Esophageal CancerpreSINONCT03937362
Pre-Surgery If Needed for Oesophageal Cancer
An observational study of Esophageal Cancer, run by Shanghai Chest Hospital at 4 sites in 4 countries.
Trial summary
A 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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Esophageal Cancer
- What is being tested?
- First clinical response evaluation (CRE-1) and Second clinical response evaluation (CRE-2)
- Type of treatment
- Injection or infusion
- How many people
- 200 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 8 Aug 2019to 31 May 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Histologically confirmed esophageal squamous cell carcinoma;
- Tumor located in the chest;
- Clinical stage cT1N1-2M0, cT2-4aN0-2M0, according to the 8th Edition of the AJCC TNM classification for Esophageal Cancer;
- Age > 20 at the date of informed consent;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of two or less;
- Considered fit to undergo nCRT followed by surgical resection;
- Expected survival time more than three months;
- Written informed consent by the patient.
Who cannot join
- Patient with a second primary tumor;
- Previous major surgery in the chest or upper abdomen;
- Tumor not 18F-FDG-avid at baseline PET-CT;
- Suspected positive lymph nodes that cannot be covered by an uninterrupted radiation field that also includes the primary tumor area;
- Primary (early) lesion already removed by EMR/ESD;
- Previous history of chemotherapy and/or radiation therapy;
- Cervical esophageal cancer.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: the preSINO Trial (Pre-Surgery If Needed for Oesophageal Cancer)
A 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 resectable esophageal squamous cell carcinoma (SCC).
Read the detailed description
Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for locally-advanced esophageal cancer. After nCRT, high pathologically complete response (pCR) rates are being achieved in patients with esophageal cancer, especially squamous cell carcinoma (SCC). Surgery for esophageal cancer is risky and is associated with reduced quality of life. It is important to know that with an accurate and safe clinical evaluation strategy, some patients might delay surgery or avoid unnecessary surgery and be safely monitored instead. Therefore, an active surveillance strategy has been proposed for patients with clinically complete response (cCR) after nCRT.
The previous European preSANO trial (Lancet Oncol. 2018 Jul;19(7):965-974, PMID: 29861116) showed that the clinical response evaluations (CRE) were sufficiently accurate to detect residual tumor after nCRT in patients with mainly adenocarcinoma, however, its applicability to SCC, which is characterized by extensive lymph node metastasis, remains unknown.
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 operable esophageal SCC. Additionally, this study also explores the value of circulating-tumor DNA (ctDNA) in predicting residual disease.
Locally-advanced 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 three high-volume 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. After CRE-2, all patients without evidence of distant metastases will undergo esophagectomy. Primary endpoint is the accuracy of CRE for detecting TRG3-4 or TRG1-2 with ypN+ residual tumor with a prespecified false-negative rate of 19.5%.
Secondary endpoint includes the accuracy of detecting any residual tumor. Exploratory analyses of ctDNA will be performed in patients with available blood samples.
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).
- Conditions
- Esophageal Cancer
- Being tested
- First clinical response evaluation (CRE-1), Second clinical response evaluation (CRE-2)
- Keywords
- Esophagectomy, Neoadjuvant chemoradiotherapy, Esophageal cancer, Esophageal squamous cell carcinoma, Active surveillance
- Medical subject headings
- Esophageal Neoplasms, Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
First clinical response evaluation (CRE-1)Diagnostic test
Consisting of: endoscopy with bite-on-bite biopsies
Second clinical response evaluation (CRE-2)Diagnostic test
Consisting of: PET-CT, endoscopic bite-on-bite biopsies,EUS with FNA
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: First clinical response evaluation (CRE-1); Diagnostic Test: Second clinical response evaluation (CRE-2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10-12 weeks after completion of neoadjuvant chemoradiotherapy
Secondary outcomes (1)
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+).
Measured: 10-12 weeks after completion of neoadjuvant chemoradiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2019
- Study start8 Aug 2019
- Primary completion31 May 2023
- Study completion31 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Chest HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Chest Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, Queen Mary Hospital, Hong Kong, Erasmus Medical Center
- Responsible party
- Principal investigator, Zhigang Li, Shanghai Chest Hospital
- Investigators
- Zhigang Li, MD, PhD, Principal investigator, Shanghai Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937362
- Sponsor's protocol ID
- Chest201902
- Acronym
- preSINO
- Status last verified
- Feb 2025
- First submitted
- 1 May 2019
- Last updated
- 3 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 32143580Liu Z, Yang Y, Yu B, Yang Y, Yuan C, Chen C, Yang X, Zhang S, Li C, Chao Y, Law S, Li Z. Postoperative molecular residual disease status refines recurrence risk stratification beyond pathologic response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg. 2026 Sep;172(3):753-766.e8. doi: 10.1016/j.jtcvs.2026.04.014. Epub 2026 May 3.
PubMed 42086163Liu Z, Wang G, Yang Y, Su Y, Zhang H, Liu J, Cui P, Fan X, Yang J, Zhang Z, Gao X, Chao Y, Mostert B, van Lanschot JJB, Wijnhoven BPL, Law S, Li C, Cai S, Li Z. ctDNA detects residual disease after neoadjuvant chemoradiotherapy and guides adjuvant therapy in esophageal squamous cell carcinoma. Cell Rep Med. 2025 Sep 16;6(9):102334. doi: 10.1016/j.xcrm.2025.102334. Epub 2025 Sep 5.
PubMed 40914168
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: the preSINO Trial (Pre-Surgery If Needed for Oesophageal Cancer)
- ClinicalTrials.gov ID
- NCT03937362
- Acronym / sponsor ID
- preSINO / Chest201902
- Conditions
- Esophageal Cancer
- Keywords
- Esophagectomy, Neoadjuvant chemoradiotherapy, Esophageal cancer, Esophageal squamous cell carcinoma, Active surveillance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Shanghai Chest HospitalUniversity, hospital or other
- Collaborators
- Chang Gung Memorial Hospital, Queen Mary Hospital, Hong Kong, Erasmus Medical Center
- Study start
- 8 Aug 2019 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2024 (actual)
- First posted
- 3 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A 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 resectable esophageal squamous cell carcinoma (SCC).
Detailed description
Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for locally-advanced esophageal cancer. After nCRT, high pathologically complete response (pCR) rates are being achieved in patients with esophageal cancer, especially squamous cell carcinoma (SCC). Surgery for esophageal cancer is risky and is associated with reduced quality of life. It is important to know that with an accurate and safe clinical evaluation strategy, some patients might delay surgery or avoid unnecessary surgery and be safely monitored instead. Therefore, an active surveillance strategy has been proposed for patients with clinically complete response (cCR) after nCRT.
The previous European preSANO trial (Lancet Oncol. 2018 Jul;19(7):965-974, PMID: 29861116) showed that the clinical response evaluations (CRE) were sufficiently accurate to detect residual tumor after nCRT in patients with mainly adenocarcinoma, however, its applicability to SCC, which is characterized by extensive lymph node metastasis, remains unknown.
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 operable esophageal SCC. Additionally, this study also explores the value of circulating-tumor DNA (ctDNA) in predicting residual disease.
Locally-advanced 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 three high-volume 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. After CRE-2, all patients without evidence of distant metastases will undergo esophagectomy. Primary endpoint is the accuracy of CRE for detecting TRG3-4 or TRG1-2 with ypN+ residual tumor with a prespecified false-negative rate of 19.5%.
Secondary endpoint includes the accuracy of detecting any residual tumor. Exploratory analyses of ctDNA will be performed in patients with available blood samples.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clinical Response Evaluation | – | Diagnostic Test: First clinical response evaluation (CRE-1), Diagnostic Test: Second clinical response evaluation (CRE-2)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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- Histologically confirmed esophageal squamous cell carcinoma;
- Tumor located in the chest;
- Clinical stage cT1N1-2M0, cT2-4aN0-2M0, according to the 8th Edition of the AJCC TNM classification for Esophageal Cancer;
- Age > 20 at the date of informed consent;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of two or less;
Key exclusion criteria (7 listed)
- Patient with a second primary tumor;
- Previous major surgery in the chest or upper abdomen;
- Tumor not 18F-FDG-avid at baseline PET-CT;
- Suspected positive lymph nodes that cannot be covered by an uninterrupted radiation field that also includes the primary tumor area;
- Primary (early) lesion already removed by EMR/ESD;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| First clinical response evaluation (CRE-1)Consisting of: endoscopy with bite-on-bite biopsies | Diagnostic test | Clinical Response Evaluation |
| Second clinical response evaluation (CRE-2)Consisting of: PET-CT, endoscopic bite-on-bite biopsies,EUS with FNA | Diagnostic test | Clinical Response Evaluation |
Primary outcome
Accuracy of clinical response evaluations for detecting substantial residual locoregional disease
Time frame: 10-12 weeks after completion of neoadjuvant chemoradiotherapy
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.
1 secondary outcome
Accuracy of clinical response evaluations for detecting any residual locoregional disease
Time frame: 10-12 weeks after completion of neoadjuvant chemoradiotherapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2025.
- Background: PubMed 32143580Zhang 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.
- Derived from this study: PubMed 42086163Liu Z, Yang Y, Yu B, Yang Y, Yuan C, Chen C, Yang X, Zhang S, Li C, Chao Y, Law S, Li Z. Postoperative molecular residual disease status refines recurrence risk stratification beyond pathologic response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg. 2026 Sep;172(3):753-766.e8. doi: 10.1016/j.jtcvs.2026.04.014. Epub 2026 May 3.
- Derived from this study: PubMed 40914168Liu Z, Wang G, Yang Y, Su Y, Zhang H, Liu J, Cui P, Fan X, Yang J, Zhang Z, Gao X, Chao Y, Mostert B, van Lanschot JJB, Wijnhoven BPL, Law S, Li C, Cai S, Li Z. ctDNA detects residual disease after neoadjuvant chemoradiotherapy and guides adjuvant therapy in esophageal squamous cell carcinoma. Cell Rep Med. 2025 Sep 16;6(9):102334. doi: 10.1016/j.xcrm.2025.102334. Epub 2025 Sep 5.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhigang Li, MD, PhD principal investigator
Shanghai Chest Hospital
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Esophageal Cancer, run by Shanghai Chest Hospital at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China, Hong Kong, Netherlands, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy of clinical response evaluations for detecting substantial residual locoregional disease (time frame: 10-12 weeks after completion of neoadjuvant chemoradiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03937362, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2025.