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INTRODUCTION Only a minority of esophageal cancers demonstrates a pathological tumor response (pTR) to neoadjuvant chemotherapy (NAC). 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is often used for restaging after NAC and to assess response. Increasingly, it is used during therapy to identify unresponsive tumors and predict pTR , using avidity of the primary tumor alone. However, definitions of such metabolic tumor response (mTR) vary. We aimed to comprehensively re-evaluate metabolic response assessment using accepted parameters, as well as novel concepts of metabolic nodal stage (mN) and nodal response (mNR). PATIENTS AND METHODS This was a single-center retrospective UK cohort study. All patients with esophageal cancer staged before NAC with PET-CT and after with CT or PET-CT and undergoing resection from 2006-2014 were identified. pTR was defined as Mandard tumor regression grade 1-3; imaging parameters included metrics of tumor avidity (standardized uptake value [SUV]max/mean/peak), composites of avidity and volume (including metabolic tumor volume), nodal SUVmax, and our new concepts of mN stage and mNR. RESULTS Eighty-two (27.2%) of 301 patients demonstrated pTR. No pre-NAC PET parameters predicted pTR. In 220 patients re-staged by PET-CT, The optimal tumor ΔSUVmax threshold was a 77.8% reduction. This was as sensitive as the current PET Response Criteria in Solid Tumors (PERCIST) 30% reduction, but more specific with a higher negative predictive value (p<0.001). ΔSUVmax and Δlength independently predicted pTR, and composite avidity/spatial metrics outperformed avidity alone. Whilst both mTR and mNR were associated with pTR, in 82 patients with FDG-avid nodes before NAC we observed mNR in 10 (12.2%) not demonstrating mTR. CONCLUSION Current definitions of metabolic response are suboptimal and too simplistic. Composite avidity/volume measures improve prediction. mNR may further improve response assessment, by specifically assessing metastatic tumor sub-populations, likely responsible for disease relapse, and should be urgently assessed when considering aborting therapy on the basis of mTR alone.

Type

Journal article

Journal

Journal of Nuclear Medicine

Publisher

Society of Nuclear Medicine

Publication Date

14/07/2016

Addresses

John M Findlay, Oxford University Hospitals NHS Trust, Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, Kevin M Bradley, Oxford University Hospitals NHS Trust, Department of Nuclear Medicine, Churchill Hospital,, Oxford, OX3 7LE, United Kingdom, Lai Mun Wang, Oxford University Hospitals NHS Trust, NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, James M Franklin, Oxford University Hospitals NHS Trust, Department of Nuclear Medicine, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, Eugene J Teoh, Oxford University Hospitals NHS Trust, Department of Nuclear Medicine, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, Fergus V Gleeson, Oxford University Hospitals NHS Trust, Department of Nuclear Medicine, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, Nicholas D Maynard, Oxford University Hospitals NHS Trust, Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, Richard S Gillies, Oxford University Hospitals NHS Trust, Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, OX3 7LE, United Kingdom, Mark R Middleton, University of Oxford, Department of Oncology, Old Road Campus Research Building, Oxford, OX3 7DQ, United Kingdom

Keywords

Esophageal cancer, neoadjuvant therapy, positron-emission tomography, precision oncology