Preoperative Image-guided Identification of Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer (PRIDE)

UMC Utrecht

Status: Unknown

Conditions: Esophageal Cancer; Esophageal Squamous Cell Carcinoma; Esophageal Adenocarcinoma; Esophageal Neoplasms

Treatments: Diagnostic Test: MRI; Diagnostic Test: PET-CT; Diagnostic Test: Endoscopy; Diagnostic Test: Blood samples

Study type: Observational

Funder types: Other

Identifiers

NCT03474341

NL62881.041.17

17-941 (Other Identifier)

Project ID 10291 (Other Grant/Funding Number)

Details and patient eligibility

About

Rationale: For locally advanced esophageal cancer the standard treatment consists of 5 weeks of neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Surgery is currently performed independent of the response to nCRT and is associated with substantial morbidity. Prior knowledge of the eventual response to nCRT would greatly impact on the optimal care for many esophageal cancer patients for two imperative reasons:

Firstly, it is argued that patients who achieved a pathologic complete response (pCR, 29%) may not have benefitted from surgery. Consequently, proper identification of pathological complete responders prior to surgery could yield an organ-preserving regimen avoiding unnecessary toxicity.

Secondly, non-responders are exposed to the side effects of nCRT without showing any tumor regression. Early identification of the non-responders during nCRT would be beneficial for this group as ineffective therapy could be stopped, and for who altered treatment strategies could be explored.

Objective: To develop a multimodal model that predicts the probability of pathologic complete response to nCRT in esophageal cancer, by integrating diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in conjunction with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) scans acquired prior to, during and after administration of nCRT.

Study design: Multi-center observational study

Study population: Patients (>18 years) with potentially resectable locally advanced squamous cell- or adenocarcinoma of the esophagus or gastroesophageal junction, receiving nCRT prior to surgery.

Intervention: In addition to the standard diagnostic work-up for esophageal cancer that includes a 18F-FDG PET-CT scan at diagnosis and after nCRT, one 18F-FDG PET-CT scans will be performed during nCRT, as well as three MRI scans (before, during and after nCRT) within fixed time intervals. Furthermore, after response imaging after nCRT has been performed, but prior to surgery, patients will undergo (on an opt-out basis) an endoscopy and/or endoscopic ultrasonography (EUS) with biopsies of the primary tumor site, other suspected lesions and suspected lymph nodes. Furthermore, blood samples will be collected at three time points.

Main study parameters/endpoints: An accurate multimodal prediction model for the patients' individual probability of pathologic complete response after nCRT, based on the quantitative parameters derived from a longitudinal series of DW-MRI, DCE-MRI and 18F-FDG PET-CT datasets.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction (i.e. tumors involving both cardia and esophagus on endoscopy)
• Potentially resectable locally advanced esophageal tumor (cT1b-4a N0-3 M0): based on standard primary staging by EUS and 18F-FDG PET-CT
• Scheduled to receive neoadjuvant chemoradiotherapy according to CROSS-regimen1: weekly administration of carboplatin and paclitaxel for 5 weeks and concurrent radiotherapy (41.4 Gray in 23 fractions, 5 days per week) followed by esophagectomy
• Age > 18 years

Exclusion criteria

• Patients who meet exclusion criteria for MRI

• Patients who meet exclusion criteria for intravenous gadolinium-based contrast:

  • Glomerular Filtration Rate (GFR) of <30 mL/min/1.73m2
  • Nephrogenic Systemic Fibrosis (strict contra-indication for gadolinium-based contrast)
  • Known allergy for gadolinium-based contrast

• Patients with a blood plasma glucose concentration >10 mmol/L or poorly controlled diabetes mellitus

• Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of primary tumor prior to start of neoadjuvant chemoradiotherapy

• Pregnant or breast-feeding patients

Trial design

200 participants in 1 patient group

Resectable esophageal squamous cell- or adenocarcinoma

Description:

Patients (\>18 years) with potentially resectable locally advanced squamous cell- or adenocarcinoma of the esophagus or gastroesophageal junction, receiving nCRT according to the CROSS regimen prior to surgery. CROSS regimen: weekly carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, delivered 5 days per week on workdays with intensity modulated radiotherapy, including photon and proton therapy)

Treatment:

Diagnostic Test: Endoscopy

Diagnostic Test: PET-CT

Diagnostic Test: MRI

Diagnostic Test: Blood samples