title: The value of serum chromogranin A as a predictor of tumor burden, therapeutic response, and nomogram-based survival in well-moderate nonfunctional pancreatic neuroendocrine tumors with liver metastases.
abstract: OBJECTIVE
  To investigate the usefulness of serum chromogranin A (CgA) for the prediction of tumor burden, therapeutic response, and nomogram-based survival in well-moderate nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) with liver metastases (LMs).
  
  
  METHODS
  This prospective study included 51 NF-PNETs of LMs patients, 134 other neuroendocrine tumors, and 125 controls. Serum CgA levels were determined by enzyme-linked immunosorbent assay at baseline and after treatment. LMs tumor burden was computed simultaneously from computed tomography/MRI scan with thin slices using a semiquantitative three-dimensional reconstruction approach. Predictive CgA for therapeutic response was assessed using the response evaluation criteria in solid tumors criteria. A nomogram to predict the prognostic value of CgA with variables selected in the multivariate Cox proportional hazards model was constructed; the accuracy of the nomogram was quantified by the (concordance index) C-index and a calibration plot.
  
  
  RESULTS
  Considering NF-PNETs, CgA correlated with the tumor grade and differentiation (P<0.05). There was a nonlinear exponential regression between LMs tumor burden and CgA levels (P<0.001). The alteration in CgA correlated with therapeutic response (P<0.001). Increased CgA presented significantly lower progression-free survival than the stable/decreased CgA subgroup (P<0.001). For overall survival, a baseline CgA increase greater than 2.5 upper limit of normal level was predictive of a poor prognosis (P<0.001). Baseline CgA level, LMs tumor burden, and Ki-67 were selected as independent factors for the nomogram to predict overall survival; the nomogram showed fitting calibration with a C-index of 0.87 (95% confidence interval, 0.82-0.92).
  
  
  CONCLUSIONS
  Serum CgA could be used to reflect tumor burden, evaluate the therapeutic response, and predict the survival outcomes for NF-PNETs with LMs. An effective nomogram including CgA was proposed for prediction.
authors.affiliation: Departments of aPancreatic Surgery bClinical Laboratory cRadiology dInterventional Radiology ePathology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xu
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Baishen
authors.initials: B
authors.lastname: Pan
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D053379:Chromogranin A / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000556:secondary / Q000628:therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000556:secondary / Q000601:surgery; D049451:Nomograms; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A; D019394:Ki-67 Antigen