Clinical response assessment on DW-MRI compared with FDG-PET/CT after neoadjuvant chemoradiotherapy in patients with oesophageal cancer.

PURPOSE: In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT. METHODS: Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+). RESULTS: Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively. CONCLUSION: MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.

Added value of MRI to endoscopic and endosonographic response assessment after neoadjuvant chemoradiotherapy in oesophageal cancer.

OBJECTIVES: In order to select oesophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) for organ-preserving treatment instead of surgery, a high diagnostic accuracy is required. The aim of this study was to evaluate whether MRI had additional value to gastroscopy with biopsies and endosonographic ultrasound (EUS) with fine needle aspiration (FNA) for the detection of residual tumour after nCRT. METHODS: Twenty-two patients with oesophageal cancer eligible for nCRT followed by oesophagectomy were prospectively included. All patients underwent (T2- and diffusion-weighted) MRI and gastroscopy+EUS before and after nCRT. Histopathology after oesophagectomy was the reference standard with pathological complete response (pCR) defined as ypT0N0. Diagnostic performance regarding the detection of residual tumour was calculated for gastroscopic biopsies and for EUS-FNA without and with MRI. RESULTS: Nineteen of the 22 patients (86%) did not achieve pCR after nCRT (7 ypT+N+, 11 ypT+N0, 1 ypT0N+). Biopsies detected residual tumour in 6 of 18 ypT+ patients. After adding MRI, 16 of 18 residual tumours were assessed correctly. EUS-FNA detected 3 out of 8 ypN+ patients, while MRI did not improve detection. Overall, adding MRI improved sensitivity for detection of residual tumour to 89% (17 of 19) from 47% (9 of 19) with endoscopic biopsies and EUS-FNA only. CONCLUSION: In this small study, the detection of residual tumour after nCRT in oesophageal cancer patients was improved by the addition of MRI to gastroscopy and EUS. KEY POINTS: • In this small study, the detection of residual tumour after neoadjuvant chemoradiotherapy in oesophageal cancer patients was improved by adding MRI including diffusion-weighted images to gastroscopy and endosonographic ultrasound. • With the addition of MRI assessment to gastroscopy and endosonographic ultrasound, the considerable risk of missing residual tumours decreased from 53 to 11%, while the pitfall was overstaging in one out of three complete responders.

Diffusion-weighted MRI with ADC mapping for response prediction and assessment of oesophageal cancer: A systematic review.

PURPOSE: The aim was to perform a systematic review on the value of diffusion-weighted MRI (DW-MRI) with apparent diffusion coefficient (ADC) mapping in the prediction and assessment of response to chemo- and/or radiotherapy in oesophageal cancer. MATERIALS AND METHODS: A systematic search was performed on Pubmed, Embase, Medline and Cochrane databases. Studies that evaluated the ADC for response evaluation before, during or after chemo- and/or radiotherapy were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of the included studies. RESULTS: Fourteen studies, comprising 516 patients, in which the response to treatment in oesophageal cancer was evaluated on ADC maps were included. Acquisition parameter settings for DW-MRI and ROI placement varied substantially. The reference standard was RECIST or endoscopic assessment in eight non-surgery studies and histopathology after surgery in six studies. A high pre-treatment ADC significantly correlated with good response in three out of 12 studies; conversely, one study reported a significantly higher pre-treatment ADC in poor responders. In five out of eight studies good responders showed a significantly larger relative increase in ADC two weeks after the onset of treatment (range 23-59%) than poor responders (range 1.5-17%). After chemo- and/or radiotherapy ADC results varied considerably, amongst others due to large variation in the interval between completion of therapy and DW-MRI. CONCLUSION: DW-MRI for response evaluation to chemo- and/or radiotherapy in oesophageal cancer shows variable methods and results. A large relative ADC increase after two weeks of treatment seems most predictive for good response.

Quantification of Esophageal Tumor Motion and Investigation of Different Image-Guided Correction Strategies.

PURPOSE: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies. MATERIAL AND METHODS: Esophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations. RESULTS: Fifty-six patients with tumors located in the proximal (n = 1), mid (n = 7), or distal esophagus (n = 25) or at the gastroesophageal junction (n = 23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins. CONCLUSIONS: Substantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy.

Gross Tumor Delineation in Esophageal Cancer on MRI Compared With 18F-FDG-PET/CT.

PURPOSE: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT. METHODS: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/CT, T2W-MRI, and T2W + DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated. RESULTS: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation. CONCLUSIONS: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors.