title: Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements.
abstract: OBJECTIVE
  Immune-related response criteria (irRC) was developed to adequately assess tumor response to immunotherapy. The irRC are based on bidimensional measurements, as opposed to unidimensional measurements defined by Response Evaluation Criteria in Solid Tumors, which has been widely used in solid tumors. We aimed to compare response assessment by bidimensional versus unidimensional irRC in patients with advanced melanoma treated with ipilimumab.
  
  
  METHODS
  Fifty-seven patients with advanced melanoma treated with ipilimumab in a phase II, expanded access trial were studied. Bidimensional tumor measurement records prospectively conducted during the trial were reviewed to generate a second set of measurements using unidimensional, longest diameter measurements. The percent changes of measurements at follow-up, best overall response, and time-to-progression (TTP) were compared between bidimensional and unidimensional irRC. Interobserver variability for bidimensional and unidimensional measurements was assessed in 25 randomly selected patients.
  
  
  RESULTS
  The percent changes at follow-up scans were highly concordant between the 2 criteria (Spearman r: 0.953-0.965, first to fourth follow-up). The best immune-related response was highly concordant between the 2 criteria (κw = 0.881). TTP was similar between the bidimensional and unidimensional assessments (progression-free at 6 months: 70% vs. 81%, respectively). The unidimensional measurements were more reproducible than bidimensional measurements, with the 95% limits of agreement of (-16.1%, 5.8%) versus (-31.3%, 19.7%), respectively.
  
  
  CONCLUSIONS
  irRC using the unidimensional measurements provided highly concordant response assessment compared with the bidimensional irRC, with less measurement variability. The use of unidimensional irRC is proposed to assess response to immunotherapy in solid tumors, given its simplicity, higher reproducibility, and high concordance with the bidimensional irRC.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA. Mizuki_Nishino@dfci.harvard.edu
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Maria
authors.initials: M
authors.lastname: Gargano
authors.forename: Margaret
authors.initials: M
authors.lastname: Suda
authors.forename: Nikhil H
authors.initials: NH
authors.lastname: Ramaiya
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D018709:Statistics, Nonparametric; D009626:Terminology as Topic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab