PReoperative Identification Of Response to Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Multi-center diagnostic study investigating the distinct and combined value of MRI and PET-CT for response prediction before and response assessment during and after nCRT for esophageal cancer. The patients will be enrolled in two hospitals (UMC Utrecht and M.D. Anderson Cancer Center) during their first outpatient visit at the Department of Surgery or Radiation Oncology. At the UMC Utrecht, for study purposes three anatomical and functional MRI scans are made and two PET-CT scans, in addition to a pre-nCRT PET-CT scan which is standard care. At M.D. Anderson Cancer Center, for study purposes three anatomical and functional MRI scans are made and one PET-CT scans, in addition to a pre-nCRT and a post-nCRT PET-CT scan which are standard care. The MRI scan protocol will consist of anatomical and functional MRI scans. For the dynamic contrast-enhanced MRI (DCE-MRI) scans, a contrast agent will be administered to the patient. All MRI scans will be performed on a 1.5-Tesla MRI scanner. For the PET-CT scans, 18F-fluorodeoxyglucose (FDG) is the tracer that will be used for the assessment of abnormal glucose metabolism in the tumor. Before the start of nCRT, we schedule an MRIpre to have baseline MRI and PET-CT images in all enrolled patients. This scanning day is matched to the irradiation treatment planning PET-CT scan, which is routinely made for treatment planning purposes. Next, the patients receive standard nCRT treatment with weekly administration of 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 at UMC Utrecht and 6 weeks at M.D. Anderson Cancer Center with concurrent radiotherapy (41.4 Gy in 23 fractions in Utrecht or 50.4 Gy in 28 fractions at M.D. Anderson, delivered 5 days per week on workdays). As mentioned in the introduction, earlier studies reveal that both PET and DWI-MRI after 2 weeks of treatment showed the best distinction between responders and non-responders. Therefore, we decided to perform a PET-CTper and an MRIper scan two weeks after the start of the nCRT. Surgery will follow 6-8 weeks after finishing nCRT and all patients will undergo a preoperative MRIpost and PET-CTpost scan 1-2 weeks before surgery, combined with a standard preoperative outpatient follow-up appointment. Overall, no extra hospital visits are asked from participants as we try to schedule all study activities at days corresponding with appointments for standard care. If in individual cases an extra visit to the hospital is needed, travel expenses of this extra visit will be reimbursed. Important imaging parameters include apparent diffusion coefficient (ADC) values, standardized uptake values (SUV) and volume measurements for the different time points. The differences of these values between time points are of particular interest (delta-ADC, delta-SUV, delta-volume). The sensitivity (%), specificity (%), negative predictive value (%), positive predictive value (%), and accuracy (%) of the different imaging parameters for correctly identifying histopathological complete response will be calculated. The resection specimen will be evaluated meticulously according to standard protocol (tumor type and extension, lymph nodes, resection margins), and additionally, findings of effects of nCRT will be reported. The research population consists of patients with resectable esophageal carcinoma, scheduled to receive preoperative chemoradiation according to the CROSS-regimen. The participants will be recruited from the surgical outpatient clinic or radiation oncology department of the UMC Utrecht or M.D. Anderson Cancer Center. In total 50 participants with available histopathologic data of the resection specimen are required for this study. Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria (comparable with CROSS-criteria): * Histologically confirmed squamous-cell carcinoma, adenocarcinoma or large-cell undifferentiated carcinoma of the esophagus or esophagogastric junction (i.e. tumors involving both cardia and esophagus on endoscopy) * Potentially resectable tumor (cT1b-4a N0-3 M0): based on standard primary staging by EUS and CT * Undergoing preoperative chemoradiation according to CROSS-regimen * Age\>18 years * No history of other cancer or previous radiotherapy or chemotherapy * Signed informed consent Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: * Patients who meet exclusion criteria for MRI at 1.5T following the protocol of the department of Radiology of the UMC Utrecht * Patients who meet local exclusion criteria for intravenous contrast (Glomerular Filtration Rate (GFR) of \<45 mL/min/1.73m2, unless the patient has risk factors for contrast nephropathy according to the UMC Utrecht protocol 'Prevention contrast reaction and contrast nephropathy, Version 2 February 2012'). In patients with risk factors (2 or more of the following: 'peripheral vascular disease, heart failure, age \>75 years, anemia, symptomatic hypotension, dehydration, use of diuretics or non-steroidal anti-inflammatory drugs)', a minimum GFR of 60 mL/min/1.73m2 will be required * Patients with insulin dependent diabetes mellitus or blood plasma glucose concentration higher than 10 mmol/L * Patients with a known Gadovist allergy * Patients with a known CT-contrast allergy * Patients having difficulty understanding Dutch * Pregnant or breast-feeding patients