Pre-Surgery If Needed for Oesophageal Cancer (preSINO)

Shanghai Jiao Tong University

Status: Completed

Conditions: Esophageal Cancer

Treatments: Diagnostic Test: Second clinical response evaluation (CRE-2); Diagnostic Test: First clinical response evaluation (CRE-1)

Study type: Observational

Funder types: Other

Identifiers

NCT03937362

Chest201902

Details and patient eligibility

About

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).

Full 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).

Enrollment: 200 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

200 participants in 1 patient group

Clinical Response Evaluation

Description:

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.

Treatment:

Diagnostic Test: First clinical response evaluation (CRE-1)

Diagnostic Test: Second clinical response evaluation (CRE-2)