title: Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients.
abstract: BACKGROUND
  Radiological assessment of response to checkpoint inhibitors remains imperfect. We evaluated individual lesion and inter-patient response by response evaluation (RECIST) 1.1, immune-related response criteria (irRC), CHOI and modified CHOI (mCHOI) and correlated response with overall survival (OS).
  
  
  METHODS
  Thirty-seven patients with 567 measurable lesions treated with pembrolizumab in the Keynote 001 trial were studied. Association of response with OS was determined.
  
  
  RESULTS
  Response varied according to site; lung lesions had the highest rate of complete response (69 out of 163 (42%) vs other sites 71 out of 404 (18%), P<0.0001). Delayed response post first scan was seen in 2 out of 37 (5%) deemed progressive (PD) by RECIST and 2 out of 14 (14%) deemed PD by irRC. Modified CHOI criteria showed response of 38% (14 out of 37). Change in tumour size and density on first follow-up assessment was associated with OS with each 1000 mm2increase in tumour size from baseline increasing the hazard of dying by 25.9% (HR=1.259, (95% CI=1.116-1.420), P=0.0002). Similarly, each 20HU increase in density increased the HR by 15% (HR=1.15, (95% CI 1.045-1.260), P=0.004). Response defined by any criteria had superior OS (CHOI P=0.0084; mCHOI P=0.0183; irRC P<0.0001 and RECIST P=0.0003).
  
  
  CONCLUSIONS
  Response by any criterion was prognostic. Novel patterns of response and changes on treatment in tumour density suggest complex anti-tumour responses to immunotherapy.
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.|Clinical Discovery Unit, Early Clinical Development, AstraZeneca plc, DaVinci Building, Melbourn Science Park, Melbourn, Hertfordshire, UK.
authors.forename: Leila
authors.initials: L
authors.lastname: Khoja
authors.affiliation: Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors.forename: Minnie
authors.initials: M
authors.lastname: Kibiro
authors.affiliation: Department of Medical Imaging, University Health Network, Toronto, Ontario, Canada.
authors.forename: Ur
authors.initials: U
authors.lastname: Metser
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Craig
authors.initials: C
authors.lastname: Gedye
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hogg
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Butler
authors.affiliation: Department of Biostatistics, University Health Network, Toronto, Ontario, Canada.
authors.forename: Eshetu G
authors.initials: EG
authors.lastname: Atenafu
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D066066:Response Evaluation Criteria in Solid Tumors; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab