Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE):a multicenter observational study

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and (18)F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341

3-Dimensional target coverage assessment for MRI guided esophageal cancer radiotherapy

Purpose: This study aimed to quantify the coverage probability for esophageal cancer radiotherapy as a function of a preset margin for online MR-guided and (CB)CT-guided radiotherapy. Methods: Thirty esophageal cancer patients underwent six T2-weighted MRI scans, 1 prior to treatment and 5 during neoadjuvant chemoradiotherapy at weekly intervals. Gross tumor volume (GTV) and clinical target volume (CTV) were delineated on each individual scan. Follow-up scans were rigidly aligned to the bony anatomy and to the clinical target volume itself, mimicking two online set-up correction strategies: a conventional CBCT-guided set-up and a MR-guided set-up, respectively. Geometric coverage probability of the propagated CTVs was assessed for both set-up strategies by expanding the reference CTV with an isotropic margin varying from 0 mm to 15 mm with an increment of 1 mm. Results: A margin of 10 mm could resolve the interfractional changes for 118 out of the 132 (89%) analyzed fractions when applying a bone-match registration, whereas the CTV was adequately covered in 123 (93%) fractions when the registration was directly performed at the CTV itself (soft-tissue registration). Closer analyses revealed that target coverage violation predominantly occurred for distal tumors near the junction and into the cardia. Conclusion: Online MR-guided soft-tissue registration protocols exhibited modest improvements of the geometric target coverage probability as compared to online CBCT-guided bone match protocols. Therefore, highly conformal target irradiation using online MR-guidance can only be achieved by implementing on-table adaptive workflows where new treatment plans are daily generated based on the anatomy of the day