title: Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemotherapy: The Implications of Metabolic Nodal Response for Personalized Therapy.
abstract: Only a minority of esophageal cancers demonstrates a pathologic tumor response (pTR) to neoadjuvant chemotherapy (NAC).18F-FDG 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 reevaluate metabolic response assessment using accepted parameters, as well as novel concepts of metabolic nodal stage (mN) and metabolic nodal response (mNR).
  
  
  METHODS
  This was a single-center retrospective U.K. 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 to 2014 were identified. pTR was defined as Mandard tumor regression grade 1-3; imaging parameters included metrics of tumor avidity (SUVmax/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 restaged by PET/CT, the optimal tumor ΔSUVmaxthreshold was a 77.8% reduction. This was as sensitive as the current PERCIST 30% reduction, but more specific with a higher negative predictive value (P < 0.001). ΔSUVmaxand Δlength independently predicted pTR, and composite avidity/spatial metrics outperformed avidity alone. Although both mTR and mNR were associated with pTR, in 82 patients with18F-FDG-avid nodes before NAC we observed mNR in 10 (12.2%) not demonstrating mTR.
  
  
  CONCLUSIONS
  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 subpopulations, likely responsible for disease relapse, and should be urgently assessed when considering aborting therapy on the basis of mTR alone.
authors.affiliation: Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, United Kingdom john.findlay@oncology.ox.ac.uk.|NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Findlay
authors.affiliation: Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Bradley
authors.affiliation: NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom.|Department of Pathology, John Radcliffe Hospital, Oxford, United Kingdom; and.
authors.forename: Lai Mun
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom.
authors.forename: James M
authors.initials: JM
authors.lastname: Franklin
authors.affiliation: Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Teoh
authors.affiliation: Department of Nuclear Medicine, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Fergus V
authors.initials: FV
authors.lastname: Gleeson
authors.affiliation: Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Maynard
authors.affiliation: Oxford OesophagoGastric Centre, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Gillies
authors.affiliation: NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom.|Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Middleton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017063:Outcome Assessment, Health Care / Q000379:methods*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: esophageal cancer; neoadjuvant therapy; positron-emission tomography; precision oncology