ABSTRACT
BACKGROUND: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. METHODS: In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. RESULTS: Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis. CONCLUSIONS: A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes.
ABSTRACT
INTRODUCTION: Up to 32% of patients with esophageal cancer show a pathological complete response (ypCR) after neoadjuvant therapy. To prevent overtreatment, the indication to perform esophagectomy in these patients should be reconsidered. Implementing an organ-preserving strategy for patients with ypCR requires an accurate assessment of residual disease after neoadjuvant treatment. The aim of this study was to systematically review the effectiveness of imaging techniques used for detection of ypCR after neoadjuvant therapy but before resection in patients with esophageal cancer. METHODS: A systematic literature search of the Medline, Embase, and Cochrane Library databases was performed from January 1, 2000, to December 13, 2017. Eligible studies were diagnostic studies that compared results of imaging modalities after neoadjuvant therapy to histopathological findings in the resection specimen after esophagectomy. Methodological quality was assessed by the Cochrane Quality Assessment of Diagnostic Accuracy Studies, version 2, model. Primary outcome measures were true positive, false-positive, false-negative, and true negative values of imaging techniques predicting ypCR. A meta-analysis was performed by pooling sensitivities and specificities by using a bivariate model. RESULTS: A total of 4420 articles were identified. After exclusion of irrelevant titles and abstracts, 360 articles were reviewed in full text. In total, four imaging modalities (computed tomography [CT], positron emission tomography [PET-CT], endoscopic ultrasound [EUS], and magnetic resonance imaging [MRI]) were used for restaging. The meta-analysis was conducted with data from 56 studies involving 3625 patients. The pooled sensitivities of CT, PET-CT, EUS, and MRI for detecting ypCR were 0.35, 0.62, 0.01 and 0.80, respectively, whereas the pooled specificities were 0.83, 0.73, 0.99, and 0.83, respectively. The positive predictive value in detecting ypCR was 0.47 for CT, 0.41 for PET-CT, not applicable for EUS, and 0.61 for MRI. CONCLUSION: Current imaging modalities such as CT, PET-CT, and EUS seem to be insufficiently accurate to identify complete responders. More accurate diagnostic tests are needed to improve restaging accuracy for patients with esophageal cancer.
