Pre-Surgery If Needed for Oesophageal Cancer (preSINO)

Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: the preSINO Trial (Pre-Surgery If Needed for Oesophageal Cancer)

Prospective, multi-centre, diagnostic cohort study investigating the accuracy of positron emission tomography with computed tomography (PET-CT), endoscopic bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) for detecting residual disease after neoadjuvant chemoradiotherapy in patients with potentially curable esophageal squamous cell carcinoma (SCC).

Study Overview

• Status: Unknown
• Conditions: Esophageal Cancer
• Intervention / Treatment: Diagnostic test: First clinical response evaluation (CRE-1); Diagnostic test: Second clinical response evaluation (CRE-2)

Detailed Description

After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified.

The objective of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopic bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC.

Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to six weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopic bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another six weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopic bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of single diagnostic modalities will be correlated to pathological response in the resection specimen for calculation of sensitivity, specificity, negative predictive value and positive predictive value.

If the current study shows that major residual disease (>10% residual carcinoma at the primary tumor site and any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial).

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Xiaobin Zhang, MD; Phone Number: 18960619260 18516302162; Email: zxb5212@163.com
• Study Contact Backup: Name: Zhiang Li; Phone Number: 18960619260 18960619260; Email: dr_lizhigang@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Chest Hospital
    • Contact: Zhigang Li, MD, PhD
  • Tianjin, China
    • Not yet recruiting
    • Tianjin Medical University Cancer Institute and Hospital
    • Contact: Zhen-Tao Yu, MD, PhD
• Hong Kong
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Queen Mary Hospital
    • Contact: Simon Law, MD, PhD
• Taiwan
  • Linkou, Taiwan
    • Not yet recruiting
    • Chang Gung Memorial Hospital
    • Contact: Yin-Kai Chao, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Esophageal cancer patients who are planned to undergo nCRT according to the CROSS regimen and who will undergo surgical resection will be recruited from four Asian centres.

Description

Inclusion criteria are:

1. Histologically confirmed esophageal squamous cell carcinoma;
2. Tumor located in the chest;
3. Clinical stage cT1N1-2M0, cT2-4aN0-2M0, according to the 8th Edition of the AJCC TNM classification for Esophageal Cancer;
4. Age > 20 at the date of informed consent;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of two or less;
6. Considered fit to undergo nCRT followed by surgical resection;
7. Expected survival time more than three months;
8. Written informed consent by the patient.

Exclusion criteria are:

1. Patient with a second primary tumor;
2. Previous major surgery in the chest or upper abdomen;
3. Tumor not 18F-FDG-avid at baseline PET-CT;
4. Suspected positive lymph nodes that cannot be covered by an uninterrupted radiation field that also includes the primary tumor area;
5. Primary (early) lesion already removed by EMR/ESD;
6. Previous history of chemotherapy and/or radiation therapy;
7. Cervical esophageal cancer.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Clinical Response Evaluation; Patients with operable esophageal squamous cell carcinoma who are planned to undergo neoadjuvant chemoradiotherapy according to the CROSS regimen (intravenous carboplatin AUC 2 mg/mL/min and intravenous paclitaxel 50 mg/m2 on days 1, 8, 15, 22 and 29 with concurrent 41.4 Gy radiotherapy given in 23 fractions of 1.8 Gy on 5 days per week) followed by surgery. Patients will undergo a first clinical response evaluation (CRE-1) 4-6 week after completion of nCRT. In patients without histological evidence of residual tumor surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy.

Diagnostic test: First clinical response evaluation (CRE-1); Consisting of: endoscopy with bite-on-bite biopsies; Diagnostic test: Second clinical response evaluation (CRE-2); Consisting of: PET-CT, endoscopic bite-on-bite biopsies,EUS with FNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of clinical response evaluations for detecting substantial residual locoregional disease	The diagnostic performance in terms of sensitivity and specificity of both CRE-1 and CRE-2 for detecting TRG 3-4 residual tumor (more than 10% residual carcinoma) or TRG 1-2 residual tumor (less than 10% residual carcinoma) with residual nodal disease (ypN+) in the surgical resection specimen.	10-12 weeks after completion of neoadjuvant chemoradiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of clinical response evaluations for detecting any residual locoregional disease	The diagnostic performance in terms of sensitivity and specificity of both CRE-1 and CRE-2 for detecting pathologically non-complete response in both the primary tumor and the regional lymph nodes (TRG2-4 or ypN+).	10-12 weeks after completion of neoadjuvant chemoradiotherapy

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Collaborators: Chang Gung Memorial Hospital; Tianjin Medical University Cancer Institute and Hospital; Queen Mary Hospital, Hong Kong
• Investigators: Principal Investigator: Zhigang Li, MD, PhD, Shanghai Chest Hospital

Publications and helpful links

General Publications

• Zhang X, Eyck BM, Yang Y, Liu J, Chao YK, Hou MM, Hung TM, Pang Q, Yu ZT, Jiang H, Law S, Wong I, Lam KO, van der Wilk BJ, van der Gaast A, Spaander MCW, Valkema R, Lagarde SM, Wijnhoven BPL, van Lanschot JJB, Li Z. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study. BMC Cancer. 2020 Mar 6;20(1):194. doi: 10.1186/s12885-020-6669-y.

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2019
• Primary Completion (Anticipated): August 8, 2022
• Study Completion (Anticipated): August 8, 2022

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 1, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Active surveillance; Esophageal cancer; Esophageal squamous cell carcinoma; Esophagectomy; Neoadjuvant chemoradiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: Chest201902

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No