Esophageal Squamous Cell Carcinoma
Conditions
Keywords
Esophageal magnetic resonance imaging, Structured reporting, T staging, Tumor regression grade, Diagnostic accuracy, Neoadjuvant therapy, Multicenter study
Brief summary
This prospective, multicenter diagnostic accuracy study will develop and validate a standardized 3.0-T magnetic resonance imaging (MRI) acquisition protocol and structured reporting system for primary esophageal squamous cell carcinoma (ESCC). Approximately 500 adults scheduled for curative esophagectomy will be enrolled consecutively into two clinically defined cohorts. In Cohort A, patients proceeding directly to surgery will have MRI-based T staging compared with postoperative pathological T stage. In Cohort B, patients receiving neoadjuvant therapy before surgery will undergo paired MRI assessment, and MRI-based tumor regression grade will be compared with pathological tumor regression grade in the resected primary tumor bed. Imaging will be independently assessed by two radiologists, with adjudication by a third reader. The study will evaluate diagnostic performance, reader agreement, image quality, protocol adherence, reporting completeness, and consistency across participating centers and MRI vendors. Lymph-node staging and nodal treatment response are outside the research scope.
Detailed description
This investigator-initiated, prospective, multicenter, dual-cohort diagnostic accuracy study uses a common standardized 3.0-T esophageal MRI framework. The clinical treatment pathway, including whether a patient proceeds directly to surgery or receives neoadjuvant therapy before surgery, is determined by the treating multidisciplinary team independently of study participation. The MRI examinations are performed as part of routine clinical care. Participants are classified into one of two cohorts according to their clinical pathway. Cohort A includes patients who have received no antitumor treatment before MRI and are scheduled for upfront esophagectomy. MRI is performed within 14 days before surgery. Structured MRI-based T stage (mrT1, mrT2, mrT3, or mrT4a) is compared with postoperative pathological T stage. Cohort B includes patients scheduled to receive neoadjuvant chemoradiotherapy, chemotherapy, or immunotherapy combined with chemotherapy according to routine clinical decision-making, followed by esophagectomy. Baseline MRI is performed within 14 days before neoadjuvant treatment, and a second MRI is performed after treatment and within 14 days before surgery. Paired examinations are assigned an MRI tumor regression grade (mrTRG 1-4) and compared with pathological tumor regression grade in the resected primary tumor bed using the modified Ryan system (pTRG 0-3). Pathological good response is defined as pTRG 0-1, and the prespecified imaging dichotomy is mrTRG 1-2 versus mrTRG 3-4. The core MRI framework includes large-coverage T2-weighted imaging, tumor-axis and high-resolution oblique axial T2-weighted imaging, diffusion-weighted imaging with apparent diffusion coefficient maps, and three-dimensional T1-weighted imaging before and after gadolinium contrast administration. Participating scanners undergo parameter mapping, test-scan certification, and ongoing central quality control. Each examination is interpreted independently by two trained radiologists who are blinded to postoperative pathology, other imaging-stage results, endoscopic stage, and clinical response conclusions. Disagreements are adjudicated by a third senior radiologist. Pathological pT or pTRG is assessed by two gastrointestinal pathologists blinded to the MRI results, with adjudication when needed. At least 10% of cases are reread after an interval of at least 4 weeks to assess intrareader agreement. A total of 500 participants are planned, with 250 participants in each cohort. Consecutive enrollment will be used, and no single center should contribute more than 40% of the total sample. The study evaluates only the primary esophageal tumor. Lymph-node imaging features, N stage, and nodal treatment response are not collected for research analysis.
Interventions
DIAGNOSTIC_TESTStandardized 3.0-T Esophageal Magnetic Resonance Imaging
A standardized 3.0-T esophageal MRI framework comprising large-coverage and tumor-oriented T2-weighted imaging, high-resolution oblique axial T2-weighted imaging, diffusion-weighted imaging with apparent diffusion coefficient maps, and three-dimensional T1-weighted imaging before and after gadolinium contrast administration. Cohort A has one preoperative examination within 14 days before surgery. Cohort B has a baseline examination within 14 days before neoadjuvant treatment and a post-treatment examination within 14 days before surgery. Images are evaluated with predefined structured mrT or mrTRG criteria.
Sponsors
The First Affiliated Hospital of Zhengzhou University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years, inclusive * Histologically confirmed esophageal squamous cell carcinoma based on endoscopic biopsy or other tissue examination * Primary tumor located in the thoracic esophagus * Planned curative esophagectomy * Able to complete the required esophageal MRI examination with diagnostically adequate image quality * Able and willing to provide written informed consent * For Cohort A: no chemotherapy, radiotherapy, immunotherapy, targeted therapy, or other antitumor treatment before MRI; surgery planned within 14 days after MRI; and postoperative pathological T stage expected to be available * For Cohort B: neoadjuvant treatment followed by surgery selected by the clinical multidisciplinary team; baseline MRI completed within 14 days before neoadjuvant treatment; post-treatment MRI completed within 14 days before surgery; and pathological tumor regression grade of the primary tumor bed expected to be available
Exclusion criteria
* Adenocarcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, or another non-squamous histological type * Cervical esophageal cancer, a gastric primary tumor extending into the esophagus, or multiple primary lesions that prevent reliable imaging-pathology matching * Definite distant metastasis, unresectable T4b disease, or another reason that prevents acquisition of a surgical pathological reference standard * Previous esophageal cancer surgery, radiotherapy, or another treatment that substantially altered local esophageal anatomy * Contraindication to MRI, or contraindication to the gadolinium-based contrast agent when the required contrast-enhanced sequences cannot be completed * Severe claustrophobia, inability to follow breathing instructions, or another cause of nondiagnostic image quality that persists after a safe repeat examination * Substantial disease progression, emergency intervention, or off-protocol treatment between MRI and surgery that prevents valid imaging-pathology comparison * Inadequate surgical specimen sampling or inability to determine pathological T stage or pathological tumor regression grade
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exact agreement between MRI-based and pathological T stage in Cohort A | At postoperative pathological assessment following surgery performed within 14 days after the preoperative MRI | Proportion of evaluable Cohort A participants for whom the four-category structured MRI T stage (mrT1, mrT2, mrT3, or mrT4a) exactly matches postoperative pathological T stage (pT1, pT2, pT3, or pT4a). Linear weighted kappa and its 95% confidence interval will also be reported. |
| Area under the ROC curve of mrTRG for pathological good response in Cohort B | At postoperative pathological assessment following surgery performed within 14 days after the post-treatment MRI | Area under the receiver operating characteristic curve and 95% confidence interval for four-level MRI tumor regression grade (mrTRG 1-4) to identify pathological good response, defined as modified Ryan pTRG 0-1 versus pTRG 2-3. The prespecified imaging dichotomy is mrTRG 1-2 versus mrTRG 3-4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intrareader agreement for MRI T stage in Cohort A | At repeat central review performed at least 4 weeks after the initial image review | Cohen kappa or weighted kappa from repeat blinded assessment of at least 10% of randomly selected Cohort A examinations. |
| Agreement and rank correlation between four-level mrTRG and pTRG in Cohort B | At postoperative pathological assessment following surgery performed within 14 days after the post-treatment MRI | Weighted kappa, Spearman rank correlation, and exact agreement rate between mrTRG 1-4 and modified Ryan pTRG 0-3. |
| Sensitivity of mrTRG for pathological complete response in Cohort B | At postoperative pathological assessment following surgery; post-treatment MRI performed within 14 days before surgery | Sensitivity (percentage) of MRI tumor regression grade at each prespecified mrTRG threshold for identifying pathological complete response, defined as modified Ryan pTRG 0, using postoperative pathology as the reference standard. |
| Association of quantitative MRI changes with pathological tumor regression grade in Cohort B | From baseline MRI within 14 days before neoadjuvant treatment through postoperative pathological assessment after post-treatment MRI and surgery | Associations between treatment-related changes in tumor length, maximum wall thickness, volume, and apparent diffusion coefficient and postoperative pTRG. |
| Interreader agreement for MRI tumor regression grade in Cohort B | At the initial blinded central review of paired baseline and post-treatment MRI examinations in Cohort B, through study completion (up to 2 years) | Weighted kappa calculated from the original independent mrTRG assessments of the two radiologists. |
| Intrareader agreement for MRI tumor regression grade in Cohort B | At repeat central review performed at least 4 weeks after the initial image review | Weighted kappa from repeat blinded assessment of at least 10% of randomly selected Cohort B paired examinations. |
| Core MRI sequence completion and protocol parameter adherence rates | From the first MRI examination through study completion, up to 2 years | Proportions of examinations that complete all required core sequences and meet the predefined parameter ranges in the standardized MRI protocol. |
| Diagnostic image quality rate | From the first MRI examination through study completion, up to 2 years | Proportion of examinations graded as diagnostically acceptable (image quality grade 2-4 on the predefined four-level scale); grade 1 is nondiagnostic. |
| Structured report completeness rate | From the first MRI examination through study completion, up to 2 years | Proportion of structured research reports in which all mandatory fields are completed. |
| MRI acquisition time and structured reporting time | From the first MRI examination through study completion, up to 2 years | Duration in minutes for each MRI examination and for completion of the corresponding structured report; reasons for nonevaluable examinations will also be summarized. |
| Specificity of mrT at prespecified pathological T-stage thresholds in Cohort A | At postoperative pathological assessment following surgery; preoperative MRI performed within 14 days before surgery | Specificity (percentage) of structured MRI T staging for detecting pT2 or higher and pT3-pT4a disease. Results will be reported separately for each prespecified threshold using postoperative pathological T stage as the reference standard. |
| Positive predictive value of mrT at prespecified pathological T-stage thresholds in Cohort A | At postoperative pathological assessment following surgery; preoperative MRI performed within 14 days before surgery | Positive predictive value (percentage) of structured MRI T staging for detecting pT2 or higher and pT3-pT4a disease. Results will be reported separately for each prespecified threshold using postoperative pathological T stage as the reference standard. |
| Negative predictive value of mrT at prespecified pathological T-stage thresholds in Cohort A | At postoperative pathological assessment following surgery; preoperative MRI performed within 14 days before surgery | Negative predictive value (percentage) of structured MRI T staging for detecting pT2 or higher and pT3-pT4a disease. Results will be reported separately for each prespecified threshold using postoperative pathological T stage as the reference standard. |
| Accuracy of mrT at prespecified pathological T-stage thresholds in Cohort A | At postoperative pathological assessment following surgery; preoperative MRI performed within 14 days before surgery | Accuracy (percentage) of structured MRI T staging for detecting pT2 or higher and pT3-pT4a disease. Results will be reported separately for each prespecified threshold using postoperative pathological T stage as the reference standard. |
| Area under the ROC curve of mrT at prespecified pathological T-stage thresholds in Cohort A | At postoperative pathological assessment following surgery; preoperative MRI performed within 14 days before surgery | Area under the receiver operating characteristic curve for structured MRI T staging at the prespecified pT2-or-higher and pT3-pT4a thresholds. Each threshold will be reported separately using postoperative pathological T stage as the reference standard. |
| Specificity of mrTRG for pathological complete response in Cohort B | At postoperative pathological assessment following surgery; post-treatment MRI performed within 14 days before surgery | Specificity (percentage) of MRI tumor regression grade at each prespecified mrTRG threshold for identifying pathological complete response, defined as modified Ryan pTRG 0, using postoperative pathology as the reference standard. |
| Positive predictive value of mrTRG for pathological complete response in Cohort B | At postoperative pathological assessment following surgery; post-treatment MRI performed within 14 days before surgery | Positive predictive value (percentage) of MRI tumor regression grade at each prespecified mrTRG threshold for identifying pathological complete response, defined as modified Ryan pTRG 0, using postoperative pathology as the reference standard. |
| Negative predictive value of mrTRG for pathological complete response in Cohort B | At postoperative pathological assessment following surgery; post-treatment MRI performed within 14 days before surgery | Negative predictive value (percentage) of MRI tumor regression grade at each prespecified mrTRG threshold for identifying pathological complete response, defined as modified Ryan pTRG 0, using postoperative pathology as the reference standard. |
| Area under the ROC curve of mrTRG for pathological complete response in Cohort B | At postoperative pathological assessment following surgery; post-treatment MRI performed within 14 days before surgery | Area under the receiver operating characteristic curve for MRI tumor regression grade to identify pathological complete response, defined as modified Ryan pTRG 0, using postoperative pathology as the reference standard. |
| Agreement within one T-stage category in Cohort A | At postoperative pathological assessment following surgery performed within 14 days after the preoperative MRI | Proportion of evaluable participants for whom mrT and pT differ by no more than one ordered T-stage category. |
| Sensitivity of mrT at prespecified pathological T-stage thresholds in Cohort A | At postoperative pathological assessment following surgery; preoperative MRI performed within 14 days before surgery | Sensitivity (percentage) of structured MRI T staging for detecting pT2 or higher and pT3-pT4a disease. Results will be reported separately for each prespecified threshold using postoperative pathological T stage as the reference standard. |
| MRI T-stage overstaging and understaging rates in Cohort A | At postoperative pathological assessment following surgery performed within 14 days after the preoperative MRI | Proportions of evaluable participants in whom mrT is higher than pT (overstaging) or lower than pT (understaging). |
| Interreader agreement for MRI T stage in Cohort A | At the initial blinded central MRI review in Cohort A, through study completion (up to 2 years) | Cohen kappa or weighted kappa calculated from the original independent mrT assessments of the two radiologists. |
Countries
China
Contacts
CONTACTXiangbo Wan, PhD
PRINCIPAL_INVESTIGATORXiangbo Wan, PhD
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed