title: Optimizing immune-related tumor response assessment: does reducing the number of lesions impact response assessment in melanoma patients treated with ipilimumab?
abstract: BACKGROUND
  Investigate the impact of the reduction of the number of target lesions on immune-related response assessment in advanced melanoma patients treated with ipilimumab.
  
  
  METHODS
  Ninety patients (53 males, 37 females; age range: 25-87) with advanced melanoma treated with ipilimumab in two clinical trials were studied. Tumor measurements during trial allowing up to 5 lesions per organ and 10 lesions in total were retrospectively reviewed. A second set of tumor measurements allowing up to 2 lesions per organ and 5 lesions in total was generated. Immune-related response assessments by two measurements were compared.
  
  
  RESULTS
  The number of target lesions was significantly reduced when up to 2 per organ and 5 in total lesions were allowed (Wilcoxon P < 0.0001). The immune-related response assessment using reduced number of lesions was highly concordant with assessment using the original number of lesions (Spearman r for the percent change on 1(st)-3(rd) follow-up: 0.860-0.970; κw for best immune-related response: 0.908). Median time-to-progression was 26.9 months (95%CI: 9.1-∞) by both assessments. Interobserver agreement of measurements was high for both assessments, with the concordance correlation coefficient above 0.98.
  
  
  CONCLUSIONS
  Reduction of the number of target lesions did not significantly affect immune-related response assessment or the measurement variability in advanced melanoma patients treated with ipilimumab. Using up to 2 per organ and 5 in total target lesions is proposed to assess immune-related response, while it is important to keep other novel features of immune-related response criteria such as confirmation of progression and inclusion of new lesion measurements.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Gargano
authors.affiliation: Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Suda
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Nikhil H
authors.initials: NH
authors.lastname: Ramaiya
authors.affiliation: Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
keywords: Immune-related response criteria; Immunotherapy; RECIST; Tumor response