Biomarkers and Functional Imaging in Predicting Response of Esophageal Cancer

• Conditions: Esophageal Cancer
• Interventions: Other: Biomarkers Testing; Other: Functional Imaging analysis

• Registration Number: NCT03029793
• Lead Sponsor: Air Force Military Medical University, China

Brief Summary

The purpose of this study is to determine whether combination of molecular and biomarkers with functional imaging can predict pathologic response and clinical outcomes in squamous esophageal cancer patients who undergo trimodality therapy which includes neoadjuvant chemoradiotherapy and surgery

Detailed Description

The recommended care for the management of locally advanced esophageal cancers is neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy based on the NCCN guideline. The rate of pathologic complete response (pCR) after nCRT was around 25-30%, reflecting potential cure of unresectable esophageal cancer receiving CRT. Since esophagectomy might have substantial morbidity and mortality rate, establishing the model for predicting nCRT response and survival will guide neoadjuvant treatment decisions and personalized treatment. Thus surgery might be spared in some patients with complete responses after nCRT, and surgery could be selectively reserved for those with only partial or no response to CRT. However, reported models yield unsatisfactory results due to small sample size and low accuracy, and most cases were adenocarcinoma and few models were used to predict survival. This study will prospectively collect the tissue and blood samples of locally advanced esophageal cancer patients, detect CRT resistance biomarkers, assess the SUV value and texture parameters of 18F-FDG PET-CT as well as ADC values DWI-MRI. The investigators will use advanced statistical tools to establish the model and further validate the model in another group of patients.The investigators will also establish a model for survival prediction. This model might possibly guide the personalized treatment for esophageal squamous cell carcinoma patients in China.

Study Timeline

• Study Start: 2016-05
• Status Verified: 2017-01
• Study First Submitted: 2017-01-05
• Study First Submitted QC: 2017-01-20
• Last Update Submitted: 2017-01-20
• Study First Posted: 2017-01-24
• Last Update Posted: 2017-01-24
• Primary Completion: 2019-01
• Study Completion: 2020-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Patient must have histologic documentation of squamous carcinoma of the esophagus at Xijing Hospital.
2. Newly diagnosed Patients with localized carcinoma of the esophagus who have undergone standard testing and been evaluated by the multidisciplinary team at Xijing Hospital and are considered appropriate candidates for and are willing to undergo chemoradiotherapy followed by surgery at Xijing Hospital.
3. Patient must have undergone a baseline esophageal-gastroduodenoscopy (EGD) with biopsy and endoscopic ultrasonography at Xijing, with tissue available for biomarker analysis.
4. Patient must be willing to undergo this research and must provide written informed consent.

Exclusion Criteria

1. Patient is unable or unwilling to comply with the requirements of the protocol.
2. History of prior malignancy within the past 3 years.
3. Patients with second primary tumors.
4. Patients who received endoscopical therapy or induction chemotherapy prior to chemoradiation therapy are excluded.
5. Patient is not a candidate for chemoradiation followed by surgery.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Biomarkers and Imaging analysis	Biomarkers Testing	This study will prospectively collect the tissue and blood samples of locally advanced esophageal cancer patients, perform CRT resistance biomarkers testing and functional imaging analysis including SUV value and texture parameters of 18F-FDG PET-CT as well as ADC values DWI-MRI before treatment, 2-3 weeks after the initiation of CRT, and 4 weeks post-nCRT. The investigators will use advanced statistical tools to establish the model and further validate the model in another group of patients. The investigators will also establish a model for survival prediction.
Biomarkers and Imaging analysis	Functional Imaging analysis	This study will prospectively collect the tissue and blood samples of locally advanced esophageal cancer patients, perform CRT resistance biomarkers testing and functional imaging analysis including SUV value and texture parameters of 18F-FDG PET-CT as well as ADC values DWI-MRI before treatment, 2-3 weeks after the initiation of CRT, and 4 weeks post-nCRT. The investigators will use advanced statistical tools to establish the model and further validate the model in another group of patients. The investigators will also establish a model for survival prediction.

Primary Outcome Measures

Name	Time	Method
Pathologic Response	Approximately 12 months	Mandard tumor regression grade (TRG) was used for pathology analysis. Primary tumor and positive lymph node regression were classified into five histologic tumor regression grades. Grade 1 (complete regression) showed absence of histologically identifiable residual cancer and fibrosis extending through the different layers of the esophageal wall, with or without granuloma. Grade 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis. Grade 3 involved an increase in the number of residual cancer cells, but fibrosis still predominated. Grade 4 showed residual cancer outgrowing fibrosis. Grade 5 was characterized by the absence of regressive changes.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Approximately 4 years

Trial Locations

Locations (1)

Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 🇨🇳 Xi'an, Shaanxi, China