Combination of Chemotherapy and Adaptive MR-Guided Radiotherapy to Improve Outcomes in Patients With Esophageal Adenocarcinoma

Rationale: Esophageal cancer (EC) is the seventh most frequently diagnosed cancer and the sixth leading cause of cancer-related death worldwide. As a result of the late onset of symptoms, most patients with EC present in an advanced stage with a corresponding poor prognosis. Poor disease outcome after surgery alone (5-yr overall survival between 25-40%) prompted many researchers to explore neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant or perioperative chemotherapy (nCT/pCT) approaches. In the Netherlands, neoadjuvant chemoradiation has become standard of care for esophageal cancer since publication of the CROSS trial showing a benefit of nCRT over surgery alone for both adenocarcinoma (AC) and squamous cell carcinoma (SCC) (van Hagen et al., 2012). However, the benefit of nCRT was less pronounced in AC, which was also reflected by pathologic complete response (pCR) rates: 23% in AC vs. 49% in SCC. Furthermore, SCC and AC differ in patterns of recurrence after nCRT or chemotherapy. AC is more likely to develop distant metastases while SCC has a predisposition for locoregional recurrences. This difference in response to nCRT and in recurrence pattern indicates that histology-tailored treatment strategies should be explored. In the modern multidisciplinary discussion on the optimal approach to locally advanced adenocarcinoma of the esophagus and junction, both a trimodiality approach or perioperative chemotherapy are acceptable and evidence based. Therefore both are viable options within current guidelines. As mentioned above, patients with an AC of the esophagus are especially prone to develop distant recurrences. In addition, response to nCRT is only moderate in AC. Therefore, the investigators hypothesize that the ideal neoadjuvant treatment should consist of adding MR-guided radiotherapy to standard pCT in order to achieve maximum systemic control and achieve maximum local control. Objective: The main objective of this study is to determine the maximum tol