title: Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome.
  
  
  OBJECTIVE
  To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT).
  
  
  METHODS
  Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31-223 d).
  
  
  METHODS
  Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria.
  
  
  CONCLUSIONS
  Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p=0.02) and OS (32.5 vs 15.8 mo; p=0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations.
  
  
  CONCLUSIONS
  In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Krajewski
authors.forename: Mengye
authors.initials: M
authors.lastname: Guo
authors.forename: Annick D
authors.initials: AD
authors.lastname: Van den Abbeele
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Yap
authors.forename: Nikhil
authors.initials: N
authors.lastname: Ramaiya
authors.forename: Jyothi
authors.initials: J
authors.lastname: Jagannathan
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Fabio A B
authors.initials: FA
authors.lastname: Schutz
authors.forename: Ivan
authors.initials: I
authors.lastname: Pedrosa
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000046:Academic Medical Centers; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D001900:Boston; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D015588:Observer Variation; D010671:Phenylurea Compounds; D011237:Predictive Value of Tests; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000077210:Sunitinib