• Treatment Failure
• Treatment Outcome

• Esophageal cancer
• Esophagectomy
• Multimodal treatment
• Surgery, robot-assisted
• Thoracoscopy

• Esophageal cancer
• Esophagectomy
• Multimodal treatment
• Surgery, robot-assisted
• Thoracoscopy

• Cardiovascular disease
• Conformal
• Esophageal Neoplasms
• Hypothyroidism
• Long-term outcome
• Radiotherapy

Because of the scarcity of cervical esophageal cancer (CEC), data for this disease entity is limited. We aim to evaluate the outcomes, prognostic factors and failure patterns of CEC treated by contemporary radiotherapy (RT).

We retrospectively analyzed 86 CEC patients consecutively treated between 2007 and 2015 by definitive RT with or without concurrent chemotherapy. RT was mainly delivered with Intensity Modulated Irradiation Therapy (IMRT) or Volumetric-Modulated Arc Therapy (VMAT). Statistical analyses were performed on survival, prognostic factors and failure patterns.

The median follow-up time was 19.4 months. The 3-year overall survival (OS), local regional failure free survival (LRFFS), distant metastatic free survival (DMFS), and progression free survival (PFS) were 53.6%, 57.9%, 81.5% and 41.5%, respectively. Independent predictors for poorer OS were N stage, hoarseness and recurrent laryngeal nerve lymph node (RLN) involvement, and predictors for LRFFS were N stage and EQD2 (equivalent dose in 2 Gy fraction) to gross tumor volume (GTV), with ≥ 66Gy achieving local control of 94.7%. Patients receiving elective nodal irradiation (ENI) had better nodal regional control than those receiving involved field irradiation (IFI). 31 (36%) patients had treatment failure and 15 (17.4%), 8 (9.3%) and 14 (16.2%) patients had local, regional, and distant failure, respectively. 86.7% (13/15) local failures were within GTV, and supraclavicular region (62.5%, 5/8) was the most common regional failure site. No severe toxicities were observed.

Our results seem to indicate that good locoregional control might be achieved for CEC with adequate radiation dose and treatment planning approaches.

• cervical esophageal cancer
• definitive radiotherapy
• failure pattern
• prognostic factor
• prophylactic irradiation

• cervical esophageal cancer
• clinical results
• definitive chemoradiotherapy
• failure pattern
• intensity-modulated radiotherapy (IMRT)

• Definitive chemoradiotherapy (dCRT)
• oesophageal cancer

• Esophageal cancer
• esophagectomy
• minimally invasive surgery
• robotic surgical procedures

To report oncological outcomes and toxicity rates, of definitive platin-based chemoradiadiationtherapy (CRT) in the management of proximal esophageal cancer.

We retrospectively reviewed the medical records of patients with cT1-4 cN0-3 cM0 cervical esophageal cancer (CEC) (defined as tumors located below the inferior border of the cricoid cartilage, down to 22 cm from the incisors) treated between 2004 and 2013 with platin–based definitive CRT in four Swiss institutions. Acute and chronic toxicities were retrospectively scored using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE-NCI v.4.0). Primary endpoint was loco-regional control (LRC). We also evaluated overall survival (OS) and disease-free survival (DFS) rates. The influence of patient- and treatment related features have been calculated using the Log-rank test and multivariate Cox proportional hazards model.

We enrolled a total of 55 patients. Median time interval from diagnosis to CRT was 78 days (6–178 days). Median radiation dose was 56Gy (28–72Gy). Induction chemotherapy (ICHT) was delivered in 58% of patients. With a median follow up of 34 months (6–110months), actuarial 3-year LRC, DFS and OS were 52% (95% CI: 37–67%), 35% (95% CI: 22–50%) and 52% (95% CI: 37–67%), respectively. Acute toxicities (dysphagia, pain, skin-toxicity) ranged from grade 0 – 4 without significant dose-dependent differences. On univariable analyses, the only significant prognostic factor for LRC was the time interval > 78 days from diagnosis to CRT. On multivariable analysis, total radiation dose >56Gy (p <0.006) and ICHT (p < 0.004) were statistically significant positive predictive factors influencing DFS and OS.

Definitive CRT is a reliable therapeutic option for proximal esophageal cancer, with acceptable treatment related toxicities. Higher doses and ICHT may improve OS and DFS and. These findings need to be confirmed in further prospective studies.

• Chemotherapy
• Esophagus
• Proximal esophageal cancer
• Radiotherapy

• Adult
• Aged
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/surgery
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Metastasis
• Neoplasm Staging
• Salvage Therapy
• Survival Analysis
• Treatment Outcome
• Tumor Burden